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PubMedDate not supplied

Handicap-related problems in mothers of children with physical impairments.

An inventory was developed for the measurement of handicap-related problems experienced by mothers of children with chronic physical conditions and an initial evaluation of its psychometric properties was completed in a sample of 119 mothers of children with physical or sensory impairments. Principal component analysis of the Handicap-related Problems for Parents Inventory (HPPI) yielded three subscales, which accounted for 54% of the total variance. The HPPI demonstrated excellent internal consistency for each scale and total score. It also generally had good test-retest reliability over 6-, 12-, and 18-month periods. There was minimal covariation between HPPI scores and demographic status. Concurrent validity was demonstrated by significant correlations between appropriate HPPI scales and measures of daily stress and the child's physical condition or disability status. Support for its construct validity was obtained when expected convergent and discriminant relationships were confirmed between HPPI scales and measures of maternal adaptation, maternal social support, and child behavior problems. Among other results, HPPI scores predicted maternal adaptation 18 months later. The potential uses of the HPPI in research and intervention with mothers of children with chronic physical conditions were discussed.

Adaptation, Psychological↗
PubMed1991

The 56/58 kDa androgen-binding protein in male genital skin fibroblasts with a deleted androgen receptor gene.

Human genital skin fibroblasts (GSF) make a relatively abundant 56/58 kDa protein that binds androgens. The protein shares many properties with the approximately 100 kDa androgen receptor that is encoded by a locus in the q12 region of the X chromosome. It does not appear to be androgen-induced, yet is absent in GSF of most patients with complete androgen insensitivity (CAI). A precursor-product relation with the androgen receptor (AR) protein has been largely excluded; that it may be an unorthodox product of the AR gene has not. The 56/58 kDa protein is made by the GSF of a mentally retarded subject who has CAI because of a complete deletion of the coding portion of the AR gene. Hence, the strong constitutional and statistical correlations that have been demonstrated between the two proteins cannot arise because they share the same gene. The subject's genomic DNA hybridizes normally with 11 single-copy probes from Xq11-Xq13. Therefore, we cannot attribute her mental retardation to a contiguous gene syndrome.

Androgen-Binding Protein↗
PubMed1999

Metabolic engineering from a cybernetic perspective. 2. Qualitative investigation of nodal architechtures and their response to genetic perturbation

A cybernetic representation of the branch point development of Stephanopoulos and Vallino is formulated. The model systems are employed to translate the qualitative properties of the nodal control architectures characterized by Stephanopoulos and Vallino into a mathematical context. It is shown that a cybernetic model in which the objective is the independent maximization of the levels of branch point products is consistent with the characterization of a flexible node. In contrast, the rigid control architecture is shown to be equivalent to the maximization of the mathematical product of the branch point products. It has been demonstrated subsequently that cybernetic metabolic network models are capable of predicting the system response to enzymatic amplification. However, given the complicated nature of the subsequent models, a clear illustration of the basic mechanism by which such predictions are manifested is not forthwith. Thus, a second objective of the present work is the examination of the response of the flexible and rigid control architectures to genetic perturbation, specifically enzymatic overexpression, with the expressed aim of elucidating the mechanism by which a cybernetic model predicts metabolic network responsiveness. It is shown that the ramifications of genetic perturbation are transmitted through the cybernetic representation of a metabolic network via the resource allocation structure which acts as the conduit by which regulatory signals are transmitted to seemingly unconnected portions of the network. It is postulated that enzymatic overexpression under an artificial promoter represents, from the perspective of the microorganism, an uncontrollable resource drain that forces the metabolic network control architecture to reevaluate the standing resource allocation policy as implemented via the cybernetic control variables. In biological terms, the reevaluation of allocation policy implies a shift in the level and activity of network enzymes yielding, in some cases, qualitatively different network function. It is our position that, conceptually, this is equivalent to the conventional wisdom that genetic manipulation of a metabolic network is the impetus for shifts in the network functionality, i.e., enzyme levels as well as activity. Thus, this development provides a necessary intellectual precursor for the formulation and analysis of the model systems that follow.

Journal Article↗
PubMed1986

Acute and subacute CNS effects of milacemide in elderly people: double-blind, placebo-controlled quantitative EEG and psychometric investigations.

In a double-blind, placebo-controlled study the encephalotropic and psychotropic properties of acutely and chronically administered milacemide--a new derivative of glycine showing anti-convulsant action by increasing GABA concentrations and endogenous glycine pools in the brain--were investigated in 12 elderly subjects in their late sixties. Each subject had a treatment period of 2 weeks (with 400 mg b.i.d. and 1,200 mg b.i.d. orally administered in week 1 and 2, respectively) and another period of 2 weeks with placebo. A treatment-free interval of 1 week was introduced in between. EEG-recordings, psychometric and psychophysiological tests as well as evaluation of pulse, blood pressure and side effects were carried out at the hours 0, 2, 4, 6 and 8 after the administration of one single dose of 400 mg or placebo (acute effect), after 1 week's and 2 weeks' chronic administration (chronic effect), as well as after one additional superimposed dosage of 400 mg and 1,200 mg on days 8 and 15 of chronic treatment, respectively (super-imposed effect). Computer-assisted spectral analysis of the EEG demonstrated after single doses of 400 mg milacemide significant changes in the resting EEG indicative of improvement in vigilance (beta augmentation, acceleration of the beta centroid), while in the vigilance-controlled recording condition a dissociative vigilance shift occurred seen also after antidepressants of the amitriptyline and imipramine type (increase of both delta/theta and beta activity, decrease of alpha activity). One week chronic treatment resulted in the same V- and R-EEG profiles. However, after the 2nd weeks' treatment with higher doses as well as after one additional superimposed dosage of 1,200 mg milacemide both V- and R-EEG recordings demonstrated dissociative vigilance shifts. Time/treatment-efficacy calculations showed the chronic effect to be more pronounced than the acute effect, which peaked in the 2nd hour after oral drug administration. Psychometric analyses exhibited in noopsychic variables a significant improvement in intellectual and mnestic performance but even more so in the thymopsyche an improvement in subjective well-being and affectivity. Psychophysiological tests showed a decrease in CFF, while static and dynamic pupillometry and skin conductance measures remained unchanged. Pulse rate, systolic and diastolic blood pressure were not altered. The findings are discussed in the light of the involvement of GABA in the pathogenesis and treatment of affective disorders.

Acetamides↗
PubMedDate not supplied

Psychometric properties of ADHD rating scales among children with mental retardation I: reliability.

The reliability of Attention-Deficit/Hyperactivity Disorder (ADHD) rating scales in children with mental retardation was assessed. Parents, teachers, and teaching assistants completed ADHD rating scales on 48 children aged 5-12 diagnosed with mental retardation. Measures included the Child Behavior Checklist (CBCL), Conners Rating Scales, the Attention-Deficit/Hyperactivity Disorder Test (ADHDT), the Swanson, Nolan, and Pelham (SNAP) Checklist, the Werry-Weiss-Peters Activity Rating Scale (WWPARS), the ADD-H Comprehensive Teacher's Rating Scale (ACTeRS), and the Aberrant Behavior Checklist-Community (ABC-C). The internal consistency, test-retest, and interrater reliability of each scale was examined. Results showed best support for teacher completed scales, followed by ratings made by teaching assistants, and parent-report scales. Strong support for the internal consistency of the teacher-report measures was found, and it was quite similar to previously reported internal consistencies with typically developing children. Test-retest reliabilities of the teacher report measures were also quite good but tended to be lower than those reported for typically developing children. For teaching assistant ratings, test-retest reliabilities were adequate to very good. The internal consistency reliabilities for parent completed measures were adequate to excellent, but test-retest reliabilities were low. Interrater reliability was best for teacher-teaching assistants. The ABC-C was the only measure on which the interrater reliability was adequate for clinical purposes.

Attention Deficit Disorder with Hyperactivity↗
PubMed2005

Circadian activity rhythms in selectively bred ethanol-preferring and nonpreferring rats.

Chronic alcohol intake is associated with dramatic disruptions in sleep and other circadian biological rhythms in both humans and experimental animals. In human alcoholics, these disruptions persist during extended abstinence and appear to promote relapse to drinking. Whereas chronic ethanol intake alters fundamental properties of the circadian pacemaker in unselected rats, nothing is known concerning circadian pacemaker function in selectively bred ethanol-preferring and nonpreferring rats, which are the most widely accepted animal models of genetic predisposition to alcoholism. The present experiments were designed to characterize free-running circadian activity (wheel-running) rhythms under both constant darkness and constant light in selectively bred ethanol-preferring (P, HAD2) and nonpreferring (NP, LAD2) rats. Differences in circadian organization between ethanol-preferring and nonpreferring animals were seen for both pairs of selected lines (P vs. NP; HAD2 vs. LAD2), but these differences were not identical in the two line pairs. For example, although P rats showed shorter free-running periods than NP rats only in constant light, HAD2 rats showed shorter free-running periods than LAD2 rats only in constant darkness. In addition, ethanol-preferring HAD2 rats showed a high rate of rhythm "splitting" that was not seen in any of the other three lines. Taken together, these results suggest that the circadian pacemakers of P and NP rats differ mainly in light sensitivity, whereas those of HAD2 and LAD2 rats differ in their intrinsic period.

Camphor↗
PubMed1998

Comparison of the functional properties of three different truncated thyroid hormone receptors identified in subjects with resistance to thyroid hormone.

The tau4 domain in the extreme carboxyl (C) terminal region of thyroid hormone receptor (TR) is important to transactivation. We identified three truncated TRbeta1s with 11 (F451X), 13 (E449X) and 16 (C446X) amino acid deletions within this domain in subjects with resistance to thyroid hormone (RTH). F451X and C446X were found in a 6-year-old Japanese girl and a 31-year-old American male, respectively, who had both severe mental retardation. E449X was identified in a 16-year-old Japanese boy with no remarkable clinical symptoms except for goiter. Transient expression study revealed that all three mutants had negligible T3 binding and transcriptional activities. Each mutant TRbeta1 exhibited not only very strong dominant negative activity against wild TRbeta1, but also marked silencing activity. Interestingly, the dominant negative activity and silencing activity were significantly stronger in F451X than in E449X and C446X (P < 0.05). Gel-shift experiments revealed no apparent differences in homodimer formations of wild-type or mutant TRbeta1 proteins and in heterodimer formations with retinoid X receptor (RXR). These observations indicate that the tau4 domain affects diverse TR functions, and that the region between 11 and 13 C-terminal amino acids influences ligand-independent TR functions, including dominant negative and silencing activities. The central nervous system involvement is not necessarily determined by the dominant negative potency of the mutant TRbeta1 and other environmental or genetic factors may influence the RTH manifestations.

Adolescent↗
PubMed2000

Clinical, biochemical and molecular genetic correlations in adenylosuccinate lyase deficiency.

Adenylosuccinate lyase (ADSL) deficiency (MIM 103050) is an autosomal recessive inborn error of purine synthesis characterized by the accumulation in body fluids of succinylaminoimidazolecarboxamide (SAICA) riboside and succinyladenosine (S-Ado), the dephosphorylated derivatives of the two substrates of the enzyme. Because ADSL-deficient patients display widely variable degrees of psychomotor retardation, we have expressed eight mutated ADSL enzymes as thioredoxin fusions and compared their properties with the clinical and biochemical characteristics of 10 patients. Three expressed mutated ADSL enzymes (M26L, R426H and T450S) were thermolabile, four (A2V, R141W, R303C and S395R) were thermostable and one (del206-218), was inactive. Thermolabile mutations decreased activities with SAICA ribotide (SAICAR) and adenylosuccinate (S-AMP) in parallel, or more with SAICAR than with S-AMP. Patients homozygous for one of these mutations, R426H, displayed similarly decreased ADSL activities in their fibroblasts, S-Ado:SAICA riboside ratios of approximately 1 in their cerebrospinal fluid and were profoundly retarded. With the exception of A2V, thermostable mutations decreased activity with S-AMP to a much more marked extent than with SAICAR. Two unrelated patients homozygous for one of the thermostable mutations, R303C, also displayed a much more marked decrease in the activity of fibroblast ADSL with S-AMP than with SAICAR, had S-Ado:SAICA riboside ratios between 3 and 4 in their cerebrospinal fluid and were mildly retarded. These results suggest that, in some cases, the genetic lesion of ADSL determines the ratio of its activities with S-AMP versus SAICAR, which in turn defines the S-Ado:SAICA riboside ratio and the patients' mental status.

5' Untranslated Regions↗
PubMed2000

ATR-X mutations cause impaired nuclear location and altered DNA binding properties of the XNP/ATR-X protein.

Mutations in the XNP/ATR-X gene, located in Xq13.3, are associated with several X linked mental retardation syndromes, the best known being alpha thalassaemia with mental retardation (ATR-X). The XNP/ATR-X protein belongs to the family of SWI/SNF DNA helicases and contains three C2-C2 type zinc fingers of unknown function. Previous studies have shown that 65% of mutations of XNP have been found within the zinc finger domain (encoded by exons 7, 8, and the beginning of exon 9) while 35% of the mutations have been found in the helicase domain extending over 3 kb at the C-terminus of the protein. Although different types of mutations have been identified, no specific genotype-phenotype correlation has been found, suggesting that gene alteration leads to a loss of function irrespective of mutation type. Our aims were to understand the function of the XNP/ATR-X protein better, with specific attention to the functional consequences of mutations to the zinc finger domain. We used monoclonal antibodies directed against the XNP/ATR-X protein and performed immunocytochemical and western blot analyses, which showed altered or absent XNP/ATR-X expression in cells of affected patients. In addition, we used in vitro experiments to show that the zinc finger domain can mediate double stranded DNA binding and found that the DNA binding capacity of mutant forms in ATR-X patients is severely reduced. These data provide insights into the understanding of the functional significance of XNP/ATR-X mutations.

Active Transport, Cell Nucleus↗
PubMed1991

Treatment of epilepsy in mentally retarded patients with a slow-release carbamazepine preparation.

Pharmacokinetic properties and efficacy of a conventional (C) carbamazepine (CBZ) preparation divided into three daily doses and a slow-release CBZ preparation (SR) divided into two daily doses were evaluated in a randomized, double-blind, cross-over study. The trial started with a 8-week baseline period followed by the two treatment periods each 10 weeks long. At the end of each period, a 24-h blood sample series for determination of serum CBZ and carbamazepine-10,11-epoxide (CBZE) was collected. The occurrence of seizures was monitored day and night during the whole study period by experienced nurses. The mean age of the 20 evaluable patients was 24.9 and the duration of epilepsy 19.2 and carbamazepine treatment 7.0 years. The bioavailability of CBZ from the two preparations was similar. The mean fluctuation of serum CBZ concentration (Cmax-Cmin/Css) was 16% smaller during SR. The mean serum CBZ concentration in the morning samples was significantly (P less than 0.001) higher during SR treatment. The mean total number of seizures was approximately four per week and did not differ between the two treatments, but during the last 2 weeks of the study period the occurrence of seizures was significantly smaller during SR (P = 0.02).

Adolescent↗
PubMed2003

Psychometric properties of the Chinese version of the Mini-Mental Adjustment to Cancer (MINI-MAC) scale.

The psychometric properties of a Chinese version of the Mini-Mental Adjustment to Cancer scale (Mini-MAC) were examined among 115 Chinese cancer patients in Hong Kong. The five subscales from the original Mini-MAC (Anxious Preoccupation, Helpless-Hopeless, Fighting Spirit, Fatalism, Cognitive Avoidance) had acceptable internal reliabilities (Cronbach's alpha ranged from 0.65 to 0.88) and construct validities in our sample. Factor analysis suggested three factors: (1) Negative Emotion (alpha=0.91) contained items of the Anxious Preoccupation and the Helpless-Hopeless subscales of the original Mini-MAC, (2) Positive Attitude (alpha=0.77) combined the Fighting Spirit and the Fatalism subscales of the original version, and (3) Cognitive Avoidance (alpha=0.65) which was identical to the Cognitive Avoidance subscale of the original Mini-MAC. Construct validities of the novel factors were shown by their correlations with HADS Anxiety and Depression scores in the predicted directions. It was concluded that both the 5-factor model from the original Mini-MAC and the 3-factor model from the present study were valid in Hong Kong Chinese cancer patients. The results were discussed in terms of the meaning of the original Mini-MAC factors and cultural differences in coping functions between Chinese and UK cancer patients.

Adaptation, Psychological↗
PubMed1998

Increased neutrophil adhesive capability in Cohen syndrome, an autosomal recessive disorder associated with granulocytopenia.

BACKGROUND AND OBJECTIVE: Cohen syndrome is a multiple congenital anomalies-mental retardation syndrome associated with granulocytopenia. To date, the mechanisms involved in causing the neutropenia are unknown. In order to get insight into the mechanisms of neutropenia, we studied both the bone marrow and the functional properties of neutrophils obtained from peripheral blood (PB) or skin window (SW) exudate of a patient affected by Cohen syndrome. DESIGN AND METHODS: Assays of superoxide anion release (as reduction of cytochrome C) and cell adhesion (quantified by measuring membrane acid phosphatase) were carried out according to a microplate method whereby both parameters can be evaluated (Bellavite et al., 1992). Neutrophil surface integrins and CD62L (selectin) were evaluated by flow cytometry. RESULTS: Bone marrow did not show relevant morphological abnormalities in either erythroid or myeloid precursors. Cohen neutrophils exhibited a greater adhesive capability than control leukocytes in all the conditions studied (PB or SW, unstimulated or agonist-stimulated leukocytes). Cytofluorometric evaluation of neutrophil beta 2 integrin (CD11b) and selectin (CD62L) showed a lower mean fluorescence intensity and a lower percentage of fluorescence conjugate monoclonal Ab-positive cells in the patient than in control subjects. Moreover, a double population of neutrophils, with different affinities to the specific monoclonal antibody anti-CD11b, was observed in the patient. Superoxide anion release, expression and distribution of fluorescence conjugate MoAb anti-human CD11a were normal. INTERPRETATION AND CONCLUSIONS: Neutrophil adhesive capability was greatly increased in a case of Cohen syndrome. Cytofluorimetric expression of CD11b and CD62L molecules was consistent with a generalized neutrophil activation in vivo.

Abnormalities, Multiple↗
PubMed2005

Movement skill assessment in children with profound multiple disabilities: a psychometric analysis of the top down motor milestone test.

OBJECTIVE: To analyse the psychometric properties of the Top Down Motor Milestone Test (TDMMT), an internationally used instrument in the planning and evaluation of movement-oriented interventions. SETTING: Centres for special education in the Netherlands. SUBJECTS: Children with profound multiple disabilities. METHODS: Validity, reliability and utility of the TDMMT were evaluated. Validity was assessed by conducting a principal component analysis. Reliability was determined by evaluating the internal consistency, test-retest and inter-rater reliability. With regard to utility, the hierarchical item ordering was evaluated with a Mokken scale analysis. Inter-item and item-rest correlations were calculated to confirm the allocation of the items in the TDMMT. RESULTS: Principal component analysis did not support the presence of three underlying factors. The internal consistency was high and test-retest and inter-rater reliability varied from moderate to perfect. Scale analysis showed that the subscales of the TDMMT are strong one-dimensional scales with good internal consistency, however, the order of the items could only partly be confirmed as well as the allocation of the items into four levels of functioning. CONCLUSION: The reliability of the TDMMT is good, but validity is moderate. Results indicate that adaptations to the structure of the TDMMT should be made when used for children with profound multiple disabilities. Further psychometric evaluation of the TDMMT is necessary.

Adolescent↗
PubMed1999

Oligomerization properties of fragile-X mental-retardation protein (FMRP) and the fragile-X-related proteins FXR1P and FXR2P.

The absence of fragile-X mental-retardation protein (FMRP) results in fragile-X syndrome. Two other fragile-X-related (FXR) proteins have been described, FXR1P and FXR2P, which are both very similar in amino acid sequence to FMRP. Interaction between the three proteins as well as with themselves has been demonstrated. The FXR proteins are believed to play a role in RNA metabolism. To characterize a possible functional role of the interacting proteins the complex formation of the FXR proteins was studied in mammalian cells. Double immunofluorescence analysis in COS cells over-expressing either FMRP ISO12/FXR1P or FMRP ISO12/FXR2P confirmed heterotypic interactions. However, Western-blotting studies on cellular homogenates containing physiological amounts of the three proteins gave different indications. Gel-filtration experiments under physiological as well as EDTA conditions showed that the FXR proteins were in complexes of >600 kDa, as parts of messenger ribonuclear protein (mRNP) particles associated with polyribosomes. Salt treatment shifted FMRP, FXR1P and FXR2P into distinct intermediate complexes, with molecular masses between 200 and 300 kDa. Immunoprecipitations of FMRP as well as FXR1P from the dissociated complexes revealed that the vast majority of the FXR proteins do not form heteromeric complexes. Further analysis by [(35)S]methionine labelling in vivo followed by immunoprecipitation indicated that no proteins other than the FXR proteins were present in these complexes. These results suggest that the FXR proteins form homo-multimers preferentially under physiological conditions in mammalian cells, and might participate in mRNP particles with separate functions.

Animals↗
PubMed1979

Human inosine triphosphatase: catalytic properties and population studies.

Using a reliable 2-step colorimetric assay, some catalytic properties of human erythrocyte ITPase (inosine triphosphate pyrophosphohydrolase) (EC 3.6.1.19) were determined. The enzyme hydrolyses ITP, dITP (deoxyinosine triphosphate) and XTP (xanthine triphosphate) but not other nucleotides. IDP is a competitive inhibitor. Subcellular fractionation of cultured lymphoid-line cells showed ITPase activity to be in the cytosol. ATP and GTP hydrolysing activities were not enriched in the cytosol fraction. The range of activity was investigated in erythrocytes, peripheral leukocytes, amniotic fluid cells, skin fibroblasts, long term lymphoid lines and bone marrow fibroblasts. The mean ITPase activity was found to vary in different cell types from 4.9 to 294 units per mg protein. Fractionation of red blood cells by age revealed that the enzyme decays exponentially with erythrocyte age with a half-life of 35 days. The enzyme had a wide range of specific activity in erythrocytes from 150 normal randomly selected individuals (15--722 pmol/h/g Hb). Within the low range of erythrocyte specific activities (from 15 to 200) a correlation was found between an individual's erythrocyte activity and the activity in peripheral leukocytes. This correlation was not found at higher erythrocyte ITPase activities. Two individuals were detected who had erythrocyte ITPase activities which were close to the lowest ITPase activities of all samples tested. Thus, low or absent ITPase activity is an individual characteristic which may be expressed both in erythrocytes and in other cell types.

Cell Line↗
PubMed1999

Hepatic encephalopathy: molecular mechanisms underlying the clinical syndrome.

Hepatic encephalopathy (HE) and portal-systemic encephalopathy (PSE) are the terms used interchangeably to describe a complex neuropsychiatric syndrome associated with acute or chronic hepatocellular failure, increased portal systemic shunting of blood, or both. Hepatic encephalopathy complicating acute liver failure is referred to as fulminant hepatic failure (FHF). The clinical manifestations of HE or PSE range from minimal changes in personality and motor activity, to overt deterioration of intellectual function, decreased consciousness and coma, and appear to reflect primarily a variable imbalance between excitatory and inhibitory neurotransmission. Pathogenic mechanisms that may be responsible for HE have been extensively investigated using animal models of HE, or cultures of CNS cells treated with neuroactive substances that have been implicated in HE. Of the many compounds that accumulate in the circulation as a consequence of impaired liver function, ammonia is considered to play an important role in the onset of HE. Acute ammonia neurotoxicity, which may be a cause of seizures in FHF, is excitotoxic in nature, being associated with increased synaptic release of glutamate (Glu), the major excitatory neurotransmitter of the brain, and subsequent overactivation of the ionotropic Glu receptors, mainly the N-methyl-D-aspartate (NMDA) receptors. Hepatic encephalopathy complicating chronic liver failure appears to be associated with a shift in the balance between inhibitory and excitatory neurotransmission towards a net increase of inhibitory neurotransmission, as a consequence of at least two factors. The first is down-regulation of Glu receptors resulting in decreased glutamatergic tone. The down-regulation follows excessive extrasynaptic accumulation of Glu resulting from its impaired re-uptake into nerve endings and astrocytes. Liver failure inactivates the Glu transporter GLT-1 in astrocytes. The second factor is an increase in inhibitory neurotransmission by gamma-aminobutyric acid (GABA) due to (a) increased brain levels of natural benzodiazepines; (b) increased availability of GABA at GABA-A receptors, due to enhanced synaptic release of the amino acid; (c) direct interaction of modestly increased levels of ammonia with the GABA-A-benzodiazepine receptor complex; and (d) ammonia-induced up-regulation of astrocytic peripheral benzodiazepine receptors (PBZR). Brain ammonia is metabolised in astrocytes to glutamine (Gln), an osmolyte, and increased Gln accumulation in these cells may contribute to cytotoxic brain edema, which often complicates FHF. Glutamine efflux from the brain is an event that facilitates plasma-to-brain transport of aromatic amino acids. Tryptophan and tyrosine are direct precursors of the aminergic inhibitory neurotransmitters, serotonin and dopamine, respectively. Changes in serotonin and dopamine and their receptors may contribute to some of the motor manifestations of HE. Finally, oxindole, a recently discovered tryptophan metabolite with strong sedative and hypotensive properties, has been shown to accumulate in cirrhotic patients and animal models of HE.

Hepatic Encephalopathy↗
PubMed2004

High prevalence of SLC6A8 deficiency in X-linked mental retardation.

A novel X-linked mental retardation (XLMR) syndrome was recently identified, resulting from creatine deficiency in the brain caused by mutations in the creatine transporter gene, SLC6A8. We have studied the prevalence of SLC6A8 mutations in a panel of 290 patients with nonsyndromic XLMR archived by the European XLMR Consortium. The full-length open reading frame and splice sites of the SLC6A8 gene were investigated by DNA sequence analysis. Six pathogenic mutations, of which five were novel, were identified in a total of 288 patients with XLMR, showing a prevalence of at least 2.1% (6/288). The novel pathogenic mutations are a nonsense mutation (p.Y317X) and four missense mutations. Three missense mutations (p.G87R, p.P390L, and p.P554L) were concluded to be pathogenic on the basis of conservation, segregation, chemical properties of the residues involved, as well as the absence of these and any other missense mutation in 276 controls. For the p.C337W mutation, additional material was available to biochemically prove (i.e., by increased urinary creatine : creatinine ratio) pathogenicity. In addition, we found nine novel polymorphisms (IVS1+26G-->A, IVS7+37G-->A, IVS7+87A-->G, IVS7-35G-->A, IVS12-3C-->T, IVS2+88G-->C, IVS9-36G-->A, IVS12-82G-->C, and p.Y498) that were present in the XLMR panel and/or in the control panel. Two missense variants (p.V629I and p.M560V) that were not highly conserved and were not associated with increased creatine : creatinine ratio, one translational silent variant (p.L472), and 10 intervening sequence variants or untranslated region variants (IVS6+9C-->T, IVS7-151_152delGA, IVS7-99C-->A, IVS8-35G-->A, IVS8+28C-->T, IVS10-18C-->T, IVS11+21G-->A, IVS12+15C-->T, *207G-->C, IVS12+32C-->A) were found only in the XLMR panel but should be considered as unclassified variants or as a polymorphism (p.M560V). Our data indicate that the frequency of SLC6A8 mutations in the XLMR population is close to that of CGG expansions in FMR1, the gene responsible for fragile-X syndrome.

Amino Acid Sequence↗
PubMedDate not supplied

The stereotyped behavior scale: psychometric properties and norms.

The Stereotyped Behavior Scale (SBS) is an empirically developed behavior rating scale for adolescents and adults with mental retardation (Rojahn, Tassé & Sturmey, 1997). Since the original publication, one item was deleted and two items were merged, leaving 24 items. In an additional change, severity scales were added to the frequency scales. In this paper, psychometric properties and (relative) norms for the new SBS are presented. In the psychometric study, 45 adults with mental retardation from a residential facility participated. Of these, 15 were selected for high-rates or very severe forms of stereotyped behaviors, 15 for mild to moderate rates or less severe stereotypies, and 15 for the low rates or absence of stereotyped behaviors. Direct care staff familiar with the participants completed the SBS and the "Stereotypy" subscale of the Aberrant Behavior Checklist-Residential (ABC-R) (Aman, Singh, Stewart & Field, 1985). For 15 participants, two raters independently completed the SBS. In addition, 45-min direct behavior observations were conducted on 16 participants. After approximately four weeks, the instruments were completed a second time by the same raters. As for reliability, the SBS frequency and severity scale total scores yielded test-retest intraclass coefficients (ICC) of 0.93 and 0.71, ICC interrater agreement of 0.76 and 0.75, and each had an internal consistency a of 0.91. For criterion validity, the SBS frequency and severity scores correlated with the ABC-R "Stereotypy" score at 0.80 and 0.84 (Pearson r), with systematic behavior observations at 0.50 and 0.65 (Pearson r), and with the a priori classification at 0.50 and 0.65 (Spearman p). From a previous data set of 550 individuals with stereotypic behavior, normative data (percentile ranks and T-scores) were derived. The data were presented in two tables, one showing a breakdown of gender by age groups, and the second one of age groups by level of functioning.

Adult↗