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Biomedical subjects

A L Barnett

Publications and source records attributed to A L Barnett.

14 recordsLinked to original sources

Can the Griffiths scales predict neuromotor and perceptual-motor impairment in term infants with neonatal encephalopathy?

AIMS: To examine the predictive value of early developmental testing for identifying neuromotor and perceptual-motor impairment at school age in children with neonatal encephalopathy (NE). METHODS: Eighty full term infants with NE were followed longitudinally. Where possible, children were tested on the Griffiths scales at 1 and 2 years and at 5-6 years, on the Touwen Examination, Movement ABC, and WPPSI. The relation between the Griffiths scores and later outcome measures was examined using correlation coefficients and sensitivity and specificity values. RESULTS: By 2 years, 25 children with cerebral palsy were too severely impaired to be formally assessed and remained so at 5-6 years. Abnormal Griffiths scores were obtained by 12% and 7% of the children at 1 and 2 years respectively. At 5-6 years, 33% had poor Movement ABC scores and 15% poor WPPSI scores. The highest correlation between Griffiths scores and the outcome measures was for the Movement ABC (0.72), although this accounted for only 50% of the variance. Sensitivity scores for the Movement ABC were below 70% but specificity was 100%. CONCLUSIONS: A poor score on the Griffiths scales at 1 and/or 2 years is a good predictor of impairment at school age. However, a normal score in the early years cannot preclude later neurological, perceptual-motor, or cognitive abnormalities.

Brain Diseases↗

Visual function at school age in children with neonatal encephalopathy and low Apgar scores.

OBJECTIVE: To assess different aspects of visual function at school age in children who suffered from neonatal encephalopathy. METHOD: Thirty nine full term infants with neonatal encephalopathy, low Apgar scores, and early neonatal imaging were studied using a battery of tests assessing different aspects of visual function (crowding acuity, stereopsis, visual fields) at school age. The results were compared with brain magnetic resonance imaging (MRI) findings and, when possible, with the results of the assessment of visual function performed at 5 and 12 months, available in 24 of the 39 children examined at school age. RESULTS: Sixteen of the 39 children (41%) had abnormal results at school age in at least one of the visual tests used. Seven of these 16 were untestable on all tests. The remaining 23 children (59%) had normal results. CONCLUSIONS: The presence and severity of visual impairment was related to the severity of brain lesions. Moderate or severe basal ganglia lesions and severe white matter changes were always associated with abnormal visual function. Infants with normal MRI, minimal basal ganglia lesions, and minimal or moderate white matter involvement tended to have normal vision. It was also found that the assessment of visual function performed in the first year was a reliable indicator of visual function at school age. With two exceptions, the results on the 5 month visual assessment were predictive of visual outcome at school age. In the remaining two cases, a normal visual outcome at 5 years was associated with visual abnormalities at 5 months but these had already normalised by the age of 1 year.

Apgar Score↗

Modular organization of the Friend murine leukemia virus envelope protein underlies the mechanism of infection.

Retrovirus infection is initiated by receptor-dependent fusion of the envelope to the cell membrane. The modular organization of the envelope protein of C type retroviruses has been exploited to investigate how binding of the surface subunit (SU) to receptor triggers fusion mediated by the transmembrane (TM) subunit. We show that deletion of the receptor-binding domain (RBD) from SU of Friend murine leukemia virus (Fr-MLV) abolishes infection that is restored by supplying RBD as a soluble protein. Infection by this mechanism remains dependent on receptor expression. When membrane attachment of the virus lacking RBD is reestablished by inserting the hormone erythropoietin, infection remains dependent on the RBD/receptor complex. However, infection increases 50-fold to 5 x 10(5) units/ml on cells that also express the erythropoietin receptor. Soluble RBD from Fr-MLV also restores infection by amphotropic and xenotropic MLVs in which RBD is deleted. These experiments demonstrate that RBD has two functions: mediating virus attachment and activating the fusion mechanism. In addition, they indicate that receptor engagement triggers fusion by promoting a subgroup-independent functional interaction between RBD and the remainder of SU and/or TM.

Cell Line, Transformed↗

Clumsiness, dyspraxia and developmental co-ordination disorder: how do health and educational professionals in the UK define the terms?

At the turn of the century, the idea that there might be a discrete childhood syndrome, which had 'clumsiness' of movement as its defining symptom, began to emerge. Since then numerous labels have been applied to the syndrome. In spite of recent attempts to standardise the terminology used, variation continues to compromise inter-professional communication and interpretation of research. The aim of this study was to determine how the three terms 'Clumsy', 'Dyspraxia' and 'Developmental Co-ordination Disorder (DCD)' are viewed by health and educational professionals in the UK. Two hundred and thirty-four adults (57% from the health professions and 43% from education) provided a written definition of each term. Content analysis of the 702 definitions was used to determine: (1) the extent to which the terms were familiar/acceptable to the respondents; and (2) to capture differences in the meaning of the term being defined. The results indicated that the terms 'DCD' and 'Dyspraxia' were less familiar than the term 'clumsy' which was, however, least acceptable. Amongst those professionals who were familiar with all three terms, there was general agreement that all were used to describe some sort of overall movement difficulty. Beyond that point, divergence of understanding and inter-professional differences in emphasis emerged. The implications of these differences for clinical and educational practice, research and policy making are discussed.

Adult↗

Receptor binding transforms the surface subunit of the mammalian C-type retrovirus envelope protein from an inhibitor to an activator of fusion.

The envelope protein (Env) of murine leukemia viruses (MLVs) is composed of a surface subunit (SU) and a transmembrane subunit (TM), which mediates membrane fusion, resulting in infection. SU contains a discrete N-terminal receptor binding domain (RBD) that is connected to the remainder of Env by a short, proline-rich segment. Previous studies suggest that after receptor binding, the RBD interacts directly with the remainder of Env to trigger fusion (A. L. Barnett, R. A. Davey, and J. M. Cunningham, Proc. Natl. Acad. Sci. USA 98:4113-4118, 2001). To investigate the role of the RBD in activating fusion, we compared infection by several MLVs that are defective unless rescued in trans by the addition of soluble RBD to the culture medium. Infection by MLV lacking a critical histidine residue near the N terminus of the viral RBD is dependent on the expression of receptors for both the RBD in the viral Env and the soluble RBD supplied in trans. However, infection by MLVs in which the RBD has been deleted or replaced by the ligand erythropoietin are dependent only on expression of the receptor for the soluble RBD. We were able to expand the host range of xenotropic MLV to nonpermissive murine fibroblasts only if the RBD was deleted from the xenotropic viral envelope and the soluble RBD from ecotropic Friend MLV was supplied to the culture medium. These findings indicate that receptor binding transforms the RBD from an inhibitor to an activator of the viral fusion mechanism and that viruses lacking the critical histidine residue at the N terminus of the RBD are impaired at the activation step.

Animals↗

In vitro host range of Autographa californica nucleopolyhedrovirus recombinants lacking functional p35, iap1 or iap2.

We have examined the host range in different insect cell lines of Autographa californica nucleopolyhedrovirus (AcMNPV) recombinants lacking p35, iap1 or iap2. These genes encode, or are predicted to encode, anti-apoptotic proteins. Abrogation of p35 reduced the ability of AcMNPV to replicate in permissive cell lines derived from Spodoptera frugiperda insects by inducing apoptosis. In semi-permissive cell lines, such as Lymantria dispar and Spodoptera littoralis cells, we observed cytopathic effects after infection with AcMNPV but little virus production. Infection of these cells by AcMNPV lacking p35 resulted in apoptosis. However, p35-deficient viruses were still able to replicate normally in Trichoplusia ni, Mamestra brassicae and Panolis flammea cell lines. Disruption of AcMNPV iap1 and iap2 was found not to affect virus replication in any of the cell lines. It was also possible to disrupt both iap1 and iap2 in the same virus without loss of infectivity. A virus without iap1 and p35 demonstrated identical growth characteristics and host range to a virus lacking p35. We conclude that in cells which respond to AcMNPV infection by initiating programmed cell death, the p35 gene product alone is sufficient to inhibit apoptosis. Removal of iap1 or iap2 has no effect on virus replication, even in cell lines which do not undergo apoptosis in response to AcMNPV infection. Our results with two semi-permissive cell lines further indicate that whilst p35 is important in blocking block apoptosis, other factors are involved in restricting AcMNPV replication within these cells.

Animals↗

Skin fibroblast beta-adrenergic receptor function in manic-depressive illness.

Beta-adrenergic receptor function was assessed in cultured skin fibroblasts obtained from bipolar patients and normal volunteers by measurement of the cyclic adenosine monophosphate (cAMP) response to isoproterenol. No group differences were observed. To assess regulation of receptor desensitization, fibroblasts were incubated for 24 hr with isoproterenol, and then the cAMP response to isoproterenol was determined. Subsensitivity to rechallenge with isoproterenol did not distinguish bipolar patients from controls.

Bipolar Disorder↗

Controlled primary functionalization of agarose affinity supports by carboxymethylation and subsequent addition of spacer units.

Experimental details are given for the O-carboxymethylation of cross-linked agarose beads with chloroacetate in aqueous sodium hydroxide, formation of a tandem 2-amino-ethylamide derivative, and coupling of beta-alanine residues to the aminoethyl groups using a new reagent, N-phthalimidyl N'-ethylsulfonylethoxycarbonyl-beta-alaninate. An ideal support for attaching affinity ligands results. Extent of derivatization was controlled by the time and temperature of the first reaction. Functional group densities were estimated by using hydrogen ion binding measurements for carboxyls and a new reagent, N-succinimidyl 3-[2-(4-nitrophenylamino)ethyldithio]propionate, for assaying reactive amino groups on solid supports. Synthesis and use of the new reagents are described.

Chemical Phenomena↗

Beta-adrenoceptor function in human adult skin fibroblasts: a study of manic-depressive illness.

Catecholamine theories of affective illness provide a rationale for the study of beta-adrenoceptor function in these disorders. Skin fibroblasts were grown in tissue culture from skin biopsies of normal volunteers and manic-depressive subjects for measurement of isoprenaline-stimulated production of cyclic AMP. Monolayers of fibroblasts in wells were incubated for 3 min with or without 0.5 microM-isoprenaline. The cyclic AMP was isolated by ion-exchange chromatography and quantitated by radioimmunoassay. The isoprenaline-stimulated levels of cyclic AMP in manic-depressive subjects (n = 12) were no different from those in normal volunteers (n = 13). Thus, no evidence was found for abnormal beta-adrenoceptor function in manic-depressive illness.

Adenylyl Cyclases↗

Liquid-chromatographic study of fluorescent compounds in hemodialysate solutions.

We have separated and identified three endogenous, naturally fluorescent substances in uremic hemodialysate by using reversed-phase liquid chromatography with fluorescence detection. Co-chromatography with authentic standards, monitoring peak shifts after enzymic treatment, and spectrofluorescence measurements were used to confirm the identity of indican, tryptophan, and indole-3-acetic acid. Concentrations of indican were about 1.5 those of tryptophan and considerably greater than those of indole-3-acetic acid in hemodialysate samples from 12 renal patients. These three compounds, as well as eight unidentified components, were consistently present in dialysate samples from each of the 12 patients.

Chromatography, High Pressure Liquid↗

The Movement Assessment Battery for Children: a comparison of 4-year-old to 6-year-old children from Hong Kong and the United States.

OBJECTIVE: There is little information available on the appropriateness of tests developed in the West for children of different ethnicities. The aim of this study was to examine the suitability of the Movement Assessment Battery for Children (Movement ABC) for use with Hong Kong Chinese preschool children. METHOD: The performance of 255 Hong Kong Chinese children between the ages of 4 years and 6 years was compared with that of the 493 children of the same age from the United States who took part in the most recent standardization of the Movement ABC. RESULTS: The test content was found to be suitable for use with Hong Kong Chinese children. However, cross-cultural differences were found on a number of the test items. Chinese children performed significantly better on items contained in the manual dexterity and dynamic balance sections, whereas American children were better at the projection and reception of moving objects. CONCLUSION: These findings highlight the need to ensure that norms for all tests are appropriate for the specific cultural groups being assessed.

Child↗