Biomedical subjects

J E Roberts

Publications and source records attributed to J E Roberts.

At least 37 records · Page 2Linked to original sources

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↗

PubMed2000

Photooxidation of lens alpha-crystallin by hypericin (active ingredient in St. John's Wort).

Hypericin is the active ingredient in the over the counter antidepressant medication St. John's Wort. Hypericin produces singlet oxygen and other excited state intermediates that indicate it should be a very efficient phototoxic agent in the eye. Furthermore it absorbs in the UV and visible range, which means it can potentially damage both the lens and the retina. Lens alpha-crystallin, isolated from calf lenses, was irradiated in the presence of hypericin (5 x 10(-5) M, 10 mM ammonium bicarbonate, pH 7.0) and in the presence and absence of light (> 300 nm, 24 mW/cm2). Hypericin-induced photosensitized photopolymerization as assessed by sodium dodecylsulfate-polyacrylamide gel electrophoresis. Further analysis of the oxidative changes occurring in alpha-crystallin using mass spectrometry showed specific oxidation of methionine, tryptophan and histidine residues, which increased with irradiation time. Hypericin did not damage the lens protein in the dark. Damage to alpha-crystallin could undermine the integrity of the lens directly by protein denaturation and indirectly by disturbing chaperone function. Therefore, in the presence of light, hypericin can induce changes in lens protein that could lead to the formation of cataracts. Appropriate precautions should be taken to protect the eye from intense sunlight while on this antidepressant medication.

Animals↗

PubMed2000

Photochemical studies on xanthurenic acid .

The tryptophan metabolite xanthurenic acid (Xan) has been isolated from aged human cataractous lenses. The photophysical properties of Xan were examined to determine if it is a potential chromophore for age-related cataractogenesis. We found that Xan produces singlet oxygen (psi delta = 0.17 in CD3OD) with the same efficiency as the lenticular chromophore N-formyl kynurenine and quenches singlet oxygen at a rate similar (2.1 x 10(7); CD3OD) to other tryptophan metabolites found in the eye. As the mechanisms of induction of cataracts may also involve redox reactions, the interactions of hydrated electrons (e(aq)-), the azide radical (N3*) and hydroxyl radical (OH*) with Xan were studied using the technique of pulse radiolysis. The reaction rate constants of e(aq)-, N3* and OH* with Xan were found to be of the same order of magnitude as other tryptophan metabolites. The rate constant for reaction of Xan with e(aq)- solvated electrons was found to be diffusion controlled (k = 1.43 x 10(10) M(-1) s(-1); the reaction with N3* was very fast (k = 4.0 x 10(9) M(-1) s(-1)); and with OH* was also near diffusion controlled (k = 1.0 x 10(10) M(-1) s(-1)). Superoxide O2*- production by irradiated Xan in methanol was detected by electron paramagnetic resonance and substantiated by determining that the enhanced rate of oxygen consumption of Xan irradiated in the presence of furfuryl alcohol was lowered by superoxide dismutase.

Cataract↗

PubMed2000

Sex differences on a computerized mental rotation task disappear with computer familiarization.

The area of cognitive research that has produced the most consistent sex differences is spatial ability. Particularly, men consistently perform better on mental rotation tasks than do women. This study examined the effects of familiarization with a computer on performance of a computerized two-dimensional mental rotation task. Two groups of college students (N=44) performed the rotation task, with one group performing a color-matching task that allowed them to be familiarized with the computer prior to the rotation task. Among the participants who only performed the rotation task, the 11 men performed better than the 11 women. Among the participants who performed the computer familiarization task before the rotation task, how ever, there were no sex differences on the mental rotation task between the 10 men and 12 women. These data indicate that sex differences on this two-dimensional task may reflect familiarization with the computer, not the mental rotation component of the task. Further research with larger samples and increased range of task difficulty is encouraged.

Adult↗

PubMed2000

Behavior and autonomic nervous system function assessed via heart period measures: the case of hyperarousal in boys with fragile X syndrome.

Physiological responses may inform us about and help us to interpret behavioral responses. For example, hyperarousal may be a source of behavior problems in children with fragile X syndrome (FXS). To evaluate this approach, we examined heart period data in specific contexts in boys with FXS and in normally developing chronological-age-matched boys. Spectral analysis was used to evaluate the parasympathetic and sympathetic nervous systems' contributions to heart period. Boys with FXS had shorter interbeat intervals, lower parasympathetic activity, and similar sympathetic activity. Also, the groups were differentially responsive to experimental challenge. These results have important implications for our understanding of the basic nervous system dysfunction in FXS and for the strategies likely to be effective in terms of pharmacological intervention with these children. These methods can be applied to a variety of contexts and populations, including children who are sensory defensive, socially avoidant, inattentive, or hyperactive.

Arousal↗

PubMed2000

The uptake, location and fluorescence of hypericin in bovine intact lens.

PURPOSE: To determine the uptake, location and fluorescence of hypericin, the active ingredient in St. John's Wort, in situ in the isolated intact calf lens. METHODS: The absorption and fluorescence spectra of hypericin 10(-5 ) M were measured in DMSO/phosphate buffer, pH 7.4) [PBS] (1/10 in volume) in the presence of alpha-crystallin (0.5 and 1.1 mg/ml). Bovine lenses were incubated in the dark for 24 hours in 10(-4) M hypericin in a DMSO/PBS (1/10 in volume) mixture. Diffused hypericin fluorescence emission was detected with a fluorescence stereomicroscope from the PBS washed lens surface. A lens-holder specially built for front-surface excitation-detection was used to measure fluorescence emission and excitation spectra of intact lenses incubated with hypericin solutions. RESULTS: As increasing concentrations of alpha-crystallin were added, the absorption and fluorescence spectra of hypericin in DMSO/PBS (1/10 in volume) changed, indicating a binding between the chromophore and the lens protein. Fluorescence emission spectra detected from the lens surface (lambda( em) = 601 and 651 nm; lambda(exc) = 550 nm) confirmed that hypericin does bind to the ocular tissues. CONCLUSIONS: The results we obtained in simplified model systems can provide clues to investigate the effects of hypericin on lens properties in physiological conditions. Hypericin could in fact bind to lens protein thus increasing the retention time of hypericin in the eye and possibly altering a-crystallin properties as a chaperone. Should therefore hypericin be taken up by the lens, this can be detected, non-invasively by its fluorescence. Therefore, ophthalmologists may use a slit-lamp or scanning fluorometry to monitor the uptake of hypericin in the eyes of patients using St. John's Wort or receiving high doses of hypericin while undergoing photodynamic therapy.

Absorption↗

PubMed1999

Effects of hydrosalpingeal fluid on murine embryo development and implantation.

PURPOSE: Our purpose was to evaluate the effects of various concentrations of hydrosalpingeal fluid (HSF) on the preimplantation development and implantation of murine embryos. METHODS: One-cell mouse embryos were cultured in KSOM culture medium with 0.1, 1.0, 10, or 50% HSF, without and with lactate supplementation. Late-stage embryos were transferred into the uteri of pseudopregnant CD-1 females to determine implantation rates. The embryo transfer technique used was developed by our group and its effectiveness was evaluated during this experiment. RESULTS: Blastocyst development in the 0.1, 1.0, 10, and 50% group was 45, 55.0, 12.5, and 17.5%, respectively, with lactate supplementation, and 35.0, 52.5, 12.5, and 5.0%, respectively, without lactate supplementation, while in the KSOM (control) group it was 63.8%. Blastocyst development was reduced compared to controls in the 10% HSF and 50% HSF groups. Implantation rates for the 0.1 and 1.0% groups with lactate supplementation were 43.0 and 25.0%, respectively, and those with lactate supplementation were 50.6 and 61.8%, respectively, while in the KSOM group the implantation rate was 65.5%. None of the implantation rates were significantly different. CONCLUSIONS: Hydrosalpingeal fluid has a concentration-dependent inhibitory effect on in vitro murine embryo development, but it has minimal effects on implantation rates.

Animals↗

PubMed1999

Level and perceived stability of self-esteem prospectively predict depressive symptoms during psychoeducational group treatment.

OBJECTIVES: To investigate the combined roles of level and perceived stability of self-esteem in prospectively predicting depression. DESIGN: Symptoms of depression and anxiety were measured both before and after psychoeducational treatment for depression; level and perceived stability of self-esteem were measured before treatment. METHOD: Participants were 26 adults (16 female), age range 21-75 years. RESULTS: More stable self-esteem was associated with greater depressive symptomatology at treatment completion, particularly among participants who began treatment with the lowest self-esteem. Effects were specific to symptoms of depression in contrast with anxiety. CONCLUSION: These results suggest that a stable, well-consolidated negative self-concept is associated with prolonged depression and a poor response to psychosocial interventions.

Adult↗

PubMed1999

A longitudinal study of otitis media with effusion among 2- to 5-year-old African-American children in child care.

OBJECTIVE: To prospectively document the prevalence of otitis media with effusion (OME) in 86 African-American children between ages 2 and 5 years. STUDY DESIGN: Eighty-six children in center-based child care whose ear status had been followed from infancy continued to be observed. Middle ear status was assessed by pneumatic otoscopy and tympanometry biweekly. RESULTS: The prevalence of OME decreased as children became older. The mean proportion of examinations demonstrating bilateral OME (BOME) ranged from 12% between 24 to 30 months to 4% between 54 to 60 months of age. The mean proportion of exams revealing bilateral normal ears increased from 77% at 24 to 30 months to 88% at 54 to 60 months of age. Although 60 children had experienced BOME that lasted 4 months or longer in the 6- to 24-month age period, only 8 of these children experienced at least 4 months of continuous BOME between 24 to 60 months. CONCLUSIONS: The proportion of time with BOME decreased progressively with increasing age in this population. Only 8 of 60 children who had experienced more than 4 consecutive months of BOME before 2 years of age continued to manifest persistent effusion or experience recurrences of prolonged BOME after 2 years of age.

Age Factors↗

PubMed1999

Photophysical studies on antimalarial drugs.

Most drugs used in the treatment of malaria produce phototoxic side effects in both the skin and the eye. Cutaneous and ocular effects that may be caused by light include changes in skin pigmentation, corneal opacity, cataract formation and other visual disturbances including irreversible retinal damage (retinopathy) leading to blindness. The mechanism for these reactions in humans is unknown. We irradiated a number of antimalarial drugs (amodiaquine, chloroquine, hydroxychloroquine, mefloquine, primaquine and quinacrine) with light (lambda > 300 nm) and conducted electron paramagnetic resonance (EPR) and laser flash photolysis studies to determine the possible active intermediates produced. Each antimalarial drug produced at least one EPR adduct with the spin-trap 5,5-dimethyl-1-pyrroline N-oxide in benzene: superoxide/hydroperoxyl adducts (chloroquine, mefloquine, quinacrine, amodiaquine and quinine), carbon-centered radical adducts (all but primaquine), or a nitrogen-centered radical adduct only (primaquine). In ethanol all drugs except primaquine produced some superoxide/hydroperoxyl adduct, with quinine, quinacrine, and hydroxychloroquine also producing the ethoxyl adduct. As detected with flash photolysis and steady-state techniques, mefloquine, quinine, amodiquine and a photoproduct of quinacrine produced singlet oxygen ([symbol: see text]delta = 0.38; [symbol: see text]delta = 0.36; [symbol: see text]delta = 0.011; [symbol: see text]delta = 0.013 in D2O, pD7), but only primaquine quenched singlet oxygen efficiently (2.6 x 10(8) M-1 s-1 in D2O, pD7). Because malaria is a disease most prevalent in regions of high light intensity, protective measures (clothing, sunblock, sunglasses or eye wraps) should be recommended when administering antimalarial drugs.

Antimalarials↗

PubMed1999

Photophysical studies of A2-E, putative precursor of lipofuscin, in human retinal pigment epithelial cells.

With age, human retinal pigment epithelial cells accumulate lipofuscin that can absorb photons in the visible range leading to light-induced damage and impaired vision. A putative precursor of lipofuscin, 2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E, 5E,7E- octatetraenyl]-1-(2-hydroxyethyl)-4-[4-methyl-6-(2,6,6-trimethyl-1 - cyclohexen-1-yl)-1E,3E,5E-hexatrienyl]-pyridinium (A2-E), has recently been isolated and characterized from aged human retinal pigment epithelial cells. We have found that A2-E inhibits the growth of human retinal pigment epithelial cells at concentrations greater than 1 microM. Time-resolved fluorescence measurements of 1 microM A2-E in solution, performed under 413 nm excitation, showed that fluorescence wave forms integrated across the spectrum (450-600 nm) were best-fitted with three decay times in the nanosecond and subnanosecond time scale: 6.6, 1.9 and 0.33 ns. Untreated retinal pigment epithelial cells were characterized by three fluorescence lifetimes: 6.3, 1.7 and 0.35 ns. In retinal pigment epithelial cells treated with 1 microM A2-E, the fluorescence decay was significantly faster, with the marked presence (approximately equal to 30%) of a fourth short lifetime (0.12 ns). These fluorescence decay times for A2-E bound to human retinal pigment epithelial cells are similar to those of lipofuscin granules isolated from aged human retinal pigment epithelial cells. This similarity supports the hypothesis that A2-E is a precursor of lipofuscin and suggests that A2-E may play a role in the overall light damage associated with age-related retinal diseases.

Aging↗

PubMed1999

The effects of two stereoisomers of N-acetylcysteine on photochemical damage by UVA and blue light in rat retina.

High doses of light can cause damage to the retina, e.g. during intraocular surgery. Previously, thiols have been demonstrated to protect against retinal damage in various damage models. Such protection is very promising for clinical practice. Retinal light damage can be caused by a relatively short exposure to high irradiance levels. These conditions occur during intraocular surgery. In the current study we therefore investigated whether the thiol N-acetylcysteine protects against retinal light damage under high irradiance conditions in the rat retina. Two stereoisomers of this thiol were tested for protection against two spectrally defined types of retinal light damage. Shortly after administration N-acetyl-L-cysteine in doses of 270-1000 mg/kg intraperitoneally protected against 380 nm (UVA) light but not against 470 nm (blue) light. Two hours after injection the protection had diminished. We observed no protection by the stereoisomer N-acetyl-D-cysteine. From this study we conclude that N-acetyl-L-cysteine protects stereospecifically against retinal damage in the UV but not in the visible part of the spectrum. This limits the possible applications.

Acetylcysteine↗

PubMed1998

Pulse radiolysis studies of melatonin and chloromelatonin.

The endogenous indole melatonin and the melatonin receptor agonist 6-chloromelatonin block the proliferation of both dermal and uveal melanoma cells by mechanisms that may involve redox reactions. The interactions of hydrated electrons, the azide radical, hydroxyl radicals and superoxide with melatonin and its 6-chloro analogue have been studied using the technique of pulse radiolysis. The reaction rate constants of eaq- and N3 x with these compounds were found to be dependent on substitution at the sixth position. The rate constants for reaction of 6-chloromelatonin and melatonin with solvated electrons are 4.5 x 10(9) M-1 s-1 and 4.2 x 10(8) M-1 s-1, respectively. The reaction rate constants of N3 x with malatonin and chloromelatonin are 9.8 x 10(9) M-1 s-1 and 3.5 x 10(9) M-1 s-1 and 3.5 x 10(9) M-1 s-1, respectively. Melatonin and 6-chloromelatonin react with hydroxyl radicals at near diffusion controlled rates (1.3 x 10(10) M-1 s-1, 8.2 x 10(9) M-1 s-1). Melatonin and 6-chloromelatonin did not react with superoxide radicals and we calculate an upper limit of 1.0 x 10(4) M-1 s-1 for the rate constant for reaction of melatonin and 6-chloromelatonin with superoxide ion.

Electron Spin Resonance Spectroscopy↗

PubMed1998

Autistic behavior in young boys with fragile X syndrome.

A sample of 57 boys with fragile X syndrome (fraX) between the ages of 24 and 133 months was rated using the Childhood Autism Rating Scale (CARS) to assess the extent to which autism and autistic features were evident in a young population. Fourteen subjects (approximately 25% of the sample) scored above the cutoff for autism, suggesting a relatively high incidence of autistic behavior. All but 2 of these 14 were in the mildly or moderately autistic range, however, and only a few items received severe ratings, suggesting that severe autism is relatively rare in fraX, at least during the early years. The CARS resulted in a continuum of autistic ratings in the fraX population, but no particular items on the CARS contributed disproportionately to autism ratings. A visual comparison of ratings on an autistic, non-fraX sample revealed similar profiles of ratings, suggesting that differentiating fraX and autism on the basis of CARS ratings is not likely. Within the fraX group, chronological age and socioeconomic status did not correlate with CARS ratings, but severity of delay was strongly related, such that more severely delayed children scored higher (more autistic) on the CARS.

Autistic Disorder↗

PubMed1998

Interactions of African American infants and their mothers: relations with development at 1 year of age.

The relationships between aspects of mother-infant interaction and both communication and cognitive skills at 1 year of age were examined in 92 African American dyads, of whom 64 (70%) fell below the poverty line. Ratings of warmth, sensitivity, responsiveness, encouragement of initiative, stimulation, and elaborativeness during a semistructured play interaction were correlated with measures of global cognition, expressive and receptive communication, and communication use. The overall quality of the home environment and maternal ratings of stimulation and elaborativeness were the most consistent correlates of infant communication measures. Relationships were stronger in middle-income than lower-income dyads. These results support the linkage of didactic and functional aspects of maternal behavior to cognitive and communication skills at 1 year of age for African American infants.

Adult↗

PubMed1998

Ltx1, a mouse locus that influences the susceptibility of macrophages to cytolysis caused by intoxication with Bacillus anthracis lethal factor, maps to chromosome 11.

The lethal factor (LF) toxin that is produced by Bacillus anthracis plays an important role in the pathogenesis of anthrax. LF has mononuclear phagocyte-specific intoxicating effects that are not well understood. We have identified genetic differences in inbred mouse strains that determine whether their cultured macrophages are susceptible to the cytolytic effect of LF intoxication. Our identification of resistant and susceptible mouse strains enabled us to analyse crosses between these strains and to map a single responsible gene (called Ltx1) to chromosome 11. Ltx1 probably influences intoxication events that occur after the delivery of LF to the cytosol, as all mouse macrophages are killed by polypeptides containing the catalytic domain of Diphtheria toxin fused to the domain of LF required for cytosolic transport. Furthermore, the susceptibility phenotype is dominant to resistance, suggesting that resistance is caused by an absence of or polymorphism in a molecule that acts jointly with, or downstream of, the activity of LF. Our mapping of Ltx1 is a crucial first step in its positional cloning, which will provide more information about the mechanism of LF intoxication.

Animals↗

PubMed1998

Effects of melatonin, its precursors and derivatives on the growth of cultured human uveal melanoma cells.

The effects of melatonin, its precursors and derivatives on the growth of cultured human uveal melanoma cells were studied. The melanoma cells were plated into 24-well plates. Melatonin, its 6-hydroxy or 6-chloro derivative, serotonin, tryptophan or kynurenine was added to the medium in concentrations of 0.001 to 1000 nM. After 5 days the cells were detached, counted, and compared with the controls. Melatonin inhibited the growth of uveal melanoma cell lines in a dose-dependent manner (0.1-10 nM). This growth inhibition occurred at concentrations of melatonin (2 nM) found in human aqueous humour. The melatonin derivatives also inhibited the growth of uveal melanoma cells; 6-chloromelatonin was more potent than melatonin and 6-hydroxymelatonin was the least active (6-chloromelatonin > melatonin > 6-hydroxymelatonin). The precursors of melatonin (tryptophan and serotonin) and the abnormal metabolite of tryptophan (kynurenine) did not inhibit the growth of the melanoma cells, indicating that changes to the metabolic processes of melatonin may play a role in the pathogenesis of uveal melanoma.

Cell Division↗

PubMed1998

Otitis media, the caregiving environment, and language and cognitive outcomes at 2 years.

OBJECTIVE: To examine the relationship between otitis media with effusion (OME) and associated hearing loss between 6 and 24 months of age and children's language and cognitive development at 2 years of age. STUDY DESIGN: A prospective cohort design in which 86 African-American infants who attended group child-care centers were recruited between 6 and 12 months of age. Between 6 and 24 months, assessments included serial ear examinations using otoscopy and tympanometry, serial hearing tests, two ratings of the childrearing environment at home and in child care, and language and cognitive outcomes at 2 years. RESULTS: Children experienced either unilateral or bilateral OME an average of 63% and reduced hearing sensitivity an average of 44% of the time between 6 and 24 months of age. Although proportion of time with OME or with hearing loss was modestly correlated with measures of language and cognitive skills, these relationships were no longer significant when the ratings of the home and child-care environments were also considered. Children with more OME or hearing loss tended to live in less responsive caregiving environments, and these environments were linked to lower performance in expressive language and vocabulary acquisition at 2 years. CONCLUSIONS: Both OME and hearing loss were more strongly related to the quality of home and child-care environments than to children's language and cognitive development. Study results might be explained either by suggesting that children in less responsive caregiving environments experience conditions that make them more likely to experience OME and/or by suggesting that it may be more difficult for caregivers to be responsive and stimulating with children with more OME.

Black People↗