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Biomedical subjects

Deborah Jones

Publications and source records attributed to Deborah Jones.

17 recordsLinked to original sources
PubMed2007

Chronic hexosamine flux stimulates fatty acid oxidation by activating AMP-activated protein kinase in adipocytes.

The hexosamine biosynthesis pathway (HBP) serves as a nutrient sensor and has been implicated in the development of type 2 diabetes. We previously demonstrated that fatty acid oxidation was enhanced in transgenic mouse adipocytes, wherein the rate-limiting enzyme of the HBP, glutamine:fructose-6-phosphate amidotransferase (GFA), was overexpressed. To explore the molecular mechanism of the HBP-induced fatty acid oxidation in adipocytes, we studied AMP-activated protein kinase (AMPK), an energy sensor that stimulates fatty acid oxidation by regulating acetyl-CoA carboxylase (ACC) activity. Phosphorylation and activity of AMPK were increased in transgenic fat pads and in 3T3L1 adipocytes treated with glucosamine to stimulate hexosamine flux. Glucosamine also stimulated phosphorylation of ACC and fatty acid oxidation in 3T3L1 adipocytes, and these stimulatory effects were diminished by adenovirus-mediated expression of a dominant negative AMPK in 3T3L1 adipocytes. Conversely, blocking the HBP with a GFA inhibitor reduced AMPK activity, ACC phosphorylation, and fatty acid oxidation. These changes are not explained by alterations in the cellular AMP/ATP ratio. Further demonstrating that AMPK is regulated by the HBP, we found that AMPK was recognized by succinylated wheat germ agglutinin, which specifically binds O-GlcNAc. The levels of AMPK in succinylated wheat germ agglutinin precipitates correlated with hexosamine flux in mouse fat pads and 3T3L1 adipocytes. Moreover, removal of O-GlcNAc by hexosaminidase reduced AMPK activity. We conclude that chronically high hexosamine flux stimulates fatty acid oxidation by activating AMPK in adipocytes, in part through O-linked glycosylation.

3T3-L1 Cells↗
PubMed2006

Improving dietary habits in disadvantaged women with HIV/AIDS: the SMART/EST women's project.

There is a lack of information on whether brief nutrition education can succeed in improving longer-term dietary patterns in disadvantaged populations with HIV/AIDS. In the SMART/EST II Women's Project 466 disadvantaged women with HIV/AIDS were randomized to one of four groups and received a two-phase training consisting of a coping skills/stress management and nutrition education provided either in a group or individually. At baseline the majority of participants had excessive fat and sugar consumption and suboptimal intakes of vegetables, fruits, calcium-rich foods and whole grains. Dietary patterns for all participants improved after the nutrition intervention primarily due to decreases in high fat and high sugar foods such as soda and fried foods and were still significantly better 18 months later. There were only short-term differences in improvements between the four groups. These findings support the value of even brief nutrition education for disadvantaged women living with HIV/AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Development and implementation of a medication adherence training instrument for persons living with HIV: the MATI.

Recent advances in the medical management of HIV offer the potential for increased longevity, improved quality of life, and the treatment of HIV as a chronic, rather than terminal, illness. The advent of highly active antiretroviral therapy (HAART) has required the necessity of strict adherence to complex medication regimens. As a vital factor in the successful outcome of HAART therapy, adherence-focused treatment represents a teaching opportunity for practitioners involved in the care and management of persons who are HIV positive. Scores of articles have been published regarding nonadherence, and numerous strategies have been employed to encourage adherence. Despite these efforts, medication adherence continues to present problems for patients and health care providers. This article discusses prior and existing adherence interventions for people living with HIV and outlines the rationale related to the development of a structured protocol, the Medication Adherence Training Instrument (MATI), for the evaluation and enhancement of HIV medication adherence by health care providers. The key components to the MATI throughout all sessions are to provide information, enhance motivation, and assess current levels of adherence and HIV-related knowledge.

Adult↗
PubMed2005

Decreased depression up to one year following CBSM+ intervention in depressed women with AIDS: the smart/EST women's project.

This prospective multisite Phase III clinical trial (Miami, New York, New Jersey) investigated the long-term (one year) effects of a 10-week group cognitive-behavioral stress management/expressive supportive therapy (CBSM+) intervention on disadvantaged minority women living with AIDS. The CBSM+ intervention consisted of 10-weekly group session of stress management, cognitive-behavioral skill training, relaxation techniques and expressive-supportive therapeutic strategies. The primary study outcome was self-reported depression scores as measured by the BDI. The CBSM+ Group intervention significantly decreased depression scores on the BDI for women following the intervention and maintained the decreased level at one-year follow-up.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Hyperglycemia and inhibition of glycogen synthase in streptozotocin-treated mice: role of O-linked N-acetylglucosamine.

Glycogen synthase is post-translationally modified by both phosphate and O-linked N-acetylglucosamine (O-GlcNAc). In 3T3-L1 adipocytes exposed to high concentrations of glucose, O-GlcNAc contributes to insulin resistance of glycogen synthase. We sought to determine whether O-GlcNAc also regulates glycogen synthase in vivo. Glycogen synthase activity in fat pad extracts was inhibited in streptozotocin (STZ)-treated diabetic mice. The half-maximal activation concentration for glucose 6-phosphate (A(0.5)) was increased to 830 +/- 120 microm compared with 240 +/- 20 microm in control mice (C, p < 0.01), while the basal glycogen synthase activity (%I-form) was decreased to 2.4 +/- 1.4% compared with 10.1 +/- 1.8% in controls (p < 0.01). Glycogen synthase activity remained inhibited after compensatory insulin treatment. After insulin treatment kinetic parameters of glycogen synthase were more closely correlated with blood glucose (A(0.5), r(2) = 0.70; %I-form, r(2) = 0.59) than insulin levels (A(0.5), r(2) = 0.04; %I-form, r(2) = 0.09). Hyperglycemia also resulted in an increase in the level of O-GlcNAc on glycogen synthase (16.1 +/- 1.8 compared with 7.0 +/- 0.9 arbitrary intensity units for controls, p < 0.01), even though the level of phosphorylation was identical in diabetic and control mice either with (STZ: 2.9 +/- 1.0 and C: 3.2 +/- 0.8) or without (STZ: 12.2 +/- 2.8 and C: 13.8 +/- 3.0 arbitrary intensity units) insulin treatment. In all mice the percent activation of glycogen synthase that could be achieved in vitro by recombinant protein phosphatase 1 (230 +/- 30%) was significantly greater in the presence of beta-d-N-acetylglucosaminidase (410 +/- 60%, p < 0.01). This synergistic stimulation of glycogen synthase due to codigestion by protein phosphatase 1 and beta-d-N-acetylglucosaminidase was more pronounced in STZ-diabetic mice (310 +/- 70%) compared with control mice (100 +/- 10%, p < 0.05). The findings demonstrate that O-GlcNAc has a role in the regulation of glycogen synthase both in normoglycemia and diabetes.

Adipose Tissue↗
PubMed2004

A comparison of cup-to-disc ratio measurement in normal subjects using optical coherence tomography image analysis of the optic nerve head and stereo fundus biomicroscopy.

PURPOSE: To determine the relationships between morphometric optic nerve head (ONH) characteristics defined using optical coherence tomography (OCT) and clinical judgments of cup-to-disc (CD) ratios. METHODS: CD ratios were estimated in 20 subjects by two experienced clinicians using stereo fundus biomicroscopy. Sagittal OCT images were obtained in positions defined by clinicians corresponding to the location of their horizontal and vertical CD ratio estimates. To estimate CD ratios using the OCT images, disc width was defined as the separation of the terminations of the retinal pigment epithelium on each side of the image. OCT cup widths were determined using two criteria: the first measured the separation of cup walls halfway down each side and the second estimated the separation 1/3 down each side. Cups that were less than 150 microm deep were defined as flat for the OCT images. Data were analysed using mean and standard deviation of the differences between clinical estimates and imaging techniques as well as using intraclass correlations (ICC). RESULTS: Between techniques, the range of ICCs for the 1/2 depth criterion was 0.74-0.90 and for the 1/3 criterion was 0.59-0.81. The limits of agreement for the 1/2 criterion were also better than the 1/3 criterion. CONCLUSION: Accurate measures of CD ratio may be derived from OCT ONH images. Estimates of clinical CD ratios in normal subjects appear to be made using depth judgments closer to 1/2 of the way down the cup than 1/3.

Adult↗
PubMed2003

Activation of the hexosamine signaling pathway in adipose tissue results in decreased serum adiponectin and skeletal muscle insulin resistance.

Overexpression of the rate-limiting enzyme for hexosamine synthesis (glutamine:fructose-6-phosphate amidotransferase) in muscle and adipose tissue of transgenic mice was previously shown to result in insulin resistance and hyperleptinemia. Explanted muscle from transgenic mice was not insulin resistant in vitro, suggesting that muscle insulin resistance could be mediated by soluble factors from fat tissue. To dissect the relative contributions of muscle and fat to hexosamine-induced insulin resistance, we overexpressed glutamine:fructose-6-phosphate amidotransferase 2.5-fold, specifically in fat under control of the aP2 promoter. Fasting glucose, insulin, and triglycerides were unchanged in the transgenic mice; leptin and beta-hydroxybutyrate levels were 91% and 29% higher, respectively. Fasted transgenic mice have mild glucose intolerance and skeletal muscle insulin resistance in vivo. In fasting transgenic mice, glucose disposal rates with hyperinsulinemia were decreased 27% in females and 10% in males. Uptake of 2-deoxy-D-glucose into muscle was diminished by 45% in female and 21% in male transgenics. Serum adiponectin was also lower in the fasted transgenics, by 37% in females and 22% in males. TNF alpha and resistin mRNA levels in adipose tissue were not altered in the fasted transgenics; levels of mRNA for leptin were increased and peroxisome proliferator-activated receptor gamma decreased. To further explore the relationship between adiponectin and insulin sensitivity, we examined mice that have been refed for 6 h after a 24-h fast. Refeeding wild-type mice resulted in decreased serum adiponectin and increased leptin. In transgenic mice, however, the regulation of these hormones by refeeding was lost for adiponectin and diminished for leptin. Refed transgenic female and male mice no longer exhibited decreased serum adiponectin in the refed state, and they were no longer insulin resistant as by lower or unchanged insulin and glucose levels. We conclude that increased hexosamine levels in fat, mimicking excess nutrient delivery, are sufficient to cause insulin resistance in skeletal muscle. Changes in serum adiponectin correlate with the insulin resistance of the transgenic animals.

3-Hydroxybutyric Acid↗
PubMed2003

A comparison of cup-to-disc ratio evaluation in normal subjects using stereo biomicroscopy and digital imaging of the optic nerve head.

The cup-to-disc (CD) ratio evaluated using stereoscopic biomicroscopy was compared with that evaluated by viewing a non-stereo digital image of the optic nerve head. Twenty normal subjects (mean age 26 +/- 4 years) were evaluated by two observers. The average CD ratio was 0.29 with a range of 0-0.80. The intra-class correlations between the observers ranged from 0.82 to 0.96, when comparing horizontal and vertical CD ratios for both evaluation techniques. The mean CD ratio was significantly smaller when viewing the digital image (0.25 +/- 0.01) compared with stereoscopic observation (0.33 +/- 0.03, p < 0.0001). Although the mean differences between the two techniques were small, the percentage of CD ratios that differed by >or=0.2 were between 5 and 25% of evaluations. Caution should be exercised when using stereoscopic and non-stereo digital evaluations of CD ratio interchangeably to assess longitudinal progression in a multi-clinician setting.

Adult↗
PubMed2003

Visual acuity assessment: a comparison of two tests for measuring children's vision.

PURPOSE: To compare the Kay Picture Test and the logMAR Crowded Test. METHODS: Monocular visual acuity measurement was attempted on 103 paediatric subjects (aged between 2.5 and 16 years) attending eye clinics, using each of the visual acuity tests. RESULTS: The results obtained with the two tests were found to be comparable as confirmed with the Intra-class Correlation Coefficient, which revealed good agreement between the two tests. There was significant correlation between the visual acuity results measured and high conformity in the results from the weaker eye. There was a statistical difference in acuity scores between the tests; the Kay Picture Test gave a lower logMAR score with a mean difference of 0.08 logMAR. This 0.08 difference represents an actual difference of less than one line of acuity measure which can be considered to be clinically insignificant. There was a significant difference in the ability to perform each of the tests under binocular conditions, with more of the 50 children, aged 5 and under, able to perform the Kay Picture Test than the logMAR Crowded Test. CONCLUSIONS: The results obtained with the two tests are comparable. Both tests can be considered to be appropriate for amblyopia detection and the use of picture-based logMAR tests should be considered for younger children.

Adolescent↗
PubMed2002

Glutamate infusion coupled with hypoxia has a neuroprotective effect in the rat.

Traumatic brain injury leads to a rise in glutamate, interference with oxygen supply and secondary neuronal death in the region surrounding the primary lesion. In the present experiments we have examined the effect of combining glutamate infusion with hypoxia on both brain metabolism and neuronal death. We have used microdialysis in unanaesthetised rats with a novel dual assay for glucose and lactate to monitor the temporal relation of changes in these metabolites resulting from infusion of 100 mM glutamate alone or combined with a reduction of inspired oxygen to 8%. In a parallel series of experiments we have compared the size of neuronal lesions under the same experimental conditions. We have used MAP2 antibody staining to measure the size of the neuronal lesion. Our results demonstrate that a 30 min glutamate infusion causes an immediate increase in neuronal glucose utilisation and a rise in lactate production. When hypoxia is added during the last 15 min of glutamate infusion there is a small rise in glucose and a large additional increase in lactate. The size of the neuronal lesions produced by infusion of 100 mM glutamate is reduced by the addition of hypoxia.

Animals↗