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Biomedical subjects

L A Jones

Publications and source records attributed to L A Jones.

At least 37 records · Page 2Linked to original sources
PubMed2000

The kings schizotypy questionnaire as a quantitative measure of schizophrenia liability.

We used a new self-report measure, the Kings Schizotypy Questionnaire (KSQ; Williams, M. The psychometric assessment of schizotypal personality. PhD thesis. Institute of Psychiatry, University of London, 1993), to investigate schizotypy as a quantitative measure of familial liability to schizophrenia. The KSQ was administered to 135 DSM-IV schizophrenia probands, 153 of their healthy first-degree relatives, and 267 control subjects. We found that the questionnaire clearly differentiated schizophrenic from non-schizophrenic individuals, but failed to differentiate the relatives from controls. Possible reasons for this include defensive responding among relatives, self-selection bias among relatives, differences in data collection methods, and the possibility that positive aspects of schizotypy may not be closely related to familial liability to schizophrenia.

Adult↗
PubMed2000

Dendritic cell-based immunotherapy of prostate cancer: immune monitoring of a phase II clinical trial.

We assessed both non- and peptide-specific immune responses in prostate cancer patients before and after immunotherapy with dendritic cells exogenously pulsed with the prostate-specific membrane antigen-derived peptides, PSM-P1 and PSM-P2. For all subjects, we observed that clinical responses were strongly associated with two indicators of immunocompetence: skin test responses to recall antigens and cytokine secretion by T cells after nonspecific stimulation. In a subset of responders, we observed cytokine secretion or cytotoxicity against the immunizing peptides or an immunodominant epitope from an influenza recall antigen. The clinical results support the use of monitoring for overall immunocompetence to help determine why a patient has or has not responded to therapy. Moreover, it could be useful as an inclusion criterion to select those more likely to benefit from treatment.

Antigens, Surface↗
PubMed2000

Visual and haptic feedback in the control of force.

The ability to control index finger and elbow flexion forces was measured while subjects used either haptic feedback or both haptic and visual feedback to control the forces exerted. Over a 120-s time period subjects were able to control the finger forces ranging from 2 to 6 N to within 1 N using only haptic feedback, and elbow flexion forces to within 4.5 N over a force range of 10-30 N. At the same force amplitude there was no significant difference between the two muscle groups in the precision or accuracy with which the force could be controlled, suggesting that there is not a proximal to distal gradient in force control as has been found for the control of limb movement and position.

Adult↗
PubMed2000

Repeat sizes at CAG/CTG loci CTG18.1, ERDA1 and TGC13-7a in schizophrenia.

A number of studies using the repeat expansion detection (RED) technique have suggested an association between unknown large CAG/CTG repeats and schizophrenia. The polymorphic CAG/CTG repeat loci CTG18.1 and ERDA1 have been reported to account for a high proportion (approximately 90%) of the large repeats detected by RED and may therefore be responsible for the cited association. The recently described locus TGC13-7a contains a highly polymorphic CTA/TAG and CAG/CTG composite repeat, and is thus another authentic candidate. In the present investigation, each locus was analysed for association with schizophrenia in a sample of 206 patients and 219 group-matched controls. No evidence for association of CTG18.1, ERDA1 and/or TGC13-7a with schizophrenia was found. The combined data accounted for only 54% of the CAG/CTG arrays of > 40 repeats found in our previous RED analysis.

Adult↗
PubMed2000

No evidence for association between a non-synonymous polymorphism in the gene encoding human metabotropic glutamate receptor 7 and schizophrenia.

The cDNA sequence of the gene encoding human metabotropic glutamate receptor type 7 (mGluR7) contains the single nucleotide polymorphism 1536A > T [GenBank sequence X94552 (Makoff et al., 1996)]. This sequence variation is predicted to result in an amino acid change (F433Y) in the gene product and thus has the potential to affect receptor function. Since disturbances in glutamate function have been implicated in the pathophysiology of schizophrenia, we have used a novel and robust polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay to genotype this polymorphism in a case-control sample comprising 181 schizophrenic patients and 182 group-matched unaffected individuals. No evidence was found for association between this polymorphism and schizophrenia. We have also localised mGluR7 to chromosome 3p25-22 using radiation hybrid (RH) mapping.

Alleles↗
PubMed2000

Immunologic approaches to antigen discovery for cancer vaccines.

Since the early 1990s, scientists have identified an ever-expanding number of antigens to serve as targets for experimental cancer treatments, based on the stimulation of a patient's immune system. Using both immune cells and serum to screen potential candidates, several promising antigens are currently components of vaccines directed against a wide range of tumour types. These antigens vary in their tumour- and tissue-specificity. Their utility as a single reagent or as part of a multi-dimensional approach is as varied as the genes themselves. However, there are already reports indicating that the promise of evoking a clinically beneficial immune response, toward human tumours, is being fulfilled. In this review, we provide a summary of the current status of immunologic approaches to antigen discovery. We also discuss the need for additional, supportive data from non-immunologic techniques, as well as the progression of the preclinical process towards target validation.

Antigens↗
PubMed2000

Neonatal estradiol exposure alters mouse mammary estrogen receptor alpha expression.

The rate of prepubertal ductal morphogenesis as well as the incidence of hyperplastic growth in the adult mouse mammary gland is enhanced by 5 days of neonatal estradiol exposure. It is unknown whether estradiol acts through its nuclear receptor to affect growth in the neonatal gland. Immunohistochemical analysis indicates that estrogen receptor alpha (ER) is present in both the mammary epithelium and stroma before estradiol exposure is initiated at day 1. By 7 days of age, the frequency of ER-positive epithelial and stromal cells is significantly reduced in mammary glands of estradiol-exposed mice compared to controls. Coincident with this decrease in mammary ER is growth inhibition of the estradiol-exposed gland. At day 21, the exposed glands exhibit precocious epithelial outgrowth while significantly fewer stromal cells express ER compared to controls. By day 35, the exposed epithelium fills the fat pad while the exposed stromal cells express significantly more ER. To study the function of mammary ER, we have established mammary epithelial cell lines from oil and estradiol treated mice. Two cell lines from oil-treated and two from estradiol-exposed glands maintain ER expression in culture. Transient transfection of these ER-positive cell lines with a reporter vector containing an estrogen response element (ERE) demonstrates that the immunodetected ER is functional as a transcription factor in response to 100 nM estradiol. The in vitro transcriptional activity in response to estradiol is anti-estrogen sensitive, requires the presence of the ERE, and is independent of neonatal treatment in vivo. Our data indicate that neonatal estradiol exposure alters ER expression and mammary growth, but does not alter ER function.

Animals↗
PubMed2000

AC/A ratio, age, and refractive error in children.

PURPOSE: To examine how the response AC/A ratio (the amount of accommodative convergence per unit of accommodative response) varies as a function of refractive error and age, to determine whether it is a risk factor for the onset of myopia, and to examine the relation between ocular structural features and the AC/A ratio. METHODS: Accommodation was stimulated by a letter target presented in a Badal system at 0.00, 2.25, and 4.37 D to 828 children aged 6 through 14 years in 1996. Of these, 726 had no myopia in 1996 and were available for examination the following year. Accommodative response and cycloplegic refractive error were measured by autorefraction and convergence by monitoring the relative movement of Purkinje images I and IV. Lens radii of curvature were measured by video phakometry, corneal radius of curvature by topography, and ocular axial dimensions by A-scan ultrasonography. RESULTS: Adjusted for age, the response AC/A ratio was highest in myopes (6.39 delta/D), intermediate in emmetropes (3.94 delta/D), and lowest in hyperopes (3.40 delta/D; P < 0.0001; two-way analysis of variance [ANOVA]). The stimulus AC/A ratio did not vary with refractive error. Adjusted for refractive error, the response AC/A ratio did not change as a function of age. In non-myopic children, having a response AC/A ratio of 5.84 delta/D or more elevated the risk of development of myopia within 1 year by 22.5 times (95% CI = 7.12-71.1). In a subsample of children without myopia who had refractive errors less than +0.75 D, having a response AC/A ratio of 5.84 delta/D or more elevated the risk of development of myopia within 1 year by 3.21 times (95% CI = 1.14-9.07). The AC/A ratio was associated with all measured ocular features except lens spherical volume. Only the negative correlations with refractive error and the shape of the crystalline lens (Gullstrand lens power) were significant in a multiple regression model (adjusted R2 = 0.16). CONCLUSIONS: An elevated response AC/A ratio was associated with myopia and was an important risk factor for its rapid onset. The association between higher AC/A ratios and flatter crystalline lens shapes, as well as other reported features of accommodation in myopia, may be explained by "pseudocycloplegia," which the authors define as tension on the crystalline lens that increases the level of effort needed to accommodate. Accommodative deficits in myopia may be the functional consequences of the underlying anatomy of the enlarged eye.

Accommodation, Ocular↗
PubMed1999

No evidence for allelic association between schizophrenia and a functional variant of the human dopamine beta-hydroxylase gene (DBH).

Dopamine beta-hydroxylase (DBH), the enzyme that converts dopamine to norepinepherine, has been proposed as being involved in the aetiology of schizophrenia. Previous work identified a functional polymorphism at nucleotide 910 of the DBH gene that results in a codon change in the mature protein Ala304Ser, with the mutant allele being associated with a lower enzymatic activity. In this study we performed an RFLP analysis in an association study consisting of 178 unrelated schizophrenic patients and 178 unrelated control subjects, matched for age, sex, and ethnicity. The frequency of the Ser304 DBH allele was 0.10 in the patient group and 0.08 in the control group, with no significant allelic or genotypic association observed. Therefore, we were unable to obtain evidence that this polymorphism contributes directly to susceptibility to schizophrenia.

Adult↗
PubMed1999

Expression of chimeric granulocyte-macrophage colony-stimulating factor/interleukin 2 receptors in human cytotoxic T lymphocyte clones results in granulocyte-macrophage colony-stimulating factor-dependent growth.

Adoptive immunotherapy with ex vivo-expanded antigen-specific cytotoxic T lymphocytes (CTLs) has been shown to clear viral infections and eliminate tumors in murine models. Clinical trials have also reported promising data for the use of adoptive immunotherapy to treat cytomegalovirus (CMV) and Epstein-Barr viral (EBV) infections in bone marrow transplant recipients. For these indications, the need for ex vivo-expanded CTLs is often short lived, until the immune system is reconstituted by the donor transplant. In chronic disease settings, increased longevity of adoptively transferred CTLs and generation of memory will be necessary. The additional administration of helper functions normally supplied by antigen-specific T helper (Th) cells will probably be essential for long-term survival of adoptively transferred CTLs. Toward this goal of supplying helper functions, we transduced human CTLs with chimeric GM-CSFR/IL-2R receptors that deliver an IL-2 signal on binding GM-CSF. Clones expressing the chimeric receptors proliferated in response to GM-CSF. Stimulation with antigen induced GM-CSF production and resulted in an autocrine growth loop such that the CTL clones proliferated in the absence of exogenous cytokines. This type of genetic modification has potential for increasing the circulating half-life and, by extension, the efficacy of ex vivo-expanded CTLs.

Animals↗
PubMed1999

CAG repeat length in the hKCa3 gene and symptom dimensions in schizophrenia.

BACKGROUND: Long CAG repeats in the hKCa3 potassium channel gene have been associated with schizophrenia. We sought evidence for associations between this polymorphism and aspects of the schizophrenia phenotype. METHODS: Associations were investigated between CAG repeat length and gender, age of illness onset, and psychotic symptom dimensions in 203 unrelated individuals with DSM-IIIR schizophrenia. RESULTS: No association was found between CAG repeat length and gender or age of onset. Long CAG repeats were associated with higher negative symptom dimension scores. CONCLUSIONS: This study provides preliminary evidence that genetic liability to negative symptoms in schizophrenia may be partly mediated through the hKCa3 gene.

Adult↗
PubMed1999

High rates of schizophrenia in adults with velo-cardio-facial syndrome.

BACKGROUND: Velo-cardio-facial syndrome (VCFS), a syndrome characterized by an increased frequency of schizophrenia and bipolar disorder, is associated with small interstitial deletions of chromosome 22q11. METHODS: We evaluated 50 adults with VCFS using a structured clinical interview (Schedules for Clinical Assessment in Neuropsychiatry or Psychiatric Assessment Schedule for Adults With Developmental Disability if IQ <50) to establish a DSM-IV diagnosis. The schizophrenia phenotype in individuals with VCFS and schizophrenia was compared with a matched series of individuals with schizophrenia and without VCFS (n = 12). The King's Schizotypy Questionnaire was administered to individuals with VCFS (n = 41), their first-degree relatives (n = 68), and a series of unrelated normal controls (n = 316). All individuals with VCFS deleted for the N25 probe (n = 48) were genotyped for a genetic polymorphism in the COMT gene that results in variations in enzymatic activity. RESULTS: Fifteen individuals with VCFS (30%) had a psychotic disorder, with 24% (n = 12) fulfilling DSM-IV criteria for schizophrenia. In addition, 6 (12%) had major depression without psychotic features. The individuals with schizophrenia had fewer negative symptoms and a relatively later age of onset compared with those with schizophrenia and without VCFS. We found no evidence that possession of the low-activity COMT allele was associated with schizophrenia in our sample of individuals with VCFS. CONCLUSIONS: The high prevalence of schizophrenia in this group suggests that chromosome 22q11 might harbor a gene or genes relevant to the etiology of schizophrenia in the wider population.

Adolescent↗
PubMed1999

Heritability estimates for psychotic disorders: the Maudsley twin psychosis series.

BACKGROUND: Previous twin studies have supported a genetic contribution to the major categories of psychotic disorders, but few of these have employed operational diagnostic criteria, and no such study has been based on a sample that included the full range of functional psychotic disorders. METHODS: A total of 224 twin probands (106 monozygotic, 118 dizygotic) with a same-sex co-twin and a lifetime history of psychosis was ascertained from the service-based Maudsley Twin Register in London, England. Research Diagnostic Criteria psychotic diagnoses were made on a lifetime-ever basis. Main-lifetime diagnoses of DSM-III-R and International Statistical Classification of Diseases, 10th Revision schizophrenia were also made. Probandwise concordance rates and correlations in liability were calculated, and biometrical model fitting applied. RESULTS: A substantial genetic contribution to variance in liability was confirmed for the major diagnostic categories except Research Diagnostic Criteria depressive psychosis and unspecified functional psychosis, where familial transmission was confirmed, but the relative contribution of genetic and common environmental factors was unclear. Heritability estimates for Research Diagnostic Criteria schizophrenia, schizoaffective disorder, mania, DSM-III-R schizophrenia, and International Statistical Classification of Diseases, 10th Revision schizophrenia were all between 82% and 85%. None of the estimates differed significantly from any other. CONCLUSIONS: Heritability estimates for schizophrenia, schizoaffective disorder, and mania were substantial and similar. Population morbid risk estimates were inferred rather than directly measured, but the results were very similar to those from studies where morbid risks were directly estimated.

Adult↗
PubMed1999

Comparative studies of Cu-64-ATSM and C-11-acetate in an acute myocardial infarction model: ex vivo imaging of hypoxia in rats.

Copper labeled diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) is a promising agent for the imaging of hypoxic tissues. In the present study 64Cu(t1/2 = 12.8 h) labeled Cu-ATSM was used in combination with 11C (t1/2 = 20.3 min) labeled acetate as a regional perfusion marker to visualize hypoxic rat heart tissue in an acute left anterior descending (LAD) coronary artery occluded rat model using an ex vivo tissue slice imaging technique. 64Cu-ATSM was injected intravenously c.a. 10 min after occlusion and rats were sacrificed by cervical dislocation 10 min after injection. Carbon-11-acetate was injected 1 min before sacrifice to obtain a measure of blood flow. The heart was dissected, frozen, and cut into 1-mm thick slices with a gauged slicer, and 11C images were obtained with an electronic autoradiography instrument. After decay of 11C, 64Cu images were obtained in the same manner. In ischemic regions, where there was low 11C accumulation, 64Cu showed high accumulation when compared with normal regions. In rats with a large occlusion, the center of the ischemia did not show any accumulation of either 11C or 64Cu, indicating no blood supply. Cu-ATSM appears to be useful for the detection of hypoxia with contrast being observed at short times (10 min) postinjection.

Acetates↗
PubMed1999

Agricultural hazard data from a population-based survey of cash grain farms: Ohio observations.

In response to congressional concerns, the National Institute for Occupational Safety and Health (NIOSH) initiated a multistate agricultural surveillance effort in 1990. The Farm Family Health and Hazard Surveillance (FFHHS) program involved separate population-based surveillance efforts by six state agencies or universities which gathered health and hazard data on farm operators and farm families. The results of the Ohio program are presented as an example of the data collection capabilities developed during the course of this project, which include the application of these data in documenting the prevalence of specific agricultural occupational hazards as well as the current attitudes of agricultural operators toward control and elimination of safety and health hazards. Specifically, three operationally defined areas of hazard audit (Structures, Landscape, and Mobile Equipment) are examined for the prevalence of such safety hazards as potential electrical shock, slippery or badly maintained walkways, inadequate chemical and fuel storage, and missing farm equipment moving-part guards. Questionnaire survey response examples are presented as an indication of farm operator attitudes toward safety and health training, on-site professional service access, and use of personal protective equipment. Current plans for data use and distribution, and the potential applications of the data as an occupational safety and health tool are also discussed.

Agricultural Workers' Diseases↗
PubMed1999

A two-stage genome scan for schizophrenia susceptibility genes in 196 affected sibling pairs.

We undertook a systematic search for linkage in 196 affected sibling pairs (ASPs) with DSMIV schizophrenia. In stage 1 we typed 97 ASPs with 229 microsatellite markers at an average inter-marker distance of 17.26 cM. Multipoint affected sib pair analysis identified seven regions with a maximum lod score (MLS) at or above the level associated with a nominal pointwise significance of 5%, on chromosomes 2q, 4p, 10q, 15q, 18p, 20q and Xcen. In stage 2 we genotyped a further 54 markers in 196 ASPs together with parents and unaffected siblings. This allowed the regions identified in stage 1 to be typed at an average spacing of 5.15 cM, while the region of interest on chromosome 2 was typed to 9.55 cM. Analysis was performed on the whole data set. Simulation studies suggested that we would expect one multipoint MLS of 1.5 per genome scan in the absence of linkage. An MLS of 3 would be expected only once in every 20 genome scans and thus corresponds to a genome-wide significance of 0.05. We obtained three multipoint MLSs >1.5 and, on this basis, the results on chromosomes 4p, 18q and Xcen can be considered suggestive. However, none approached a genome-wide significance of 0. 05. The power of this study was >0.95 to detect a susceptibility locus of lambda(s)= 3 with a genome-wide significance of 0.05, but only 0.70 to detect a locus of lambda(s)= 2. Our results suggest that common genes of major effect (lambda(s)> 3) are unlikely to exist for schizophrenia.

Chromosome Mapping↗
PubMed1999

Dimensions of psychosis in affected sibling pairs.

Factor analytical studies of schizophrenia symptoms have consistently suggested three or more symptom dimensions, but it is not known whether any of these dimensions have a genetic basis. The purpose of this study was to investigate to what extent the dimensions show familial aggregation. Symptom ratings were made using the SAPS and SANS and the OPCRIT checklist on the members of 109 sibling pairs with DSM-IV schizophrenia or schizoaffective disorder. Factor analyses were performed on the ratings of both instruments, and correlations were made of within-pair factor scores. Analyses were also performed on the 89 pairs in which both members had a diagnosis of schizophrenia. Factor analysis of SAPS and SANS ratings resulted in positive, negative, and disorganization factors; analysis of OPCRIT ratings resulted in positive, negative, disorganization, and first-rank delusion factors. Only the disorganization dimension showed significant within-pair correlations, but these were of modest size and not significantly greater than the correlations for the other dimensions. None of the dimensions showed sufficient familial aggregation to suggest that they are close markers of genetic or common environmental factors that contribute liability to schizophrenia. They may be weakly associated with such factors and with factors that do not contribute liability to schizophrenia but do influence the form taken by the illness.

Adult↗