Biomedical subjects

J E Roberts

Publications and source records attributed to J E Roberts.

At least 19 recordsLinked to original sources

PubMed2005

Blink rate in boys with fragile X syndrome: preliminary evidence for altered dopamine function.

BACKGROUND: Dopamine, a neurotransmitter involved in motor and cognitive functioning, can be non-invasively measured via observation of spontaneous blink rates. Blink rates have been studied in a number of clinical conditions including schizophrenia, autism, Parkinsons, and attention deficit/hyperactivity disorder with results implicating either hyper or hypo dopaminergic states. METHODS: This study examined spontaneous blink rate in boys with fragile X syndrome (FXS). Blink rates of boys (4-8 years old) with FXS (n = 6) were compared with those of age-matched typically developing boys (n = 6) during active and passive tasks. Blink rates (blinks per minute) for each task were compared between the two groups. Then, the relation between blink measures and core FXS-related features [problem behaviours, arousal, fmr 1 protein (FMRP)] were examined within the group of boys with FXS. RESULTS: Blink rate in boys with FXS was significantly higher than typically developing boys during passive tasks. Within the FXS group, there were significant correlations between blink rate and problem behaviours and physiological arousal (i.e. heart activity) but not with FMRP. CONCLUSIONS: Observed differences in spontaneous blink rate between boys with and without FXS and the relation between blink rate and physiological and behavioural measures in boys with FXS suggests that further work examining dopamine dysfunction as a factor in the pathophysiology of FXS may be warranted.

Arousal↗

PubMed2004

Maternal serum levels of interferon-gamma and interleukin-2 soluble receptor-alpha predict the outcome of early IVF pregnancies.

BACKGROUND: Elevated maternal serum levels of interleukin-2 soluble receptor-alpha (IL-2 sRalpha), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) have been associated with pregnancy loss. The aim of our study was to evaluate the predictive value of these cytokines in the outcome of early IVF pregnancies. METHODS: One hundred and fifty-nine consecutive IVF patients who were subsequently diagnosed to have a biochemical pregnancy (n = 23), a first-trimester miscarriage (n = 19) or a normal term delivery (n = 117) were included in this study. Serum was collected from the initial pregnancy test, 11 days after a day 3 embryo transfer, and all samples were analysed for IL-2 sRalpha, TNF-alpha and IFN-gamma by commercially available enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: IL-2 sRalpha levels were significantly higher in patients with an early pregnancy loss compared with patients with a normal term delivery (849.5 +/- 69.6 versus 693.5 +/- 31.2 pg/ml, P = 0.02), and a cut-off point of IL-2 sRalpha >1000 pg/ml predicted a poor pregnancy outcome (44.4 versus 22.7% pregnancy loss, IL-2 sRalpha >or=1000 versus IL-2 sRalpha <1000 pg/ml; P = 0.02). IFN-gamma-positive patients had twice the risk for poor IVF pregnancy outcome compared with IFN-gamma-negative subjects (40.8 versus 20.0%, respectively; P < 0.02), including a significantly lower implantation rate (37.6 +/- 0.05 versus 50.0 +/- 0.03%, respectively; P = 0.02). There was no difference in pregnancy outcome based upon serum levels, or the ability to detect the presence of TNF-alpha. No differences in levels of these cytokines were found based on the aetiology of the patients' infertility. CONCLUSIONS: Elevated maternal serum levels of IL-2 sRalpha and IFN-gamma as early as 11 days after embryo transfer are associated with poor IVF pregnancy outcome.

Adult↗

PubMed2003

Focal length variability and protein leakage as tools for measuring photooxidative damage to the lens.

Hypericin is the ingredient used to standardize the popular over-the-counter antidepressant medication St. John's Wort. Because hypericin readily produces singlet oxygen and other excited state intermediates, it is a very efficient phototoxic agent in the eye that can potentially induce the development of the cataract photooxidative mechanism. Hypericin absorbs in the UV and visible ranges, binds to the lens crystallins (alpha, beta and gamma) and damages these proteins through a photooxidative mechanism. Effects were measured previously using fluorescence, UV and mass spectrometry. We report here two additional methods to monitor lens damage: (1) measuring focal length variability using a ScanTox instrument and (2) measuring protein leakage from the damaged lens. Because nonenzymic glycation results in free radical production, we chose to use elevated glucose concentrations as a convenient model for studying oxidative stress. To compare and contrast photooxidative damage against oxidative damage to the lens, we also measured the focal length variability and protein leakage induced by the presence of elevated glucose concentrations. We found that the total accumulated protein leakage was positively correlated (r = 0.9) with variability in focal length. Lenses treated with hypericin and irradiated with UVB had an increase in focal length variability as compared with the lenses that were only UVB-irradiated. Lenses without UVB irradiation had much lower focal length variability than irradiated lenses. For non-hypericin-treated lenses, UVB-irradiated lenses had a larger variability (4.58 mm) than the unirradiated lenses (1.78 mm). The lenses incubated in elevated glucose concentrations had a focal length variability (3.23 mm) equivalent to that of the unirradiated hypericin-treated lenses (3.54 mm). We conclude that photooxidative damage by hypericin results in changes in the optical properties of the lens, protein leakage and finally cataract formation. In contrast to this, high concentrations of glucose induced protein leakage but not changes in optical properties or the opacity associated with a cataract. This work provides further evidence that people should protect their eyes from intense sunlight when taking St. John's Wort.

Animals↗

PubMed2001

Ocular phototoxicity.

The human eye is constantly exposed to sunlight and artificial lighting. Therefore the eye is exposed to UV-B (295-320 nm), UV-A (320-400 nm), and visible light (400-700 nm). Light is transmitted through the eye and then signals the brain directing both sight and circadian rhythm. Therefore light absorbed by the eye must be benign. Damage to the young and adult eye by intense ambient light is avoided because the eye is protected by a very efficient antioxidant system. In addition, there are protective pigments such as the kynurenines, located in the human lens, and melanin, in the uvea and retina, which absorb ambient radiation and dissipate its energy without causing damage. After middle age there is a decrease in the production of antioxidants and antioxidant enzymes. At the same time, the protective pigments are chemically modified (lenticular 3-hydroxy kynurenine pigment is enzymatically converted into the phototoxic chromophore xanthurenic acid; melanin is altered from an antioxidant to pro-oxidant) and fluorescent chromophores (lipofuscin) accumulate to concentrations high enough to produce reactive oxygen species. We have known for some time that exposure to intense artificial light and sunlight either causes or exacerbates age-related ocular diseases. We now know many of the reasons for these effects, and with this knowledge methods are being developed to interfere with these damaging processes.

Adult↗

PubMed2001

Cardiovascular indices of physiological arousal in boys with fragile X syndrome.

In this study, the relationship between physiological arousal, as indexed by heart rate variability, was examined in boys with fragile X syndrome (FXS) and typically developing boys matched on chronological age. In addition, the relationship of heart activity to clinical and molecular factors in the group of boys with FXS was examined. Results suggest that boys with FXS have higher levels of heart activity during the passive phases, as reflected in shorter heart periods. This high level of heart activity appears to be due to increased sympathetic activity and reduced parasympathetic activity. Boys with FXS did not display the expected patterns of heart activity in response to phases of increasing challenge, and sympathetic and parasympathetic systems did not appear coordinated in these boys with FXS. Clinical factors may be related to neural regulation of heart activity while molecular factors do not appear to be.

Antiporters↗

PubMed2001

Effects of leuprolide acetate on adhesion formation and wound healing in the rat model.

STUDY OBJECTIVE: To assess the effects of a hypoestrogenic state on adhesion formation and reformation and on wound healing in the rat model. DESIGN: Prospective, randomized study (Canadian Task Force classification I). SUBJECTS: Forty-eight female Sprague-Dawley rats. INTERVENTIONS: Rats were injected with gonadotropin-hormone releasing hormone (GnRH) agonist and control rats with normal saline. Two weeks later (day zero) laparotomy was performed to create adhesions and a full-thickness wound on the flank. On day 14 the adhesions were scored and liberated. The rats were sacrificed on day 28 and adhesion reformation was evaluated. The wound surface area was measured serially until complete closure. MEASUREMENTS AND MAIN RESULTS: Mean adhesion scores on day 14 after adhesion formation were not significantly different between GnRH agonist and control groups. Preadhesiolysis and postadhesiolysis scores were not significantly different. There was no significant difference in size of wounds between groups on days zero, 7, or 14. CONCLUSION: Administration of a GnRH agonist does not seem to influence postoperative adhesion formation or wound healing in the rat model. (J Am Assoc Gynecol Laparosc 8(1):124-128, 2001)

Animals↗

PubMed2001

Complex syntax production of African American preschoolers.

This study examined changes in the complex syntax production of 85 3- and 4-year-old African American children and the role of child (i.e., gender, age, African American English) and family (i.e., home environment) factors. The mean percentage of utterances containing one or more complex syntax forms was 6.2% at 3 years and 11.7% at 4 years. Girls produced more complex syntax forms than did boys. Complex syntax production increased significantly between age 3 and age 4 and correlated positively with mean length of utterance in words. Children from more responsive and stimulating home environments produced more complex syntax at 4 years. African American English was not related to the amount of complex syntax used.

Child Language↗

PubMed2001

Meta-analysis of the relationship between HIV infection and risk for depressive disorders.

OBJECTIVE: Each of 10 published studies investigating the relationship between HIV infection and risk for depressive disorders concluded that HIV-positive individuals are at no greater risk for depression than comparable HIV-negative individuals. This study used meta-analytic techniques to further examine the relationship between depressive disorders and HIV infection. METHOD: Meta-analytic techniques were used to aggregate and reanalyze the data from 10 studies that compared HIV-positive and HIV-negative individuals for rates of major depressive disorder (N=2,596) or dysthymic disorder (N=1,822). RESULTS: The frequency of major depressive disorder was nearly two times higher in HIV-positive subjects than in HIV-negative comparison subjects. On the other hand, findings were inconclusive with regard to dysthymic disorder. Rates of depression do not appear to be related to the sexual orientation or disease stage of infected individuals. CONCLUSIONS: Although the majority of HIV-positive individuals appear to be psychologically resilient, this meta-analysis provides strong evidence that HIV infection is associated with a greater risk for major depressive disorder. Future research should focus on identifying pathways of risk and resilience for depression within this population.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Receptive and expressive communication development of young males with fragile X syndrome.

We prospectively examined the developmental trajectories of receptive and expressive communication skills of 39 young males, 20 to 86 months of age, with fragile X syndrome. Eight showed features characteristic of autism. Children were tested one to three times using a standardized language test. They showed marked delays in language development, but substantial individual variability. Participants acquired expressive language skills more slowly than receptive language over time, gaining receptive language at about half the rate expected for typically developing children and expressive language at one third the rate. Both cognitive skills and autistic characteristics of the young males with fragile X syndrome related to receptive and expressive communication development, but neither predicted the discrepancies between expressive and receptive language acquisition over time.

Child↗

PubMed2001

Early childhood otitis media in relation to children's attention-related behavior in the first six years of life.

OBJECTIVE: This study examined whether otitis media with effusion (OME) and associated hearing loss during the first 4 years of life were related to the ratings of parents, teachers, and clinicians of children's attention and behavior in the first 6 years of life. METHODS: In a prospective study, 85 black children were recruited from community-based child care programs when they were between 6 and 12 months old. OME and hearing status were monitored repeatedly from 6 months to 4 years old. Measures of attention and behavior were collected from parents, teachers, and clinicians when the children were infants, preschoolers, and first graders. RESULTS: On average, children experienced either bilateral or unilateral OME 30% of the time and hearing loss 19.9% of the time between 6 months and 4 years old. Descriptive and inferential analyses revealed no significant associations between OME or hearing loss and the measures of attention or behavior completed by parents, teachers, and clinicians. CONCLUSIONS: In this sample of children, there was no relationship between amount of early childhood OME or hearing loss and measures of attention or behavior in the first 6 years of life as reported by parents, teachers, and clinicians.otitis media, hearing, attention, behavior.

Attention↗

PubMed2001

Photooxidation of lens proteins with xanthurenic acid: a putative chromophore for cataractogenesis.

The tryptophan metabolite, xanthurenic acid (Xan), is produced through a transamination reaction in high concentrations in human lenses with age and has been isolated from aged human cataractous lenses. It has appreciable absorption between 300 and 400 nm (lambda max = 334 nm), the range absorbed by the human lens. Our recent studies have shown that unlike most tryptophan metabolites in the eye, Xan is photochemically active, producing both superoxide and singlet oxygen. To determine if Xan could act as a photosensitizer and photooxidize cytosolic lens proteins, alpha-, beta- and gamma-crystallins were irradiated (lambda > 300 nm, 12 mW/cm2) in the presence and absence of Xan. Upon irradiation and in the presence of Xan, lens proteins polymerized in the order alpha > beta > gamma as assessed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Further analysis of the photolyzed alpha-crystallin by mass spectrometry indicated that histidine, tryptophan and methionine residues were oxidized at specific positions in a dose-dependent (irradiation time) manner. In alpha A-crystallin two forms of oxidized histidine 154 were observed, 2-imidazolone and 2-oxohistidine. Our results suggest that naturally occurring Xan is a chromophore capable of photosensitization and photooxidation of lens proteins. Furthermore, this compound could play a role in age-related cataractogenesis.

Cataract↗

PubMed2000

Photophysical studies on melatonin and its receptor agonists.

Previous work has demonstrated that melatonin inhibits the growth of both dermal and uveal melanoma cells. Recent clinical trials have found that melatonin is an efficacious treatment for metastatic dermal melanoma. The goal of this study was to provide further insight into the oncostatic mechanism(s) of melatonin. The inhibition of the growth of uveal melanoma cells is dose-dependent (0.1-10 nM) within the range of endogenous melatonin concentrations (2 nM) found in the human aqueous humor. We know that this inhibition of growth is receptor-mediated, at least in part, because uveal melanoma cell growth was also blocked by the agonists of melatonin receptors. There are two known membrane receptors for melatonin (Mel(1a) and Mel(1b)) and one known nuclear receptor (Mel2). To determine if singlet oxygen production and/or quenching contributed to the growth inhibition of melatonin, we examined the photophysical properties of melatonin and its agonists. Using flash photolysis, we determined that melatonin and its membrane receptor agonist 6-chloromelatonin (Mel(1a-b), Lilly, Indianapolis, IN) produced very little singlet oxygen (psidelta = 0.073 and psidelta = 0.01, respectively). There was no detectable singlet oxygen phosphorescence at 1,270 nm for the nuclear receptor agonist CG-52608 (Mel2, Novartis, Basel, Switzerland). In contrast, the agonist of the Mel(1b) receptor, S-20098 (Servier, Paris, France), produced singlet oxygen with a quantum efficiency of psidelta = 0.34. Singlet oxygen was quenched by melatonin and 6-chloromelatonin at approximately the same rate (6.1 x 10(7) M(-1)s(-1) and 6.0 x 10(7) M(-1)s(-1) in CD3OD), while the rate of quenching for the nuclear receptor agonist CG-52608 and membrane receptor agonist S-20098 was less (2.2 x 10(7) M(-1)s(-1) and 1.5 x 10(7) M(-1) s(-1), respectively). It appears that the production of singlet oxygen by melatonin would not be sufficient to directly block the proliferation of melanoma cells, but may activate gene products that could contribute to the oncostatic effect.

Acetamides↗

PubMed2000

Melatonin receptors in human uveal melanocytes and melanoma cells.

Previous work has demonstrated that melatonin inhibits growth of cultured human uveal melanoma cells. The goal of this study was to determine the expression of mRNA encoding the melatonin receptor subtypes and the effect of specific melatonin receptor agonists on cell growth of uveal melanoma cells and melanocytes. RNA expression of the human melatonin Mel1a and Mel1b receptor subtypes was determined by reverse transcription-polymerase chain reaction (RT-PCR) amplification of RNA isolated from two melanoma cell lines and from one cell line of normal melanocytes. PCR-amplified cDNA encoding the Mel1b melatonin receptor subtype, but not the Mel1a subtype, was detected in reverse-transcribed RNA obtained from both normal uveal melanocytes and melanoma cell lines. Uveal melanoma cells and melanocytes were cultured for 24 hr, then melatonin or one of its membrane receptor agonists, 6-chloromelatonin (Mel1a-1b) or S-20098 (Mel1b) or its putative nuclear agonist, CGP-52608 (Mel2), was added to the medium. After 5 days, the cells were detached, counted, and compared to untreated controls. Melatonin and its membrane receptor agonists (Mel1a-1b and Mel1b), but not its putative nuclear receptor agonist (Mel2), inhibited the growth of uveal melanoma cells, but not normal melanocytes, at very low concentrations. In uveal melanoma cells, the expression of RNA encoding the Mel1b receptor suggests that the growth inhibiting effect of melatonin on uveal melanoma cells is related to activation of the melatonin Mel1b membrane receptor. Furthermore, the expression of RNA encoding melatonin receptors in normal uveal melanocytes suggests that melatonin may play a role in the function of these cells.

Acetamides↗

PubMed2000

Cumulative risk and early cognitive development: a comparison of statistical risk models.

Although it is generally accepted that social risk factors predict delays in early cognitive and language development, there is less agreement about how to represent such associations statistically. Using data collected prospectively on 87 African American children during their first 4 years, this study examined 3 analytic methods for describing a child's level of social risk: (a) individual risk variables, (b) factor scores derived from those risk variables, and (c) a risk index computed by tallying the number of risk conditions present. Comparisons indicated that the individual-risk-variables approach provides better overall prediction of developmental outcomes at a particular age but is less useful in predicting developmental patterns. The risk-factor approach provides good prediction of developmental trajectories when sample sizes are moderate to large. Finally, the risk-index approach is useful for relating social risk to developmental patterns when a large number of risk variables are assessed with a small sample or when other constructs are of primary interest.

Black or African American↗

PubMed2000

A comparison of two life stress assessment approaches: prospective prediction of treatment outcome in recurrent depression.

Research on life stress has been characterized by inconsistent results, which some researchers attribute to different assessment methodologies. Generally, studies have used either self-report checklists or investigator-based interviews. To test whether different results are derived from these approaches, the authors compared information from a self-report measure of life stress with the additional data available from a follow-up investigator-based measure in prospectively predicting the outcome of treatment for recurrent major depression. The 2 approaches produced different results, with investigator-based life events predicting lower probability of remission and self-report life events either predicting increased likelihood of remission or not predicting at all. The results demonstrated that methodology may account for some of the inconsistencies in the life stress literature.

Adult↗

PubMed2000

Light and immunomodulation.

The immune system is susceptible to a variety of stresses. Recent work in neuroimmunology has begun to define how mood alteration, stress, the seasons, and daily rhythms can have a profound effect on immune response through hormonal modifications. Central to these factors may be light through an eye-brain hormonal modulation. In adult primates, only visible light (400-700 nm) is received by the retina. This photic energy is then transduced and delivered to the visual cortex and, by an alternative pathway, to the suprachiasmatic nucleus (SCN), the hypothalamic region that directs circadian rhythm. Visible light exposure also modulates the pituitary and pineal glands, leading to neuroendocrine changes. Melatonin, norepinephrine, and acetylcholine decrease with light activation, whereas cortisol, serotonin, GABA, and dopamine levels increase. The synthesis of vasoactive intestinal polypeptide (VIP), gastrin releasing peptide (GRP), and neuropeptide Y (NPY) in rat SCN has been shown to be modified by light. These induced neuroendocrine changes can lead to alterations in mood and circadian rhythm as well as immune modulation. An alternative pathway for immune modulation by light is through the skin. Visible light (400-700 nm) can penetrate epidermal and dermal layers of the skin and may directly interact with circulating lymphocytes to modulate immune function. In contrast to visible light, in vivo exposure to UV-B (280-320 nm) and UV-A (320-400 nm) radiation can alter normal human immune function only by a skin-mediated response. It is therefore important, when reporting neuroendocrine immune findings, to control the intensity, timing and wavelength of ambient light.

Adult↗

PubMed2000

Sex differences on a mental rotation task: variations in electroencephalogram hemispheric activation between children and college students.

The area of cognitive research that has produced the most consistent sex differences is spatial ability. In particular, men usually perform better on mental rotation tasks than women. Performance on mental rotation tasks has been associated with right parietal activation levels, both during task performance and prior to performance during baseline recordings. This study examined the relations among sex, age, electroencephalogram (EEG) hemispheric activation (at the 10.5 Hz to 13.5 Hz frequency band), and 2-D mental rotation task ability. Nineteen 8-year-olds (10 boys) and 20 college students (10 men) had EEG recorded at baseline and while performing a mental rotation task. Men had a faster reaction time on the mental rotation task than women, whereas there were no differences between boys and girls. After covarying for baseline EEG power values, men exhibited more activation (lower EEG power values) than women in the parietal and posterior temporal regions, whereas boys' and girls' power values did not differ in the parietal or posterior temporal regions. Furthermore, during the baseline condition, men generally exhibited more activation (lower EEG power values) throughout all regions of the scalp. Results support the hypothesis that a change that affects both brain activation and performance on mental rotation tasks occurs sometime between childhood and adulthood.

Adolescent↗

PubMed2000

Otitis media in childhood in relation to preschool language and school readiness skills among black children.

OBJECTIVE: To examine whether otitis media with effusion (OME) and associated hearing loss (HL) during the first 5 years of life were related to children's language skills during the preschool years and to school readiness skills at entry to kindergarten. METHODS: In a prospective study, the ears of 85 black children primarily from low-income families and recruited from community-based childcare programs were repeatedly examined from 6 months to 5 years of age for the presence of OME and from 6 months to 4 years of age for HL when well and ill with OME. Assessments were made annually of the children's child-rearing environments at home and in childcare, and children's language skills between 3 and 5 years of age and readiness skills in literacy and math were evaluated at entry into kindergarten. RESULTS: Children had either bilateral or unilateral OME approximately 30.4% and HL 19.6% of the observation time. OME and associated HL were significantly positively correlated with some measures of expressive language at 3 and 4 years of age; however, these direct relationships were no longer significant when the child's gender, socioeconomic status, maternal educational level, and the responsiveness and support of the home and childcare environments were also considered. Further, both OME and HL were moderately correlated with school readiness skills at entry to school, with children having more OME scoring lower in verbal math problems and with children with more HL scoring lower in math and recognizing incomplete words. These associations continued to remain significant even after partialing out the child and family background factors. CONCLUSIONS: There was not a significant relationship between children's early OME history or HL and language skills during the preschool years. However, children with more frequent OME had lower scores on school readiness measures. These associations were moderate in degree, however, and the home environment was more strongly related to academic outcomes than was OME or HL. These results should be interpreted cautiously when generalizing to other populations.

Auditory Threshold↗