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1.
Ecotoxicol Environ Saf ; 184: 109669, 2019 Nov 30.
Article in English | MEDLINE | ID: mdl-31536847

ABSTRACT

Cotton hosts a variety of arthropod pests requiring intensive control mostly with insecticides, which in turn may impact beneficial insects and the environment. Therefore, insect control in cotton fields preconizes the use of selective insecticides that offer pest control but conserve natural enemies. In this work, we measured the impact of recommended insecticides on the abundance of predatory insects and predation upon sentinel preys in the field. Further, the survival of four key selected predatory insects of cotton ecosystem, representing chewing and sucking feeding habits and different pest species attacked [Chrysoperla externa Hagen, Eriopis connexa (Germar), Podisus nigrispinus (Dallas) and Orius insidiosus (Say)], were assessed when exposed to the dried residues of the tested insecticides. Mortality of sentinel prey caused by natural enemies was higher in areas treated with selective insecticides relative to the non-selective ones, and most of time similar to the untreated areas. Furthermore, areas treated with non-selective insecticides experienced prolonged impact between sprays depending on the insecticide applied. Seasonal abundance of predatory insects was 2× greater in fields under selective and untreated fields compared to those under non-selective recommendation. Survival of predators exposed to the dried residues of the selective insecticides pymetrozine, chlorantraniliprole, pyriproxyfen, and cyantraniliprole were greater than when exposed to the non-selective lambda-cyhalothrin, malathion, dimethoate, and thiamethoxam. Among the non-selective insecticides, malathion and dimethoate exhibited shorter residual time compared to the thiamethoxam and lambda-cyhalothrin + thiamethoxam. Therefore, the recommendation of selective insecticides provides benefits for cotton pest management by maintaining the action of the natural enemies present in the field.


Subject(s)
Coleoptera/drug effects , Gossypium/growth & development , Heteroptera/drug effects , Insect Control/methods , Insecticides/pharmacology , Predatory Behavior/drug effects , Animals , Ecosystem , Models, Theoretical
2.
Psychol Med ; 48(4): 679-691, 2018 03.
Article in English | MEDLINE | ID: mdl-28780927

ABSTRACT

BACKGROUND: Deficits in social cognition may be among the most profound and disabling sequelae of paediatric traumatic brain injury (TBI); however, the neuroanatomical correlates of longitudinal outcomes in this domain remain unexplored. This study aimed to characterize social cognitive outcomes longitudinally after paediatric TBI, and to evaluate the use of sub-acute diffusion tensor imaging (DTI) to predict these outcomes. METHODS: The sample included 52 children with mild complex-severe TBI who were assessed on cognitive theory of mind (ToM), pragmatic language and affective ToM at 6- and 24-months post-injury. For comparison, 43 typically developing controls (TDCs) of similar age and sex were recruited. DTI data were acquired sub-acutely (mean = 5.5 weeks post-injury) in a subset of 65 children (TBI = 35; TDC = 30) to evaluate longitudinal prospective relationships between white matter microstructure assessed using Tract-Based Spatial Statistics and social cognitive outcomes. RESULTS: Whole brain voxel-wise analysis revealed significantly higher mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in the sub-acute TBI group compared with TDC, with differences observed predominantly in the splenium of the corpus callosum (sCC), sagittal stratum (SS), dorsal cingulum (DC), uncinate fasciculus (UF) and middle and superior cerebellar peduncles (MCP & SCP, respectively). Relative to TDCs, children with TBI showed poorer cognitive ToM, affective ToM and pragmatic language at 6-months post-insult, and those deficits were related to abnormal diffusivity of the sCC, SS, DC, UF, MCP and SCP. Moreover, children with TBI showed poorer affective ToM and pragmatic language at 24-months post-injury, and those outcomes were predicted by sub-acute alterations in diffusivity of the DC and MCP. CONCLUSIONS: Abnormal microstructure within frontal-temporal, limbic and cerebro-cerebellar white matter may be a risk factor for long-term social difficulties observed in children with TBI. DTI may have potential to unlock early prognostic markers of long-term social outcomes.


Subject(s)
Brain Injuries, Traumatic/physiopathology , Brain Injuries, Traumatic/psychology , Diffusion Tensor Imaging , Social Behavior , White Matter/pathology , Adolescent , Australia , Brain Injuries, Traumatic/diagnostic imaging , Child , Cognition , Female , Humans , Linear Models , Longitudinal Studies , Male , Multivariate Analysis , Neuropsychological Tests , Prospective Studies , Theory of Mind , Time Factors , White Matter/diagnostic imaging
3.
Child Psychiatry Hum Dev ; 49(1): 109-122, 2018 02.
Article in English | MEDLINE | ID: mdl-28523378

ABSTRACT

Evidence-based parenting interventions have been developed and evaluated largely with mothers. This study examined practitioner reports of rates of father attendance, barriers to engagement, organizational support for father-inclusive practice, participation in training in father engagement, and competencies in working with fathers. It also explored predictors of practitioner competence and rates of father attendance. Practitioners (N = 210) who delivered parenting interventions completed an online survey. Participants reported high levels of confidence in engaging fathers, but only one in three had participated in training and levels of father attendance in parenting interventions were low. Logistic regressions showed that high levels of practitioner competence were predicted by participation in training. Moderate levels of father attendance (vs. low levels) were predicted by greater number of years of experience while high levels of attendance (vs. low levels) were predicted by greater experience, higher levels of competence and higher levels of organizational support. The implications of the findings to informing policy and practice for enhancing father engagement are discussed.


Subject(s)
Father-Child Relations , Fathers/psychology , Parenting/psychology , Professional Competence , Psychology/standards , Social Workers , Surveys and Questionnaires , Female , Humans , Logistic Models , Male , Social Workers/psychology
4.
Eur Psychiatry ; 30(5): 555-61, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25618445

ABSTRACT

RESEARCH IN CONTEXT: Parents of children with life threatening illness or injuries are at elevated risk of distress reactions, involving symptoms of acute stress disorder, depression and anxiety. Currently, the impact of child illness factors is unclear, and to date research systematically examining the prevalence of these psychological reactions across different illness groups with an acute life threat is sparse. This is important to explore given that studies show that parent functioning impacts on the psychological adjustment and recovery of the ill child. WHAT DOES THIS STUDY ADD?: At four weeks following a child's diagnosis of a serious illness, 49-54% of parents met DSM-IV criteria for acute stress disorder, across a number of illness groups, whereas 15-27% of parents were in the moderate/severe range for depression and anxiety, and 25-31% for stress. Results from this study demonstrate that rates and severity of these psychological reactions in parents of seriously ill children do not vary according to illness type. BACKGROUND: A life threatening childhood illness/injury can lead to significant distress reactions in parents, with independent studies finding such reactions in several different illness groups. To date, there is limited research systematically comparing the prevalence of adverse parental psychological reactions across different childhood illness groups with an acute life threat. This study aimed to investigate the frequency and severity of symptoms of acute traumatic stress, depression, anxiety and general stress in parents, following admission of their child to hospital for a life threatening illness. The study also aimed to explore the relationship between these symptoms, and to determine whether they differ according to illness/injury. METHODS: Cross-sectional data from a prospective, longitudinal study are reported. Participants were 194 parents of 145 children (49 couples), admitted to cardiology (n=53), oncology (n=40) and pediatric intensive care units (n=52), for serious illnesses/injuries. Parents completed self-report questionnaires within four weeks of hospital admission. RESULTS: Rates of acute traumatic stress (P=0.262), depression (P=0.525), anxiety (P=0.453) and general stress symptoms (P=0.720) in parents were comparable across illness type, with 49-54% reaching criteria for acute stress disorder, 15-27% having clinical levels of depression and anxiety, and 25-31% for general stress. Anxiety was most strongly associated with acute traumatic stress (r=0.56), closely followed by stress (r=0.52) and depression (r=0.49), with all correlations highly significant (P<0.001). CONCLUSIONS: These findings provide evidence that the child's medical condition is not associated with parents' experience of clinically significant psychological symptoms, and emphasize the importance for health care providers to be aware of these potential psychological reactions in parents, regardless of the type of illness.


Subject(s)
Anxiety/epidemiology , Critical Illness/psychology , Depression/epidemiology , Parents/psychology , Stress Disorders, Post-Traumatic/epidemiology , Adult , Anxiety/psychology , Australia/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Depression/psychology , Female , Humans , Intensive Care Units, Pediatric , Longitudinal Studies , Male , Parent-Child Relations , Prevalence , Prospective Studies , Stress Disorders, Post-Traumatic/psychology
5.
Neurology ; 76(8): 719-26, 2011 Feb 22.
Article in English | MEDLINE | ID: mdl-21339499

ABSTRACT

OBJECTIVES: Fetal exposure to some antiepileptic drugs (AEDs) carries increased risk of major birth defects, and may be associated with reduced intellectual abilities. The impact on language remains unclear. This study aimed to investigate the impact of fetal AED exposure on language skills. METHODS: Women with epilepsy and their children were recruited to this observational study through the Australian Pregnancy Register for Women with Epilepsy and Allied Disorders. Language skills of 102 AED-exposed children were assessed using the Clinical Evaluation of Language Fundamentals, fourth edition (CELF-4). Assessments were conducted blind to drug. Maternal epilepsy, pregnancy, and medical histories were obtained from prospectively collected records. RESULTS: Mean CELF-4 Core Language scores of children exposed to sodium valproate in monotherapy (mean 91.5, SD 17.5) or polytherapy (mean 73.4, SD = 22.3) were significantly below the standardized test mean of 100 (p < 0.05). Mean language scores of children exposed to carbamazepine or lamotrigine monotherapy, or polytherapy without sodium valproate, were not significantly different from normal. First-trimester sodium valproate dose was negatively correlated with language scores, and significantly predicted language scores after controlling for other group differences. CONCLUSIONS: Fetal exposure to sodium valproate increases the risk of language impairment. This should be taken into account when making treatment decisions for women with epilepsy of childbearing age.


Subject(s)
Anticonvulsants/adverse effects , Language Development Disorders/etiology , Language , Prenatal Exposure Delayed Effects/physiopathology , Analysis of Variance , Chi-Square Distribution , Child , Dose-Response Relationship, Drug , Epilepsy/drug therapy , Female , Humans , Language Development Disorders/diagnosis , Male , Observation , Predictive Value of Tests , Pregnancy
6.
Int J Dev Neurosci ; 29(2): 137-43, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21147212

ABSTRACT

Traumatic brain injury (TBI) in children results in damage to the developing brain, particularly in severely injured individuals. Little is known, however, of the long-term structural aspects of the brain following childhood TBI. This study investigated the integrity of the brain 10 years post-TBI using magnetic resonance imaging volumetrics in a sample of 49 participants with mild, moderate and severe TBI, evaluated against a normative sample of 20 individuals from a pediatric database with comparable age and gender distribution. Structural integrity was investigated in gray and white matter, and by manually segmenting two regions of interest (hippocampus, amygdala), potentially vulnerable to the effects of childhood TBI. The results indicate that more severe injuries caused a reduction in gray and white brain matter, while all TBI severity levels resulted in increased volumes of cerebrospinal fluid and smaller hippocampal volumes. In addition, enlarged amygdala volumes were detected in severely injured patients compared to their mild and moderate counterparts, suggesting that childhood TBI may disrupt the development of certain brain regions through diffuse pathological changes. The findings highlight the lasting impact of childhood TBI on the brain and the importance of monitoring brain structure in the long-term after early injury.


Subject(s)
Amygdala/anatomy & histology , Amygdala/pathology , Brain Injuries/pathology , Hippocampus/anatomy & histology , Hippocampus/pathology , Adolescent , Amygdala/growth & development , Atrophy/pathology , Brain Mapping/methods , Child , Child, Preschool , Hippocampus/growth & development , Humans , Infant , Longitudinal Studies , Magnetic Resonance Imaging , Male , Prospective Studies
7.
J Neurol Neurosurg Psychiatry ; 76(3): 401-8, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15716536

ABSTRACT

OBJECTIVE: To examine the contributions of injury severity, physical and cognitive disability, child and family function to outcome 30 months after traumatic brain injury (TBI) in children. DESIGN: A prospective, longitudinal, between group design, comparing function before and after injury across three levels of injury severity. SUBJECTS: One hundred and fifty children, 3.0-12.11 years old, admitted to hospital with a diagnosis of TBI. The sample was divided according to injury severity: mild (n = 42), moderate (n = 70), severe (n = 38). Children with a history of neurological, developmental, and psychiatric disorders were excluded from participation. MAIN OUTCOME MEASURES: Post injury physical function, cognitive ability (incorporating intellect, memory, and attention), behavioural and family functioning, and level of family burden. RESULTS: A dose-response relation was identified for injury severity and physical and cognitive outcome, with significant recovery documented from acute to six months after TBI. Behavioural functioning was not related to injury severity, and where problems were identified, little recovery was noted over time. Family functioning remained unchanged from preinjury to post injury assessments. The level of family burden was high at both six and 30 months after injury, and was predicted by injury severity, functional impairment, and post injury child behavioural disturbance. CONCLUSIONS: These results suggest ongoing problems for the child and significant family burden 30 months after TBI. The nature and severity of the physical and cognitive problems are closely related to injury severity, with child and family function predicted by psychosocial and premorbid factors.


Subject(s)
Brain Injuries/rehabilitation , Cognition Disorders/etiology , Cost of Illness , Family Health , Adaptation, Psychological , Adult , Child , Child, Preschool , Female , Health Status , Humans , Male , Prognosis , Prospective Studies , Severity of Illness Index
8.
Recent Results Cancer Res ; 159: 104-12, 2002.
Article in English | MEDLINE | ID: mdl-11785834

ABSTRACT

One approach to improving the results of antibody treatment of posttransplant and other lymphomas is to alter the geometry of the antibody molecule so as to enhance its cytotoxicity. When antibody alights on a cell, cytotoxicity can be exerted by initiation of apoptotic signals at the cell surface, and by recruitment of effectors to specific sites on the antibody Fc region. Other routes to cytotoxicity have been described but their generality is debatable. The effectors consist of complement, and a series of potentially cytotoxic cells (macrophages, NK cells, neutrophils and others) bearing Fc-receptors (FcR). Recent evidence suggests that the FcR-bearing cells are the more important in dealing with antibody-coated autologous cells, including tumor cells. If the antibody happens to be of the host IgG class then its Fc region (Fcgamma) will contain a site for attachment of a non-cytotoxic FcR known as FcRB (the Brambell receptor): it is this receptor, present on endothelial cells, which recycles the molecule intact if it happens to be endocytosed and thus prolongs its metabolic life. Replacement of the mouse Fcgamma by human Fcgamma is expected to have three beneficial effects: better recruitment of human effector cells, better persistence of the antibody in extracellular fluid, and removal of a major source of immunogenic epitopes. Chemical manipulations of Fab'gamma and Fcgamma modules, linking them in different geometries via their hinge regions, offers constructs with further enhancements of cytotoxicity. These include Fab2Fc2, in which the presence of dual Fc regions enhances recruitment of both complement and cellular effectors; and bispecific antibody of the same modular formula in which one of the Fab arms is specific for tumor while the other is specific for, and recruits powerfully, a cellular effector.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Immunotherapy , Lymphoma/therapy , Animals , Antibodies, Monoclonal/genetics , Antibodies, Monoclonal/immunology , Antibody-Dependent Cell Cytotoxicity/immunology , Cytotoxicity, Immunologic , Humans , Mice , Protein Engineering
9.
Brain Cogn ; 49(2): 205-7, 2002 Jul.
Article in English | MEDLINE | ID: mdl-15259390

ABSTRACT

We studied aspects of clock cognition that might underlie the sensitivity of the CDT in screening for dementia of the Alzheimer type (DAT). Two groups, 15 patients with mild-moderate DAT and 15 controls, were assessed with the CDT and specially designed tests of clock-related cognition. Patients were impaired on the CDT, but they did not differ from controls in copying a clock face or selecting the correct representation of a given time. Patients were worse than controls at distinguishing between clock and nonclock objects, detecting anomalies in clocks, and in setting time irrespective of response format. These findings suggest that semantic-conceptual aspects of clock-related cognition are important in discriminating between patients with DAT and controls.


Subject(s)
Alzheimer Disease/diagnosis , Concept Formation , Neuropsychological Tests , Psychomotor Performance , Semantics , Aged , Aged, 80 and over , Alzheimer Disease/physiopathology , Handwriting , Humans , Middle Aged , Psychometrics , Reference Values , Severity of Illness Index
10.
Pediatr Neurosurg ; 34(3): 138-48, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11359102

ABSTRACT

OBJECTIVE: To examine the relative contributions of injury severity, level of physical and cognitive disability, child behavior and family function to short-term outcome 6 months following traumatic brain injury (TBI) in children. DESIGN: Prospective, longitudinal, between-group design, comparing preinjury and postinjury measures of functional outcome across three levels of injury severity. SUBJECTS: One hundred and twelve children, aged 2-12 years admitted to the Royal Children's Hospital, Melbourne, with a diagnosis of TBI. The sample was divided into three groups, according to injury severity: mild TBI (n = 31), moderate TBI (n = 52) and severe TBI (n = 29). Children with a history of neurologic, developmental and psychiatric disorder were excluded from participation. MAIN OUTCOME MEASURES: Levels of postinjury functioning in the following domains: physical function, cognitive ability (incorporating intellect, memory and attention), behavioral and family functioning, and level of family burden. RESULTS: A clear dose-response relationship for physical and cognitive outcomes was found, with severe TBI associated with greater impairment of physical, intellectual, memory and attentional function. For psychosocial outcome, results were less clearly linked to injury severity. Preinjury behavioral and family functioning were closely related to postinjury function in these domains, with an interaction identified between family function and child behavior at 6 months postinjury. Family functioning remained unchanged postinjury, although level of burden was high, and predicted by injury severity, functional impairment and postinjury behavioral disturbance. CONCLUSIONS: These results suggest ongoing functional problems for the child and significant family burden 6 months following TBI. The nature and severity of physical and cognitive problems are most closely related to injury severity, with family functioning and child behavior better predicted by psychosocial and premorbid factors.


Subject(s)
Brain Injuries/therapy , Acute Disease , Brain Injuries/complications , Brain Injuries/diagnosis , Child , Child Behavior Disorders/diagnosis , Child Behavior Disorders/epidemiology , Child Behavior Disorders/etiology , Child, Preschool , Cognition Disorders/diagnosis , Cognition Disorders/etiology , Cost of Illness , Family/psychology , Family Health , Female , Follow-Up Studies , Glasgow Coma Scale , Humans , Male , Prospective Studies , Surveys and Questionnaires , Treatment Outcome , Wechsler Scales
11.
J Immunol ; 166(2): 1320-6, 2001 Jan 15.
Article in English | MEDLINE | ID: mdl-11145716

ABSTRACT

We describe a two-stage preparation of chemically engineered Ab constructs, employing as modules Fab'gamma from mAb or rAb, and Fc from human normal IgG1. A multivalent, optionally multispecific F(ab')(n) core is formed in stage one, and one or more Fc modules added in stage two. Examples include bispecific Fab(2)Fc(2) (for simplicity, primes and Greek letters are omitted from names of final constructs) and trivalent Fab(3)Fc(2), which are designed to kill neoplastic cells. An essential element in the construction is the availability of the Fab' in two reduced forms, Fab'(-sulfhydryl (SH))(5) and Fab'-SH. The first is obtained by full reduction of the interchain disulfide bonds (SS) in the F(ab')(2) fragment of IgG. Fab'-SH is obtained by disulfide-interchange reactions on Fab'(-SH)(5), whereby the gamma-light SS is reconstituted, an unusual intrachain SS forms in the gamma-chain hinge, and one hinge SH remains. F(ab')(2) and F(ab')(3) cores are built using partially reduced modules, being given intermodular thioether links that resist reduction. These cores are then fully reduced, making available SH groups for addition of the Fcgamma modules. In the final constructs, all intermodular links embody tandem thioether bonds arising at hinge-region cysteines. Cytotoxic activities of representative constructs, and some enhancements deriving from multiple modules, are assessed. In guinea pigs, catabolism of Fab(2)Fc(2) yielded a t(1/2) similar to that of human IgG1, although the serum Fab(2)Fc(2) revealed some proteolytic breakdown not shown by the IgG1. Immunotherapy of a guinea-pig leukemia confirmed the ability of these constructs to kill target cells in vivo.


Subject(s)
Disulfides/chemistry , Immunoglobulin Fab Fragments/chemistry , Immunoglobulin Fc Fragments/chemistry , Protein Engineering , Sulfhydryl Compounds/chemistry , Animals , Antibody-Dependent Cell Cytotoxicity , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Burkitt Lymphoma/immunology , Burkitt Lymphoma/mortality , Burkitt Lymphoma/therapy , Dimerization , Disulfides/metabolism , Dithiothreitol , Guinea Pigs , Humans , Immunoglobulin Fab Fragments/administration & dosage , Immunoglobulin Fab Fragments/genetics , Immunoglobulin Fab Fragments/metabolism , Immunoglobulin Fc Fragments/administration & dosage , Immunoglobulin Fc Fragments/genetics , Immunoglobulin Fc Fragments/metabolism , Immunoglobulin G/administration & dosage , Immunoglobulin G/chemistry , Immunoglobulin G/genetics , Immunoglobulin G/metabolism , Injections, Intravenous , Mice , Neoplasm Transplantation , Protein Engineering/methods , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/metabolism , Reducing Agents , Sulfhydryl Compounds/immunology , Sulfhydryl Compounds/metabolism , Tumor Cells, Cultured
12.
Dev Neuropsychol ; 20(1): 385-406, 2001.
Article in English | MEDLINE | ID: mdl-11827095

ABSTRACT

Although there have been significant theoretical advances in the field of child neuropsychology, developmental features of adolescence have received less attention. Progress in clinical practice is restricted due to a lack of well-standardized, developmentally appropriate assessment techniques. This article addresses these issues in relation to executive skills. These abilities are targeted for 2 reasons: first, because they are often considered to be mature during late childhood and adolescence, despite limited investigation in this age range; and second, because of their central importance to efficient day-to-day functioning. Using a normative sample of 138 children, aged 11.0 to 17.11 years, this article plots the development of executive skills through late childhood and early adolescence and interprets progress in these skills with reference to current neurological and cognitive theory.


Subject(s)
Cognition/physiology , Wechsler Scales , Adolescent , Australia , Child , Female , Humans , Male
13.
Brain Inj ; 14(8): 679-92, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10969886

ABSTRACT

Traumatic brain injury (TBI) may have a profound impact on a child's ongoing development. Various risk factors have been found to predict outcome, but considerable variability remains unexplained. This study used a prospective, longitudinal design to examine recovery of memory function following TBI within the pre school period. Ninety-six children with TBI were divided according to injury severity (mild, moderate, severe), and compared to age and SES matched healthy controls (n = 35). Children were evaluated acutely and at 6,12 and 18 months post-injury using intellectual and memory measures. Results showed a relationship between greater injury severity and poorer intellectual ability. This dose-response relationship was not clearly evident for memory function within the acute phase of recovery, but developed over time, with greater memory impairments evident for children with more severe TBI by 12 months post-injury. Children with mild TBI exhibited few memory problems. Findings are discussed in the context of theories of plasticity and recovery of function.


Subject(s)
Amnesia/diagnosis , Brain Injury, Chronic/diagnosis , Head Injuries, Closed/diagnosis , Amnesia/physiopathology , Brain Injury, Chronic/physiopathology , Child , Child, Preschool , Female , Follow-Up Studies , Glasgow Coma Scale , Head Injuries, Closed/physiopathology , Humans , Intelligence/physiology , Male , Mental Recall/physiology , Neuropsychological Tests
14.
Cell Death Differ ; 7(1): 48-58, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10713720

ABSTRACT

In this study, we demonstrate for the first time that complement attack of target cells, in the presence of suitably high levels of serum, can induce the oligonucleosomal DNA fragmentation characteristic of apoptosis. This phenomenon requires membrane permeabilisation induced by formation of the complete membrane attack complex and relies on physiologically relevant levels of serum. TUNEL analysis detected complement mediated DNA fragmentation as early as 30 min after the addition of serum and electron microscopy confirmed that chromatin became condensed after complement attack. Various experiments implicate serum DNase I as the mediator of this DNA fragmentation. Intriguingly, membrane permeability induced by melittin gave rise to similar serum dependent DNA fragmentation. The implications of these results for the study of apoptosis in vitro and in vivo are discussed.


Subject(s)
Apoptosis/immunology , Complement System Proteins/immunology , Animals , Chromatin , DNA Fragmentation , Guinea Pigs , Humans , Tumor Cells, Cultured
15.
Br J Cancer ; 82(2): 255-62, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10646874

ABSTRACT

Cranial irradiation therapy (CRT) and chemotherapy are associated with neurobehavioural deficits. Many studies have investigated late effects of these treatments, but few have evaluated changes in abilities over time. This study employed a longitudinal design to map abilities following these treatments. Three groups of children were studied: Group 1 (n = 35): children treated with CRT (18 Gy) + chemotherapy, aged 5 years or less at time of diagnosis; Group 2 (n = 19): children treated with chemotherapy alone, aged 5 years or less at time of diagnosis; Group 3 (n = 35): healthy children. All children were aged 7-13 years at time of initial assessment, with no pre-diagnosis history of neurologic, developmental, or psychiatric disorder. Intellectual and educational abilities were evaluated twice: T1, not less than 2 years post-treatment, and T2, 3 years later. Group 1 achieved poorest results at T1, with comparison groups performing similarly. At T2 group differences were maintained. For verbal skills differences remained stable. Group 1 exhibited deterioration on non-verbal and processing tasks, while comparison groups showed improved abilities. Group 1 exhibited increases in literacy skills, with educational intervention predicting progress. Results suggest cumulative deficits in non-verbal and information processing skills for children treated with CRT + chemotherapy, with other deficits remaining relatively stable over time. Improved literacy skills suggest that gains can occur with remediation.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Brain Neoplasms/psychology , Cognition Disorders/etiology , Cranial Irradiation/adverse effects , Intelligence , Brain Neoplasms/drug therapy , Brain Neoplasms/radiotherapy , Child, Preschool , Combined Modality Therapy , Education , Female , Humans , Infant , Infant, Newborn , Longitudinal Studies , Male , Mental Processes , Verbal Learning
16.
Child Neuropsychol ; 6(2): 87-100, 2000 Jun.
Article in English | MEDLINE | ID: mdl-16210206

ABSTRACT

Bacterial meningitis is a life threatening infection of the central nervous system. This illness is most prevalent early in life when the healthy child is rapidly acquiring language. This study investigated whether children with a history of bacterial meningitis were at risk for language difficulties post illness. Thirty post-meningitic children, aged between 9 years 0 months and 11 years 0 months, participated in this study. Each subject was administered a measure of non-verbal cognitive ability and a range of language tasks. These children performed poorly on applied language tasks, which tap skills used in effective discourse. These deficits occurred despite age appropriate performances on measures of linguistic/grammatical knowledge. These findings clearly illustrate that bacterial meningitis has implications for ongoing language development, which emphasises the importance of long term follow up. In developmental terms, this discrepancy between verbal knowledge and problem solving represents a dissociation between language skills which develop early in life and those which emerge later. This pattern of results suggests that bacterial meningitis may result in a delay in language development. A young age at illness was identified as an additional risk factor for adverse outcome. This study highlights the need to inform parents/guardians that post-meningitic children are at risk for experiencing language difficulties throughout childhood.


Subject(s)
Language Development Disorders/etiology , Meningitis, Bacterial/complications , Brain Damage, Chronic/diagnosis , Brain Damage, Chronic/etiology , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Intelligence , Language Development Disorders/diagnosis , Language Tests , Male , Risk
17.
Br J Cancer ; 81(1): 141-3, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10487625

ABSTRACT

The CYP17 gene codes for the cytochrome P450c17alpha enzyme that is involved in the synthesis of oestrogens. This case-control study from the South East of Scotland shows that a polymorphism of the CYP17 gene is associated with an increased risk of male breast cancer.


Subject(s)
Breast Neoplasms, Male/enzymology , Breast Neoplasms, Male/genetics , Polymorphism, Genetic , Steroid 17-alpha-Hydroxylase/genetics , Adult , Aged , Aged, 80 and over , Alleles , Androgens/blood , Breast Neoplasms/blood , Breast Neoplasms/enzymology , Breast Neoplasms/genetics , Breast Neoplasms, Male/blood , Case-Control Studies , Estrogens/blood , Female , Genotype , Humans , Male , Middle Aged , Steroid 17-alpha-Hydroxylase/metabolism
18.
Pediatr Rehabil ; 3(4): 177-86, 1999.
Article in English | MEDLINE | ID: mdl-10819430

ABSTRACT

This study investigated the developmental levels of pragmatic language skills in children following head injury (HI), in comparison to their uninjured peers. Participants were 30 head-injured and 19 healthy controls, classified into a 'young' age group, 8-9 years, and an 'old' age group, 11-12 years. Participants were administered the WISC- III, a negotiating requests task and a hint task, the latter two assessing verbal reasoning skills and abilities to be indirect, respectively. It was found that negotiation and hinting strategies were rapidly developing in these age groups, where abilities to hint were less mature for all groups. Results found a main effect for injury on cognitive and functional language tasks, reflected by lower performance levels and inflexibility in reasoning for the head-injured group. Injury sustained at an earlier age consistently predicted poorer performance on the language tasks, complicating the ongoing development of generalized and higher-order communicative skills. Severity of injury did not predict performance on either language task.


Subject(s)
Brain Injuries/complications , Communication Disorders/etiology , Analysis of Variance , Brain Injuries/physiopathology , Child , Cognition Disorders/diagnosis , Cognition Disorders/etiology , Communication Disorders/diagnosis , Female , Glasgow Coma Scale , Humans , Longitudinal Studies , Male , Neuropsychological Tests , Verbal Behavior
19.
Pediatr Rehabil ; 3(4): 159-66, 1999.
Article in English | MEDLINE | ID: mdl-10819428

ABSTRACT

Traumatic brain injury (TBI) may have a profound impact on a child's ongoing development. Various risk factors have been found to predict outcome, but considerable variability remains unexplained. This study used a prospective, longitudinal design to examine recovery of memory function following TBI within the pre-school period. Forty-four children with TBI were divided according to injury severity (mild, moderate, severe), and compared to age and SES matched healthy controls (n = 26). Children were evaluated acutely and at 12 months post-injury using the Rivermead Behavioural Memory Test for Children. Results failed to show a clear dose-response relationship between injury severity and memory function during the acute phase of recovery. However, this relationship developed over time, with greater memory impairments evident for children with more severe TBI by 12 months post-injury. Children with mild TBI exhibited few memory problems.


Subject(s)
Brain Injuries/complications , Memory Disorders/etiology , Analysis of Variance , Brain Injuries/physiopathology , Chi-Square Distribution , Child , Child, Preschool , Female , Glasgow Coma Scale , Humans , Longitudinal Studies , Male , Memory Disorders/diagnosis , Memory Disorders/physiopathology , Neuropsychological Tests , Prospective Studies , Time Factors
20.
J Immunol Methods ; 231(1-2): 169-75, 1999 Dec 10.
Article in English | MEDLINE | ID: mdl-10648936

ABSTRACT

We described previously a scheme for linking functionally intact human normal Fcgamma1, via a thioether linkage emerging from its hinge, to any molecule expressing a free sulfhydryl group (SH). The scheme entails reducing the Fc to release four SH from the two inter-gamma disulfide bonds (SS) in the hinge, blocking one SH by a stochastic alkylation, restoring by SS-interchange the inter-gamma SS whose two SH are still available, and attaching a bismaleimide linker to the one remaining SH. One thereby obtains Fc with a single maleimide group (Fc-maleimide) for attachment to the SH-displaying partner. Restoration of the inter-gamma SS is necessary if the final chimeric construct is to be able to activate the classical complement pathway. However, during this preparation of Fc-maleimide, there is apparently some SS-formation between non-homologous SH, so that not all hinges emerge with a reconstituted inter-gamma SS. To reduce this error we have modified the preparative procedure after investigating an initial partial reduction of the hinge, and reviewing the conditions for stochastic alkylation. During partial reduction by dithiothreitol, the two hinge SS were cleaved apparently randomly: there was no evidence for one bond being more susceptible to reduction than the other, and little indication that the reduction of one bond enhanced the susceptibility of the other. By limiting reduction to an average of one SS per molecule, and alkylation to 0.8 SH per molecule, a final Fc-maleimide product is obtained in which most of the molecules have passed through the entire preparation with one of their hinge SS, and by inference much of the hinge conformation, remaining intact.


Subject(s)
Immunoglobulin gamma-Chains/chemistry , Maleimides/chemistry , Sulfhydryl Compounds/chemistry , Humans , Ligands
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