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Biomedical subjects

S Turner

Publications and source records attributed to S Turner.

At least 19 recordsLinked to original sources

Resistance of primary isolates of human immunodeficiency virus type 1 to neutralization by soluble CD4 is not due to lower affinity with the viral envelope glycoprotein gp120.

Recombinant soluble CD4 (rsCD4) has potent antiviral activity against cell line-adapted isolates of the human immunodeficiency virus type 1 (HIV-1) but low activity toward HIV-1 primary isolates from patients. A simple hypothesis proposed to explain this discrepancy, which questions the therapeutic utility of soluble CD4-based approaches, is that the major envelope glycoprotein, gp120, of patient virus has lower affinity for CD4 than does gp120 from laboratory viruses. To test this hypothesis, we have produced pairs of low- and high-passage HIV-1 isolates which, depending on culture passage history, display dramatically different sensitivities to neutralization by rsCD4. Here, we present evidence that the HIV-1 major envelope glycoprotein cDNAs cloned from one such isolate pair show only minor differences in their deduced gp120 primary structures, and these occur outside regions previously shown to be involved in CD4 interactions. In addition, recombinant gp120 from a low-passage rsCD4-resistant patient virus binds rsCD4 with high affinity, equal to that previously measured for recombinant gp120 from high-passage cell line-adapted virus isolates. These data indicate that differences in CD4-gp120 affinity do not account for rsCD4 resistance in HIV-1 recently isolated from patients.

Amino Acid Sequence

The use of the Ways of Coping (Revised) questionnaire with parents of children with Down's syndrome.

The principal aim of this study was to assess the validity and usefulness of the Ways of Coping (Revised) questionnaire (Folkman & Lazarus, 1985) with a British sample of parents of children with Down's syndrome. Factor analysis yielded five subscales which were compared with those reported elsewhere. Other properties of the instrument were investigated. It was concluded that the instrument was potentially valuable to those investigating coping in families with special problems.

Adaptation, Psychological

Brief report: recent findings on the Sexual Aversion Scale.

This study provides additional information on the psychometric properties of the Sexual Aversion Scale (SAS). Results suggest a positive relationship between sexual aversion, generalized anxiety, and history of sexual victimization. Variables such as age and religiosity were unrelated to scores on the SAS, although females reported significantly more sexual anxiety than males. The factor structure of the SAS is described and suggests that sexual aversion is a multifaceted problem with at least three and possibly four different dimensions.

Adolescent

Paediatricians' practice in disclosure and follow-up of severe physical disability in young children.

Twenty-four paediatricians were asked about their policy and practice regarding disclosure and follow-up of the diagnosis of disability, and for suggestions to improve current practice. Doctors with less clinical experience were more likely to mention the presence of the child as an element of the disclosure interview, and scored higher than those with more experience on an index score of the format of the disclosure interview. Paediatricians' reported constraints on their preferred practice and findings from interviews with mothers in the same study confirmed continuing shortcomings in disclosure practice. Changes in medical training, the adoption of a written policy of good practice and the nomination of a 'key worker' for each family are suggested.

Child

Psychophysiological investigations of patients with unilateral symptoms in the hyperventilation syndrome.

Anxiety states sometimes lead to hyperventilation (HV) which may, in turn, give rise to a variety of physical symptoms. One way in which HV may present is with unilateral somatosensory symptoms, often left-sided. We report nine such cases. The mechanisms of lateralisation was examined using EEG and bilateral somatosensory evoked potentials which were carried out before and after HV. No difference in conduction velocity was found between affected and unaffected arms, but non-specific abnormalities were frequently noted in the EEGs. The results support the role of a central rather than a peripheral mechanism in the production of unilateral symptoms in HV.

Adult

Production of multimeric forms of CD4 through a sugar-based cross-linking strategy.

We have developed a three-step cross-linking procedure that is specifically targeted at the carbohydrate on a protein and applied it to CD4 as a model system for studying the role of multivalent interactions in function. In the first step CD4 was oxidized with periodate, creating aldehydes that served as targets for the subsequent chemistry. Next the aldehydes were modified with cystamine, converting the reactive group into a thiol. Finally cross-linking through the thiol moiety was generated with the homobifunctional cross-linker bismaleimidohexane. With this procedure, approximately 60% of the CD4 was converted into higher molecular weight complexes that were soluble and retained function as assessed by glycoprotein gp120 binding activity. CD4 dimers and tetramers by mass were 4 and 15 times as active as CD4 monomer in blocking virus infection with HTLV-IIIB in an in vitro cellular assay. The cross-linking chemistry provides an efficient method for producing homomultimers of a glycoprotein.

Amino Acids

Clinical trials in cancer therapy: efforts to improve patient enrollment by community oncologists.

A prerequisite for the completion of a clinical trial is the accrual of adequate numbers of patients. It is estimated that over 90-95% of all cancer patients are now treated in their local communities by practicing oncologists and are not seen by primary investigators at teaching hospitals. One risk of this trend is decreased patient enrollment into clinical trials. The private practitioner often lacks the academic oncologist's incentives to participate in clinical research. The Hoosier Oncology Group (HOG) is composed of community medical and radiation oncologists (85%) and Indiana University faculty members (15%). In an effort to improve patient enrollment onto clinical cancer research trials, HOG has attempted to identify 1) the major obstacles to patient enrollment by community oncologists and 2) potential aids to overcome such obstacles. One hundred fourteen members were surveyed and 75 responded (66%). The major obstacles were, in descending order: time demands on both the oncologist and his staff; explaining clinical trials to patients; completing flow sheets; perceived increased cost to the patient; remembering protocols; adhering to a rigid protocol. Aids identified as potentially most helpful were, in descending order: pocket-sized synopses of protocols; computer generated, individualized prompts; the availability of a clinical trials specialist to explain the clinical trial to patients and assist in obtaining informed consent; the availability of a video tape which could be used to explain clinical trials to patients. These aids are being implemented with the attempt to systemically study their impact on patient accrual.

Clinical Trials as Topic

Molecular evidence for the origin of plastids from a cyanobacterium-like ancestor.

The origin of plastids by either a single or multiple endosymbiotic event(s) and the nature of the progenitor(s) of plastids have been the subjects of much controversy. The sequence of the small subunit rRNA (Ssu rRNA) from the plastid of the chlorophyll c-containing alga Cryptomonas phi is presented, allowing for the first time a comparison of this molecule from all of the major land plant and algal lineages. Using a distance matrix method, the phylogenetic relationships among representatives of these lineages have been inferred and the results indicate a common origin of plastids from a cyanobacterium-like ancestor. Within the plastid line of descent, there is a deep dichotomy between the chlorophyte/land plant lineage and the rhodophyte/chromophyte lineage, with the cyanelle of Cyanophora paradoxa forming the deepest branch in the latter group. Interestingly, Euglena gracilis and its colorless relative Astasia longa are more related to the chromophytes than to the chlorophytes, raising once again the question of the origin of the euglenoid plastids.

Base Sequence

CD4-Pseudomonas exotoxin hybrid proteins: modulation of potency and therapeutic window through structural design and characterization of cell internalization.

Replacing the Pseudomonas exotoxin A (PE) cell binding domain with the human immunodeficiency virus (HIV) gp120 binding domain from CD4 yields a hybrid toxin (CD4-PE) with potential therapeutic use in treating acquired immunodeficiency syndrome (AIDS). To find the most therapeutically potent combination of CD4 and PE four different hybrid toxins composed of one [CD4(122)] or two [CD4(181)] Ig-like CD4 domains and sequences of PE where the binding domain was partially [PE(392)] or completely [PE(364)] removed were constructed and expressed in Escherichia coli. The number of CD4 domains determined the binding affinity to gp120 and in cell viability assays the window between specific and nonspecific cytotoxicity. The length of PE determined the potency of the drug. The optimal hybrid toxin was composed of two Ig-like domains of CD4 and PE(392). Investigation of the internalization mechanism of CD4-PE revealed that the hybrid toxin binds to target cells and is endocytosed within one hour. However, more than 6 hours are required for maximum translation inhibition. In contrast to PE which is inhibited by ammonium chloride treatment, cell toxicity of CD4-PE is not affected by ammonium chloride. Further investigations showed that the acid-induced hydrophobicity change which is required for membrane translocation is also observed with CD4-PE but at significantly higher pH than with PE.

ADP Ribose Transferases

The validity and applicability of the ADIECAS classroom rating scale in a sample of children with Down's syndrome.

The ADIECAS classroom behaviour rating scale (Evans & Hogg, 1984) was used with a sample of 123 children with Down's syndrome as part of a wider study of child and family adaptation. According to Evans & Hogg, the ADIECAS scale measures two types of behaviour: attentiveness-distractability, and inhibition-excitability. Such measures of behaviour style may be related to behaviour problems and child and family relationships for children with mental handicap. The factor structure of the 16 ADIECAS items was investigated by using confirmatory factor analysis within the LISREL program. Overall, the original factor structure was found to be a poor fit to the new data, in that, while the distractability factor replicated well, the excitability factor split into three. After examining the components of the four factors, two were discarded as containing unreliable items, and goodness of fit statistics on the two revised factors, using 10 of the original 16 items, gave the best results. Thus, the factors structure showed only limited replicability with a different subject group from the original Evans & Hogg study.

Arousal

Factors relating to self-sufficiency in children with Down's syndrome.

An index of self-sufficiency in children with Down's syndrome was developed for use in a study of the process of adaptation in families living in the Greater Manchester area. The children were 6-14 years old, and living at home. Index scores were based on the mothers' responses to a questionnaire covering their children's personal and domestic functioning and community self-sufficiency, and were obtained from 111 of the 117 mothers who took part in the study. A wide range of child- and family-related variables were found to be significantly associated with self-sufficiency scores on a univariate level. Multiple regression analysis was used to identify those variables which best predicted the level of self-sufficiency achieved. After the child's mental age, the most significant variables were excitability, behaviour problems, the extent the mother used practical means of coping, and the level of social activity experienced by the child. Together, these five variables explained 63% of the variance in self-sufficiency scores. The dynamics by which such factors may relate to self-sufficiency in children with Down's syndrome are discussed, and intervention aimed at promoting the use of practical ways of coping by parents is suggested.

Activities of Daily Living

Factors related to stress and satisfaction with life in families of children with Down's syndrome.

In a study of families of children with Down's syndrome, measures of parent, family and child characteristics were obtained from mothers and fathers. Multivariable analyses investigated their relationships to outcome measures of psychosomatic symptoms of stress and parents' perceived satisfaction with life. Personality factors were related to outcome for both parents. For mothers, the children's levels of behaviour problems, excitability and self-sufficiency were strongly related to outcome. Coping strategies, family relationships and socio-economic factors also showed significant effects. For fathers, child characteristics were not related to outcome. The marital relationship was an important factor and there was evidence that factors external to the family acted as stressors.

Adaptation, Psychological

Is the appearance of children with Down syndrome associated with their development and social functioning?

The appearance of 111 children with Down syndrome, aged six to 14 years, was rated by their class teachers as part of a larger study on factors associated with their development, social life-style and family functioning. There were no significant associations between measures of child development, communicative or independent functioning, social life, behaviour problems or with parental stress, parent-child relationships or quality of family life. Typical features of Down syndrome are not major correlates of development and social functioning, and no support could be found to justify routine cosmetic surgery aimed at ameliorating such features.

Achievement

Race and imprisonment decisions in California.

Data were analyzed for 11,553 California offenders who in 1980 were convicted of assault, robbery, burglary, theft, forgery, or drug crimes. Whether an offender was given probation or sentenced to prison for such crimes could be predicted with about 80 percent accuracy from a combination of variables that described defendant and crime characteristics and criminal justice processing. The addition of race to the prediction equation for a given crime type did not improve the accuracy of the prediction. In addition, there was no evidence that other factors related to imprisonment (for example, number of conviction counts, going to trial) masked a relation between race and imprisonment. Race also was not related to the length of prison term imposed.

Black or African American

Teratogenic effects on the neuroepithelium of the CD-1 mouse embryo exposed in utero to sodium valproate.

A causal association has now been recognized between the use of the anticonvulsant drug sodium valproate during pregnancy and the increased incidence of spina bifida in the human population. The objective of this study was to investigate the teratogenic effects of sodium valproate on the cephalic 1) neuroepithelium, 2) extracellular matrix, and 3) embryonic protein content in the CD-1 mouse embryo. Nulliparous female CD-1 mice were dosed intraperitoneally on day 8 of gestation with 340 mg/kg of sodium valproate. On day 10 of gestation, females were killed by cervical dislocation, and all live embryos were assigned to one of the following groups and processed accordingly for: 1) head measurements, 2) scanning electron microscopy, 3) total protein determination, 4) two-dimensional polyacrylamide gel electrophoresis, 5) immunohistochemistry, and 6) light microscopy. Exposure to sodium valproate at the selected dosage resulted in a 30% incidence of neural tube defects in the cranial region of these embryos. Treated embryos showed a significant reduction in head size, indicating a drug-induced microcephaly. No major differences were seen in the total embryonic protein patterns between control and treated embryos. Immunoreactivity to laminin and fibronectin showed a similar distribution in control and treated embryos except in the vasculature pattern of the hindbrain neuroepithelium. The neuroepithelium of the treated embryos showed marked disorganization when it was examined histologically, particularly in the forebrain region. Cells were disoriented, and there was a noticeable loss of intercellular adhesion in the juxtaluminal region. Increased cellular blebbing was apparent at the ependymal surface, and large protrusions of cells were seen invading the neural tube lumen. The lumen was distorted in shape and frequently contained blood cells. Irregularities and gaps were observed in the underlying basal lamina. These results suggest that treatment with sodium valproate during a critical time in neurogenesis in the CD-1 mouse embryo alters the normal architecture of the neuroepithelium, with a loss of integrity at both the basal and apical surfaces. The alterations seen in the neuroepithelium at any of these sites in this animal model could help explain the increased incidence of spina bifida seen in children of epileptic mothers receiving sodium valproate.

Abnormalities, Drug-Induced