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Biomedical subjects

C Miles

Publications and source records attributed to C Miles.

At least 19 recordsLinked to original sources
PubMed2002

Low vision services for vision rehabilitation in the United Kingdom.

AIM: Little is known about the distribution and methods of delivery of low vision services across the United Kingdom. The purpose of this study was to determine the type and location of low vision services within the UK. METHODS: Survey by means of a 29 point postal questionnaire, followed when necessary by a five point telephone questionnaire. All known potential providers of low vision services (n = 2539) including hospitals (n = 277), optician/optometry practices (n = 1683), social services (n = 177), voluntary groups (n = 190), specialist teachers (n = 205), and universities (n = 6) were surveyed. For each service provider, the type, magnitude, and geographical location were determined. The distribution of services across the United Kingdom and the ratio of providers to population density of people with a visual impairment were mapped using the Geographic Information System (GIS). RESULTS: Data were obtained on 1945 (77%) service providers: 1679 (66%) responded to the postal questionnaire and 266 (11%) to the telephone questionnaire. Of all respondents, 59% (n = 1135) offer some form of help to people with a visual disability, of which 26% (n = 497) only sell magnifiers and 33% (n = 638) provide low vision services. It is estimated that in total just under 155,000 low vision consultations are offered annually, the bulk of which are provided by hospital eye departments. The distribution was geographically uneven and there appears to be scarcity in some areas. CONCLUSION: When compared to the probable number of people with a visual impairment in the UK there are apparent inadequacies in service provision in terms of distribution, magnitude, and coordination. The results highlight a need to review current services.

Health Care Surveys↗
PubMed2001

Truncation of WT1 results in downregulation of cyclin G1 and IGFBP-4 expression.

Mutations in the WT1 gene are found in a subset of Wilms' tumours and in certain other disorders such as Denys-Drash syndrome. The WT1 gene product is a zinc finger transcription factor for which many target genes have been suggested. Here we utilise gene targeting to generate cells containing only truncated forms of WT1, in which the DNA-binding region is disrupted. Examination of gene expression in these cells using cDNA macroarrays suggests two novel WT1 transcriptional targets, cyclin G1 (Ccng1), and insulin-like growth factor binding protein 4 (Igfbp4).

Antineoplastic Agents↗
PubMed2001

Risk of acute first myocardial infarction and use of nicotine patches in a general population.

OBJECTIVES: To determine if nicotine patches, both as prescribed and used over-the-counter, increase the risk of first myocardial infarction (MI). BACKGROUND: Although nicotine patches improve smoking cessation rates, case reports have raised the hypothesis that they may increase the risk of MI. METHODS: A population-based case-control study among 68 hospitals in an eight-county region surrounding Philadelphia was performed to determine if nicotine patches increase the risk of first MI. Cases were smokers (current or within the prior year) admitted to all hospitals in the region with a first MI. Controls were smokers (current or within the prior year) without prior MI selected from the same region using random-digit dialing. Data were collected by telephone interviews and chart reviews. The study had 80% power to detect an odds ratio (OR) of 2.5. RESULTS: A total of 653 cases and 2,990 controls were interviewed. There was no association between nicotine patches and MI (OR 0.46; 95% CI: 0.09, 1.47), and the confidence interval (CI) excluded an effect from nicotine patches equal to that from cigarette smoking itself (OR < 2.5). Among those who abstained from smoking, the OR for use of nicotine patches was 0.25 (95% CI: 0.01, 1.67); among those who smoked concomitantly, the OR for patch use was 0.83 (95% CI: 0.09, 3.81). Adjustment for confounding did not alter the study's findings (OR adjusted for confounders that could mask a harmful effect of patches: 0.70; 95% CI: 0.20, 2.46). CONCLUSIONS: Nicotine patches, as used in actual practice, do not appear to be associated with an increased risk of MI.

Administration, Cutaneous↗
PubMed2000

Effects of coronary stents on cardiovascular outcomes in broad-based clinical practice.

BACKGROUND: Although stents have been shown to reduce the need for repeated percutaneous coronary intervention (PCI) in randomized trials, the effects of stents in broad-based, diverse clinical practice have not been well studied, nor has their effect on subsequent myocardial infarction or cardiac death. METHODS: A retrospective cohort study was performed that included all 43 hospitals performing PCI in Pennsylvania in the last quarter of 1995, with the use of the Pennsylvania Health Care Cost Containment Council database. All 5258 patients who underwent PCI, excluding those with previous PCI within the preceding 6 months, were included. The primary outcomes were in-hospital events (death or coronary bypass), 6-month revascularization rates, and 6-month rates of cardiac death or myocardial infarction. RESULTS: A total of 1240 patients (24%) had a stent procedure. Compared with nonstent procedures, stents reduced the risk of in-hospital events (multivariable odds ratio adjusted for patient and hospital level differences, 0.63; 95% confidence interval, 0.41-0.97), primarily because of a 52% reduction in the need for coronary bypass. Stents also reduced the need for follow-up revascularization procedures (multivariable hazard ratio, 0.72; 95% confidence interval, 0.59-0. 87), primarily because of a 31% reduction in repeated PCI. However, stents had no effect on 6-month rate of myocardial infarction or cardiac death (multivariable hazard ratio, 0.97; 95% confidence interval, 0.71-1.33). CONCLUSIONS: Using stents decreases the need for repeated PCI in broad-based clinical practice, confirming results from randomized trials. However, this study did not detect any effect on subsequent myocardial infarction or cardiac death.

Adult↗
PubMed2000

Recency and suffix effects with immediate recall of olfactory stimuli.

In contrast to our understanding of the immediate recall of auditory and visual material, little is known about the corresponding characteristics of short-term olfactory memory. The current study investigated the pattern of immediate serial recall and the associated suffix effect using olfactory stimuli. Subjects were trained initially to identify and name correctly nine different odours. Experiment 1 established an immediate correct recall span of approximately six items. In Experiment 2 participants recalled serially span equivalent lists which were followed by a visual, auditory, or olfactory suffix. Primacy was evident in the recall curves for all three suffix conditions. Recency, in contrast, was evident in the auditory and visual suffix conditions only; there was a strong suffix effect in the olfactory suffix condition. Experiment 3 replicated this pattern of effects using seven-item lists, and demonstrated that the magnitude of the recency and suffix effects obtained in the olfactory modality can equate to that obtained in the auditory modality. It is concluded that the pattern of recency and suffix effects in the olfactory modality is reliable, and poses difficulties for those theories that rely on the presence of a primary linguistic code, sound, or changing state as determinants of these effects in serial recall.

Acoustic Stimulation↗
PubMed1999

Multiple roles for the Wilms' tumor suppressor, WT1.

Wilms' tumor is a childhood kidney tumor that is a striking example of the way that cancer may arise through development gone awry. A proportion of these tumors develop as a result of the loss of function mutations in the Wilms' tumor suppressor gene, WT1. Inherited mutations in the WT1 gene can lead to childhood kidney cancer, severe gonadal dysplasia, and life-threatening hypertension. Knockouts show that the gene is essential for the early stages of kidney and gonad formation. These tissues are completely absent in null mice. The WT1 gene encodes numerous protein isoforms, all of which share four zinc fingers. There is a large body of evidence supporting the notion that WT1 is a transcription factor, particularly a transcriptional repressor. Recently, however, we obtained evidence that WT1 colocalizes and is physically associated with splice factors. What is more, one alternative splice isoform of WT1 containing three amino acids, Lys-Thr-Ser (KTS; inserted between zinc fingers 3 and 4) is preferentially associated with splice factors, whereas the other alternative splice version, lacking these three amino acids, preferentially associates with the transcriptional apparatus. Both genetic and evolutionary considerations suggest that these two different forms of the protein have different functions. We will discuss recent evidence to further implicate WT1 in splicing. Our results raise the possibility that regulation of splicing is a crucial factor in the development of the genitourinary system, and that tumors may arise through aberrant splicing. To pursue the regulation and function of WT1 in whole animals, we have been introducing the human gene and large flanking regions cloned in yeast artificial chromosomes directly into mice. These studies have allowed us to dissect the function of WT1 at late as well as at early stages in organogenesis and to identify new sites and surprising new potential functions for the gene.

Alternative Splicing↗
PubMed1999

A zinc finger truncation of murine WT1 results in the characteristic urogenital abnormalities of Denys-Drash syndrome.

The Wilms tumor-suppressor gene, WT1, plays a key role in urogenital development, and WT1 dysfunction is implicated in both neoplastic (Wilms tumor, mesothelioma, leukemias, and breast cancer) and nonneoplastic (glomerulosclerosis) disease. The analysis of diseases linked specifically with WT1 mutations, such as Denys-Drash syndrome (DDS), can provide valuable insight concerning the role of WT1 in development and disease. DDS is a rare childhood disease characterized by a nephropathy involving mesangial sclerosis, XY pseudohermaphroditism, and/or Wilms tumor (WT). DDS patients are constitutionally heterozygous for exonic point mutations in WT1, which include mutations predicted to truncate the protein within the C-terminal zinc finger (ZF) region. We report that heterozygosity for a targeted murine Wt1 allele, Wt1(tmT396), which truncates ZF3 at codon 396, induces mesangial sclerosis characteristic of DDS in adult heterozygous and chimeric mice. Male genital defects also were evident and there was a single case of Wilms tumor in which the transcript of the nontargeted allele showed an exon 9 skipping event, implying a causal link between Wt1 dysfunction and Wilms tumorigenesis in mice. However, the mutant WT1(tmT396) protein accounted for only 5% of WT1 in both heterozygous embryonic stem cells and the WT. This has implications regarding the mechanism by which the mutant allele exerts its effect.

Animals↗
PubMed1998

Complete sequencing of the Fugu WAGR region from WT1 to PAX6: dramatic compaction and conservation of synteny with human chromosome 11p13.

The pufferfish Fugu rubripes has a genome approximately 7.5 times smaller than that of mammals but with a similar number of genes. Although conserved synteny has been demonstrated between pufferfish and mammals across some regions of the genome, there is some controversy as to what extent Fugu will be a useful model for the human genome, e.g., [Gilley, J., Armes, N. & Fried, M. (1997) Nature (London) 385, 305-306]. We report extensive conservation of synteny between a 1.5-Mb region of human chromosome 11 and <100 kb of the Fugu genome in three overlapping cosmids. Our findings support the idea that the majority of DNA in the region of human chromosome 11p13 is intergenic. Comparative analysis of three unrelated genes with quite different roles, WT1, RCN1, and PAX6, has revealed differences in their structural evolution. Whereas the human WT1 gene can generate 16 protein isoforms via a combination of alternative splicing, RNA editing, and alternative start site usage, our data predict that Fugu WT1 is capable of generating only two isoforms. This raises the question of the extent to which the evolution of WT1 isoforms is related to the evolution of the mammalian genitourinary system. In addition, this region of the Fugu genome shows a much greater overall compaction than usual but with significant noncoding homology observed at the PAX6 locus, implying that comparative genomics has identified regulatory elements associated with this gene.

Amino Acid Sequence↗
PubMed1998

Estrogen and memory in a transsexual population.

The association between administered estrogen and performance on verbal memory and other cognitive tasks was examined. Male-to-female transsexuals undergoing estrogen treatment for sex reassignment (n = 29) scored higher on Paired Associate Learning (PAL) compared to a similar transsexual control group, awaiting estrogen treatment (n = 30) (P < 0.05). No differences between groups receiving and not receiving estrogen were detected on a control memory task (Digit Span) or on other cognitive tasks including Mental Rotations and Controlled Associations. There were no group differences in age. Group differences in mood or in general intellectual ability also did not explain the findings. Results suggest a specific influence of estrogen in men on verbal memory tasks, similar to that seen in prior studies of women. They are discussed in terms of differential processing demands of the two memory tasks and possible differences between estrogenic influences on Mental Rotations and Controlled Associations in men versus women.

Adult↗
PubMed1998

State-dependent memory produced by aerobic exercise.

In a free recall experiment, participants learned lists of words in two physiological states: at rest and while exercising aerobically on a bicycle ergometer. Recall of the words was required in either the state consistent with learning or in the alternative state. Word lists learned during aerobic exercise were recalled best during aerobic exercise and vice versa. Greater changes in heart rate in the changed state conditions were associated with greater retrieval decrements. Recall levels for words both learned and recalled at exercise were equivalent to those for words both learned and recalled at rest. This finding rules out the possibility that exercise per se interfered with the original learning. The study is consistent with the view that state-dependent memory should be viewed as a particular form of cue-dependent memory.

Adolescent↗
PubMed1998

Abnormal spinal fluid in hypertensive encephalopathy.

A 44-year-old white male presented with marked hypertension and encephalopathy. His spinal fluid showed a neutrophilic pleocytosis in the absence of infection. While cases of hypertensive encephalopathy with concomitant minor lymphocytic pleocytosis have been occasionally described, it is distinctly abnormal to have a neutrophilic pleocytosis in this setting.

Adult↗
PubMed1997

CCK antagonist pre-treatment inhibits meal-enhanced drug absorption in dogs.

Duodenal administration of casein and oleate increased plasma levels from oral administration of a poorly water-soluble antiepileptic drug as compared to duodenal glucose and saline in a canine model. Pre-treatment with intravenous MK-329, benzodiazepine CCK A-receptor antagonist, blocked the duodenal oleate effect on drug plasma levels in a single dog preliminary study. In a follow-up study, oral drug co-administration with Intralipid increased drug plasma levels as compared to drug co-administration with a noncaloric equivalent-volume load in seven dogs. Pre-treatment with MK-329 reduced drug plasma levels from co-administration with Intralipid toward fasted-state values. While increased drug solubility in the lipid vehicle might have been projected to account for the fed-state effect in the oral studies, the gut peptide inhibitor studies suggest that biliary secretion plays a major role in promoting the dissolution and subsequent absorption of this lipophilic drug. The data also support the hypothesis that meal-enhanced pancreatic secretion provides a greater fluid volume for drug dissolution in the small intestine. An increase in the extent of drug dissolution in the stomach, as a result of meal prolongation of gastric residence time, does not appear to contribute substantially to fed-state increases in drug plasma levels from oral drug co-administration with a lipid meal.

Animals↗
PubMed1997

Expression of the Ly-6E.1 (Sca-1) transgene in adult hematopoietic stem cells and the developing mouse embryo.

The mouse hematopoietic marker Sca-1, encoded by the Ly-6E.1 and Ly-6A.2 genes, has been instrumental in the enrichment and characterization of the stem cell for the adult blood system. In the studies reported here, we use Ly-6E.1 genomic fragments to direct expression of a lacZ marker transgene in vivo to study Ly-6E.1 specific regulatory elements in the hematopoietic stem cell and to localize these cells in the developing mouse embryo. We demonstrate that a region approximately 9 kb downstream from the transcriptional start site is required for the distinct, restricted expression pattern of the Ly-6E.1-lacZ transgene within adult hematopoietic stem cells and embryos. We also demonstrate that viable and functional lacZ-expressing hematopoietic stem cells can be enriched by FDG staining and flow cytometric sorting. The Ly-6E.1-lacZ-mediated enrichment of hematopoietic stem cells from adult transgenic bone marrow in combination with the temporal expression pattern of the transgene in the pro/mesonephros suggest an intraembryonic site of development for these cells in the mouse.

Animals↗
PubMed1997

The role of late-onset autoimmune diabetes in white familial NIDDM pedigrees.

OBJECTIVE: To determine whether autoimmunity is a prominent feature of NIDDM among diabetic members in families with a strong history of NIDDM or in families with a mixture of NIDDM and IDDM. RESEARCH DESIGN AND METHODS: We determined GAD and islet cell (ICA512) autoantibodies from 215 NIDDM individuals and from 14 individuals with impaired glucose tolerance (IGT) of 68 families, including 1 family with maturity-onset diabetes of the young (MODY) and 3 families ascertained specifically for a mixture of NIDDM and IDDM. We tested 2 control populations: 50 unrelated spouses form Utah families, including 29 spouses with either IGT or NIDDM and 198 random nondiabetic white individuals from Colorado. RESULTS: We detected either GAD or ICA512 autoantibodies in 11 members of seven families and in one spouse used as a control subject. In two families, two affected individuals showed evidence of autoimmunity, but NIDDM individuals in each of the seven families showed no evidence of autoimmunity. Among the five families with both IDDM and NIDDM individuals (three families ascertained for a mixture and two families ascertained with an incidental IDDM child), antibodies were detected in members of only one family. Antibody-positive individuals were significantly younger at diabetes onset and had low waist-to-hip ratios, but were not more likely to be insulin treated. CONCLUSIONS: Autoimmunity is an important cause of apparent NIDDM, even among families with a strong history of NIDDM. However, autoimmunity among affected family members appeared to be a chance event and not the manifestation of a different genetic cause of diabetes.

Adult↗
PubMed1996

Individual differences in reactivity to the rewarding/aversive properties of drugs: assessment by taste and place conditioning.

The ability of individual differences in the strength of conditioned taste avoidance (CTA) to predict strength of place conditioning produced by the same drug was assessed. In Phase 1, rats were assigned to High CTA and Low CTA groups on the basis of their intake of saccharin solution previously paired with morphine, amphetamine, lithium, or fenfluramine. In Phase 2, the rats received place conditioning training with the same drug used during Phase 1. The rats that displayed the strongest amphetamine-induced CTA also displayed the strongest amphetamine-induced place preference, suggesting that a common mechanism mediates both effects. On the other hand, the strength of the CTA was unrelated to the strength of the place preference or place aversion produced by morphine, lithium, or fenfluramine.

Amphetamine↗
PubMed1996

Characterization of the first definitive hematopoietic stem cells in the AGM and liver of the mouse embryo.

At day 10 in mouse gestation, the intraembryonic aorta-gonads-mesonephros (AGM) region generates the first definitive hematopoietic stem cells (HSCs) of the adult blood system. By 11 days postcoitum, the liver contains such HSCs. While HSCs of the adult bone marrow and late-stage fetal liver have been extensively characterized for cell surface markers, there has been no phenotypic description of the first HSCs during embryo development. We report here the temporal cell surface phenotype of HSCs from the AGM region and early fetal liver and show that all HSCs reside in the c-kit+ population. c-kit+ HSCs from AGM and liver are mainly CD34+ and in the AGM are in both Mac-1+ and Mac-1 fractions. These results demonstrate that during mouse ontogeny the first definitive HSCs are similar in cell surface phenotype to the HSCs of adult bone marrow but that spatial localization and developmental time are critical factors in the phenotypic assessment of this functional cell population.

Animals↗