Electrophysiologic analysis of the process of recognizing target and non-target stimuli in healthy and oligophrenic children

In an automatized experiment, with a computer on line, amplitude-temporal parameters of evoked potentials (EPs) to purposive and non-purposive stimuli (digits), were analyzed in normal and mental retarded children. At unilateral stimuli presentation to the left or right visual half-fields EPs were recorded simultaneously in projection, TPO, parietal and central areas of the left and right hemispheres. It has been shown that in normal children, differential involvement of projection and associative structures in the analysis of sensory information takes place in both hemispheres. The amplitudes of most EP components in the range of 100-400 ms to the purposive stimuli are higher than to the non-purposive ones. Considerable similarity of EPs developing in response to ipsi- and contralateral stimulations of visual fields ("direct" and "transmitted" EP) is observed. In mental retarded children significant changes are revealed in intra- and interhemisphere organization of the process of perception of purposive and non-purposive stimuli. In the right hemisphere structures there are no differential EP reactions to the two types of stimuli. Significant, in comparison with the norm, prolongation of the latencies of most EP components is noted, especially in the structures of the left hemisphere, to the purposive stimuli. In the process of perception, changes are seen of the integration of functions of both hemispheres. The totality of disturbances of systemic brain organization at perceptive activity in mental retarded children may reflect neurophysiological mechanisms of mental deficiency.     

The interaction of perception and attention at different stages in individual development

In the study carried out on children aged 10 years (51 persons), subjects aged 16-17 (11) and adults (19) characteristics of the perception and attention interaction were studied by means of electrophysiological parameters analysis (ERP, CNV, EEG) of the process of solution of various visual tasks. It has been shown that adequate brain provision of this process is based in adults both on the functional topographic differentiation and specialization of separate perceptive operations and on the possibility of controlling generalized and local activating influences according to task requirements. In children aged 10, not differing from the adults by the success of the perceptive activity, age peculiarities of its strategy are revealed connected with functional brain organization. Basic distinctive features of children perceptive activity are intensified regional specificity manifested both in responses to relevant and non-relevant stimuli, and excessive generalized activation testifying to incomplete structural-functional maturation of the frontal regions of the cerebral cortex. Increasing functional activity of these structures in ontogenesis provides for the selectivity of perceptive, cognitive and activating processes, adequate to the requirements of the task.     

EEG Spectral Characteristics in Junior Schoolchildren with Learning Problems

EEG spectral characteristics were studied in two age groups (7–8.5 and 8.5–10 years) of mentally healthy children and children with learning problems at rest and during performance of a Raven test. It was shown that slow frequencies are more pronounced in the EEG of 7- to 8.5-year-old children with learning problems than in EEG of healthy children of the same age group. An immature form of EEG activation, i.e., an increase not only in the but also in the frequencies during activity, was characteristic of these children. The reaction of the activation of the definitive type develops between the 8.5–10 years of age. This reaction is correlated with an increase in the efficiency of the sensory perceptive and sensorimotor activity. The distinctive feature of children with learning problems between 8.5–10 years of age is a greater expression of slow frequencies in the baseline EEG of the frontal (in particular, left frontal) areas of the cortex. The obtained results are considered as a reflection of a retardation of the functional maturation of the brain structures responsible for the deficit of involuntary and voluntary attention and the disorder of a systemic organization of perception and analytical–synthetic brain activity as compared to the normal age characteristics. Possible neurophysiological mechanisms responsible for learning problems in junior schoolchildren are discussed on the basis of the obtained results and evidence from the literature.     

Oxidative stress in autism: increased lipid peroxidation and reduced serum levels of ceruloplasmin and transferrin--the antioxidant proteins

Autism is a neurological disorder of childhood with poorly understood etiology and pathology. We compared lipid peroxidation status in the plasma of children with autism, and their developmentally normal non-autistic siblings by quantifying the levels of malonyldialdehyde, an end product of fatty acid oxidation. Lipid peroxidation was found to be elevated in autism indicating that oxidative stress is increased in this disease. Levels of major antioxidant proteins namely, transferrin (iron-binding protein) and ceruloplasmin (copper-binding protein) in the serum, were significantly reduced in autistic children as compared to their developmentally normal non-autistic siblings. A striking correlation was observed between reduced levels of these proteins and loss of previously acquired language skills in children with autism. These results indicate altered regulation of transferrin and ceruloplasmin in autistic children who lose acquired language skills. It is suggested that such changes may lead to abnormal iron and copper metabolism in autism, and that increased oxidative stress may have pathological role in autism.     

Heterogeneous cellular expression of creatine kinase isoenzyme during normal rat heart development

The degree to which developmentally related alterations in cardiac creatine kinase (CK) activity reflect modification of CK isoenzyme gene expression remains uncertain. The present studies addressed this question by assessing multiple aspects of CK in rat heart during the perinatal to adult transition. In addition to whole tissue, isolated and purified muscle and nonmuscle cells were studied, as well as myofibrillar, mitochondrial, and cytosolic subcellular fractions. Whole homogenate CK enzyme specific activity nearly doubled during the weanling to adult developmental period. Muscle cell CK activity increased by a similar magnitude. Nonmuscle cell activity decreased. In the adult heart, both myofibrillar and mitochondrial CK activities were augmented versus the weanling heart. The cytoplasmic fraction activity held constant during development. Electrophoretic isoenzyme analyses of both weanling and adult cardiac muscle cells indicated the presence of mitochondrial CK and MM-CK isoforms. Weanling heart nonmuscle cells contained mitochondrial, MM, MB, and BB isoforms; however, BB isoform was not detected in the adult heart nonmuscle cells. Arrhenius plots provided information regarding heart muscle and nonmuscle cell alterations during development. CK activation energies were also determined for whole tissue, muscle/nonmuscle cells, myofibrils, mitochondria, and cytosol. Results demonstrate that heterogeneous muscle/nonmuscle cellular composition and differential myofibrillar/mitochondrial subcellular composition account for normal, developmentally related changes in heart CK enzyme activity. CK isoenzyme gene expression changes were not detected in cardiac muscle cells, and transition of CK-B to CK-M gene expression is limited to nonmuscle cells during normal, weanling to adult development in the rat heart.     

Effects of differentiated membranes on the developmental program of the cellular slime mold.

In the preceding paper isolated aggregation phase membranes (prepared from Dictyostelium discoideum cells which had proceeded through 12–14 hr of the developmental cycle) were found to be capable of preventing the aggregation and subsequent morphological development of vegetative cells when mixed with these and plated under normal conditions for slime mold development. In this paper we have extended the investigations on the nature of this interaction by monitoring the display of several developmentally controlled enzymes. It appears that exogenously applied aggregation phase membrane preparations are capable of influencing biochemical events inside D. discoideum cells through their interaction with the cell surface. This interaction leads to the induction or accumulation of some developmentally controlled enzymes, as well as the repression or excretion of others. The results suggest that the formation and maintenance of correct cell-cell contacts during normal development may be of crucial importance. They also show that changes in the specific activity of some developmentally controlled enzymes may in certain conditions be wholly divorced from both morphogenesis and the normal sequence of induction.     

Congenital Perceptive Deafness: Role of Intrauterine Rubella

Rubella antibody was detected in 85 (61%) of 139 children aged from 6 months to 7 years with congenital perceptive deafness. Of the 112 children who were aged under 4 years 61 (54%) had rubella antibody (seropositive) compared with 7·1% in randomly selected children of the same age. A close correlation was found between the presence of antibody in children with perceptive deafness and (1) a maternal history of rash or contact in early pregnancy, and (2) with the presence of other rubella-type defects. Intrauterine rubella was thought to be the cause of the deafness in 82 (59%) of the 139 children, in 60 of whom deafness was the only rubella defect detected. Thus intrauterine rubella should be considered a likely cause of congenital perceptive deafness in a child under 4 years in whom rubella antibody is present.     

Accumulation of alpha-mannosidase-1 in Dictyostelium discoideum requires many developmentally essential genes

alpha-Mannosidase-1, one of the earliest known developmentally controlled gene products in the cellular slime mold Dictyostelium discoideum, accumulates intracellularly during both axenic growth and development. The accumulation of alpha-mannosidase-1 activity prematurely ceases in all of 125 randomly isolated aggregation-deficient mutants at discrete times in development resulting in significantly reduced levels of cellular enzyme activity. This suggests that, unlike other developmentally controlled enzymes in this organism, the continued accumulation of alpha-mannosidase-1 activity is controlled by a large number of genes essential for early development. alpha-Mannosidase-1 misregulation and the aggregation-deficient phenotype are caused by the same mutation since (1) morphological revertants exhibit a coreversion to both fruiting ability and wild-type alpha-mannosidase-1 accumulation and (2) normal enzyme accumulation depends on the ability to aggregate and ultimately fruit in a conditional aggregation-deficient mutant. This type of regulation does not appear to be due to differences in enzyme secretion or changes in the overall rate of total protein synthesis. Aggregation-deficient mutants continue to synthesize protein beyond the time in development at which alpha-mannosidase-1 accumulation ceases. Our studies indicate that most of the 50-125 genes required for aggregation in Dictyostelium are also required for the normal accumulation of alpha-mannosidase-1 activity.     

Aberrant Neuromagnetic Activation in the Motor Cortex in Children with Acute Migraine: A Magnetoencephalography Study

Migraine attacks have been shown to interfere with normal function in the brain such as motor or sensory function. However, to date, there has been no clinical neurophysiology study focusing on the motor function in children with migraine during headache attacks. To investigate the motor function in children with migraine, twenty-six children with acute migraine, meeting International Classification of Headache Disorders criteria and age- and gender-matched healthy children were studied using a 275-channel magnetoencephalography system. A finger-tapping paradigm was designed to elicit neuromagnetic activation in the motor cortex. Children with migraine showed significantly prolonged latency of movement-evoked magnetic fields (MEF) during finger movement compared with the controls. The correlation coefficient of MEF latency and age in children with migraine was significantly different from that in healthy controls. The spectral power of high gamma (65–150 Hz) oscillations during finger movement in the primary motor cortex is also significantly higher in children with migraine than in controls. The alteration of responding latency and aberrant high gamma oscillations suggest that the developmental trajectory of motor function in children with migraine is impaired during migraine attacks and/or developmentally delayed. This finding indicates that childhood migraine may affect the development of brain function and result in long-term problems.     

3Development-Dependent Regulation of N-Acetyl-β-d-Hexosaminidase of Cerebellum and Cerebrum of Normal and Staggerer Mutant Mice

Distinctive activities of various glycosidases were expressed in the cerebellum and cerebral cortex of mice during their development. In particular, N-acetyl-beta-D-hexosaminidase (EC 3.2.1.30) appeared to be developmentally regulated. A transient peak of enzyme activity at postnatal day 7 was characteristic for the cerebellum, whereas the activity in the cerebral cortex gradually increased through the 1st postnatal month and was maintained at a high level of activity throughout adulthood. The regulation of N-acetylhexosaminidase activity in the developing cerebellum of the staggerer mouse deviated clearly from enzyme activities in the wild-type, whereas the activity pattern in the staggerer cerebral cortex remained unaffected. In experiments mixing wild-type and staggerer cerebellum homogenates, the specific activity was additive. Thus, involvement of inhibitors or activating molecules can be excluded. This developmentally controlled regulation or disregulation in staggerer appears to be enzyme specific, sine beta-glucosidase, alpha-glucosidase, and beta-galactosidase did not exhibit such a pattern in either normal or staggerer mice. In the mutation weaver that, like staggerer, loses the majority of its cerebellar granule cells, N-acetyl-beta-hexosaminidase activity of the cerebellum was not elevated, indicating a specific defect in staggerer rather than a general effect on lysosomal enzymes due to cell death.     

V(D)J recombinase-mediated processing of coding junctions at cryptic recombination signal sequences in peripheral T cells during human development

V(D)J recombinase mediates rearrangements at immune loci and cryptic recombination signal sequences (cRSS), resulting in a variety of genomic rearrangements in normal lymphocytes and leukemic cells from children and adults. The frequency at which these rearrangements occur and their potential pathologic consequences are developmentally dependent. To gain insight into V(D)J recombinase-mediated events during human development, we investigated 265 coding junctions associated with cRSS sites at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus in peripheral T cells from 111 children during the late stages of fetal development through early adolescence. We observed a number of specific V(D)J recombinase processing features that were both age and gender dependent. In particular, TdT-mediated nucleotide insertions varied depending on age and gender, including percentage of coding junctions containing N-nucleotide inserts, predominance of GC nucleotides, and presence of inverted repeats (Pr-nucleotides) at processed coding ends. In addition, the extent of exonucleolytic processing of coding ends was inversely related to age. We also observed a coding-partner-dependent difference in exonucleolytic processing and an age-specific difference in the subtypes of V(D)J-mediated events. We investigated these age- and gender-specific differences with recombination signal information content analysis of the cRSS sites in the human HPRT locus to gain insight into the mechanisms mediating these developmentally specific V(D)J recombinase-mediated rearrangements in humans.     

Phosphorylcreatine shuttle enzymes during perinatal heart development

Mammalian heart development, from the time of weaning until adulthood, is characterized by progressive and significant enhancement in functional performance. Aerobic metabolism and contractile protein ATPase activity increase in parallel with augmented cardiac function. The present studies examined the potential contribution of phosphorylcreatine shuttle enzymes to the developmentally linked alterations in heart performance. Mitochondrial ATPase specific activity was not altered between weanling and adult heart; however, creatine kinase activity was enhanced approximately threefold. Myofibrillar ATPase activity doubled over the developmental time course, while creatine kinase activity increased to an even greater extent. Enhanced myofibrillar ATPase activity was not due to alterations in either calcium sensitivity or ATPase activity measured in purified myosin. Both the mitochondrial and myofibrillar creatine kinase enzyme activities are enhanced during normal heart growth; however, relatively greater enhancement of the myofibrillar component occurs. Thus, enzymatic reactions comprising the phosphorylcreatine shuttle system are dramatically increased during normal heart development. This mechanism deserves consideration as a potentially powerful contributor to enhanced cardiac function during the perinatal period.     

Postnatal Psychological Causes of Mental Retardation

The psychological factors present in 715 suspected retarded children were studied. Social, cultural and educational deprivation accounted for 57 cases. Personality and emotional conflicts were primary etiological factors in 15 children. Functional childhood psychosis was found in 18. A group of 89 children had no obvious definitive cause for retardation, although epilepsy, mixed eye and hand dominance, visual perceptive disorders, or poor muscle tone was present in some. In the remaining 523 children, primary brain damage was evident. A sample of 142 of these brain-damaged children revealed that 38 had neurotic symptoms, 23 were antisocial, 11 were psychotic, 28 had restless, disturbed activity, and 42 had intellectual lowering only. The authors suggest that both psychological and organic factors must be taken into consideration in order that complete diagnostic and therapeutic effectiveness be achieved.     

Age matters in the prevalence and clinical significance of ultra‐high‐risk for psychosis symptoms and criteria in the general population: Findings from the BEAR and BEARS‐kid studies

Early detection of psychosis is an important topic in psychiatry. Yet, there is limited information on the prevalence and clinical significance of high‐risk symptoms in children and adolescents as compared to adults. We examined ultra‐high‐risk (UHR) symptoms and criteria in a sample of individuals aged 8‐40 years from the general population of Canton Bern, Switzerland, enrolled from June 2011 to May 2014. The current presence of attenuated psychotic symptoms (APS) and brief intermittent psychotic symptoms (BLIPS) and the fulfillment of onset/worsening and frequency requirements for these symptoms in UHR criteria were assessed using the Structured Interview for Psychosis Risk Syndromes. Additionally, perceptive and non‐perceptive APS were differentiated. Psychosocial functioning and current non‐psychotic DSM‐IV axis I disorders were also surveyed. Well‐trained psychologists performed assessments. Altogether, 9.9% of subjects reported APS and none BLIPS, and 1.3% met all the UHR requirements for APS. APS were related to more current axis I disorders and impaired psychosocial functioning, indicating some clinical significance. A strong age effect was detected around age 16: compared to older individuals, 8‐15‐year olds reported more perceptive APS, that is, unusual perceptual experiences and attenuated hallucinations. Perceptive APS were generally less related to functional impairment, regardless of age. Conversely, non‐perceptive APS were related to low functioning, although this relationship was weaker in those below age 16. Future studies should address the differential effects of perceptive and non‐perceptive APS, and their interaction with age, also in terms of conversion to psychosis.     

On Biological Functions Mapping to the Heterochromatin of DROSOPHILA MELANOGASTER

We examined the behavior of an autosomal recessive maternal-effect mutation, abnormal-oocyte (abo), that is located in the euchromatin of the left arm of chromosome 2. When homozygous in females, abo results in a marked reduction in the probability that an egg produced by a mutant mother will develop into an adult. However, this probability is increased if the fertilizing sperm delivers to the egg either a normal allele of the maternal-effect gene or a specific type of heterochromatin (called ABO) that is located in small regions of the X and Y chromosome constitutive heterochromatin as well as in some autosomal heterochromatin. These regions, moreover, all react to Hoechst 33258 fluorescent dye identically and specifically. The amelioration of the maternal effect produced by this heterochromatin differs temporally from that caused by the normal allele of the euchromatic gene: the heterochromatin reduces only precellular blastoderm mortality, whereas the normal allele of the euchromatic gene reduces only postblastoderm mortality. Thus, although the genome of the preblastoderm Drosophila embryo is apparently mostly silent, the ABO-containing heterochromatin functions at this early time. Finally, preliminary data indicate that abo is but one member of a cluster of linked genes, each of which interacts with its own normal allele and with a different, locus-specific, heterochromatic factor. From these observations, it appears that Drosophila heterochromatin contains developmentally important genetic elements, and that a functional concomitant of heterochromatic location is gene action at a developmental stage during which the activity of the euchromatic genome is as yet undetectable. Some general implications of these inferences are considered.     

Psychophysiological and neurophysiological features of the organization of visuo-spatial performance in right-handed and left-handed six- to seven-year-old children

The developmental features of individual components of the visual perception and brain functional organization during visuo-spatial activity of different complexity were studied in right-handed and left-handed 6–7-year-old children. The results of psychophysiological testing of their visual perception testify to the underdevelopment of the mechanisms of integrative brain activity. Some specific features of the brain functional organization were revealed in the left-handed children during visuo-spatial performance. More autonomous functioning of the cerebral hemispheres and the duplication of the activation processes in the right and left hemisphere during visuo-spaital performance of different complexity are characteristic of these children. This is probably associated with the involvement of compensatory mechanisms, which enable the performance reliability.     

Comparative EEG study in normal and autistic children

The work represents the results of a comparative study of spectral power as well as averaged coherence in alpha, beta and gamma EEG bands in 5-to-7-year-old autistic and healthy boys in the state of rest and under cognitive load (mental calculation). The mean age of the examined children was 6 years 4 months. In both healthy and autistic children, there was a clear-cut baseline frontal-occipital gradient of the alpha activity. Performance of the cognitive task led to enhancement of spectral power in the alpha1 band and shifting its maximum to the left hemisphere, did not change the activity in the alpha2 band, and considerably increased the spectral power in the alpha3 band. In healthy children, the spectral power and average coherence of the fast rhythms increased in the central and frontal areas of the left hemisphere. The right-side dominance of the spectral power of the alpha band was revealed in autistic children both in the baseline and during cognitive task. The spectral power of the gamma band was higher in autistic children than in healthy children in the baseline. The cognitive task did not change this fast activity in autistic children.     

Analysis of azide-insensitive Ca2+-dependent ATPase activity in atrial specimens from patients with coronary or valvular heart disease

The activity of the azide-insensitive Ca2+-dependent ATPase (highly enriched in myofibrillar ATPase activity) was studied in specimens of both right and left atria which were taken from patients with ischemic and/or valvular heart disease during coronary by pass and/or valvular substitution. A significantly lower enzymatic activity was found in atrial specimens from patients with left ventricular heart failure in comparison to the atrial fragments obtained from the patients with normal heart function. Such an inhibition reflected a significant increase in the Km of the enzyme for ATP and was associated with a concomitant reduction in Vmax, both more evident in the left atrial fragments. Moreover, tissue homogenates of atrial specimens from failing hearts exhibited a lower protein SH group content when compared to the atrial homogenates from the heart with normal left ventricular heart function.     

Helical structure of the human umbilical cord.

The helical structure of the human umbilical cord has been studied on 528 full-term cords from normal deliveries, 18 cords from aborted and developmentally normal fetuses with a CR length of 1.2-19.5 cm, 10 cords from monozygotic twins. In order to resolve the discrepancy in the nomenclature of the twist direction, a method has been suggested which takes into account the direction to which the fetus must have rotated to produce the twist. The incidence of the right helical pattern was 64.58%, of the left helical pattern 15.15%, and of the mixed patterns 17.43%; the twists were indeterminate in 1.89% and absent in 0.95% of the cords. Details of the mixed patterns are listed. The number of the uniform right twists ranged from 1 to 29 (7.5) and that of the left twists from 1 to 19 (6.7). There exists an exponential relation between the number of the twists and the ratio between length and thickness of the cords. The twists begin to appear during the early part of the 8th week, and their final number is possibly attained soon after the 9th week of development. In view of the absence of concordance in monozygotic twins, the helical nature of the cord is possibly controlled by factors which may be partly genetic and partly environmental.     

Alteration in amino-glycerophospholipids levels in the plasma of children with autism: a potential biochemical diagnostic marker

Currently, there is no biochemical test to assist in the behavioral diagnosis of autism. We observed that levels of phosphatidylethanolamine (PE) were decreased while phosphatidylserine (PS) were increased in the erythrocyte membranes of children with autism as compared to their non-autistic developmentally normal siblings. A new method using Trinitrobenezene sulfonic acid (TNBS) for the quantification of PE and PS (amino-glycerophospholipids, i.e., AGP) in the plasma of children was developed and standardized. Wavelength scans of TNBS-PE and TNBS-PS complexes gave two peaks at 320 nm and 410 nm. When varying concentrations of PS and PE were used, a linear regression line was observed at 410 nm with TNBS. Using this assay, the levels of AGP were found to be significantly increased in the plasma of children with autism as compared to their non-autistic normal siblings. It is proposed that plasma AGP levels may function as a potential diagnostic marker for autism.