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PubMed2006

Theoretical investigations on dual-beam illumination electronic speckle pattern interferometry.

Contrary to what is found in most of the existing scientific literature, where a specific frame is developed, the theory of speckle interferometry is (conveniently) presented here as a particular case of the more general theory of holographic interferometry. In addition to the intellectual benefit of dealing with a single unified theory, this brings about many advantages when it comes to discuss fundamental topics such as the three-dimensional evolution of the complex amplitude of the diffuse optical wavefronts, the degree of approximation of the leading formulas, the loss of fringe contrast, the decorrelation effects, the real influence of the terms generally neglected in out-of-focus regions. In the same way, the statistical properties of the speckle fields, usually treated as a separate subject matter, are also integrated in the theory, thus providing a comprehensive knowledge of the qualitative features of speckle interferometry methods, otherwise difficult to understand.

Journal Article↗
PubMed2001

[A.A. Malinovskiĭ and significance of the system approach in gerontology].

A.A Malinovsky allocated 4 most important principles of the system theory: discreteness/rigidity of system, presence of feedback, occurrence of new properties at association of elements in system, a continuity and the maximal fitness in evolution. He believed that the essential factor determining life longevity of the individual are his species-specific characteristics. A.A. Malinovsky together with coworkers has revealed the attributes most connected to increase of terms of life: a high degree of the cephalization and the big sizes of a body. He also emphasized, that with an exit on a high intellectual level people have occupied especially position at which the biological factors influencing life longevity, began to lose paramount signification, value of long life has increased. The increase of life longevity has resulted in the important consequence--to increase of the number of diseases at late age. The diseases with hereditary predisposition have got the big weight. A.A. Malinovsky considered 4 basic levels of a condition of functions of an organism. The level of the maximal pressure--mobilization of all forces of an organism on type of "emergency alarm", promotes wear process of an organism and disorder of its separate functions. Damage of the weakest link translates an organism from a stable condition in pathological when the depression of one function reduces a level of others which in turn, even more can suppress the first, resulting in to a vicious circle (a positive feedback). A.A. Malinovsky has entered concept about increasing "disregulation" of the functions of an organism during ageing as to the main reason limiting human life. He assumed, that such rigid system (organism) which has strong link (subsystem), and other subsystems function approximately at one level has the greatest stability. It is possible, that presence of weakest links is connected to size of a genetic load. Our paper demonstrates the importance of A.A. Malinovsky system approach for such field of knowledge as gerontology.

Aging↗
PubMed2001

Theoretical perspectives on language and communication problems in mental retardation and developmental disabilities.

We argue that researchers interested in language and communication problems in mental retardation or any other developmental disorder should view such problems as emerging within the broader context of the behavioral profile, or phenotype, associated with a particular genetic condition. This will require understanding the direct and indirect effects of genes on the development of language and communication and thereby an understanding of the complex relations that exist between language and other dimensions of psychological and behavioral functioning as well as an understanding of the environments in which the developing person acts and is acted upon. We believe that the dominant model for understanding language and communication problems--the nativist approach, which emphasizes the child's innate capacity for acquiring language and characterizes language as consisting of a set of context-free deterministic rules that operate on abstract representations--is inconsistent with an emphasis on indirect genetic effects. We review recent evidence that undermines the nativist approach--evidence concerning the initial state of the language-learning child, the role of environmental input, the competence-performance distinction, and modularity. In place of nativism, we argue for Emergentism, which is a model in which language is seen to emerge from the interaction between the child's biological abilities to map statistical properties of the language input into a distributed representation and the characteristics of the language learning environment and for the purpose of engaging in real-time, meaningful language use.

Child↗
PubMed2001

The future of hypertension therapy: sense, antisense, or nonsense?

Hypertension is a debilitating disease with significant socioeconomic and emotional impact. Despite recent success in the development of traditional pharmacotherapy for the management of hypertension, the incidence of this disease is on the rise and has reached epidemic proportions by all estimates. This has led many to conclude that traditional pharmacotherapy has reached an intellectual plateau, and novel approaches for the treatment and control of hypertension must be explored. We have begun to investigate the possibility of treating and/or curing hypertension by using genetic means. In this review, we will provide evidence in favor of targeting of the renin-angiotensin system by antisense gene therapy as an effective strategy for the lifelong prevention of hypertension in the spontaneously hypertensive rat model. In addition, we will discuss the properties of an ideal vector for the systemic delivery of genes and the potential experimental hurdles that must be overcome to take this innovative approach to the next level of evaluation.

Adenoviridae↗
PubMed2005

Modulation of dendritic spines in epilepsy: cellular mechanisms and functional implications.

Epilepsy patients often suffer from significant neurological deficits, including memory impairment, behavioral problems, and psychiatric disorders. While the causes of neuropsychological dysfunction in epilepsy are multifactorial, accumulating evidence indicates that seizures themselves may directly cause brain injury. Although seizures sometimes result in neuronal death, they may also cause more subtle pathological changes in neuronal structure and function, including abnormalities in synaptic transmission. Dendritic spines receive a majority of the excitatory synaptic inputs to cortical neurons and are critically involved in synaptic plasticity and learning. Studies of human epilepsy and experimental animal models demonstrate that seizures may directly affect the morphological and functional properties of dendritic spines, suggesting that seizure-related changes in spines may represent a mechanistic basis for cognitive deficits in epilepsy. Novel therapeutic strategies directed at modulation of spine motility may prevent the detrimental effects of seizures on cognitive function in epilepsy.

Animals↗
PubMed1994

Risperidone in the treatment of pervasive developmental disorder.

Elevated concentrations of blood serotonin have been documented in autistic children and mentally retarded adults. Antiserotonergic pharmacotherapy has been partially effective in treating a subgroup of children with autistic disorder. Therefore, the possibility is raised that an antiserotonergic treatment may be of value to adult psychiatric patients with a history of pervasive developmental disorder. Two such cases are described where the patients underwent psychiatric and neuropsychological examination before and after treatment with risperidone, a potent 5-HT2 antagonist with additional D2 antagonistic properties. Particular improvements were documented in both patients, despite long histories of cognitive compromise and high likelihood of damage to the central nervous system.

Adolescent↗
PubMed1993

Overview of imaging science.

The traditional disciplines of science are grounded in the observation and measurement of object properties. Recent advances in digital computer technology have spawned numerous computer-based imaging systems that extend the range of observation and measurement into realms that would otherwise be inaccessible. More importantly, the same set of principles, concepts, strategies, and methods may be used to address the generic issues involved in the production and use of all digitized images. Recognition of this fact is giving rise to the new discipline of imaging science, with its own intellectual agenda.

Journal Article↗
PubMed1998

Purified recombinant Fmrp exhibits selective RNA binding as an intrinsic property of the fragile X mental retardation protein.

Fragile X syndrome is caused by the transcriptional silencing of the FMR1 gene due to a trinucleotide repeat expansion. The encoded protein, Fmrp, has been found to be a nucleocytoplasmic RNA-binding protein containing both KH domains and RGG boxes that associates with polyribosomes as a ribonucleoprotein particle. RNA binding has previously been demonstrated with in vitro-translated Fmrp; however, it remained uncertain whether the selective RNA binding observed was an intrinsic property of Fmrp or required an associated protein(s). Here, baculovirus-expressed and affinity-purified FLAG-tagged murine Fmrp was shown to bind directly to both ribonucleotide homopolymers and human brain mRNA. FLAG-Fmrp exhibited selectivity for binding poly(G) > poly(U) >> poly(C) or poly(A). Moreover, purified FLAG-Fmrp bound to only a subset of brain mRNA, including the 3' untranslated regions of myelin basic protein message and its own message. Recombinant isoform 4, lacking the RGG boxes but maintaining both KH domains, was also purified and was found to only weakly interact with RNA. FLAG-purified I304N Fmrp, harboring the mutation of severe fragile X syndrome, demonstrated RNA binding, in contrast to previous suggestions. These data demonstrate the intrinsic property of Fmrp to selectively bind RNA and show FLAG-Fmrp as a suitable reagent for structural characterization and identification of cognate RNA ligands.

Animals↗
PubMed2003

Preliminary analysis of the psychometric properties of the Mood, Interest & Pleasure Questionnaire (MIPQ) for adults with severe and profound learning disabilities.

OBJECTIVE: There are few reliable and valid methods for assessing emotional constructs in adults with severe and profound learning disabilities who are unable to self report. The aims of this study were to develop an informant questionnaire on affect for use in relation to adults with severe and profound learning disabilities and to examine its psychometric properties. METHOD: The Mood, Interest & Pleasure Questionnaire (MIPQ) is a 25-item Likert scale questionnaire with two subscales (mood and interest & pleasure). The MIPQ and the Aberrant Behavior Checklist were completed on 53 participants with severe or profound learning disabilities, who were partly or non-verbal. Of these, 23 participants (43%) were included in an examination of test-retest and inter-rater reliability of the MIPQ. RESULTS: Reliability of the MIPQ was good for subscales and total score: test-retest and inter-rater reliability coefficients for the total score were .87 and .76, respectively. Internal consistency was excellent (.94). A significant correlation between the MIPQ total score and the Aberrant Behavior Checklist's 'lethargy, social withdrawal' subscale provided preliminary evidence of construct validity (r (48) = -.59, p < .001). CONCLUSIONS: A preliminary analysis of the psychometric properties of the MIPQ is encouraging and further validation of the measure is warranted. The measure might be used to examine depression in people with severe and profound learning disabilities as well as in investigations of issues such as quality of life.

Adult↗
PubMed1994

Balancing social acceptability with treatment effectiveness of an intrusive procedure: a case report.

The debate over social acceptability of intrusive procedures has led some school districts to adopt policies allowing punishment for only the most extreme forms of destructive behavior. We investigated the effectiveness of selectively implementing punishment for only the most severe topographies of aggression and property destruction, while less extreme behaviors were ignored. Results indicated that severe behaviors were reduced to near-zero levels only when both severe and less severe behaviors were similarly punished.

Aggression↗
PubMed2000

[Gabaergic hypothesis of epilepsy and clinical experience: controversial actions of the new generation gabamimetic antiepileptic drugs].

Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in CNS can elevate level of neuronal excitability by the mechanisms of hyperpolarization. Gabaergic hypothesis of epileptogenesis influenced development of a group of gabamimetic antiepileptic drugs (AEDs). Powerful conventional AEDs barbiturates and benzodiazepines can directly activate GABA-A receptor but their usefulness is limited by development of dependence and tolerance to antiseizure activity. The second generation AEDs have been achieved by a rationale synthesis of compounds that could mimic or augment the activity of endogenous GABA. Vigabatrin (VGB) irreversibly inhibits GABA-T activity, tiagabine (TGB) inhibits GABA-reuptake system (GAT-1) and gabapentin (GPT) enhances GABA turnover in CNS. New drugs with selective and specific influence on GABA neurotransmission are non-toxic and well-tolerated, but some side-effects (aggravation of seizures, visual field deficit and psychotic reactions) seems to be strictly connected with their pharmacodynamic properties. Absence and probably myoclonic seizures noted in about 10% of patients under VGB seems to be the result of disturbed GABA inhibition in thalamic interneurons and non-controlled hyperactivity of excitatory neocortex-thalamus-neocotrex circuits. Perimetric examination might reveal peripheral, persistent binasal visual field deficit in about 30% of patients treated with VGB. This is probably the effect of cytotoxic influence of enormous accumulation of GABA in retinal neurons. Barbiturates and benzodiazepines can exacerbate intellectual functioning and behaviour. Some emotional and reactive disturbances are more characteristic for newer drugs. Serious depressive reactions and psychoses were observed respectively in 12.5 and 2.5% epileptics under VGB and anecdotically after TGB or GPT therapy. Newer selective and specific gabamimetic AEDs play an essential role as add-on therapy of pharmaco-resistant epilepsy, but they did not bring significant qualitive change in the possibilities of pharmacotherapy.

Epilepsy↗
PubMed2006

Adjunctive lamotrigine for refractory epilepsy in adolescents with mental retardation.

Epilepsy is a major comorbid condition in adolescents with mental retardation and is often characterized by multiple seizure types that are refractory to treatment. This study (n = 22) describes a subanalysis of data from a larger multicenter study of adjunctive lamotrigine therapy in patients with mental retardation and refractory epilepsy and focuses on the outcome measures of seizure reduction, safety and tolerability, and impact on behaviors in adolescents with mental retardation and refractory epilepsy. The study kept baseline antiepileptic drugs constant and titrated lamotrigine over 8 weeks to the target dose, followed by an 8-week maintenance phase and then a 12-week optimization phase during which all antiepileptic drugs and lamotrigine could be altered as clinically indicated. Sixty percent of subjects had a 50% decrease in seizures by the end of the maintenance phase and a mean 39% reduction in seizure frequency by the end of the maintenance phase (25% by end of study) compared with baseline. Global improvements were observed in most patients, with statistically significant improvements in the Aberrant Behavior Checklist and the Habilitative Improvement Scale, which is predictive of less need for supportive care in activities of daily living and thus enhanced potential for greater independence. Lamotrigine-associated improvements in behavior can be attributed to improved control of seizures, a reduction in concomitant antiepileptic drugs, and/or direct mood-stabilizing and behavior-enhancing properties independent of the antiseizure effects of the drug. The results of this study suggest that lamotrigine is an important treatment option in adolescents with mental retardation and comorbid epilepsy.

Adolescent↗
PubMed1983

A review of sociometric procedures in the assessment of social competencies in children.

In this review, sociometric procedures for the assessment of social competence in children are considered. Both the traditional nomination procedures as well as the more recently developed rating procedures are described and discussed in terms of the psychometric properties and utility as research tools. In addition, peer and teacher assessment procedures are reviewed. While by definition not sociometric measures, they provide comparable data and can be used in similar fashion. The implications of using these procedures with retarded children is discussed and research recommendations are offered.

Child↗
PubMed1983

Fuzzy and crisp set-theoretic-based classification of health and disease. A qualitative and quantitative comparison.

Conventional cluster analyses of patient populations are intended to assist in the identification and characterization of groups that may represent etiological or pathological subtypes within a particular disease class. These methods have been criticized as being insensitive to subtle patient differences, which may be masked as a result of the all-or-nothing concept of cluster membership intrinsic to crisp set-theoretic-based grouping algorithms. As an alternative to conventional clustering procedures, several investigators have studied the use of fuzzy classification methods. In general, these measure a patient's clinical status in terms of a real number defined on the closed unit interval, reflecting the extent or degree to which a particular grouping entity characterizes the patient. This paper compares and contrasts the applications of crisp and fuzzy set-theoretic-based clustering procedures to a set of data describing the cognitive and intellectual functioning of a group of subjects participating in a longitudinal study of aging. Emphasis is placed on both qualitative and quantitative aspects corresponding, respectively, to the clinical interpretation of cluster definitions, and the robustness or sensitivity of the classification procedures to changes in patient profiles over time. The fuzzy set-theoretic-based model was found to be more sensitive to changes in subject level of functioning over time, to provide superior quantitative protrayals of patterns of aging, and to reflect properties of the aging process derived from other research.

Aged↗
PubMed1980

Intelligence-related differences in the relative salience of object-property relationships.

Three groups of nonretarded children, ranging in age from 8 to 16 years, and a group of EMR 16-year olds (MA = 10) were asked to verify statements about the properties of animate and inaminate objects. Properties were of four types: intrinsic-action (e.g., "sharks can swim"), extrinsic-action (e.g., "horses can be ridden"), static (e.g., "turtles have shells"), and superordinate category (e.g., "dogs are animals"). Results indicated that retarded subjects, relative to nonretarded subjects of all ages, responded particularly slowly to static property statements when objects were animate and to intrinsic-action properties when objects were inanimate. These data suggest intelligence-related differences in the types of semantic properties that are most strongly associated with particular object concepts and, as such, may be indicative of fundamental differences in the way in which the core meaning of individual concepts is represented in semantic memory.

Adolescent↗
PubMed2002

Exploring the etiology of haploinsufficiency.

The focus of this essay is the phenomenon of haploinsufficiency (HI), a manifestation of genetic dominance that arises when only one allele of a normally diploid locus is present. Specifically, I examine the nature of HI for transcription factor genes. Although the concept of HI applies to many such genes, there is a potentially large variety of mechanisms that underlie it. Even when the phenomenon is linked in all cases to reduced absolute gene expression levels, there are several well-documented cases where the explanation is not reduced expression per se but altered stoichiometry. I will discuss the notion of haploimbalance in general and evaluate the property of transcriptional synergy within the context of HI. This kind of non-linear behaviour can probably explain a large proportion of the cases of HI, as well as the variability in most HI phenotypes and the fact that several factors in the same pathway may be dosage sensitive. For the sake of generality, a theoretical analysis of simple non-linear HI systems is also attempted. This article is certainly another preliminary exploration of the complex matters of HI, which remain an intellectual challenge from many points of view.

Animals↗
PubMed1997

Case report: subependymal diffuse heterotopia. Clinical, EEG, and neuroimaging findings.

We report the case of a 41 year-old woman with a slight mental retardation and epilepsy. MRI showed a diffuse subependymal heterotopia. The cognitive level supports the view that the ectopic cells are probably not important for the normal cortical functions but that they are likely able to maintain some of the electric properties of normal neurons, even if with altered discharge modalities. The genetic etiology of subependymal neuronal migration disorders is discussed. This is the second reported case of diffuse subependymal heterotopia in a female patient.

Adult↗