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Biomedical subjects

J Rogers

Publications and source records attributed to J Rogers.

At least 19 recordsLinked to original sources
PubMed2007

Virulent spores of Bacillus anthracis and other Bacillus species deposited on solid surfaces have similar sensitivity to chemical decontaminants.

AIMS: To compare the relative sensitivity of Bacillus anthracis and spores of other Bacillus spp. deposited on different solid surfaces to inactivation by liquid chemical disinfecting agents. METHODS AND RESULTS: We prepared under similar conditions spores from five different virulent and three attenuated strains of B. anthracis, as well as spores of Bacillus subtilis, Bacillus atrophaeus (previously known as Bacillus globigii), Bacillus cereus, Bacillus thuringiensis and Bacillus megaterium. As spore-surface interactions may bias inactivation experiments, we evaluated the relative binding of different spores to carrier materials. The survival of spores deposited on glass, metallic or polymeric surfaces were quantitatively measured by ASTM standard method E-2414-05 which recovers spores from surfaces by increasing stringency. The number of spores inactivated by each decontaminant was similar and generally within 1 log among the 12 different Bacillus strains tested. This similarity among Bacillus strains and species was observed through a range of sporicidal efficacy on spores deposited on painted metal, polymeric rubber or glass. CONCLUSIONS: The data obtained indicate that the sensitivity of common simulants (B. atrophaeus and B. subtilis), as well as spores of B. cereus, B. thuringiensis, and B. megaterium, to inactivation by products that contain either: peroxide, chlorine or oxidants is similar to that shown by spores from all eight B. anthracis strains studied. SIGNIFICANCE AND IMPACT OF THE STUDY: The comparative results of the present study suggest that decontamination and sterilization data obtained with simulants can be safely extrapolated to virulent spores of B. anthracis. Thus, valid conclusions on sporicidal efficacy could be drawn from safer and less costly experiments employing non-pathogenic spore simulants.

Alloys↗
PubMed2006

Inflammatory changes parallel the early stages of Alzheimer disease.

Alzheimer disease (AD) is the most prominent cause of dementia in the elderly. To determine changes in the AD brain that may mediate the transition into dementia, the gene expression of approximately 10,000 full-length genes was compared in mild/moderate dementia cases to non-demented controls that exhibited high AD pathology. Including this latter group distinguishes this work from previous studies in that it allows analysis of early cognitive loss. Compared to non-demented high-pathology controls, the hippocampus of AD cases with mild/moderate dementia had increased gene expression of the inflammatory molecule major histocompatibility complex (MHC) II, as assessed with microarray analysis. MHC II protein levels were also increased and inversely correlated with cognitive ability. Interestingly, the mild/moderate AD dementia cases also exhibited decreased number of T cells in the hippocampus and the cortex compared to controls. In conclusion, transition into AD dementia correlates with increased MHC II(+) microglia-mediated immunity and is paradoxically paralleled by a decrease in T cell number, suggesting immune dysfunction.

Aged↗
PubMed2006

Increased insulin secretory capacity but decreased insulin sensitivity after correction of iron overload by phlebotomy in hereditary haemochromatosis.

AIMS/HYPOTHESIS: We recently demonstrated that humans with hereditary haemochromatosis have decreased insulin secretory capacity with a compensatory increase in insulin sensitivity. We therefore determined how these measures change after correction of tissue iron overload. SUBJECTS AND METHODS: Five non-diabetic subjects who had been studied previously at the time of initial diagnosis by means of the OGTT and frequently sampled intravenous glucose tolerance tests (FSIVGTT) underwent phlebotomy to normalise their serum ferritin. After normalisation of ferritin they were studied again (33+/-4 months after the initial studies) by OGTT and FSIVGTT. RESULTS: Normalisation of tissue iron stores resulted in an average 1.8-fold increase in the integrated area under the insulin curve during OGTT (p<0.0001), but no significant change in the area under the glucose curve (10% decrease, p=0.32). After phlebotomy, there was a 2.2-fold increase in insulin secretory capacity as determined by FSIVGTT (acute insulin response to glucose [AIRg], p<0.02) but a concomitant 70% fall in insulin sensitivity (Si, p<0.05). The disposition index (AIRgxSi) was unchanged (5% increase, p=0.90). BMI and fasting glucose were unchanged. At the time of diagnosis of haemochromatosis, four of the subjects had IGT. After normalisation of ferritin, two achieved NGT and two remained with IGT, despite 2.5- and 3.7-fold increases in insulin secretory capacity. CONCLUSIONS/INTERPRETATION: Insulin secretory capacity improves after normalisation of iron stores in subjects with hereditary haemochromatosis. Glucose tolerance status improves incompletely because of decreased insulin sensitivity after phlebotomy. We conclude that tissue iron levels are an important determinant of insulin secretion and insulin action.

Blood Glucose↗
PubMed2006

FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders revisited.

The recent identification of TGFBR2 mutations in Marfan syndrome II (MFSII) [Mizuguchi et al. (2004); Nat Genet 36:855-860] and of TGFBR1 and TGFBR2 mutations in Loeys-Dietz aortic aneurysm syndrome (LDS) [Loeys et al. (2005); Nat Genet 37:275-281] [OMIM 609192] has provided direct evidence of abnormal signaling in transforming growth factors beta (TGF-beta) in the pathogenesis of Marfan syndrome (MFS). In light of this, we describe the phenotypes and genotypes of five individuals. Patient 1 had MFS and abnormal cranial dura. Patient 2 had severe early onset MFS and an abnormal skull. Patients 3 and 4 had probable Furlong syndrome (FS). Patient 5 had marfanoid (MD) features, mental retardation (MR), and a deletion of chromosome 15q21.1q21.3. All patients had a condition within the MFS, MD-craniosynostosis (CS) or MD-MR spectrum. The names of these entities may become redundant, and instead, come to be considered within the spectrum of TGF-beta signaling pathway disorders. Two recurrent heterozygous FBN1 mutations were found in Patients 1 and 2, and an identical novel heterozygous de novo TGFBR1 mutation was found in Patients 3 and 4, in whom altered fibrillin-1 processing was demonstrated previously [Milewicz et al. (2000); Am J Hum Genet 67:279]. A heterozygous FBN1 deletion was found in Patient 5. These findings support the notion that perturbation of extracellular matrix homeostasis and/or remodeling caused by abnormal TGF-beta signaling is the core pathogenetic mechanism in MFS and related entities including the MD-CS syndromes.

Abnormalities, Multiple↗
PubMed2006

High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis.

AIMS/HYPOTHESIS: The prevalence and mechanisms of diabetes in hereditary haemochromatosis are not known. We therefore measured glucose tolerance, insulin secretory capacity and insulin sensitivity in adults with haemochromatosis. SUBJECTS AND METHODS: Subjects recruited from referrals to a haemochromatosis clinic underwent OGTT and frequently sampled IVGTT. A chart review of former clinic patients was also performed. RESULTS: The prevalence of diabetes (23%) and IGT (30%) was increased in haemochromatosis compared with matched control subjects (0% diabetes and 14% IGT). Subjects with haemochromatosis and diabetes were overweight (14%) or obese (86%). The prevalence of diabetes, as determined by chart review of fasting glucose values, in subjects who had haemochromatosis and were in the 40-79 years age range was 26%. Overall, patients with haemochromatosis and control subjects had similar values for acute insulin response to glucose and insulin sensitivity. However, patients with haemochromatosis and IGT had a 68% decrease in acute insulin response to glucose (p<0.02) compared with those with NGT. They were not insulin-resistant, exhibiting instead a 62% increase in insulin sensitivity (NS). Haemochromatosis subjects with diabetes exhibited further declines in acute insulin response to glucose, insulin resistance, or both. CONCLUSIONS/INTERPRETATION: Diabetes and IGT are common in haemochromatosis, justifying screening for diabetes and therapeutic phlebotomy. The major abnormality associated with IGT is decreased insulin secretory capacity. Diabetes is usually associated with obesity and concomitant insulin resistance.

Adult↗
PubMed2006

The genomic sequence and analysis of the swine major histocompatibility complex.

We describe the generation and analysis of an integrated sequence map of a 2.4-Mb region of pig chromosome 7, comprising the classical class I region, the extended and classical class II regions, and the class III region of the major histocompatibility complex (MHC), also known as swine leukocyte antigen (SLA) complex. We have identified and manually annotated 151 loci, of which 121 are known genes (predicted to be functional), 18 are pseudogenes, 8 are novel CDS loci, 3 are novel transcripts, and 1 is a putative gene. Nearly all of these loci have homologues in other mammalian genomes but orthologues could be identified with confidence for only 123 genes. The 28 genes (including all the SLA class I genes) for which unambiguous orthology to genes within the human reference MHC could not be established are of particular interest with respect to porcine-specific MHC function and evolution. We have compared the porcine MHC to other mammalian MHC regions and identified the differences between them. In comparison to the human MHC, the main differences include the absence of HLA-A and other class I-like loci, the absence of HLA-DP-like loci, and the separation of the extended and classical class II regions from the rest of the MHC by insertion of the centromere. We show that the centromere insertion has occurred within a cluster of BTNL genes located at the boundary of the class II and III regions, which might have resulted in the loss of an orthologue to human C6orf10 from this region.

Animals↗
PubMed2006

Abnormal haemoglobin levels in acute coronary syndromes.

BACKGROUND: Anaemia is an adverse prognostic marker in acute coronary syndromes (ACS), but the epidemiology of abnormal haemoglobin levels in such patients is uncertain. AIMS: To investigate the prevalence, nature and predictors of abnormal haemoglobin levels in ACS patients at admission. DESIGN: Observational study. METHODS: All emergency admissions from January to April 2005 were assessed within 24-48 h of hospital admission. ACS patients (unstable angina, non-ST-elevation or ST-elevation myocardial infarction) were enrolled (n = 320, 190 men). Clinical information was recorded. RESULTS: Overall, 71% had unstable angina; 18% non-ST-elevation myocardial infarction (MI), and 11% ST-elevation MI. Mean +/- SD haemoglobin was 14.3 +/- 1.7 g/dl in men and 13.2 +/- 1.5 g/dl in women. Abnormal haemoglobin was more common in men (65, 34%) than in women (34, 22%) (p = 0.013). Anaemia (haemoglobin <13 g/dl in men, or <12.0 g/dl in women) was recorded in 35 (18%) men and 24 (18%) women. All had admission haemoglobin >8 g/dl, and anaemia was usually normocytic. Multivariate predictors of anaemia (OR, 95%CI) were age (1.07, 1.04-1.1) and serum albumin (0.90, 0.81-1.00). Elevated haemoglobin (>16 g/dl) was recorded in 30 (16%) men and 4 (3%) women (p < 0.01), and was more common in ST-elevation MI patients (26%) than in unstable angina or non-ST elevation MI patients (9%) (p = 0.005). In patients who underwent invasive management with a post-procedure haemoglobin the following day (n = 85), 15 (18%) new cases of anaemia were detected. Admission duration correlated with haemoglobin (p < 0.01), creatinine (p < 0.01), troponin I (p < 0.01) and C-reactive protein (p < 0.01). Anaemia was more common in those who died in hospital (3, 60%) than in those who survived (56, 18%) (adjusted p = 0.0135). DISCUSSION: Abnormal haemoglobin levels were common in our ACS admissions. Anaemia was generally mild. Increasing age and interventional management were associated with anaemia, which in turn was associated with adverse in-hospital outcomes. Interventions to prevent and detect anaemia in this setting merit prospective testing.

Anemia↗
PubMed2006

The LRC haplotype project: a resource for killer immunoglobulin-like receptor-linked association studies.

There is increasing evidence for epistatic interactions between gene products (e.g. KIR) encoded within the Leukocyte Receptor Complex (LRC) with those (e.g. HLA) of the Major Histocompatibility Complex (MHC), resulting in susceptibility to disease. Identification of such associations at the DNA level requires comprehensive knowledge of the genetic variation and haplotype structure of the underlying loci. The LRC haplotype project aims to provide this knowledge by sequencing common LRC haplotypes.

Chromosome Mapping↗
PubMed2006

What should we say?

Abstract ethics mostly focuses on what we do. One form of action is a speech act. What we say can have profound effects. We can and should choose our words and how we speak wisely. When someone close to us suffers an injury or serious illness, a duty of beneficence requires that we support that person through beneficial words or actions. Though our intentions are most often benign, by what we say we often make the unfortunate person feel worse. Beginning with two personal accounts, this article explains what can go wrong in the compassionate speech of wellwishers, and uncovers some of the reasons why people say things that are hurtful or harmful. Despite a large body of clinical evidence, there is no perfect strategy for comforting a friend or relative who is ill, and sometimes even the best thing to say can still be perceived as insensitive and hurtful. In some cases, we may have good reason to knowingly say a hurtful or insensitive thing. Saying these 'wrong' things can sometimes be the best way to help a person in the long term. To complicate matters, there can be moral reasons for overriding what is good for the patient. What kind of admonishments should we make to a badly behaved patient? What is the value of authenticity in our communication with the people we love? These questions demand an ethical defence of those speech acts which are painful to hear but which need to be said, and of those which go wrong despite the best efforts of the wellwisher. We offer an ethical account, identifying permissible and impermissible justifications for the things we say to a person with a serious injury or illness.

Affect↗
PubMed2006

The semantics of procedures and diseases in SNOMED CT.

OBJECTIVES: SNOMED CT is emerging as a reference terminology for the entire health care process. It claims to be founded on logic-based modelling principles. In this article, we analyze a special encoding scheme for diseases and procedures in SNOMED CT, the so-called relationship groups (RGs), which had been devised to avoid ambiguities in definitions. METHODS: We reformulate SNOMED CT's relationship groups in the format of description logics in order to check whether RGs serve the needs they were designed for. RESULTS: We show that a considerable proportion of relationship groups represent hidden mereological relations. We also report discrepancies encountered between the defined semantics of many SNOMED CT terms and their intuitive meaning, as well as inconsistencies detected between the definition of various complex composed terms and the definition of their top-level parents. CONCLUSIONS: We formulate recommendations for improving SNOMED CT by replacing most occurrences of relation groups by formally more adequate "part-of" relations.

Anatomy↗
PubMed2005

Surface complexation studied via combined grazing-incidence EXAFS and surface diffraction: arsenate on hematite (0001) and (10-12).

X-ray diffraction [crystal-truncation-rod (CTR)] studies of the surface structure of moisture-equilibrated hematite reveal sites for complexation not present on the bulk oxygen-terminated surface, and impose constraints on the types of inner-sphere sorption topologies. We have used this improved model of the hematite surface to analyze grazing-incidence EXAFS results for arsenate sorption on the c (0001) and r (10-12) surfaces measured in two electric vector polarizations. This work shows that the reconfiguration of the surface under moist conditions is responsible for an increased adsorption density of arsenate complexes on the (0001) surface relative to predicted ideal termination, and an abundance of "edge-sharing" bidentate complexes on both studied surfaces. We consider possible limitations on combining the methods due to differing surface sensitivities, and discuss further analysis possibilities using both methods.

Adsorption↗
PubMed2005

Cross-species replication of a serum osteocalcin quantitative trait locus on human chromosome 16q in pedigreed baboons.

Osteocalcin (OC), a serum marker of bone formation, in its intact form reflects osteoblast activity. It is of interest to clinicians and bone biologists due to easy measurability and potential utility as an identifier of those at risk for fracture and other complications associated with bone metabolism disorders. The only published linkage study in humans shows significant evidence for a quantitative trait locus (QTL) affecting OC levels on 16q. We used the baboon, a primate model for skeletal maintenance and turnover, to detect and quantify the effects of genes on serum OC levels and to localize chromosomal regions harboring the responsible loci. We assayed OC levels in 591 pedigreed animals, assessed OC heritability, and conducted a genomewide linkage scan for evidence of QTLs affecting this phenotype. Heritability in these baboons is 0.24. Suggestive linkage is evident with markers in a region homologous to human chromosome 16q. This first genomewide linkage scan in a nonhuman primate for QTLs affecting bone formation as reflected by OC levels provides cross-species replication of the QTL on chromosome 16q previously localized in humans. Given the concordance of results of the only two genome scans for this trait in two primate species, further studies of this region are warranted.

Animals↗
PubMed2005

A quantitative trait locus for normal variation in forearm bone mineral density in pedigreed baboons maps to the ortholog of human chromosome 11q.

Baboons share many anatomical, physiological, and developmental characteristics with humans that make them excellent models for human bone maintenance and turnover. We conducted statistical genetic analyses, including a whole-genome linkage screen, of dual-energy x-ray absorptiometry-acquired measures of areal bone mineral density (aBMD), currently the most reliable single predictor of susceptibility to osteoporotic fracture in humans, from three forearm sites on the radius and ulna of 667 pedigreed baboons. We used a maximum likelihood-based variance decomposition approach to detect and quantify the effects of genes on normal variation in aBMD in the forearm of these baboons and to localize these effects to chromosomal regions. We estimated significant heritability for aBMD at all three sites and found evidence for a quantitative trait locus (QTL) contributing significantly to the genetic effects on this trait in a region of the baboon genome homologous to human chromosome 11q12-13. This first reported genome-wide linkage screen in a nonhuman primate for QTLs affecting forearm aBMD provides important cross-species replication of a QTL found in humans. The concordance of our results in a nonhuman primate with those reported for humans provides strong evidence that a gene (or genes) in this region affects normal variation in BMD.

Animals↗
PubMed2005

Inferior late functional and metabolic outcomes in African American simultaneous kidney-pancreas recipients.

The aim of this study was to determine the impact of ethnicity on the major endpoints of a prospective, multi-center, randomized trial of 2 dosing regimens of daclizumab compared with no antibody induction in simultaneous kidney-pancreas transplantation (SKPT). A total of 298 patients were randomized into 3 groups: daclizumab 1 mg/kg/dose every 14 days for 5 doses (Group I, n = 107), daclizumab 2 mg/kg/dose every 14 days for 2 doses (Group II, n = 113), and no antibody induction (Group III, n = 78). All patients received tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. Thirty-seven patients (12.4%) were African American (AA) and 261 were non-African American (NAA). Demographic and transplant characteristics were comparable between AA and NAA patients. At 3 years, there were no differences in patient, kidney, or pancreas graft survival rates. Rejection rate was similar between AA and NAA. Although mean serum creatinine (SCr) levels at 1 year were comparable between AA and NAA patients (AA 1.5 mg/dL vs NAA 1.3 mg/dL; P = .23), by 3 years AA patients had higher mean SCr levels (AA 2.1 mg/dL vs NAA 1.5 mg/dL; P < .0001) and lower calculated glomerular filtration rate (GFR) (AA 45 mL/min vs NAA 56 mL/min; P = .01). Mean HgbA1C, total cholesterol, and diastolic blood pressure (BP) were higher in AA patients at 3 years, compared with NAA patients. In conclusion, in this study, AA patients had worse late functional and metabolic outcomes after SKPT compared with NAA patients. Further longitudinal follow-up is needed to determine the ultimate impact of these findings on long-term patient and graft survival.

Adult↗
PubMed2005

Impact of the metabolic syndrome on long-term outcomes in simultaneous kidney-pancreas transplantation.

The metabolic syndrome (MS) has been implicated as an important nonimmunologic risk factor for chronic renal transplant dysfunction. The aim of this study was to determine the impact of the MS on outcomes in simultaneous kidney-pancreas transplantation (SKPT). Data were available on 241 patients enrolled in a prospective, multicenter randomized study of daclizumab compared with no antibody induction in SKPT. Presence of MS before and after SKPT was defined using NCEP-ATP III (National Cholesterol Education Program Adult Treatment Panel III) criteria. Body mass index (BMI) was used as a surrogate for waist circumference. MS was present in 59% of patients pretransplantation but only in 19% of patients 1 year after SKPT (P < .0001). Demographic and transplant characteristics were well matched for those with MS (MS+) and without MS (MS-) at 1 year. Presence of MS at 1 year was associated with the following changes at 3 years: increased serum creatinine level (1.65 mg/dL MS- vs 2.05 mg/dL MS+; P = .13); decreased modification of diet in renal disease calculated glomerular filtration rate (GFR; 58 mL/min MS- vs 48 mL/min MS+; P = .02); increased HgbA1C level (5.6% MS- vs 6.6% MS+; P < .001); and lower pancreas graft (PG) survival rate (88% MS- vs 71% MS+; P = .01). Linear regression analysis identified MS+ and the subgroup of MS+ without functioning PG at 1 year as independent risk factors for renal dysfunction, whereas MS+ with functioning PG at 1 year was not a risk factor for renal dysfunction. Presence of MS at 1 year is associated with long-term renal dysfunction after SKPT. Efforts to decrease early PG failure may help mitigate against MS-associated renal dysfunction.

Adult↗
PubMed2005

Genome-wide scan of resistin mRNA expression in omental adipose tissue of baboons.

INTRODUCTION: The hormone resistin was recently discovered in adipose tissue of mice. Functional tests suggest a role for resistin in the regulation of insulin sensitivity. However, human studies have reported controversial results on the metabolic function of this hormone. METHODS: A 1 g omental adipose tissue biopsy was obtained from 404 adult baboons. Resistin mRNA expression was assayed by real-time, quantitative RT-PCR, and univariate and bivariate quantitative genetic analyses were performed, via the variance decomposition approach. A genome scan analysis was conducted using resistin mRNA abundance in omental adipose tissue as a quantitative phenotype. RESULTS: A significant heritability of h2 = 0.23 (P = 0.003) was found for resistin mRNA abundance in omental adipose tissue. A genome scan detected a quantitative trait locus for resistin expression with an LOD score of 3.8, in the region between markers D19S431 and D19S714, corresponding to human chromosome 19 p13. This chromosomal region contains genes related to insulin resistance phenotypes, such as resistin, insulin receptor, angiopoietin-like 4 protein and LDL receptor. CONCLUSIONS: Individual variation in resistin mRNA expression has a significant genetic component, and a gene or genes on chromosome 19 p13 may regulate resistin mRNA levels in baboon omental adipose tissue.

Adipose Tissue↗
PubMed2004

Genotype-by-sex and environment-by-sex interactions influence variation in serum levels of bone-specific alkaline phosphatase in adult baboons (Papio hamadryas).

While more than 77% of the people in the US with osteoporosis are women, the contributions of genotype-by-sex (G x S) and environment-by-sex interactions to sex differences in osteoporosis risk factors have not been studied. To address this issue, we conducted a statistical genetic analysis of serum concentrations of bone-specific alkaline phosphatase (Bone ALP), a highly specific marker of osteoblast function that is elevated in persons with conditions like osteoporosis characterized by excessive bone turnover or rapid bone loss. We assayed Bone ALP from 657 pedigreed baboons using a commercially available ELISA kit. Using a maximum likelihood variance decomposition approach, we treated sex as an environmental milieu in which genes influencing Bone ALP levels are expressed. We modeled the genetic covariance in Bone ALP between all relative pairs conditional on their sex so that the covariance is the product of the kinship, the genetic correlation between trait levels in the two sexes, and the genetic variances in the two sexes. Sex-specific maximum likelihood estimates (MLE) of residual heritability for Bone ALP were greater for females than for males (h2 = 0.44 vs. h2 = 0.26, respectively), but likelihood ratio tests revealed only a marginally significant difference in sex-specific genetic variances (P = 0.057). In contrast, the between-sex genetic correlation (rhoG = 0.43) was significantly less than 1.0 (P = 0.037), and the difference in sex-specific environmental variances was highly significant (P = 0.00006). We report the first evidence for G x S interactions influencing variation in an osteoporosis risk factor. The diminished between-sex genetic correlation implies that different genes influence Bone ALP levels in the two sexes. The significant differences between environmental variances suggest that unmeasured factors, including those from the internal, biological environments of the two sexes, account for a greater proportion of the Bone ALP variation in males.

Alkaline Phosphatase↗