Search PubMed⌕ Search

Biomedical subjects

A Simmons

Publications and source records attributed to A Simmons.

At least 19 recordsLinked to original sources
PubMed2005

Complement regulatory proteins are incorporated into lentiviral vectors and protect particles against complement inactivation.

Lentiviral vectors pseudotyped with G glycoprotein from vesicular stomatitis virus (VSV-G) and baculovirus gp64 are inactivated by human complement. The extent of vector inactivation in serum from individual donors was examined and results showed wide donor-dependent variation in complement sensitivity for VSV-G-pseudotyped lentivectors. Amphotropic envelope (Ampho)-pseudotyped vectors were generally resistant to serum from all donors, while gp64-pseudotyped vectors were inactivated but showed less donor-to-donor variation than VSV-G. In animal sera, the vectors were mostly resistant to inactivation by rodent complement, whereas canine complement caused a moderate reduction in titer. In a novel advance for the lentiviral vector system, human complement-resistant-pseudotyped lentivector particles were produced through incorporation of complement regulatory proteins (CRPs). Decay accelerating factor (DAF)/CD55 provided the most effective protection using this method, while membrane cofactor protein (MCP)/CD46 showed donor-dependent protection and CD59 provided little or no protection against complement inactivation. Unlike previous approaches using CRPs to produce complement-resistant viral vectors, CRP-containing lentivectors particles were generated for this study without engineering the CRP molecules. Thus, through overexpression of native DAF/CD55 in the viral producer cell, an easy method was developed for generation of lentiviral vectors that are almost completely resistant to inactivation by human complement. Production of complement-resistant lentiviral particles is a critical step toward use of these vectors for in vivo gene therapy applications.

Animals↗
PubMed2004

Word retrieval in amyotrophic lateral sclerosis: a functional magnetic resonance imaging study.

The cognitive impairment revealed in some non- demented amyotrophic lateral sclerosis (ALS) patients is characterized by executive dysfunction with widely repeated deficits on tests of verbal (letter) fluency. However, conflicting evidence exists of an impairment on other word retrieval tasks, such as confrontation naming, which do not place heavy demands on executive processes. Previous research has demonstrated intact confrontation naming in the presence of verbal fluency deficits, although naming deficits have been described in other studies. In this investigation, functional MRI (fMRI) techniques were employed to explore whether word retrieval deficits and underlying cerebral abnormalities were specific to letter fluency, which are more likely to indicate executive dysfunction, or were also present in confrontation naming, indicating language dysfunction. Twenty-eight non-demented ALS patients were compared with 18 healthy controls. The two groups were matched for age, intelligence quotient, years of education, and anxiety and depression scores. Two compressed-sequence overt fMRI activation paradigms were employed, letter fluency and confrontation naming, which were developed for use with an older and potentially impaired population. In ALS patients relative to controls, the letter fluency fMRI task revealed significantly impaired activation in the middle and inferior frontal gyri and anterior cingulate gyrus, in addition to regions of the parietal and temporal lobes. The confrontation naming fMRI task also revealed impaired activation in less extensive prefrontal regions, including the inferior frontal gyrus and regions of the temporal, parietal and occipital lobes. These changes were present despite matched performance between patients and controls during each activation paradigm. The pattern of dysfunction corresponded to the presence of cognitive deficits on both letter fluency and confrontation naming in the ALS group. This study provides evidence of cerebral abnormalities in ALS in the network of regions involved in language and executive functions. Moreover, the findings further illustrate the heterogeneity of cognitive and cerebral change in ALS.

Aged↗
PubMed2004

Persecutory delusions and the determination of self-relevance: an fMRI investigation.

BACKGROUND: People with persecutory delusions regard ambiguous data in the social domain as self-relevant and selectively attend to threatening information. This study aimed to characterize these social cognitive biases in functional neuroanatomical terms. METHOD: Eight schizophrenic patients with active persecutory delusions and eight matched normal controls underwent functional magnetic resonance imaging while determining the self-relevance of ambiguous self-relevant or unambiguous other-relevant neutral and threatening statements. RESULTS: In determining self-relevance, the deluded subjects showed a marked absence of rostral-ventral anterior cingulate activation together with increased posterior cingulate gyrus activation in comparison to the normal subjects. The influence of threat on self-relevance determination did not yield statistically significant differences between deluded and normal subjects. CONCLUSIONS: Abnormalities of cingulate gyrus activation while determining self-relevance suggest impaired self-reflection in the persecutory deluded state. This may contribute to persecutory belief formation and maintenance.

Adult↗
PubMed2004

Lateralisation of language function in young adults born very preterm.

OBJECTIVE: To explore, using functional magnetic resonance imaging (MRI), the functional organisation of phonological processing in young adults born very preterm. SUBJECTS: Six right handed male subjects with radiological evidence of thinning of the corpus callosum were selected from a cohort of very preterm subjects. Six normal right handed male volunteers acted as controls. METHOD: Blood oxygenation level dependent contrast echoplanar images were acquired over five minutes at 1.5 T while subjects performed the tasks. During the ON condition, subjects were visually presented with pairs of non-words and asked to press a key when a pair of words rhymed (phonological processing). This task alternated with the OFF condition, which required subjects to make letter case judgments of visually presented pairs of consonant letter strings (orthographic processing). Generic brain activation maps were constructed from individual images by sinusoidal regression and non-parametric testing. Between group differences in the mean power of experimental response were identified on a voxel wise basis by analysis of variance. RESULTS: Compared with controls, the subjects with thinning of the corpus callosum showed significantly reduced power of response in the left hemisphere, including the peristriate cortex and the cerebellum, as well as in the right parietal association area. Significantly increased power of response was observed in the right precentral gyrus and the right supplementary motor area. CONCLUSIONS: The data show evidence of increased frontal and decreased occipital activation in male subjects with neurodevelopmental thinning of the corpus callosum, which may be due to the operation of developmental compensatory mechanisms.

Adolescent↗
PubMed2003

Self-responsibility and the self-serving bias: an fMRI investigation of causal attributions.

We use causal attributions to infer the most likely cause of events in the social world. Internal attributions imply self-responsibility for events. The self-serving bias describes the tendency of normal subjects to attribute the causation of positive events internally ("I am responsible em leader ") and negative events externally ("Other people or situational factors are responsible em leader "). The self-serving bias has been assumed to serve a positive motivational function by enhancing self-esteem. Abnormalities of attributional style have been implicated in both depression and psychosis. We examined the neural basis of both self-responsibility and the self-serving bias using functional magnetic resonance imaging during the performance of attributional decision tasks. We found that the determination of self-responsibility recruits areas previously implicated in action simulation (bilateral premotor cortex and cerebellum), suggesting that such higher order social cognition is related to simpler internal models of goal-directed action. The dorsal striatum, previously implicated in motivated behavior, mediates the self-serving bias.

Adult↗
PubMed2003

Prevalence of autism and parentally reported triggers in a north east London population.

BACKGROUND: The recorded prevalence of autistic spectrum disorders has risen over recent decades. Measles, mumps and rubella (MMR) vaccine has been blamed, by causing a "new variant" form of "regressive autism" associated with "autistic enterocolitis". AIMS: To estimate the prevalence of autism and to assess any changes in parental perception regarding the onset or causes of autism. METHODS AND RESULTS: A total of 567 children with autistic spectrum disorder in five districts in north east London were identified, born 1979-98. Reported autism, excluding the 94 cases of Asperger's syndrome, increased by year of birth until 1992, since when prevalence has plateaued. This flattening off persisted after allowing for expected delay in diagnosis in more recent birth cohorts. The age at diagnosis of autistic spectrum disorder was estimated to have decreased per five year period since 1983, by 8.7% for childhood autism and by 11.0% for atypical autism. There was some evidence that MMR was more likely to be mentioned as a trigger after August 1997 than before. CONCLUSIONS: The prevalence of autism, which was apparently rising from 1979 to 1992, reached a plateau from 1992 to 1996 at a rate of some 2.6 per 1000 live births. This levelling off, together with the reducing age at diagnosis, suggests that the earlier recorded rise in prevalence was not a real increase but was likely due to factors such as increased recognition, a greater willingness on the part of educationalists and families to accept the diagnostic label, and better recording systems. The proportion of parents attributing their child's autism to MMR appears to have increased since August 1997.

Adolescent↗
PubMed2002

The neural correlates of intentional and incidental self processing.

The neuroscientific study of the 'Self' is just beginning to emerge. We used functional Magnetic Resonance Imaging (fMRI) to investigate cerebral activation while subjects processed words describing personality traits and physical features, in two experiments with contrasting designs: incidental and intentional. In the first experiment (intentional self processing), subjects were presented with personality trait adjectives and made judgements as to their self descriptiveness (versus non self descriptiveness). In the second experiment (incidental self processing), subjects categorised words according to whether they described physical versus psychological attributes, while unaware that the words had been arranged in blocks according to self descriptiveness. The subjects had previously rated all words for self descriptiveness 6 weeks prior to the scanning session. A reaction time advantage was present in both experiments for self descriptive trait words, suggesting a facilitation effect. Common areas of activation for the two experiments included the left superior parietal lobe, with adjacent regions of the lateral prefrontal cortex also active in both experiments. Differential signal changes were present in the left precuneus for the intentional and the right middle temporal gyrus for the incidental experiment. The results suggest that self processing involves distinct processes and can occur on more than one cognitive level with corresponding functional neuroanatomic correlates in areas previously implicated in the awareness of one's own state.

Adult↗
PubMed2002

Sensitivity of the Procleix HIV-1/HCV assay for detection of human immunodeficiency virus type 1 and hepatitis C virus RNA in a high-risk population.

The Procleix HIV-1/HCV Assay is a high-throughput nucleic acid test for the simultaneous detection of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) RNA during blood donor screening. This study evaluated the clinical sensitivity of the Procleix assay and assessed the assay's ability to identify HIV-1- and HCV-infected individuals undetected by standard serologic tests. Plasma samples were obtained prospectively from 539 individuals at high risk for HIV-1 and HCV infection at seven clinics affiliated with Johns Hopkins University. Samples were tested in the Procleix HIV-1/HCV Assay and, if reactive, were then tested in the Procleix HIV-1 and HCV discriminatory assays to differentiate the source of viral RNA positivity. Of these 539 subjects, 287 (53.2%) tested reactive in the Procleix HIV-1/HCV Assay. In discriminatory assay testing, 12 of 287 subjects (4.2%) were reactive for HIV-1 RNA only, 260 (90.6%) were reactive for HCV RNA only, and 11 (3.8%) were coinfected with HIV-1 and HCV. The clinical sensitivity for samples tested neat was 100% for HIV-1 and 99.3% for HCV. Three subjects with Procleix HCV reactive/seronegative results seroconverted upon follow-up and were confirmed as Procleix HCV yield cases. The Procleix HIV-1/HCV Assay is a highly sensitive test that detects ongoing and early HIV-1 and HCV infection in a significant number of subjects at high risk for these diseases. Confirmation of Procleix yield cases upon follow-up demonstrated the ability of the Procleix HIV-1/HCV Assay to detect the presence of HIV-1 and HCV in blood earlier than standard serologic tests.

AIDS Serodiagnosis↗
PubMed2002

Recall bias, MMR, and autism.

Parents of autistic children with regressive symptoms who were diagnosed after the publicity alleging a link with measles, mumps, and rubella (MMR) vaccine tended to recall the onset as shortly after MMR more often than parents of similar children who were diagnosed prior to the publicity. This is consistent with the recall bias expected under such circumstances.

Attitude to Health↗
PubMed2001

Effects of estrogen replacement therapy on human brain aging: an in vivo 1H MRS study.

Estrogen replacement therapy (ERT) may preserve cognitive function in postmenopausal women, but the mechanism is unknown. Thus, the authors studied aging of parietal lobe and hippocampus using proton MR spectroscopy. ERT naïve postmenopausal women had a significant increase in choline-containing compounds (Cho) compared to long-term ERT users and young women. Cho reflects increased neuronal/glial membrane turnover. Thus, ERT's "neuroprotective" effect may include modulating the effects of age on neural integrity in brain regions involved in cognitive function.

Adult↗
PubMed2001

Neuroimaging correlates of negative priming.

Many theoretical accounts of selective attention and memory retrieval include reference to active inhibitory processes, such as those argued to underlie the negative priming effect. fMRI was used in order to investigate the areas of cortical activation associated with Stroop interference, Stroop facilitation and Stroop negative priming tasks. The most significant activation within the negative priming task was within the inferior parietal lobule, left temporal lobe and frontal lobes. Areas of cortical activation are discussed with reference to theoretical accounts of the negative priming effect.

Adult↗
PubMed2001

Volumetric analysis reveals corticospinal tract degeneration and extramotor involvement in ALS.

BACKGROUND: Pathologic changes in the motor cortex and corticospinal tracts in ALS may be reflected by abnormal signal intensities on conventional MRI. The sensitivity of these changes in detecting underlying pathology remains unclear. METHOD: The authors used automated image analysis to quantify volumes of cerebral gray and white matter in 16 patients with ALS (eight limb onset, eight bulbar onset) and eight normal controls. Previously they had demonstrated a reduction in N-acetyl aspartate/creatine + phosphocreatine (NAA/[Cr + PCr]) measured by (1)H-MRS in the subcortical white matter in the motor cortex region in the patients with bulbar-onset ALS. To determine whether this resulted from axonal degeneration, they also compared gray and white matter volumes in the patients with limb- and bulbar-onset ALS. RESULTS: There were no differences in the total brain volumes of gray or white matter for the three subject groups (p > 0.23). Comparison of the total ALS group and controls revealed localized deficits in gray matter volume centered on Brodmann areas 8, 9, and 10 bilaterally. Comparison of the patients with limb- and bulbar-onset ALS revealed deficits in the white matter volume in the bulbar-onset group, extending bilaterally from the precentral gyrus into the internal capsule and brainstem, consistent with the course of the corticospinal tract. There was no loss in gray matter volume in the precentral gyri. CONCLUSIONS: The loss of gray matter in the frontal regions (total ALS group) provides further support that ALS is a multisystem disorder. In addition, there is in vivo evidence of axonal degeneration in the subcortical white matter in the motor region in patients with bulbar-onset ALS. This is consistent with a "dying back" process affecting cortical motoneurons in bulbar-onset ALS.

Adult↗
PubMed2001

An fMRI study of reduced left prefrontal activation in schizophrenia during normal inhibitory function.

Functional magnetic resonance imaging (fMRI) was used to investigate the hypothesis that schizophrenia is associated with a dysfunction of prefrontal brain regions during motor response inhibition. Generic brain activation of six male medicated patients with schizophrenia was compared to that of seven healthy comparison subjects matched for sex, age, and education level while performing 'stop' and 'go-no-go' tasks. No group differences were observed in task performance. Patients, however, showed reduced BOLD signal response in left anterior cingulate during both inhibition tasks and reduced left rostral dorsolateral prefrontal and increased thalamus and putamen BOLD signal response during stop task performance. Despite good task performance, patients with schizophrenia thus showed abnormal neural network patterns of reduced left prefrontal activation and increased subcortical activation when challenged with motor response inhibition.

Adult↗
PubMed2001

Corpus callosum area and functioning in schizophrenic patients with auditory--verbal hallucinations.

Auditory--verbal hallucinations (AVH) are a characteristic feature of schizophrenia. Patients with AVHs have been found to differ from non-hallucinating patients in volumes of certain asymmetrical brain structures on MRI, and on certain neuropsychological measures. There is also evidence of corpus callosum (CC) abnormalities in schizophrenia, and it has been proposed that abnormalities of inter-hemispheric transmission may underlie hallucinations and other symptoms. The aim of this study was to examine whether patients with AVHs have smaller corpora callosa than those without AVH, and whether CC size is related to performance on neuropsychological tests of functional cerebral asymmetry. Seventy-one DSM-IV male schizophrenics were recruited on the basis of their hallucination history plus 33 matched normal controls. Twenty-nine patients had no history of AVH, and 42 had a strong history of AVH. The mid-sagittal surface area and longitudinal length of the CC were measured from T(1)-weighted spin echo images. Callosal area was divided into four sections. There were no significant differences in any of the measurements between the two patient groups, or between patients with schizophrenia and controls. There was no association between CC measures and handedness, or performance on dichotic listening or finger tapping tasks. The results of this study do not lend support for there being a major morphological abnormality of the corpus callosum in schizophrenic patients, or for a specific relationship to AVH. However, a significant association between CC area and overall grey and white matter volumes was noted in the hallucinating patients and, to a lesser extent, in the non-hallucinators, which may point to differing influences on brain development or degeneration in such patients compared with normal controls.

Adolescent↗
PubMed2001

Structural magnetic imaging of the hippocampus in early onset schizophrenia.

BACKGROUND: Previous literature suggests that hippocampal volume reductions in schizophrenia may occur either during adolescence or at the point of transition to overt psychosis. The authors tested these hypotheses by examining the hippocampal formation in adolescents with recent onset schizophrenia. METHODS: We compared the volumes of the left and right hippocampus, obtained using stereologic methods from magnetic resonance brain images, from 40 adolescents with recent onset schizophrenia to those of an equal number of matched healthy control subjects. Symptoms were rated using the Positive and Negative Syndrome Scale. RESULTS: Compared with control subjects, adolescents with schizophrenia had reduced whole brain volume. After adjusting for brain volume, no group differences were observed in hippocampal volume. Duration of illness was negatively correlated with the volume of the left hippocampus. We found no effect of pregnancy and birth complications or family history of psychosis on hippocampal volumes. There was a negative correlation between severity of psychopathology and hippocampal volumes, which was significant for negative symptoms. CONCLUSIONS: Specific hippocampal volume reductions in early onset schizophrenia do not seem to predate the onset of or to occur at the point of transition to psychosis but may develop in adolescence during the early stages of the illness.

Adolescent↗
PubMed2001

Cutting edge: a NK complex-linked locus governs acute versus latent herpes simplex virus infection of neurons.

Herpes simplex causes latent infections that periodically reactivate. Specific immunization attempts are failing to control herpes, prompting a fresh look at which host responses predominate. We report a NK complex-linked genetic locus, Rhs1, whose alleles influence the magnitude of experimental herpes simplex. Rhs1 provided rapid control of primary infection but caused a reciprocal increase in the number of latently infected neurons. Thus, in principle, establishment of latency is a consequence of efficient front line defense against herpesvirus infection. Based on conservation between human and mouse NK complexes, the data predict the presence of a human Rhs1 orthologue on chromosome 12p12-13.

Acute Disease↗
PubMed2001

Are auditory hallucinations the consequence of abnormal cerebral lateralization? A morphometric MRI study of the sylvian fissure and planum temporale.

BACKGROUND: Auditory verbal hallucinations (AVHs) are a characteristic feature of schizophrenia. Patients with schizophrenia have been found to have reduced volumes of a variety of brain structures as well as a reduction in right-left asymmetries, using postmortem and magnetic resonance imaging (MRI) measures. There is also evidence that patients with AVHs differ in these structural asymmetries, relative to those patients who do not hallucinate. The aim of this study was to examine whether patients with and without a prominent history of AVHs differ, both from each other and in comparison with normal subjects, in the asymmetry of the sylvian fissure (SF) and planum temporale (PT). METHODS: We recruited 74 DSM-IV male patients with schizophrenia (on the basis of their AVH history) and 32 matched normal control subjects. Thirty patients had no history of AVHs and 44 had a strong definitive history of AVHs. The SF length and PT area and volume were measured on a three-dimensional MRI spoiled GRASS volume sequence. Absolute measures and laterality coefficients were calculated. RESULTS: : All groups had the normal leftward asymmetry in both the SF and PT. Planum temporale volume and surface area and SF length were all larger in the left hemisphere. There were no significant differences in any measures between the two patient groups or between schizophrenic patients and control subjects. Greater leftward asymmetry of the SF correlated with hallucinations and thought disorder within the prominent hallucinator group. An association was found between handedness and brain size, but this did not interact with diagnosis. CONCLUSIONS: The results of this study do not confirm reports, based on smaller samples, of reduced structural asymmetries of either the SF or PT in schizophrenia, nor do they indicate a specific relationship to a propensity to experience AVHs. A modest correlation between leftward asymmetry of the SF and some positive symptomatology was found.

Adult↗