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Biomedical subjects

Jonathan Brown

Publications and source records attributed to Jonathan Brown.

5 recordsLinked to original sources
PubMed2025

The extracellular vesicle transcriptome provides tissue-specific functional genomic annotation relevant to disease susceptibility in obesity.

We characterized circulating extracellular vesicles (EVs) in obese and lean humans, identifying transcriptional cargo differentially expressed in obesity (277 unique genes; false discovery rate < 10%). Since circulating EVs may have broad origin, we compared this obesity EV transcriptome with expression from human visceral-adipose-tissue-derived EVs from freshly collected and cultured biopsies from the same obese individuals, observing high concordance. Using a comprehensive set of adipose-specific epigenomic and chromatin conformation assays, we found that the differentially expressed transcripts from the EVs were those regulated in adipose by body mass index-associated SNPs (p < 5 &#xd7; 10-8) from a large-scale genome-wide association study (GWAS). Using a phenome-wide association study of the regulatory SNPs for the EV-derived transcripts, we identified a substantial enrichment for inflammatory phenotypes, including type 2 diabetes. Collectively, these findings represent the convergence of the GWAS (genetics), epigenomics (transcript regulation), and EV (liquid biopsy) fields, enabling powerful future genomic studies of complex diseases.

Humans↗
PubMed2004

Detection of Mycobacterium tuberculosis (TB) in vitro and in situ using an electronic nose in combination with a neural network system.

The use of volatile production patterns produced by Mycobacterium tuberculosis and associated bacterial infections from sputum samples were examined in vitro and in situ using an electronic nose based on a 14 sensor conducting polymer array. In vitro, it was possible to successfully discriminate between M. tuberculosis (TB) and control media, and between M. tuberculosis and M. avium, M. scrofulaceum and Pseudomonas aeruginosa cultures in the stationary phase after 5-6h incubation at 37 degrees C based on 35 samples. Using neural network (NN) analysis and cross-validation it was possible to successfully identify 100% of the TB cultures from others. A second in vitro study with 61 samples all four groups were successfully discriminated with 14 of 15 unknowns within each of the four groups successfully identified using cross-validation and discriminant function analysis. Subsequently, lipase enzymes were added to 46 sputum samples directly obtained from patients and the head space analysed. Parallel measurements of bacterial contamination were also carried out for confirmation using agar media. NN analysis was carried out using some of the samples as a training set. Based on the NN and genetic algorithms of up to 10 generations it was possible to successfully cross-validate 9 of 10 unknown samples. PCA was able to discriminate between TB infection alone, the controls, M. avium, P. aeruginosa and a mixed infection. These findings will have significant implications for the development of rapid qualitative systems for screening of patient samples and clinical diagnosis of tuberculosis.

Algorithms↗
PubMed2004

Urinary isoflavone kinetics: the effect of age, gender, food matrix and chemical composition.

Urinary isoflavone excretion is used to monitor compliance and examine biological effects. The present study determined if there were alterations in urinary isoflavone excretion following the ingestion of different soya foods and if age and gender potentially modified profiles. Twenty premenopausal women, seventeen post-menopausal women and twenty men received a defined single oral bolus dose (0.44 mg isoflavones/kg body weight) of soya milk, textured vegetable protein (TVP) or tempeh on three separate occasions. Baseline and four consecutive complete 24 h pooled urines were collected during each period. Urinary genistein recovery was influenced by gender and food matrix. For women the urinary genistein recovery was higher following soya-milk consumption compared with TVP (P<0.05). Tempeh consumption also resulted in an increased urinary genistein recovery relative to soya milk in premenopausal women (P<0.052). No differences in urinary genistein recoveries between soya foods were observed in the men. Although urinary daidzein excretion was similar across the foods studied and was not affected by age or gender, conversion to its intestinal metabolite, equol, resulted in potential matrix and chemical composition effects; urinary equol excretion was higher (P<0.01) following tempeh ingestion among equol producers. Together these data suggest that the fractional absorption of genistein is potentially different in men and women and is influenced by the food matrix and chemical composition. Furthermore, the data suggest that the metabolism of daidzein may be altered by the chemical composition of the isoflavones ingested. Further studies are required to examine the effect of higher intake and define the relative influence of these factors in elderly population groups.

Adolescent↗
PubMed2002

Completion of advance directives by older health maintenance organization members: the role of attitudes and beliefs regarding life-sustaining treatment.

OBJECTIVES: This study examined whether older health maintenance organization (HMO) members' attitudes and beliefs regarding life-sustaining treatment were associated with their completion of advance directives (ADs). DESIGN: A mailed survey of 1,247 subjects, aged 75 and older, participating in a randomized trial comparing two educational interventions designed to increase AD completion: mailed written materials versus written materials plus a videotape. AD completion was documented by medical record review. SETTING: The initial trial took place in October 1994 at a large group-model HMO in the Denver metropolitan area. The survey was mailed to participants 3 months after the trial. PARTICIPANTS: All HMO members aged 75 and older who received medical care at one of the medical offices (n = 1247) were mailed the survey. Participants were the 735 members who returned the survey. MEASUREMENTS: AD completers were compared with noncompleters on survey items pertaining to attitudes and beliefs regarding life-sustaining treatment. RESULTS: Of survey respondents, AD completers (n = 313) differed from noncompleters (n = 422) in their agreement with the following attitudinal/belief statements: (1) Putting my wishes for life-sustaining treatment in writing is too binding (completers = 12, noncompleters = 35); (2) I prefer that my family decide what kind of medical care is best for me if I should become unable to communicate my wishes (completers = 69, noncompleters = 88); and (3) My physician clearly understands my wishes for life-sustaining treatment (completers = 76, noncompleters = 43; all values, P< .0001). CONCLUSIONS: Completers were more likely to believe that their physicians understood their wishes and less likely to think that ADs are too binding. More noncompleters wanted their family to decide, even though an AD would increase their families' ability to do so. AD completion rates might increase if they were characterized as a way to preserve flexibility in a complex medical system, help families reach amicable decisions on behalf of their loved ones, and increase patients' confidence that their physician understands their wishes for life-sustaining treatment.

Advance Directives↗