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Biomedical subjects

D Bloom

Publications and source records attributed to D Bloom.

At least 19 recordsLinked to original sources
PubMed2001

Memory impairment in schizophrenia: a study using event-related potentials in implicit and explicit tasks.

Although memory impairment is recognized as a major fact of schizophrenia, only a few studies have investigated memory impairments with specifically designed event-related potential (ERP) protocols. In this study, ERPs were recorded from 15 schizophrenia patients and 15 matched control subjects during implicit and explicit memory tasks for unfamiliar faces. The results showed that patients have a reduced modulation of an N400-like component in both the implicit and explicit tasks that suggests a deficient integration of incoming information with personal knowledge. Patients also displayed an enhanced frontally distributed activity in the explicit task that may represent an impairment in the integration of intrinsic contextual information, a disturbance in the ability to inhibit proactive interference or a combination of both processes. Finally, the modulation of the late positive component did not differ from that in control subjects in both implicit and explicit tasks, suggesting that the impairment in mnemonic binding processes suggested in schizophrenia is more qualitative, i.e. incomplete or inappropriate, due to the anomalies in antecedent processes. The correlations observed between impairments of ERP modulation and symptoms further support these interpretations.

Adult↗
PubMed2000

Association between the methylenetetrahydrofolate reductase 677C-->T missense mutation and schizophrenia.

The schizophrenia phenotype is heterogeneous with respect to clinical presentation, long-term response to medication, and outcome, possibly reflecting genetic heterogeneity and/or the presence of modifier genes. Compared to non-responders, schizophrenic patients who are responders to neuroleptic medications are characterized by a high female/male ratio, a better long-term outcome and more frequently disturbed dopamine neurotransmission. In this study, we compared two groups of schizophrenic patients selected on the basis of their long-term response to neuroleptics (excellent responders and non-responders) and a group of healthy volunteers, with regard to a missense mutation (677C-->T) in the methylenetetrahydrofolate reductase (MTHFR) gene. This polymorphism was chosen because it is functional and was previously associated with schizophrenia. The present study revealed a significant association between schizophrenia and allele T of this gene. This association was entirely due to an over-representation of allele T in responder patients compared to controls; nonresponder patients did not differ from controls. Genotype TT was more frequent in responder patients compared to controls, thus replicating the findings of Arinami et al. These results strongly suggest that the MTHFR gene is involved in the pathogenesis of schizophrenia characterized by a rapid and sustained therapeutic response to typical neuroleptics and/or a good long-term prognosis/favorable therapeutic outcome.

Adult↗
PubMed1999

Analysis of 14 CAG repeat-containing genes in schizophrenia.

Recently, it has been suggested that trinucleotide repeat-containing genes may be involved in the etiology of schizophrenia. This study was aimed at investigating putative associations between allelic variants or expansions of CAG repeat-containing genes (CAGrCG) and schizophrenia or its variability with respect to responsiveness to conventional neuroleptics. CAG repeat allelic variants of 14 expressed sequences were compared among three groups of subjects: neuroleptic-responder (R; n = 43) and neuroleptic-nonresponder (NR; n = 63) schizophrenic patients, and a control group (C; n = 122). No CAG expansions, in the range of those observed in neurodegenerative diseases, were identified in these 14 expressed sequences. The sizes of CAG repeat for the hGT1 gene were marginally different among the three groups of subjects (Kruskal-Wallis H (2, 456) = 10.48, Bonferroni corrected P = 0.047). Comparisons among the different groups indicated that neuroleptic responders have shorter alleles compared to controls (Mann-Whitney adjusted Z = -3.23, P = 0.0012). NR patients were not different from controls. These preliminary results suggest that the hGT1 gene, or a gene in its vicinity, may be involved in the etiology of schizophrenia or in modifying the disease phenotype with regard to outcome and/or neuroleptic responsiveness. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:694-699, 1999.

Adolescent↗
PubMed1999

Prostaglandin E2 enhancement of interferon-gamma production by antigen-stimulated type 1 helper T cells.

Prostaglandin E2 (PGE2) is a potent mediator generated in immune tissues by cyclooxygenation of arachidonic acid. PGE2 affects T cell functions through four homologous G protein-coupled receptors termed EP1R, EP2R, EP3R, and EP4R that differ in tissue distribution and signaling. Antigen-evoked secretion of interferon-gamma (IFN-gamma) by sperm whale myoglobin-specific Th1 cells of DBA/2 mouse I-Ed-restricted clones, that express EP3Rs and EP4Rs, was enhanced a maximum of 3-fold by 10(-10) to 10(-8) M PGE2 and 2.5-fold each for the EP1R/EP3R-directed agonist sulprostone (10(-8) and 10(-7) M) and for the EP4R/EP3R/EP2R agonist misoprostol (10(-9) M). Neither PGE2 nor the synthetic analogs affected secretion of IFN-gamma by PMA plus ionomycin-stimulated clones of Th1 cells. Antigen-evoked secretion of IFN-gamma by influenza hemagglutinin-specific mouse lymph node Th1 cells, that also express EP3Rs and EP4Rs, was increased a maximum of 12-fold by 10(-9) to 10(-8) M PGE2, 14-fold by 10(-9) M sulprostone, and 10-fold by 10(-9) M misoprostol. Production of IFN-gamma by either type of Th1 cell was not affected significantly by 10(-6) M PGE2 alone. The generation of IFN-gamma by antigen-stimulated Th1 cells thus is significantly enhanced by physiologically relevant concentrations of PGE2.

Animals↗
PubMed1999

Lack of association between the hSKCa3 channel gene CAG polymorphism and schizophrenia.

Genetic anticipation, a phenomenon characterized by increased severity of symptoms and earlier age at onset of a disease in successive generations, is believed to be present in schizophrenia. In several neurodegenerative diseases showing anticipation, the mutation causing the disease is an expanded trinucleotide repeat. Therefore, genes containing trinucleotide repeats prone to expansion have become a suitable family of candidate genes in schizophrenia. A human calcium-activated potassium channel gene (hSKCa3), possibly mapping to chromosome 22q11-13, a region previously linked to schizophrenia, was recently described. This gene contains two contiguous expressed CAG repeat stretches. Recently, long allelic variants of one of these CAG repeats were found to be overrepresented in schizophrenic patients compared to normal controls. In this study we attempted to replicate this result and to study the relationship between the length of this CAG repeat on the one hand and the severity and age at onset of the disease on the other hand. No association with the disease or correlation with the severity of schizophrenia was identified. In addition, hSKCa3 was mapped to chromosome 1. Our results do not support the involvement of this particular CAG repeat-containing gene in schizophrenia.

Adult↗
PubMed1999

Polyglutamine-containing proteins in schizophrenia.

Genetic anticipation, manifested by increased severity and earlier age-at-onset of the disease over successive generations, is reported in schizophrenia. The molecular basis of anticipation in several neurodegenerative diseases is unstable coding CAG repeat expansions. Anticipation was reported in schizophrenia. Recently, studies suggested that enlarged CAG/CTG repeats are over represented in schizophrenic patients compared to normal controls. Together, these observations suggest that unstable CAG repeats may play a role in the etiology of schizophrenia. The purpose of this study is to test for the presence of polyglutamine-expanded tracts, encoded by CAG repeats, in total protein extracts derived from lymphoblastoid cell lines of schizophrenic patients. Proteins from schizophrenic patients (n = 59) and normal controls (n = 73) were separated by means of SDS-polyacrylamide gel electrophoresis, wet blotted onto nitrocellulose membrane and probed with a monoclonal antibody (mab 1C2) recognizing expanded polyglutamine arrays. Three abnormal bands corresponding to protein(s) of molecular weight of approximately 50 kDa were identified in two unrelated schizophrenic patients and in a sibling of one of these patients. None of the normal controls tested positive for this abnormal band. These results suggest that expanded polyglutamine-containing proteins, though rare, may play a role in the pathogenesis of schizophrenia.

Age of Onset↗
PubMed1999

A behaviour study on the potential for direct transmission of tuberculosis from possums (Trichosurus vulpecula) to alpacas (Lama pacos), and the converse from alpacas to possums.

AIMS: To evaluate the potential for the direct transmission of tuberculosis from possums to alpacas, and vice versa. METHODS: A field study was conducted on an alpaca farm in Northland, New Zealand on 7 January 1999. Observations were recorded on the interaction of one group of male alpacas with a simulated dead possum, one male and one female alpaca group with a simulated terminally tuberculous possum, and one group of male alpacas with a normal possum in an enclosure from which the animals could not escape. The possum was sedated with ketamine as hydrochloride to simulate death (inactive; no movement), and terminal illness (active, inco-ordinated movement around the paddock). The observations were based on the focal animal sampling technique, they were un-replicated, and recorded visually and manually with intermittent still photography. RESULTS: Both male and female alpacas showed strongly inquisitive interaction with the possum. They clustered around the possum (focal animal) very soon after it was observed by the first member of the group. The interest of the majority of both sex groups remained high for the observation periods of approximately 30 minutes, and most individuals remained within 5 metres of the possum for that time. Approximately 50% of the alpacas were within possible aerosol transmission distance of 2 metres from the sedated, erratically mobile possum with their heads towards it for approximately 50% of the two observation periods. Aggressive behaviour was recorded for a young male with stamping on the moving possum. Similar, but more vigorous and prolonged stamping behaviour was recorded for a female with a young (<1 week) offspring (cria). The stamping behaviour was accompanied by very close nose to nose contact of the alpaca and possum. At one point the female threw the possum approximately 1.5 metres in the air with her teeth. The group of male alpacas placed in an enclosure with an unsedated normal possum generally moved away from the possum during its rapid active attempts to escape. When it became inactive their approaches were cautious and only once elicited a defence reaction from the possum, from which they recoiled. One male made one attempt to stamp on the active possum. Soon after the possum became inactive in a small loose hay pile, the alpacas lost interest in it. CONCLUSIONS: The alpaca / possum behavioural interactions show there is potential for direct aerosol transmission of tuberculosis from possums to alpacas, but probably not from alpacas to possums.

Journal Article↗
PubMed1999

Enhancement by vasoactive intestinal peptide of gamma-interferon production by antigen-stimulated type 1 helper T cells.

Vasoactive intestinal peptide (VIP) is a neuroendocrine mediator in immune tissues that affects many T cell functions through two homologous high-affinity G-protein-coupled receptors, termed VIPR1 and VIPR2. Antigen-stimulated secretion of gamma-interferon (IFN-gamma) by sperm whale myoglobin-specific Th1 cells of DBA/2 mouse I-Ed-restricted clones, which express VIPR1 and VIPR2, was enhanced by 10(-10) M to 10(-7) M VIP. Enhancement of IFN-gamma secretion reached a mean maximum of fourfold for VIP and threefold for a VIPR2-selective agonist, without any effect of a VIPR1-selective agonist. Secretion of IFN-gamma by PMA and ionomycin-stimulated clones of Th1 cells was not altered by VIP. Antigen-stimulated secretion of IFN-gamma by T cell receptor-transgenic, influenza hemagglutinin-specific, and cytokine-differentiated mouse lymph node Th1 cells, which also express VIPR1 and VIPR2, was enhanced by 10(-10) M to 10(-8) M VIP. Enhancement of IFN-gamma secretion increased to a maximum of 14-fold for VIP, 14-fold for the VIPR2-selective agonist, and 20-fold for the VIPR1-selective agonist. In contrast to VIP suppression of interleukin production and lack of effect on IFN-gamma production by T cells stimulated with anti-CD3 antibody or a mitogenic lectin, generation of IFN-gamma by antigen-stimulated T cells is enhanced significantly by physiological concentrations of VIP.

Animals↗
PubMed1999

Atypical presentation of Clostridium difficile colitis in patients with cystic fibrosis.

OBJECTIVE: This report describes the unusual presentation of Clostridium difficile colitis in five patients with cystic fibrosis and the role of CT in first suggesting the correct diagnosis in this group of patients. Because of the absence of watery diarrhea and the presence of abdominal bloating and decreased stooling, cystic fibrosis patients with C. difficile colitis will be treated for stool impaction, meconium ileus equivalent, or distal intestinal obstruction syndrome. CT of the abdomen, performed in these five patients because of their lack of improvement after standard therapy for stool impaction, showed an extensive pancolitis later confirmed to be caused by C. difficile infection. CONCLUSION: In patients with cystic fibrosis, imaging findings of a pancolitis should raise the possibility of C. difficile colitis despite the lack of watery diarrhea. Anticlostridial treatment can be initiated before bacteriologic confirmation is obtained.

Adult↗
PubMed1999

T102C polymorphism in the 5HT2A gene and schizophrenia: relation to phenotype and drug response variability.

Although genes play a major role in the etiology of schizophrenia, no major genes involved in this disease have been identified. However, several genes with small effect have been reported, though inconsistently, to increase the risk for schizophrenia. Recently, the 5HT2A 2 allele (T102C polymorphism) was reported to be over-represented in patients with schizophrenia. Other reports have found an excess of allele 2(C) only in schizophrenic patients who are resistant to clozapine, not in those who respond to clozapine. In this study, the 5HT2A receptor allele 2 frequencies were compared between 2 groups of patients with schizophrenia (39 responders and 63 nonresponders) based on long-term outcome and response to typical neuroleptics. A control group of 90 healthy volunteers screened for mental disorders was also included. Genotype 2/2 tended to be more frequent in patients with schizophrenia with poor long-term outcome and poor response to typical neuroleptics (Bonferroni corrected p = 0.09). This difference was significant in men (Bonferroni corrected p = 0.054) but not in women. In addition, the age at first contact with psychiatric care was significantly younger in the patients with schizophrenia with genotype 2/2 than in patients with genotype 1/1. These result suggest that the 5HT2A-receptor gene may play a role in a subset of schizophrenia characterized by poor long-term outcome and poor response to neuroleptics.

Adult↗
PubMed1998

Event-related brain potentials during an extended visual recognition memory task depict delayed development of cerebral inhibitory processes among 6-month-old infants with Down syndrome.

Development of cerebral inhibitory processes among individuals with Down syndrome (DS) may be delayed at an early age. In support of this hypothesis, sensory-evoked potentials (EPs) and event-related brain potentials (ERPs) have previously delineated altered habituation to stimuli among infants with DS. The purpose of the current study was to provide extended experience with visual stimuli among 6-month-old infants with and without DS (nDS) to determine if altered ERP and behavioral response decrements would be evident even after repeated presentations of stimuli. An 80/20% oddball paradigm was employed. Infants with DS and nDS were matched according to age and gender. Infants with DS demonstrated significantly larger Nc areas, Nc peak amplitudes, Nc2 areas and, inversely, significantly smaller peak Pb amplitudes when compared to infants nDS. Contrasts of the two study groups were most robust within ERP measures from frontal (Fz) and parietal (Pz) recording sites. Infants with DS also demonstrated a significantly slower decrement of most ERP components with repetitive stimulus experience. Most noteworthy was the observation of little or no decrement of ERP components at Fz among infants with DS. Both infants with DS and nDS demonstrated significantly larger Nc peak amplitudes, Nc areas, Nc2 areas, Pb peak amplitudes and NSW areas to rare stimuli. While significant probability and experiential trends were observed in visual fixation measures across both study groups, there were no significant differences of visual attention between infants with DS or nDS. These data demonstrate the value of ERPs within the study of atypical cognitive development during infancy and support the concept of altered inhibitory processes in the brain of infants with DS.

Brain↗
PubMed1998

Neuropsychological and neurophysiological indices of auditory processing impairment in children with multiple complex developmental disorder.

OBJECTIVE: To evaluate whether children with borderline disorder (also referred to as multiple complex developmental disorder) (BD/MCDD) and comorbid attention-deficit hyperactivity disorder (ADHD) demonstrate evidence of abnormal attention and/or auditory processing impairments as indexed by both behavioral and physiological measures. METHOD: Three groups of children were compared in two different experiments on behavioral rating scales (Conners Parent Rating Scale and Child Behavior Checklist), behavioral accuracy to auditory and visual target detection tasks, selected neuropsychological tests, and brain physiology (event-related potentials) collected during auditory and visual target detection tasks. RESULTS: The results demonstrate that children with BD/MCDD differ from children with ADHD in the (1) prevalence of internalizing and externalizing behaviors, (2) neuropsychological deficits related to auditory processing, and (3) event-related potential brain physiology associated with auditory cognitive target attention tasks. CONCLUSION: Some of the pervasive pathology described in children with BD/MCDD may be due to biological vulnerabilities, particularly problems with auditory processing. Auditory processing impairments in such children deserves special attention with respect to both understanding their behavioral symptoms and developing a comprehensive treatment plan.

Adolescent↗
PubMed1998

An intertypic herpes simplex virus helicase-primase complex associated with a defect in neurovirulence has reduced primase activity.

R13-1 is an intertypic recombinant virus in which the left-hand 18% of the herpes simplex virus type 1 (HSV-1) genome is replaced by homologous sequences from HSV-2. R13-1 is nonneurovirulent and defective in DNA replication in neurons. The defect was localized to the UL5 open reading frame by using marker rescue analysis (D. C. Bloom and J. G. Stevens, J. Virol. 68:3761-3772, 1994). To provide conclusive evidence that UL5 is the only HSV-2 gene involved in the restricted replication phenotype of R13-1, we have characterized the phenotype of a recombinant virus (IB1) in which only the UL5 gene of HSV-1 was replaced by HSV-2 UL5. Data from 50% lethal dose determinations and the in vivo yields of virus suggested that IB1 has the same phenotypic characteristics as R13-1. UL5 is the helicase component of a complex with helicase and primase activities. All three subunits of this complex (UL5, UL8, and UL52) are required for viral DNA replication in all cell types. The intertypic complex HSV-2 UL5-HSV-1 UL8-HSV-1 UL52 was purified and biochemically characterized. The primase activity of the intertypic complex was 10-fold lower than that of HSV-1 UL5-HSV-1 UL8-HSV-1 UL52. The ATPase activity was comparable to that of the HSV-1 enzyme complex, and although the helicase activity was threefold lower, this did not interfere with the synthesis of leading strands by the HSV polymerase. One explanation for these findings is that the interactions between the subunits of the helicase-primase intertypic complex that are important for the full function of each subunit are inappropriate or weak.

Animals↗
PubMed1997

MRI artifacts following anterior cervical diskectomy.

BACKGROUND: Magnetic resonance imaging (MRI), despite being an excellent imaging technique in neurosurgical practice, is unfortunately susceptible to numerous artifacts. Some of these artifacts are easily identifiable and do not interfere; however, others are more subtle and can be easily mistaken for false pathology. Postoperative MRI can further complicate the imaging interpretation, by producing another group of artifacts. It is imperative for practicing neurosurgeons, as well as neuroradiologists, to have a clear understanding of these postoperative artifacts. METHODS: We discuss four cases who had been operated for anterior cervical decompression with bony fusion. All the patients had a postoperative MRI of the cervical region that showed a "false compression" of the cervical cord. The normal computed tomography (CT) scan in some cases and the discrepancy with the clinical condition of the patients excluded the diagnosis of compression of the cervical cord. RESULTS: The overall appearance of the postoperative MRI can be very difficult to interpret. The artifact seen following anterior cervical diskectomy is an example of such a situation. We have confirmed that the postoperative MRIs showing artifacts do not indicate cord or root compression; a routine postoperative plain X ray or CT scan of the operated area can also confirm the absence of compression. CONCLUSION: These are examples of cases in which the postoperative MRI had an unexpected metallic artifact that not only caused difficulty in the interpretation of the images but at times suggested a clinical problem when actually there was none. Very thin cut CT scans may not show these artifacts that are picked up by the sensitive MRI study. A proper clinical evaluation and selection of the appropriate MRI techniques and the MRIs can eliminate or at least decrease the incidence of the artifacts. Above all, further education of practicing physicians is needed to avoid false alarms caused by these metallic artifacts.

Adult↗