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Biomedical subjects

D Mrazek

Publications and source records attributed to D Mrazek.

15 recordsLinked to original sources
PubMed2004

How common is attention-deficit/hyperactivity disorder? Towards resolution of the controversy: results from a population-based study.

Attention-deficit/hyperactivity disorder (AD/HD) is a common behavioral disorder among children, yet there is uncertainty about many aspects of AD/HD, including its precise frequency of occurrence, presence of comorbid conditions, long-term outcomes and the impact of treatment on long-term outcome. The objectives of the studies described in this paper were to address these important questions about AD/HD. The study subjects were from a population-based birth cohort, and included all children born in Rochester, Minnesota, from 1976 to 1982, who remained in the community after the age of 5 y (n = 5718). Complete medical and school records were available for all members of the birth cohort, including detailed information about AD/HD symptoms, psychometric test and questionnaire results, medical and non-medical treatments, and long-term academic and psychosocial outcomes. This information was used to identify 375 subjects from the birth cohort with AD/HD, based on well-defined research criteria. The estimated cumulative incidence of AD/HD at the age of 19y was 7.5% (95% confidence interval 6.5-8.4). Data from these 375 subjects with AD/HD will be used in ongoing studies of this disorder.

Adolescent↗
PubMed2001

Novel mechanism for age-related macular degeneration: an equilibrium shift between the angiogenesis factors VEGF and PEDF.

We investigated gene expression profiles of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in differentiated and non-differentiated retinal pigment epithelial (RPE) cells during oxidative stress. Human RPE cells were grown in culture on laminin-coated flasks to obtain differentiated features. Cells cultured on plastic were used as non-differentiated controls. After confluence, hydrogen peroxide (H2O2) was added for 48 h, then, total RNA was extracted and used for RT-PCR and Northern blot analysis. Medium conditioned by RPE was used for ELISA, Western blotting, and in vitro angiogenesis assay. As a result, differentiated RPE cells expressed significantly higher levels of VEGF protein, as compared to their non-differentiated counterparts. The expression pattern remained consistent even after cellular exposure to H2O2. Conversely, while elevated levels of PEDF transcript and protein were seen in differentiated RPE cells, compared to non-differentiated cells, a marked decrease at both PEDF mRNA and protein levels was seen after treatment with H2O2. Moreover, this decrease in PEDF expression was dosage dependent. In in vitro angiogenesis assay, conditioned medium from differentiated human RPE cells after exposure to H2O2 showed a dramatic increase in tubular formation and migratory activity of microvascular endothelial cells. These data suggest that, in physiological conditions, a critical balance between PEDF and VEGF exists, and PEDF may counteract the angiogenic potential of VEGF. Under oxidative stress, PEDF decreases disrupting this balance. This equilibrium shift may be significant in promoting a pathological condition of RPE cells and contributing to choroidal neovascularization in age-related macular degeneration.

Aging↗
PubMed2001

Upregulation of pigment epithelium-derived factor after laser photocoagulation.

PURPOSE: To determine the changes in the expression of pigment epithelium-derived factor in cultured human retinal pigment epithelial cells and rat retinas after laser photocoagulation. METHODS: Experimental study of laser photocoagulation on human retinal pigment epithelial cells in culture and on adult rats. Reverse transcription-polymerase chain reaction and semiquantitative polymerase chain reaction analysis were used. RESULTS: After photocoagulation, the mRNA expression of pigment epithelium-derived factor was upregulated in human retinal pigment epithelial cells at 6 hours and then gradually decreased. Compared with controls, significantly higher levels of pigment epithelium-derived factor were observed in rat retinas from 6 to 24 hours after laser photocoagulation (P <.005), and they were still higher than before photocoagulation at 2 weeks. CONCLUSION: An upregulation of pigment epithelium-derived factor in retinal pigment epithelial cells and in the retina after photocoagulation suggests that pigment epithelium-derived factor plays a role in inhibiting neovascularization by its antiangiogenic activity.

Animals↗
PubMed2001

Pigment epithelium derived factor as a neuroprotective agent against ischemic retinal injury.

PURPOSE: Pigment epithelium-derived factor (PEDF) is a protein shown to have neurotrophic activity. The purpose of this study was to determine whether PEDF is neuroprotective of retinal neurons that are exposed to transient ischemia-reperfusion. METHODS: Transient retinal ischemia was produced by increasing the intraocular pressure for 45 min in albino rats eyes. Immediately after reperfusion, PEDF was injected intravitreally into the experimental eyes. Injury was evaluated morphologically and by measuring the thickness of the inner retinal layers (IRL) and by counting the number of retinal ganglion cells (RGC) in epon embedded sections. RESULTS: Morphologic and morphometric analysis of the thickness of the IRL and the counting of RGC demonstrated that PEDF injected immediately after reperfusion protected the eyes partially but significantly from the ischemic injury. CONCLUSIONS: Intravitreal injection of PEDF even after the ischemia can ameliorate retinal injury. PEDF may be useful in preventing neuronal degeneration in the inner retina resulting from ischemia.

Animals↗
PubMed2001

In vivo protection of photoreceptors from light damage by pigment epithelium-derived factor.

PURPOSE: To determine whether pigment epithelium-derived factor (PEDF) exhibits neurotrophic and neuroprotective activities in vivo for photoreceptor cells. METHODS: Sprague-Dawley albino rats were injected intravitreally with 2 microg PEDF or a mixture of 1 microg basic fibroblast growth factor (bFGF)/1 microg PEDF in a volume of 1 microl phosphate-buffered saline (PBS). Animals were exposed to constant light for different periods at an illuminance level of 1200 to 1500 lux. The electroretinogram (ERG) waveforms of both eyes in the same animal were simultaneously recorded to evaluate functional protection. The morphologic protection was evaluated by quantitative histology. RESULTS: Intravitreal injection of PEDF before exposure to constant light resulted in significant morphologic and functional protection of photoreceptor cells in the retina of light-damaged rats. This protection depended on the duration and severity of light damage. The protection was eliminated by extending the light exposure to 10 days. Injection of PEDF at 0, 1, and 2 days after constant light exposure did not provide significant protection above that seen in PBS-injected eyes. Combination of PEDF with bFGF improved functional protection of photoreceptor cells. CONCLUSIONS: The data demonstrate that PEDF protected photoreceptor cells against light damage. This is significant, because it may open new avenues for the study of molecular mechanisms underlying degenerative processes. This, in turn, may lead to the development of therapeutic strategies for the prevention and treatment of degenerative diseases of the retina.

Animals↗
PubMed1999

Pigment epithelium-derived factor protects cultured retinal neurons against hydrogen peroxide-induced cell death.

Pigment epithelium-derived factor (PEDF) is a neurotrophic protein synthesized and secreted by retinal pigment epithelial (RPE) cells in early embryogenesis and has been shown to be present in the extracellular matrix between the RPE cells and the neural retina. It induces neuronal differentiation and promotes survival of neurons of the central nervous system from degeneration caused by serum withdrawal or glutamate cytotoxicity. Because the role of PEDF in the retina is still unknown, we examined its ability to protect cultured retinal neurons against hydrogen peroxide (H(2)O(2))-induced cell death. Retinas of 0-2-day-old Sprague-Dawley rats were isolated and dissociated, and the neurons were maintained for 2 weeks in a synthetic serum-free medium. Immunocytochemical labeling showed that 50-60% of the cultured cells were rod photoreceptors. Treatment with H(2)O(2) induced significant death of retinal neurons in a dose- and time-dependent manner. Pretreatment with PEDF prior to insult greatly attenuated H(2)O(2)-induced cytotoxicity, and its effect was shown to be dose dependent. Cytotoxicity was determined by 3,(4,5-dimethylthiazol-2-yl)2, 5-diphenyl-tetrazolium bromide and lactate dehydrogenase assays, and apoptotic cell death was evaluated by the TdT-mediated digoxigenin-dUTP nick-end labeling assay. The present study also showed that H(2)O(2)-induced retinal neuron death was by apoptosis that could be inhibited by PEDF. Combination of PEDF with basic fibroblast growth factor, brain-derived neurotrophic factor, or ciliary neurotrophic factor improves the protection. These data strongly suggest that PEDF is a potential neuroprotective agent in the treatment of retinal degeneration.

Animals↗
PubMed1998

Genetic association between atopy and behavioral symptoms in middle childhood.

The relationship of atopic and behavioral symptoms in a community sample of 66 monozygotic and 141 dizygotic twin pairs, ages 4-11 years, was investigated via mother report questionnaires. Within-person correlation between atopic symptoms and Child Behavior Checklist internalizing symptoms (CBCL-INT) was .21 (p < .001) for the total sample. Cross-correlations between atopy and CBCL-INT were .26 for monozygotic and .04 for dizygotic twins. A common and specific factor model applied to the data revealed that the cross-correlation between atopy and CBCL-INT was mainly due to genetic influences (77% of the covariance). This study supports the hypothesis that there is a shared genetic risk for atopy and internalizing symptoms.

Analysis of Variance↗
PubMed1997

Evolution and revolution in child psychiatry: ADHD as a disorder of adaptation.

Current knowledge about early plasticity and children's responsiveness to environmental modifications as well as the atheoretical nature of current nosological systems necessitate alternative models to explain the phenomena of childhood behavioral and emotional disturbances. Evolutionary biology provides one such framework. It organizes data from the behavioral and cognitive sciences and parallels similar efforts in other areas of medicine and biology. Through an evolutionary biological lens, some mental disorders are better viewed as an adaptive response to early pathogenic environments and/or reflect the optimization of brain function to some environments at the cost of poorer response to the demands of other environments. As an example, the authors examine attention-deficit/hyperactivity disorder (ADHD) in relation to evolutionary theories of psychology and biology and clarify the potentially adaptive nature of characteristics of inattention, impulsivity, and motoric hyperactivity, depending on the nature of child's environments. Reframing ADHD characteristics according to evolutionary theory has important treatment implications for clinicians and offers researchers opportunities for novel scientific discoveries.

Adaptation, Psychological↗
PubMed1991

Current status of research activity in American child and adolescent psychiatry: Part I.

A survey of research activity of American academic child psychiatrists was completed in February, 1989. The survey demonstrated an increase in research activity since the 1983 report in the Current Status of Child Psychiatry. A definition of a researcher was derived from a study of internists and general psychiatrists and applied to the 488 respondents (78.5% of sample), and it was found that males outnumber females and that researchers contribute significantly more to the literature and education than nonresearchers. Early research exposure and mentoring are important influences on a research career. Recommendations by researchers for future training of researchers are presented. Periodic surveys are encouraged.

Academic Medical Centers↗
PubMed1985

The nature and qualities of parenting provided by women raised in institutions.

A repeated pattern of difficulties in parenting is often found in successive generations of the same families. That finding, together with a concern to identify potential adverse influences upon child behaviour and development, was the focus of this study into the parenting provided by women who were raised within institutions. Relationships with their 2- to 3-year-old infants were assessed using complementary interview and naturalistic observational techniques. Differences in parenting styles between the case and comparison groups were on the whole subtle. Ex-care women were relatively less sensitive to their children's cues and, in response to their demands and opposition, exercised control by confrontation rather than by circumvention.

Affect↗
PubMed1984

Observation of parent-child interaction with two- to three-year-olds.

A method of home observations of mother-child interaction is described. Its development is outlined in terms of the relevant conceptual and methodological issues, and the concomitant tactical decisions involved in development are discussed. The scheme focuses on parental responsivity, affect, social communication and social control, and a novel combination of time-interval and event-sequential recording is used to discriminate parental functioning in these areas. The measures have been shown to have a satisfactorily high level of reliability, and preliminary analysis indicates construct validity.

Affect↗
PubMedDate not supplied

Child and adolescent psychiatry in general children's hospitals. A survey of chairs of psychiatry.

This article characterizes the academic, administrative, clinical service, and fiscal characteristics of departments of psychiatry in traditional children's hospitals to determine the characteristics of fiscally successful programs. A survey of chairs of psychiatry from short-term general children's hospitals was conducted based on 38 questions addressing the descriptive characteristics of their respective departments. The characteristics of psychiatry programs identified as fiscally successful were compared to those of programs that required subsidy. Nine of 45 eligible children's hospitals (20%) did not have a department or section of psychiatry, and surveys were returned by 35 of 36 department chairs (97% response). Considerable variation exists in the academic, administrative, clinical services, and fiscal characteristics of programs, although over half are operating at a deficit. Fiscal success was associated with availability of inpatient and intermediate levels of psychiatric care, better integration of the psychiatry program within the children's hospital, and adequate fiscal information being provided to the psychiatry chair. Additional research regarding the potential of psychiatric services to generate clinical success and cost savings is warranted. Pediatric health care professionals and third-party payers should be educated regarding the relevance of psychiatric services within children's hospitals and in physically ill children.

Adolescent↗