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Biomedical subjects

S Plummer

Publications and source records attributed to S Plummer.

30 records · Page 2Linked to original sources
PubMed1992

The ontogeny of peroxisome-proliferator-activated receptor gene expression in the mouse and rat.

The expression of the gene coding for peroxisome-proliferator-activated receptor (PPAR), a novel transacting factor belonging to the steroid superfamily, has been determined in the mouse and rat throughout development using hybridization histochemistry. Messenger RNA is demonstrable in the liver and brown fat from the fetal period onwards and, additionally, in the heart, kidney and gut post-natally. It is proposed that the upregulation of transcription of peroxisomal beta oxidation genes in specific tissues follows binding of the receptor to its natural ligand. Thus PPAR may have an important role in cold adaptation and non-shivering thermogenesis as well as in detoxification.

Adipose Tissue, Brown↗
PubMed1992

Radiation hybrid map spanning the Huntington disease gene region of chromosome 4.

Radiation hybrid (RH) mapping was used to construct a map of 11 markers in the distal 4 Mb of the short arm of chromosome 4, the region containing the Huntington disease gene. Two different methods for deriving the order of the markers were compared and both arrived at the same order as being the most likely. This order is also consistent with both the physical map constructed using pulsed-field gel electrophoresis (PFGE) and the meiotic linkage map. Comparing the RH map to the map determined by PFGE provided the means to equate RH map units (centirays) with actual physical distance in kilobases of DNA. In addition, a simple procedure for reducing the complexity of human DNA in radiation hybrids is described. One cell line isolated using this procedure contains, as its only human DNA, approximately 2 Mb surrounding the Huntington disease gene.

Chromosome Mapping↗
PubMed1992

Sequence-tagged sites (STSs) spanning 4p16.3 and the Huntington disease candidate region.

The generation of sequence-tagged sites (STSs) has been proposed as a unifying approach to correlating the disparate results generated by genetic and various physical techniques being used to map the human genome. We have developed an STS map to complement the existing physical and genetic maps of 4p16.3, the region containing the Huntington disease gene. A total of 18 STSs span over 4 Mb of 4p16.3, with an average spacing of about 250 kb. Eleven of the STSs are located within the primary candidate HD region of 2.5 Mb between D4S126 and D4S168. The availability of STSs makes the corresponding loci accessibility to the general community without the need for distribution of cloned DNA. These STSs should also provide the means to isolate yeast artificial chromosome clones spanning the HD candidate region.

Base Sequence↗
PubMed1991

A gene encoding a fibroblast growth factor receptor isolated from the Huntington disease gene region of human chromosome 4.

The gene responsible for Huntington disease (HD), an autosomal dominant neurodegenerative disorder, is located near the terminus of the short arm of chromosome 4. Detailed genetic linkage and physical mapping studies have defined a region of approximately 2.5 million basepairs where the disease gene is likely to be located. Efforts to identify the disease gene are now focused on the identification and characterization of expressed genes in this region. Nucleotide sequence analysis of a cDNA clone derived from the HD gene region has revealed that it encodes a member of the fibroblast growth factor subfamily of tyrosine kinase receptors, some members of which are known to be involved in the differentiation and survival of certain cell types within the central nervous system. Histochemical analysis using in situ hybridization revealed its expression in many areas of the brain, among them being the caudate and putamen. The nature of this gene, FGFR3, and its map location make it a possible candidate for the HD gene.

Amino Acid Sequence↗
PubMed1991

O(6)-methylguanine-DNA methyltransferase and uracil DNA glycosylase in human broncho-alveolar lavage cells and peripheral blood mononuclear cells from tobacco smokers and non-smokers.

Because interindividual variations in the activities of DNA repair enzymes may be a risk factor in the pathogenesis of lung diseases, O(6)-methylguanine-DNA methyltransferase (O(6)-MT) and uracil DNA glycosylase (UDG) were measured in broncho-alveolar lavage cell (BALC) and peripheral blood mononuclear cell (PBM) samples from 57 healthy volunteers (25 smokers and 32 non-smokers). According to cotinine determination in 39 cases where serum for this was available, 38% of the self-acclaimed non-smokers had greater than 10 ng/ml of cotinine in their serum. Whether grouped into smokers and non-smokers according to clinical history or by serum cotinine, there were no statistically significant differences between these groups in O(6)-MT or UDG in either of the cell types. However, a tendency towards lower values in smokers was seen. The highest intraindividual variation in O(6)-MT activity was 7-fold, while the highest interindividual variation reached 18-fold. For UDG, the respective values were 24- and 307-fold. Although the distribution of O(6)-MT in BALC was different from that in PBM, the data are consistent with unimodality in both of the cell types. These findings suggest that exposure to cigarette smoke is not entirely responsible for the wide interindividual variation in O(6)-MT and UDG DNA repair activities.

Adult↗
PubMed1987

Strain differences in the metabolic activation of aflatoxin B1 in the rat.

It has been reported that female Fischer rats are much more susceptible to the hepatocarcinogenic effects of aflatoxin B1 than female DA rats. Female Fischer rats are approximately twice as active as female DA rats in producing adducts of aflatoxin B1 with DNA in vivo, in freshly isolated hepatocytes and with hepatic microsomal fractions. There was no difference between the hepatic microsomal fractions from Fischer and DA rats in the production of adducts between aflatoxin B1 and microsomal protein. The difference between the strains in the formation of adducts with DNA was not due to either the activity of glutathione S-transferases or to the selective destruction of cytochrome P-450 in the DA strain. None of the differences reported here was of sufficient magnitude to explain the difference in susceptibility of the rat strains to the hepatocarcinogenic effects of aflatoxin B1.

Aflatoxin B1↗
PubMed1986

Is the activation of aflatoxin B1 catalysed by the same form of cytochrome P-450 as that 4-hydroxylating debrisoquine in rat and/or man?

A possible association between the metabolic activation of aflatoxin B1 (AFB1) to a mutagen and the 4-hydroxylation of debrisoquine, which shows genetic variation both in man and in the rat, was investigated. Hepatic microsomal fractions from female DA and Fischer rats catalyse, at the same rate, the conversion of AFB1 to a mutagenic and arylating metabolite, that bound covalently to microsomal proteins. Debrisoquine was without effect on either of these reactions. In contrast, metyrapone did inhibit the mutagenic activation of AFB1. Microsomal fraction from human liver was also capable of activating AFB1 to a mutagenic and arylating metabolite. Again, debrisoquine was without appreciable effect on these reactions. In contrast, cimetidine caused profound inhibition of the mutagenic activation of AFB1. It is concluded that the activation of AFB1 to a mutagenic, and presumably carcinogenic, metabolite is catalysed by a different form of cytochrome P-450 from that catalysing the 4-hydroxylation of debrisoquine, both in rat and in man.

Aflatoxin B1↗
PubMed1985

Late systolic click from isolated tricuspid valve prolapse simulating paradoxical splitting of the second heart sound.

A 72 year old woman was thought to have a paradoxically split second heart sound. Echocardiography with simultaneous phonocardiography revealed a late systolic click resulting from isolated tricuspid valve prolapse. Respiratory variation of the click in relation to the second heart sound resulted in an auscultatory phenomenon simulating paradoxical splitting of the second heart sound.

Aged↗
PubMed1977

Functional considerations in the use of procedural timeout and in effective alternative.

Two single-subject experiments were conducted with students in special preschool classes. In Experiment I, the subject's disruptive, appropriate, and inappropriate play behaviors were measured as a function of three independent variables: reinforcement, a typical timeout procedure, and regularly paced teacher instructions. In an ABA reversal within a multiple baseline across two teachers, all three independent variables comprised the A conditions and procedural timeout was omitted in B. Experiment II examined a second subject's appropriate and inappropriate eating as a function of the same three variables. Two teachers conducted baseline and paced instruction-plus-reinforcement conditions in multiple baseline across teachers. Subsequently, one teacher performed a series of reversals and replications with various combinations of a typical timeout procedure and reinforcement mixed with paced instructions. The results of both experiments suggest that timeout did not produce response decrement in a punishment paradigm, but rather produced response increment in a negative reinforcement paradigm. These results prevailed, even though a reinforcer was operating in the environment before introducing timeout. Paced instructions (delivering instructions to the child at a set pace regardless of the child's behavior) appears to be an alternative when timeout is not effective and, in conjunction with reinforcement, was demonstrated to reduce inappropriate behavior to near zero.

Autistic Disorder↗
PubMedDate not supplied

Adjustment to perceived ovarian cancer risk.

Eighty-three women who perceived themselves to be at risk for ovarian cancer completed a battery of surveys. In addition to demographics, subjects were asked to complete the Brief Symptom Inventory, Multidimensional Health Locus of Control, Death Anxiety Scale, Taylor Anxiety Scale, Index of Sexual Satisfaction, Impact of Event Scale, and the Marlowe-Crowne Social Desirability Scale. Overall, the respondents were more similar to normal controls than to psychiatric outpatients. A correlation was drawn between higher levels of education and lower scores on the Brief Symptom Inventory, which measures characteristics such as somatization, obsessive compulsive behaviors, interpersonal sensitivity, and anxiety. However, those who had the highest scores on the Death Anxiety Scale were less likely to comply with the recommendation for a physical/gynecological examination. Patients who were most influenced by an external locus of control or 'powerful other' were more compliant with their physicians' recommendations for testing and examination. It is the authors' belief that individualized educational efforts and the presence of a solid support system may increase women's adherence to the recommended health care practices.

Adaptation, Psychological↗