Biomedical subjects

L M Williams

Publications and source records attributed to L M Williams.

At least 19 recordsLinked to original sources

PubMed2001

Syndromes of schizophrenia and smooth-pursuit eye movement dysfunction.

There have been a number of studies on smooth pursuit eye movement (SPEM) dysfunction in schizophrenia. However, the association between SPEM dysfunction and particular clinical symptoms remains unclear. We examined SPEM dysfunction in relation to schizophrenic symptoms using both the positive/negative dichotomy and the three-syndrome model. Subjects included 78 patients with schizophrenia and 60 healthy control subjects. SPEM performance was indexed by root mean square error. Symptom profiles were assessed using the Positive and Negative Syndrome Scale (PANSS), and the three-primary syndromes were identified by factor analysis of PANSS ratings (Psychomotor poverty: deficit negative symptoms; Disorganization: defined primarily by thought disorder; and Reality distortion: hallucinations and delusions). Compared with controls, the schizophrenia group showed significant impairment in global SPEM function. The three-syndrome approach produced more specific findings than the dichotomous model. Of the three syndromes, only the Disorganization dimension showed a significant association with increased global SPEM dysfunction. The specificity of SPEM dysfunction to Disorganization was verified in comparisons among schizophrenia subgroups and the control group. By contrast, the general domains of positive and negative symptoms were both found to be modestly associated with SPEM dysfunction. The separation of positive and negative symptoms that contribute to Disorganization from those that define Reality Distortion and Psychomotor Poverty has revealed significant new associations between SPEM and schizophrenic symptoms. These findings are interpreted in light of the proposal that the Disorganization syndrome is the central form of pathology in schizophrenia.

Adolescent↗

PubMed2001

Arousal dissociates amygdala and hippocampal fear responses: evidence from simultaneous fMRI and skin conductance recording.

The experience and appraisal of threat is essential to human and animal survival. Lesion evidence suggests that the subjective experience of fear relies upon amygdala-medial frontal activity (as well as autonomic arousal), whereas the factual context of threat stimuli depends upon hippocampal-lateral frontal activity. This amygdala-hippocampus dissociation has not previously been demonstrated in vivo. To explore this differentiation, we employed functional magnetic resonance imaging (fMRI) and simultaneous skin conductance response (SCR) measures of phasic arousal, while subjects viewed fearful versus neutral faces. fMRI activity was subaveraged according to whether or not the subject evoked an arousal SCR to each discrete face stimulus. The fMRI-with arousal and fMRI-without arousal data provided a distinct differentiation of amygdala and hippocampal networks. Amygdala-medial frontal activity was observed only with SCRs, whereas hippocampus-lateral frontal activity occurred only in the absence of SCRs. The findings provide direct evidence for a dissociation between human amygdala and hippocampus networks in the visceral experience versus declarative fact processing of fear.

Adult↗

PubMed2001

An integration of 40 Hz Gamma and phasic arousal: novelty and routinization processing in schizophrenia.

OBJECTIVES: Frontal and lateralized schizophrenia disturbances were examined in terms of arousal-modulated changes in 40 Hz Gamma activity. METHODS: Forty patients with schizophrenia and 40 age- and gender-matched controls were studied in a conventional auditory ERP oddball paradigm. We investigated sub-averaged Gamma activity based upon a simultaneous measure of electrodemal skin conductance response (phasic arousal) to differentiate novelty (large responses) from routinization (small or no responses). Both early Gamma (Gamma 1) and later induced Gamma (Gamma 2) activities were examined. RESULTS: Patients with schizophrenia (compared with controls) had significantly reduced Gamma 1 amplitude in the right hemisphere for novelty processing and delayed Gamma 2 latency in the left hemisphere for both novelty and routinization. Overall, reduced Gamma 1 amplitude in patients with schizophrenia was also evident. CONCLUSIONS: These findings indicate that the normal laterality of Gamma activity is specifically disturbed in schizophrenia in response to novel, but not routine (familiar) stimuli. The distinct pattern of findings suggests a dysregulation of activation across left and right hemispheres during initial attention and preparatory phases of information processing, in particular, in patients with schizophrenia.

Adult↗

PubMed2001

The long-term mental health consequences of child sexual abuse: an exploratory study of the impact of multiple traumas in a sample of women.

The current study examined exposure to multiple traumas as mediators of the relationship between childhood sexual abuse and negative adult mental health outcomes. Participants were 174 women interviewed in the third wave of a longitudinal study of the consequences of child sexual abuse. Child sexual abuse victims reported a lifetime history of more exposure to various traumas and higher levels of mental health symptoms. Exposure to traumas in both childhood and adulthood other than child sexual abuse mediated the relationship between child sexual abuse and psychological distress in adulthood. There were also some significant direct effects for child sexual abuse on some outcome measures. Results point to the importance of understanding the interconnected nature of trauma exposure for some survivors.

Adult↗

PubMed2001

Understanding links among childhood trauma, dissociation, and women's mental health.

Interrelationships among pathological dissociation, child and adult trauma exposure, and adult mental health symptoms were examined in a sample of low-income, mostly African-American women. Dissociation was significantly related to both trauma exposure and mental health symptoms but did not mediate this relationship. Implications for research and practice are discussed.

Adult↗

PubMed2001

Characterization of an antibody to the human melatonin mt1 receptor.

Melatonin acts via high affinity, G-protein coupled, seven transmembrane domain receptors. To precisely localize these receptors, antibodies were raised in chickens against a 15 amino acid fragment at the intracellular C-terminal region of the human melatonin receptor subtype mt1 (DSSNDVADRVKWKPS, mt(1338-352)). A chimeric form of the receptor with a hydrophilic Flag peptide (DYKDDDDK) in sequence with the extracellular N-terminus (Flag-mt1) was generated by polymerase chain reaction and expressed in mammalian cell lines. An IgY antibody (Y31), which gave high antibody titres by enzyme-linked immunosorbent assay, was used to localize Flag-mt1 in stably transfected cells by immunofluoresence. Flag-mt1 localization with Y31 was identical to that obtained with the M5 antibody directed against the Flag epitope and was mainly localized to the Golgi apparatus with some staining at the cell surface. No staining was seen in untransfected cells with either antibody. Y31 staining was abolished using antibody preabsorbed with peptide antigen. Y31 immunofluorescence in fetal human kidney sections was restricted to nephrogenic regions and matched that of 2-((125)I)iodomelatonin binding and mt1 gene expression by in situ hybridization. Y31 was used to immunoprecipitate biotinylated membrane proteins from Flag-mt1 stably transfected and untransfected CHO cells. Western blotting of immunoprecipitated proteins revealed two major bands specific to stably transfected cells, one at 63 kDa and one at 86 kDa. The first band almost certainly corresponds to the glycosylated form of Flag-mt1 and the second band to receptor dimers. Thus, Y31 antibody is suitable for use in detecting the human mt1 receptor subtype in tissues and in transfected cells.

Amino Acid Sequence↗

PubMed2001

Processing of threat-related affect is delayed in delusion-prone individuals.

OBJECTIVES: On the basis of previous reports of an attentional bias for threat-related emotional material in deluded schizophrenics (e.g. Bentall & Kaney, 1989), the present study examined the proposal that a similar bias would be demonstrated by delusion-prone individuals, reflected by longer response latencies for the task of processing threat-related facially displayed affects (e.g. anger, fear). DESIGN: A non-randomized matched group design was employed to examine the performance of delusion-prone individuals in comparison with a control group. METHODS: 50 psychiatrically healthy participants completed the Peters et al. Delusions Inventory (PDI) as an index of delusional ideation (Peters, Day, & Garety, 1996; Peters, Joseph, & Garety, 1999). Subjects were presented with a standard set of facial stimuli depicting happy, sad, neutral, fearful and angry emotion expressions (Mazurski & Bond, 1993). Reaction times for the task of identifying each type of affect were compared between groups of high and low scorers on the PDI. RESULTS: Highly delusion-prone individuals displayed a significant delay in processing angry facial expressions in comparison with low scorers on the PDI. CONCLUSIONS: The increased response latency for processing angry expressions was interpreted as evidence of attentional bias for material posing a threat to the self, supporting previous cognitive data in relation to deluded patients. Threatening facial expressions may be regarded with increased significance by delusion-prone individuals, and it is possible that this bias is involved in the formation of delusional beliefs.

Adolescent↗

PubMed2000

First isolation of an aquatic birnavirus from farmed and wild fish species in Australia.

During routine sampling and testing, as part of a systematic surveillance program (the Tasmanian Salmonid Health Surveillance Program), an aquatic birnavirus was isolated from 'pin-head' (fish exhibiting deficient acclimatisation on transfer to saltwater) Atlantic salmon Salmo salar, approximately 18 mo old, farmed in net-pens located in Macquarie Harbour on the west coast of Tasmania, Australia. The isolate grows readily in a range of fish cell lines including CHSE-214, RTG-2 and BF-2 and is neutralised by a pan-specific rabbit antiserum raised against infectious pancreatic necrosis virus (IPNV) Ab strain and by a commercial pan-specific IPNV-neutralising monoclonal antibody. Presence of the virus was not associated with gross clinical signs. Histopathological examination revealed a range of lesions particularly in pancreatic tissue. The virus was localised in pancreas sections by immunoperoxidase staining using the polyclonal antiserum and by electron microscopy. Examination by electron microscopy demonstrated that the virus isolated in cell culture (1) belongs to the family Birnaviridae, genus Aquabirnaviridae; (2) was ultrastructurally and antigenically similar to virus identified in the index fish; (3) is related to IPNV. Western blot analysis using the polyclonal rabbit antiserum confirmed the cross-reactions between various aquatic birnavirus isolates. In addition, PCR analysis of isolated viral nucleic acid from the index case indicated that the virus is more closely related to IPNV fr21 and N1 isolates than to other birnavirus isolates available for comparison. Sampling of other fish species within Macquarie Harbour has demonstrated that the virus is present in several other species of fish including farmed rainbow trout Oncorhynchus mykiss, wild flounder Rhombosolea tapirina, cod Pseudophycis sp., spiked dogfish Squalus megalops and ling Genypterus blacodes.

Animals↗

PubMed2000

The neural correlates of orienting: an integration of fMRI and skin conductance orienting.

In fMRI studies, the averaging of neural activity across multiple trials might obscure important psychophysiological subprocesses. The orienting response (OR) is a distinctive subprocess signalling the active orientation of attention towards potentially significant events. We sought to elucidate fMRI activity associated with visual stimuli that did or did not evoke simultaneously recorded electrodermal ORs (using customised skin conductance recording). 'With-OR' stimuli were associated with significant activity in the hippocampus, anterior cingulate and ventromedial prefrontal cortex. Averaged analysis revealed activity only in the expected visual circuits. Our results suggest that potentially significant stimuli (with-OR) activate different functional networks to familiar (without-OR) stimuli, and that orienting may therefore be an informative subprocess to consider in cognitive fMRI studies.

Attention↗

PubMed2000

Expression of clock gene in the brain of rainbow trout: comparison with the distribution of melatonin receptors.

To identify brain structures potentially acting as biological clocks in rainbow trout (Oncorhynchus mykiss), the expression sites of a trout homolog of the mouse clock gene were studied and compared with that of melatonin receptors (Mel-R). For this purpose, a partial sequence of the trout clock gene, including a PAS domain, was obtained by reverse transcription-polymerase chain reaction and used to perform in situ hybridization. The highest density of clock transcripts was observed in the periventricular layer (SPV) of the optic tectum, but a weaker expression was detected in some pretectal nuclei, such as the posterior pretectal nucleus (PO) and the periventricular regions of the diencephalon. Comparison of the hybridization signal in fish sacrificed at 08:00 and 17:00 did not indicate major changes in clock expression levels. Comparison of adjacent sections alternatively treated with clock and Mel-R probes suggests that both messengers are probably expressed in the same cells in the SPV and PO. In addition, in situ hybridization with a glutamate decarboxylase 65 probe, demonstrates that cells expressing clock and Mel-R in the optic tectum are gamma-aminobutyric acid neurons. The tight overlapping between the expression of Mel-R and clock transcripts in cells of the PO and SPV suggests a functional link between these two factors. These results indicate that the optic tectum and the pretectal area of the rainbow trout are major sites of integration of the melatonin signal, express the clock gene, and may act as biological clocks to influence behavioral and endocrine responses in trout.

Amino Acid Sequence↗

PubMed2000

Lipopolysaccharide induces actin reorganization and tyrosine phosphorylation of Pyk2 and paxillin in monocytes and macrophages.

The bacterial endotoxin LPS is a potent stimulator of monocyte and macrophage activation and induces adhesion of monocytes. Morphological changes in response to LPS have not been characterized in detail, however, nor have the signaling pathways mediating LPS-induced adhesion been elucidated. We have found that LPS rapidly induced adhesion and spreading of peripheral blood monocytes, and that this was inhibited by the Src family kinase inhibitor PP1 and the phosphatidylinositide 3-kinase inhibitor LY294002. LPS also stimulated actin reorganization, leading to the formation of filopodia, lamellipodia, and membrane ruffles in Bac1 mouse macrophages. Proline-rich tyrosine kinase 2 (Pyk2), a tyrosine kinase related to focal adhesion kinase, and paxillin, a cytoskeletal protein that interacts with Pyk2, were both tyrosine phosphorylated in response to LPS in monocytes and macrophages. Both tyrosine phosphorylation events were inhibited by PP1 and LY294002. Adhesion also stimulated tyrosine phosphorylation of Pyk2 and paxillin in monocytes, and this was further enhanced by LPS. Finally, Pyk2 and paxillin colocalized within membrane ruffles in LPS-stimulated cells. These results indicate that LPS stimulation of monocytes and macrophages results in rapid morphological changes and suggest that Pyk2 and/or paxillin play a role in this response.

Actins↗

PubMed2000

Childhood physical and sexual abuse as risk factors for heavy drinking among African-American women: a prospective study.

OBJECTIVE: This study examines the associations among characteristics of child sexual abuse. childhood physical abuse, lack of parental care, and heavy drinking in a relatively young, urban population of African-American women all of whom have documented histories of child sexual abuse. METHODOLOGY: The sample consists of 113 African American child victims who were brought to a city hospital emergency room for treatment and collection of forensic evidence in the 1970s and re-interviewed as adults in the 1990s. RESULTS: The results of this research suggest that multiple incidents of child sexual abuse, more than the characteristics of such abuse is an important predictor of adult heavy alcohol use and binge drinking. These results remain even after controlling for the effects of parental drinking behavior. CONCLUSION: Although the victim of multiple child sexual assaults is more likely to suffer force and penetration, these analyses suggest that it is the multiple victimization and not the force or penetration that drives the relationship between child sexual assault and drinking behaviors.

Adolescent↗

PubMed2000

Academic maturity: qualifications to teach the nurse professionals of the future.

In a recent survey of Queensland academic managers and graduates of pre-registration and nursing postgraduate programs, it was found that within levels of management there exists a disparity related to the minimal qualifications of educators of nurses. The preferred minimal level of academic preparation of heads of departments of nursing was generally ess than that proposed by recent consumers of tertiary education. Recent postgraduate and graduate students displayed their academic maturity through their preferences for highly qualified and academically qualified educators at all levels. The variety of educators involved in tertiary education included academics teaching within universities; clinical laboratory teachers teaching the skills of nursing practice; clinical faci itators who are responsible for groups of students in the clinical area; and clinical mentors, the clinicians who support and nurture students on a one-to-one basis. Ten managers of nursing programs (N=20), fourteen postgraduates (N=61) and 90 graduates (n=302) of Queensland tertiary nursing programs responded to the survey. While the final samples were small, the outcomes suggest increasing graduate expectations of thei educators and the need for a re-evaluation of measures of quality in academic teaching.

Attitude of Health Personnel↗

PubMed2000

Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism.

Trypsin and mast cell tryptase cleave proteinase-activated receptor 2 and, by unknown mechanisms, induce widespread inflammation. We found that a large proportion of primary spinal afferent neurons, which express proteinase-activated receptor 2, also contain the proinflammatory neuropeptides calcitonin gene-related peptide and substance P. Trypsin and tryptase directly signal to neurons to stimulate release of these neuropeptides, which mediate inflammatory edema induced by agonists of proteinase-activated receptor 2. This new mechanism of protease-induced neurogenic inflammation may contribute to the proinflammatory effects of mast cells in human disease. Thus, tryptase inhibitors and antagonists of proteinase-activated receptor 2 may be useful anti-inflammatory agents.

Animals↗

PubMed2000

Eye movement dysfunction as a biological marker of risk for schizophrenia.

OBJECTIVE: Our aim was to review smooth pursuit eye movement (SPEM) studies in schizophrenia and groups at high risk for schizophrenia, with a view to evaluating the utility of SPEM dysfunction as a biological marker of risk for schizophrenia. METHOD: Smooth pursuit eye movement studies, related saccade function and the unresolved issues in this area of schizophrenia research were addressed. The different perspectives on the trait marker status of SPEM dysfunction, provided by both high-risk studies and related developmental research were considered. Attention was also given to the relationship between eye movement dysfunction and symptom profiles. RESULTS: Converging evidence points to the robust and specific nature of SPEM dysfunction in schizophrenia, and highlights the role of frontal lobe and a related network dysfunction. The vast majority of 'high risk' studies support the view that SPEM dysfunction is also genetically specific to schizophrenia, and is not simply due to the overt expression of this illness. Studies assessing SPEM in relation to symptomatology show an association with the Disorganisation syndrome in particular. CONCLUSIONS: Evidence for the specificity of SPEM dysfunction to diagnosed schizophrenia, as well as to healthy individuals with a genetic vulnerability to schizophrenia, suggests that the SPEM task has efficacy as a test of gene carrier status in schizophrenia, and therefore as a trait marker of risk for schizophrenia. Future studies should seek to explore the relationships between SPEM and other eye movement dysfunctions (antisaccades, express saccades), in view of evidence that some of these dysfunctions also show specificity for schizophrenia.

Genetic Markers↗

PubMed2000

Adult sexual revictimization among black women sexually abused in childhood: a prospective examination of serious consequences of abuse.

This study is a prospective investigation of adult sexual revictimization among 113 Black women with documented histories of childhood sexual abuse. The purpose was to obtain information on the frequency of sexual abuse in both childhood and adulthood and to determine which characteristics of the child sexual abuse were predictive of revictimization. Thirty percent of the participants were revictimized and physical force predicted subsequent victimization. This study also investigated possible sexual behavioral correlates of revictimization. Revictimized women reported more involvement in prostitution and partner violence. Finally, the present study considered the reproductive and sexual health correlates of revictimization. When compared to women abused in childhood only, revictimized women experienced more problems conceiving, repeated vaginal infections, sexually transmitted diseases, and painful intercourse. Suggestions for intervention are discussed.

Adolescent↗

PubMed2000

Late component ERPs are associated with three syndromes in schizophrenia.

Previous studies have revealed various abnormalities in late-component ERP amplitude and latency in schizophrenia, considered as a diagnostic category. The aim of this study was to investigate the within-sample associations between late-component ERPs and three primary syndromes of schizophrenia Reality Distortion, Psychomotor Poverty and Disorganisation. Subjects included 40 schizophrenics and 40 age and sex matched nonpsychiatric controls. Auditory ERPs (N100, N200, P200, P300) were elicited using an auditory oddball paradigm. Between-group analyses of target data showed reduced N100, N200 and P300 amplitude, increased P200 amplitude and delayed N200 latency in schizophrenics compared to controls. For non-target data, schizophrenics showed similarly reduced N100 amplitude and delayed N200 latency. Within-group analyses of target data showed that the three syndromes (determined by principal component analysis of PANSS ratings) were differentiated by ERP latency, but not amplitude (Disorganisation delayed left hemisphere P200 and P300 latency; Reality Distortion earlier global, midline and left hemisphere N200 latency; Psychomotor Poverty delayed posterior N100 latency). Notably, only Disorganisation showed a divergent pattern of associations with non-target ERP data: reduced P200 amplitude and delayed N100 latency.

Adolescent↗

PubMed1999

Visual scanpaths in schizophrenia: is there a deficit in face recognition?

There is substantial evidence that schizophrenics have deficits in face processing. We hypothesised that this difficulty is due to abnormalities in the visual scanning of faces. The specificity of these abnormalities to recognisable faces, the effect of task difficulty and their relationships to three primary symptom dimensions were examined. An infrared corneal reflection technique was used to record the visual scanpaths of 63 schizophrenics and 60 non-psychiatric controls while viewing non-degraded ('recognisable') and degraded ('not recognisable') faces. In the concurrent recognition task, subjects were asked to select the previously viewed face from among seven (exposure 1) or three (exposure 2) options. Both groups were unable to accurately recognise degraded faces, but schizophrenics were less accurate than controls for non-degraded faces in the more difficult task condition. Schizophrenics maintained a relatively 'restricted' scanpath style across both faces, but scanpath disturbances were most apparent for non-degraded faces. Analysis of fixation distribution to non-degraded faces showed that, unlike controls, schizophrenics did not concentrate their fixations on salient features. Scanpath aberrations showed only minimal associations with symptom dimensions. These results suggest that schizophrenic individuals have a specific deficit in the visual scanning of faces, that is a distinct case of a fundamental problem in complex object processing.

Adult↗