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Biomedical subjects

M Dixon

Publications and source records attributed to M Dixon.

At least 19 recordsLinked to original sources

Hypnotic susceptibility and verbal automaticity: automatic and strategic processing differences in the Stroop color-naming task.

The original hypothesis of Dixon, Brunet, and Laurence (1990) that highly hypnotizable (HH) subjects process words more automatically than do low hypnotizable (LH) subjects was retested in a paradigm that separated strategic from automatic processes in the Stroop color-naming task. The words red and blue preceded a color patch that was red or blue. Subjects were told that the word predicted the opposite color 75% of the time. Automatic and strategic processes were assessed by varying the interstimulus interval (ISI) between the word and the color patch. Both HH and LH subjects showed significant strategic effects (faster incongruent-trial, color-naming reaction times than congruent-trial reaction times at ISIs over 400 ms), but only HH subjects showed significant automaticity (significantly faster congruent-trial reaction times than incongruent-trial reaction times at 16.7 ms, the lowest ISI).

Adult

Linkage disequilibrium between two highly polymorphic microsatellites.

The PCR was used to amplify genomic DNA from two microsatellite (dC-dA)n.(dG-dT)n sequences found to be present in the same chromosome 5 genomic clone. Analysis of the haplotype frequencies of these two interspersed repeat sequences in individuals showed strong allelic association or linkage disequilibrium. Six alleles were found for p599 (CA)n with a PIC value of 0.71 and 8 alleles were seen for lambda 599 (CA)n with a PIC value of 0.74. The two microsatellites are separated by approximately 7 kb. Analysis of the length variations for the two microsatellites showed that they were positively correlated, a finding that has no obvious explanation. The strong linkage disequilibrium found demonstrates stability during evolution for these novel markers. Therefore they should be powerful new tools for studying genetic drift and admixture of populations. Furthermore, disequilibrium data from microsatellites can be used in the fine mapping and cloning of disease genes.

Alleles

Subcellular fate of the int-2 oncoprotein is determined by choice of initiation codon.

Fibroblast growth factors (FGFs) have been implicated in many aspects of cell growth and differentiation both in normal and neoplastic settings. For example, the mouse int-2 gene, which encodes an FGF-related product, is a frequent target of proviral activation in carcinomas induced by mouse mammary tumour virus, but apparently functions at discrete stages of normal embryonic development. Six classes of int-2 messenger RNA have been identified in embryonic cells, each of which is predicted to encode the same 245-amino-acid protein. But all known int-2 transcripts include sequences upstream of the AUG codon presumed to be the initiation codon. Here we report an additional N-terminally extended int-2 gene product initiated at an in-frame CUG codon. In COS-1 cells transiently transfected with appropriate int-2 complementary DNAs, the AUG-initiated product is found predominantly in the secretory pathway, whereas the CUG-initiated form is localized to the nucleus. These data indicate that the Int-2 oncoprotein could influence cellular behaviour by two distinct mechanisms.

Amino Acid Sequence

The human homeobox gene HOX7 maps to chromosome 4p16.1 and may be implicated in Wolf-Hirschhorn syndrome.

A cosmid containing the human sequence (HOX7) homologous to the mouse homeogene Hox-7 was isolated from a genomic cosmid library. There is only one highly conserved homologous gene in the human genome. The C-terminal two-thirds of the HOX7 homeobox DNA sequence has been determined; there are no predicted amino acid changes from the mouse sequence. Data from mouse/human hybrid cell lines show that HOX7 maps to human chromosome 4p16.1, a region that is syntenic with part of mouse chromosome 5, the site of the murine Hox-7 gene. Analysis of chromosomes from two patients with Wolf-Hirschhorn syndrome, which is characterised by profound dysmorphologies, indicates that the HOX7 locus is deleted. Although not all Wolf-Hirschhorn syndrome patients analysed were deleted for HOX7, the combination of positional data and functional correlation with mouse expression implicates HOX7 as a candidate gene for this syndrome.

Animals

Localization of a locus for Charcot-Marie-Tooth neuropathy type Ia (CMT1A) to chromosome 17.

Phenotypic data for 71 genetic markers for members of five Caucasian kindreds were tested for linkage with the autosomal dominant mutations causing Charcot-Marie-Tooth (hereditary motor sensory) neuropathy type I, characterized by markedly reduced nerve conduction velocities. Lod score analysis gave no evidence of linkage to the closely linked chromosome 1 loci SPTA1-FY-F5-AT3 and APOA2. In contrast, these mutations were found to map closely (zeta = 10.828, theta = 0.0) to D17S58, an anonymous segment of DNA from 17p11.2-p11.1, and thus define the CMT1A locus. Segregation information data for an inferred recombinant offspring indicated that the CMT1A locus is probably proximal to MYH2, the locus encoding adult skeletal muscle myosin heavy polypeptide 2, which maps to 17p13. Analysis of the lod scores on a per kindred basis gave no evidence of genetic heterogeneity.

Charcot-Marie-Tooth Disease

Hypnotizability and automaticity: toward a parallel distributed processing model of hypnotic responding.

We tested a hypothesis from parallel distributed processing theory that highly hypnotizable subjects have greater connection strengths along verbal pathways and would show greater Stroop effects than low hypnotizable subjects. Using Cheesman & Merikle's (1986) paradigm, which varied cue visibility and probability, we assessed automatic and strategic effects on Stroop performance. Compared with 9 low and 9 moderately hypnotizable subjects, 9 highly hypnotizable ones showed significantly greater Stroop effects for both visible- and degraded-word trials. No strategic differences emerged for the 3 hypnotizability groups. These findings support the contention that highly hypnotizable persons have stronger verbal connection strengths than their moderately and low susceptible counterparts, and they may account for highly hypnotizable persons' propensity to disregard personal attributions and label their responses in hypnosis as being involuntary.

Adult

Cyclosporin A and vehicle toxicity in primary cultures of rabbit renal proximal tubule cells.

The capability of cyclosporin to produce direct injury to primary proximal tubular renal cells was studied. These cells, when grown on Millicell inserts, retain the functional polarity of the proximal tubule, i.e., generate a transepithelial pH gradient (apical compartment acidic) that is reversibly blocked by amiloride addition only if it is added to the apical compartment. Administration of ouabain to the basal compartment also blocks the generation of the transepithelial pH gradient. Additionally, the cells were more responsive to parathyroid hormone (PTH), a proximal tubule characteristic, than to arginine vasopressin (AVP), a distal tubule characteristic. The following substances were tested for their effect on the capacity of these cells to generate a pH gradient: Sandimmune, the commercial form of cyclosporin A; the free form of the drug; Cremophor EL, the vehicle used in the commercial preparation; and ethanol, the vehicle used to dissolve the free form. Sandimmune, at 25-50 microM, inhibited the generation of the pH gradient within 24 h. Surprisingly, Cremophor also blocked the development of a pH gradient, although somewhat less effectively. In contrast, 10 microM cyclosporin, regardless of the form tested, had no effect for up to 96 h. These findings show that cyclosporin, in the form of Sandimmune, has a direct toxic effect on these cells; they also suggest that the vehicle, Cremophor, may contribute to the well-established nephrotoxicity of cyclosporin A.

Amiloride

Characterization of int-2: a member of the fibroblast growth factor family.

int-2 was discovered as a proto-oncogene transcriptionally activated by MMTV proviral insertion during mammary tumorigenesis in the mouse. Sequence analysis showed int-2 to be a member of the fibroblast growth factor family of genes. In normal breast and most other adult mouse tissues, int-2 expression was not detected except for low levels in brain and testis. However, using in situ hybridization, expression was found at a number of sites during embryonic development, from day 7 until birth. An analysis of the int-2 transcripts found in embryonal carcinoma cells revealed six major classes of RNA initiating at three promoters and terminating at either of two polyadenylation sites. Despite the transcriptional complexities, all size classes of RNA encompass the same open reading frame. Using an SV40 early promoter to drive transcription of an int-2 cDNA in COS-1 cells, several proteins were observed. These were shown to be generated by initiation from either of two codons: One, a CUG, leads to a product which localizes extensively to the cell nucleus and partially to the secretory pathway. In contrast, initiation at a downstream AUG codon results in quantitative translocation across the endoplasmic reticulum and the accumulation of products ranging in size from 27.5 x 10(3) Mr to 31.5 x 10(3) Mr in organelles of the secretory pathway. These proteins represented glycosylated and non-glycosylated forms of the same primary product with or without the signal peptide removed. These findings suggest the potential for a dual role of int-2; an autocrine function acting at the cell nucleus, and a possible paracrine action through a secreted product.

Amino Acid Sequence

Organization, design, and implementation of an interventional cardiology patient care unit.

We have described the major steps required to open a new ICPCU. The unit allows for a comprehensive standardized approach to the education of patients undergoing interventional cardiology procedures and offers the optimal setting for nursing research in the field of interventional cardiology and cardiovascular nursing. Primarily, the advent of this unit has supported the implementation of primary nursing, allowed for optimal continuity of patient care, and contributed to a decrease in the length of hospital stay of these patients and an increase in patient and family satisfaction.

Angioplasty, Balloon, Coronary

How does puffing behavior alter during the smoking of a single cigarette?

We examined changes in puffing behavior during the course of a single cigarette in 76 subjects seen on 6 occasions each (456 cigarettes). The puff volume fell on average by 33% during a cigarette and puff duration by 39%, the interpuff interval rose by 75%, but the pressure drop and the maximum flow and pressure achieved during puffing hardly changed. There were highly significant differences between subjects but not between sessions, or when subjects were grouped according to tar yield of the cigarette or by sex. Individual puff volumes with a single cigarette were highly correlated with puff duration (except in a few individuals with irregular puffing patterns), but not generally with maximum flow rate, suggesting that most smokers reduce volume by taking shorter puffs. This is unlikely to reflect mechanical factors or smoke temperature, and may be a response to changing smoke composition. Variation in puffing patterns between individuals may reflect differences in sensitivity to smoke components and individuals who show little fall in puff volume also show small responses on switching to cigarettes with different tar and nicotine yields. The individual response to smoke might be assessed by an analysis of puffing on a single cigarette.

Behavior

The structure and function of the int-2 oncogene.

The classification of int-2 as a growth factor is based primarily on the similarities between the predicted amino acid sequence and that of basic fibroblast growth factor (bFGF), as well as other members of this expanding family of related proteins. In this review, we summarise the background to the identification of int-2 as a proto-oncogene in virally induced mouse mammary tumours and describe key features of the structure and expression of both the mouse and human homologues. The normal sites of int-2 expression include specific embryonic cell types suggesting multiple inductive or morphogenetic roles. Recent progress in the characterisation of the int-2 product will be discussed in relation to the similarities and differences between int-2 and other FGFs.

Amino Acid Sequence

Detection and characterization of the fibroblast growth factor-related oncoprotein INT-2.

Products of the fibroblast growth factor-related proto-oncogene int-2 have been detected by using a monoclonal antibody and polyclonal antisera raised against synthetic peptides predicted from the DNA sequence. COS-1 monkey cells transfected with int-2 DNA linked to the simian virus 40 early promoter contained at least four int-2-specific proteins, presumably representing modified forms of the expected 27-kilodalton primary translation product. The level of expression was increased approximately six- to eightfold by mutation of sequences around the presumed initiation codon, negating their capacity to encode a short oligopeptide in the +1 reading frame. Both tunicamycin inhibition and in vitro translation experiments indicated that some of the modifications correspond to asparagine-linked glycosylation, for which the sequence predicts a single site. In line with the similarities between INT-2 and other fibroblast growth factors, the in vitro translation products functioned as weak mitogens for mammary epithelial cells.

Amino Acid Sequence

Randomized controlled trial of an educational booklet for patients presenting with back pain in general practice.

A randomized controlled trial was used to evaluate an educational booklet on back pain for patients presenting to five group practices during one calendar year. The booklet had no immediate effect on consultations for back pain, but in the period from two weeks to one year after presentation significantly fewer patients in the group receiving the booklet consulted with back pain (35.6%) than in the control group (42.2%) (P less than 0.05). There were no significant differences between the booklet and control groups in certified absence from work owing to back pain. Referral to hospital, referral to physiotherapy, admissions to hospital and laminectomies were all less common in the booklet group. The reduction in the combined referral rate to physiotherapy and hospital, and the reduction in laminectomy rate almost reached statistical significance at the 5% level. In replying to a questionnaire sent one year after entry to the study 94.1% of respondents in the booklet group said that they had read the book, 84.0% said that they found it useful, and 68.0% said that they still had a copy. Scores on a 15-item test of knowledge about back pain were significantly higher in the group of patients who had received the booklet than in the control group. The results suggest that the booklet had some effect in altering both the knowledge and behaviour of patients with back pain. The provision of an educational booklet was a method of giving information which was appreciated by both patients and doctors.

Adult

Controlled-release drug delivery of diphosphonates to inhibit bioprosthetic heart valve calcification: release rate modulation with silicone matrices via drug solubility and membrane coating.

Calcification (CALC) is the most frequent cause of the clinical failure of bioprosthetic heart valves (BHV) fabricated from glutaraldehyde pretreated porcine aortic valves or bovine pericardium. The present investigation describes the formulation, characterization, and the in vivo efficacy of prolonged controlled-release silicone matrices containing the anticalcification agent disodium 1,1-hydroxyethylidene diphosphonate (Na2EHDP). Controlled release of EHDP was regulated by codispersions of Na2EHDP and the less soluble salt Ca2EHDP. Prolonged and constant release rates (zero-order) were obtained by coating silicone matrices with permeable silicone membranes, which were prepared by leaching with acetone pre-embedded polyethyleneglycol. All EHDP-containing matrices (co-implanted subdermally with BHV cusps in rats) significantly inhibited BHV CALC without detectable adverse effects on bone mineral and calcium metabolism. Matrices containing Na2EHDP:Ca2EHDP ratios of 10:90 or greater with respect to Na2EHDP completely inhibited CALC. Significant inhibition of BHV CALC was also observed with prereleased matrices (5 months in vitro), thus demonstrating prolonged efficacy. It is concluded that sustained release of effective anticalcification therapy without side effects was achieved by using codispersions of calcium and sodium EHDP salts, and that a delayed and/or constant release rate of EHDP was obtained by coating reservoir-type matrices with silicone membranes that were pre-embedded with polyethyleneglycol.

Animals