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Biomedical subjects

J Clayton

Publications and source records attributed to J Clayton.

At least 55 records · Page 3Linked to original sources
PubMed1993

Correlation of apomorphine- and amphetamine-induced turning with nigrostriatal dopamine content in unilateral 6-hydroxydopamine lesioned rats.

In the unilateral 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease, controversy exists concerning the use of apomorphine- or D-amphetamine-induced rotations as reliable indicators of nigrostriatal dopamine depletion. Our objective was to evaluate which, if either, drug-induced behavior is more predictive of the extent of nigrostriatal dopamine depletion. Fischer 344 and Sprague-Dawley rats were unilaterally injected with 9 micrograms/4 microliters/4 min 6-hydroxydopamine into the medial forebrain bundle. The animals were behaviorally tested with apomorphine (0.05 mg/kg, s.c.) and D-amphetamine (5.0 mg/kg, s.c.). Following testing, the brains were removed and the right and left striata, substantia nigra and ventral tegmental area were dissected free and quickly frozen at -70 degrees C for analysis of catecholamine content by high performance liquid chromatography coupled with electrochemical detection. Our results indicate that an animal which has greater than a 90% depletion of dopamine in the striatum might not rotate substantially on apomorphine, without a concomitant depletion of > 50% of the DA content in the corresponding substantia nigra. No correlations were seen involving depletions of the ventral tegmental area and the extent of the lesions to the striatum. Submaximally lesioned (75-90% depleted) rats were found to rotate on D-amphetamine but not on apomorphine. In addition, control rats that did not receive lesions were often seen to rotate extensively on D-amphetamine. We therefore conclude that maximal lesions of the striatum and substantia nigra are required to generate rotations demonstrable with low dose apomorphine but not with D-amphetamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗
PubMed1993

Tumor necrosis factor microsatellites in four European populations.

The human genome contains a large number of interspersed simple repeat sequences that vary in length among individuals and can therefore serve as highly informative polymorphic markers. Several such variable sites (microsatellites) have been described within the TNF genes within the MHC. In this study, individuals from four Caucasian populations have been typed for three TNF-associated microsatellites in order to define their haplotypes. Of the 208 possible haplotypes, eight exist at a high frequency in all populations and account for approximately 60% of the haplotypes studied, but with marked variations in their frequencies among populations. A few population/sample-specific haplotypes have been identified. The ability of alleles to define haplotypes uniquely varies not only among the loci, but also among the alleles: some alleles displaying complete gametic association (linkage disequilibrium) and others displaying very little.

Alleles↗
PubMed1993

Multiple sclerosis susceptibility: population and twin study of polymorphisms in the T-cell receptor beta and gamma genes region. French Group on Multiple Sclerosis.

Multiple sclerosis (MS) is a demyelinating auto-immune disease of the central nervous system with a suspected genetic component. Previous publications have demonstrated that MS susceptibility is influenced by Major Histocompatibility Complex (MHC) genes and recent studies have focused on additional susceptibility genes. The accumulation of activated T-cells in demyelinating MS lesions, the possible auto-immune mechanism of this disease and the functional relationship between MHC and T cell receptor (TCR) molecules support the hypothesis that TCR genes are good candidates to influence MS development. Published results in this domain are conflicting and still a matter of controversy. In the present study we analysed the influence of V beta, C beta, P lambda G3 and V gamma gene polymorphisms defined by Restriction Fragments Length Polymorphism (RFLP) on 48 pairs of monozygotic and dizygotic twins with at least one of each pair affected, and also in 63 unrelated MS patients for V gamma gene polymorphism. These results have been compared with those in the non affected twins and with data from a control group (Beall et al., 1989) regarding C beta and V beta polymorphisms and with a local control population for V gamma. No significant correlation between C beta, V gamma or P lambda G3 polymorphisms and MS was found, only a non significant tendency to reduced P lambda G3 allele sharing among dizygotic non concordant twin pairs was observed. However one V beta 11, 25 kb allele and a haplotype defined by V beta 11 and C beta alleles showed a correlation with MS susceptibility of borderline significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1993

Application of maximum likelihood statistics for the population and family studies of inheritance of the chimpanzee R-C-E-F and V-A-B-D blood groups.

Maximum likelihood statistics were applied to the analysis of serological data to confirm the originally proposed genetic models of the chimpanzee R-C-E-F and V-A-B-D systems. Five hundred ninety-nine chimpanzees, including 81 parents of 114 offspring, were tested for R-C-E-F, and 60 parents of 80 offspring were tested for V-A-B-D blood groups. An estimation-maximization procedure was used to obtain maximum likelihood estimates and support intervals of the haplotype frequencies. For each haplotype, the null hypothesis of nonexistence was evaluated. The frequencies obtained by this method do not differ significantly from those calculated by the square root formula, but put these estimates on a statistically more rigorous footing.

Animals↗
PubMed1992

Inflammatory leukocytes and cytokines in the peptide-induced disease of experimental allergic encephalomyelitis in SJL and B10.PL mice.

Experimental allergic encephalomyelitis (EAE) was generated in SJL and B10.PL mice by using the synthetic myelin basic protein peptides. Inflammation in brain and spinal cord preceded clinical signs of disease. Infiltrating lymphocytes were predominantly Lyt1+ (CD5+), L3T4+ (CD4+) T cells, until day 18. After that, F4/80+ monocyte/macrophages outnumbered T cells. Ia+ cells were microglia, macrophages, and endothelial cells, but Ia was not detectable on astrocytes in this EAE model. Ia+ endothelial cells appeared later in the disease than Ia+ microglia and macrophages, suggesting that antigen presentation at the blood-brain barrier is not initially responsible for inflammation. Cells staining for interferon gamma, interleukin 2 (IL-2), and IL-2 receptors were more prominent than IL-4, IL-5, lymphotoxin (LT), and tumor necrosis factor alpha (TNF-alpha), which occurred transiently in the second week and were associated with fewer cells. TNF-alpha and LT were never seen in spinal cord, suggesting that these cytokines are not responsible for initiation of clinical disease. Few or no cells stained for IL-6, IL-1, or transforming growth factor beta. Control animals injected with complete Freund's adjuvant in saline or control antigen demonstrated no inflammatory cell infiltration or cytokine production. Thus, our findings suggest a peptide-induced EAE model in which Th1 T-cell-macrophage interactions result in the disease process.

Animals↗
PubMed1992

Anonymous markers located on chromosome 6 in the HLA-A class I region: allelic distribution in genetic haemochromatosis.

Two yeast artificial chromosomes of the HLA class I region were subcloned. Four of the subclones studied displayed restriction polymorphisms that corresponded to six bi-allelic series. Allelic distribution of the anonymous markers was then studied by comparing a control population with a group of patients with familial haemochromatosis. Only one marker presents an unequivocal association with the haemochromatosis gene and is 100 kb centromeric to HLA-A. This association however is not as strong as with HLA-A3. The results suggest two possible locations for the haemochromatosis gene: less than 100 kb centromeric to the HLA-A locus, or on the telomeric side.

Alleles↗
PubMed1992

A new polymorphism of thyroxin-binding globulin in three African groups (Mali) with endemic nodular goitre.

The thyroxin-binding globulin (TBG) polymorphism was investigated in three African groups: two belonged to the Bwa villages of Mali, and the third was a Dogon group living in the same area. The Bwa groups were characterized by the occurrence of nodular goitres, whereas the Dogon population did not show similar pathological symptoms. Females were more affected by goitre than males in the affected villages. The TBG polymorphism enabled us to demonstrate the presence of an undescribed allele (TBG C1) in these populations. The frequency of the TBG S allele was also higher than previously published in other African groups. We observed a disequilibrium in the distribution of the C and S alleles in the population, with an excess of homozygous TBG S individuals. No clear relationship between the TBG polymorphism and the number of nodules can be drawn.

Alleles↗
PubMed1991

Genetic aspects of breast cancer.

Of all the factors contributing to breast cancer risk, a strong family history of the disease is the most powerful. Familial clustering is said to have been noted by the Ancient Romans but formal documentation began in the mid-nineteenth century (reviewed in Ref. 1). The French physician Paul Broca noted that in one family (probably his wife's) over four generations 10 out of 24 women had died from breast cancer while several more individuals, of both sexes, had suffered other malignancies. He concluded that this very large excess of cancers could not reasonably be attributed to chance. At the same time he recognized that occasional familial clusters of relatively common conditions would be expected even in the absence of any genetic predisposition and discounted several published reports of 'hereditary cancers', including some of the families collected by his English contemporary Sir James Paget.

Breast Neoplasms↗