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Biomedical subjects

G Prescott

Publications and source records attributed to G Prescott.

14 recordsLinked to original sources
PubMed2001

Acute respiratory effects of particles: mass or number?

OBJECTIVES: To determine whether associations might be found, in patients with chronic airflow obstruction, between symptoms, peak flow rate (PEF), and particle mass and numbers, and to assess which measure was most closely associated with changes in health. Epidemiological studies have shown associations between particulate air pollution and cardiovascular and respiratory disease, and it has been proposed that these may be mediated by particles of nm size (ultrafine). METHODS: Relations were investigated between symptom scores, PEF, and bronchodilator use in 44 patients aged > or =50 years with chronic obstructive pulmonary disease, and daily measurements of both mass of ambient particles of aerodynamic diameter less than 10 microm (PM10) and numbers of ultrafine particles (<100 nm), allowing for meteorological variables. Symptom scores, bronchodilator use, and PEF were recorded daily for 3 months. Counts of ultrafine particles were made by the TSI model 3934 scanning mobility particle sizer (SMPS) and PM10 measurements by the tapered element oscillating microbalance (TEOM). RESULTS: Ultrafine particle counts indoors and outdoors were significantly correlated, those indoors being about half of those outdoors. No associations were found between actual PEF and PM10 or ultrafine particles. However, there was a 19% increase in the rate of 10% decrements in daytime PEF with increases in PM10 from 10 to 20 microg/m(3) which was of borderline significance (p=0.05). A change in PM10 from 10 to 20 microg/m(3) was significantly associated with a 14% increase in the rate of high scores of shortness of breath (p=0.003). A similar change in PM10 as a moving average of the same day and 2 previous days was associated with a 31% increase in the rate of high scores for cough (p=0.02). Cough symptoms were also associated with lower temperatures (p=0.02). Higher use of medicines was also associated with higher PM10, but the increases were very small in clinical terms. CONCLUSIONS: Evidence was not found to support the hypothesis that the component of particulate pollution responsible for effects on respiratory symptoms or function resides in the fraction below 100 nm diameter. The consistent associations between symptoms and PM10 suggest that a contribution of the coarser fraction should not be dismissed. Further studies will be needed before the conclusions of this specific project may be generalised.

Aged↗
PubMed2000

Contribution of circulating renin to local synthesis of angiotensin peptides in the heart.

The activity of a local cardiac renin-angiotensin system (RAS) has long been suspected in the promotion of cardiac pathologies including hypertrophy, ischemia, and infarction. All of the components of the RAS cascade have been demonstrated to be synthesized within the heart with the possible exception of the first enzyme in the cascade, renin. In the current study, we provide direct evidence that circulating renin can contribute to cardiac-specific synthesis of angiotensin peptides. Furthermore, we demonstrate this effect is independent of blood pressure and that in animals of comparable blood pressure, elevated circulating renin significantly enhances cardiac fibrosis. These results may serve to explain some of the cardiac pathologies associated with the RAS.

Angiotensin I↗
PubMed2000

Radical radiotherapy for inoperable non-small cell lung cancer: what factors predict prognosis?

We set out to determine the factors that predict the outcome of conventional radical radiotherapy for inoperable non-small cell lung cancer. A retrospective casenote review was carried out of all 69 patients treated between 1986 and 1992 at the Northern Ireland Centre for Clinical Oncology, Belfast, with radical radiotherapy for inoperable non-small cell lung cancer. The tumour dose ranged from 45 Gy to 67.5 Gy, delivered in 15-30 fractions, 5 days per week over 3-6 weeks. All patients were followed up for 5 years. The disease was TNM Stage T1-T4N0-N2M0. The majority of tumours (51) were squamous. Overall survival was 63.8% (44-patients; 95% confidence interval (CT) 51.3-75.2) at one year; median survival was 16 months and 5-year survival was 13% (nine patients; 95% CI 6.1-23.3). Five-year survival for the 36 patients with stage T1 or T2 disease was 5.6% (2 patients). Five-year survival for the 33 patients with stage T3 or T4 disease, all with tumours at or near the carina, was 21.2% (seven patients). A WHO performance status of 0 or 1 (P = 0.03, Cox proportional hazards model) was associated with a better chance of survival.

Adult↗
PubMed1997

Genetic characterization of novel strains of rats derived from crosses between Wistar-Kyoto and spontaneously hypertensive rats, and comparisons with their parental strains.

Two novel strains of rats have recently been generated from hybrid crosses of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The breeding pairs chosen to create these strains were initially selected on the basis of two mutually exclusive phenotypic traits, so that the rats called WKHT are hypertensive but not hyperactive, whereas the rats called WKHA are hyperactive but not hypertensive. These strains have been refined by inbreeding on a strict brother-sister basis for more than 25 generations. To increase usefulness of these strains, we characterized them by use of genetic methods, including DNA finger-printing and simple sequence length polymorphism (SSLP) analyses. We found that these two novel strains are more closely related genetically to either SHR or WKY rats than the degree to which the latter two strains are related to one another; heterozygosities of SSLP marker alleles were extremely rare in WKHA and WKHT, indicating that these strains can be considered as truly inbred (in contrast to WKY rats from two sources); and it was almost always possible to match the SSLP marker alleles found in WKHA and WKHT rats with similarly sized alleles in the parental SHR and WKY alleles, indicating that the WKHA and WKHT strains constitute true mixes of the genomes of SHR and WKY rats. Furthermore, immunogenetic analyses indicated that WKY and WKHT rats belonged to the RT1 l haplotype, whereas SHR and WKHA rats belonged to the k haplotype. These results extend the usefulness of WKHA and WKHT rats for further genetic and physiologic studies.

Alleles↗
PubMed1994

Linkage disequilibrium analysis of childhood-onset spinal muscular atrophy (SMA) in the French-Canadian population.

Spinal muscular atrophy (SMA) is, after Duchenne muscular dystrophy, the most common neuromuscular disorder in childhood. The gene responsible for childhood SMA has been mapped to the q11.2-q13.3 region of chromosome 5. We have extended our linkage studies of SMA in the French-Canadian population to include microsatellite markers at the D5S125, D5S351, D5S435, JK53CA1/2 and MAP1B loci. These markers span about 4 cM of the SMA candidate region. We observed significant evidence for linkage between SMA and all the markers tested. The analysis of recombinant chromosomes provide evidence for the following genetic order: D5S125-D5S435-MAP1B-3'-JK53CA1/2 and places D5S351 proximal to JK53CA1/2. Furthermore, we confirm the current localization of the SMA gene distal to D5S435. Finally, we provide demonstration of significant linkage disequilibrium between childhood-onset SMA and four of the five marker loci, D5S125, D5S435, D5S351 and JK53CA1/2. Analysis of SMA-region haplotypes suggests that there may be a predominant SMA allele that is present on about 17% of SMA chromosomes in this sample of the French-Canadian population. We conclude that the observed linkage disequilibrium is likely due to genetic drift among regions of Quebec, consistent with this population's early history.

Age of Onset↗
PubMed1994

Association between Ag1-CA alleles and severity of autosomal recessive proximal spinal muscular atrophy.

The gene for autosomal recessive proximal spinal muscular atrophy (SMA) has been mapped to an 850-kb interval on 5q11.2-q13.3, between the centromeric D5S823 and telomeric D5S557 markers. We report a new complex marker, Ag1-CA, that lies in this interval, whose primers produce one, two, or rarely three amplification-fragment-length variants (AFLVs) per allele. Class I chromosomes are those which amplify a single AFLV allele, and class II chromosomes are those which amplify an allele with two or three AFLVs. Ag1-CA shows highly significant allelic association with type I SMA in both the French Canadian (Hôpital Sainte-Justine [HSJ]) and American (Ohio State University [OSU]) populations (P < .0001). Significant association between the Ag1-CA genotype and disease severity was also observed. Type I patients were predominantly homozygous for class I chromosomes (P = .0003 OSU; P = .0012 HSJ), whereas the majority of type II patients were heterozygous for class I and II chromosomes (P = .0014 OSU; P = .001 HSJ). There was no significant difference in Ag1-CA genotype frequencies between type III patients (P = .5 OSU; P = .25 HSJ) and the paired normal chromosomes from both carrier parents. Our results indicate that Ag1-CA is the most closely linked marker to SMA and defines the critical candidate-gene region. Finally, we have proposed a model that should be taken into consideration when screening candidate SMA genes.

Alleles↗
PubMed1993

Identification of cis-acting elements involved in the regulation of the pathogenesis-related gene STH-2 in potato.

We have characterized a genomic clone containing the potato pathogenesis-related genes STH-2 and STH-21. The two genes are found 4 kb apart on the same chromosome and their sequences are highly similar. They present the same transcriptional orientation and are both interrupted by a single intron. A chimaeric gene consisting of 1015 bp of 5'-flanking sequence and part of the first exon of STH-2 fused to the bacterial beta-glucuronidase gene was highly-expressed in tubers of transgenic potato plants after wounding and elicitor treatments. The levels of activity observed in these transgenic plants parallel those observed for the accumulation of STH-2 mRNAs under similar conditions. This indicates that cis-acting elements necessary for the proper activation of the gene are present within 1 kb of 5'-flanking sequences. Functional analysis of 5' deletions of the STH-2/GUS constructs by transient expression in leaf protoplasts revealed the presence of an upstream regulatory sequence between -135 and -52 which contains a TGAC motif, and a possible negative regulatory region between -52 and -28. A factor present in nuclear extracts of wounded potato tubers was found to bind specifically to nucleotides located between -135 to -105, suggesting that this region contains important cis-regulatory elements.

Amino Acid Sequence↗
PubMed1980

Mosaic and hypermodal cells in amniotic fluid cell cultures.

Karyotypic results from a series of 975 consecutive amniotic fluid specimens studied for prenatal diagnosis are reported. In only 32% of specimens were all cells analyzed euploid. Two thirds (63%) of the specimens studied were hypomodal in at least one cell; 25% of the studies were hypomodal in three or more cells. In contrast, only 3.5% of the studies were hypermoidal in one or more cells. Most frequently an additional chromosome 2 was present in these hypermodal cells. Cells with other than a diploid chromosome constitution may be mistakenly identified as evidence of mosaicism. This is especially likely when the involved chromosome is one associated with a clinically defined syndrome.

Amniotic Fluid↗
PubMed1980

The recurrence risk for neural tube defects in the United States: a collaborative study.

To determine the recurrence risk for patients with one prior pregnancy affected with neural tube defects (NTD), the authors have pooled data from eight testing centers. In 831 pregnancies studied because one sib was affected with an NTD, the recurrence rate was 3.0%, with 95% confidence limits of 2.0-4.3%, and 99% confidence limits of 1.8-4.8%. The recurrent lesion, whether spina bifida or anencephaly, tended to be concordant with the first to a significant degree. Only 12.2% of recurrent NTD were different from the first, with 95% confidence limits of 4.1-26.2%, and 99% confidence limits of 1.7-30.9%. Both an accurate recurrence risk and the information that a recurrent NTD lesions tends to be concordant with that in the first affected child are useful in the genetic counseling of patients in the United States and in the selection of appropriate prenatal diagnostic studies.

Female↗
PubMed1978

Significance of meconium in midtrimester diagnostic amniocentesis.

The importance of meconium passage as a sign of the third-trimester fetus in distress is well known. The significance of similar observations in the midtrimester fetus is much less certain. The increasing use of amniocentesis during the middle trimester for the diagnosis of genetic disease makes ascertainment of such data important. Ten instances of meconium-stained amniotic fluid in the last 514 amniocenteses performed at our institution for antenatal genetic diagnosis are reported. Seven pregnancies have ended at term with normal deliveries. Three pregnancies have terminated with fetal death. Meconium staining may be a sign of impending fetal death when passed during the second trimester. When accompanied by alpha-fetoprotein elevation two of three pregnancies terminated with fetal death.

Adult↗
PubMed1976

9p trisomy identified by Giemsa-11.

The Giemsa-11 technique specifically stains the secondary constriction region of chromosome 9. We report cytologic evidence for 9p trisomy in a 4 1/2-year-old girl with moderate retardation and multiple anomalies, using the Giemsa-11 technique.

Abnormalities, Multiple↗
PubMed1976

Pacemaker-induced change in prosthetic valvular sounds.

Variable intensity and timing of valvular sounds were noted in two patients with permanent pacemakers and prosthetic valves. In the first patient, who had a mitral and a tricuspid prosthesis, valvular opening sounds became widely separated with a change from nodal to ventricular paced rhythm. In a second patient, who had a mitral prosthesis in sinus rhythm with first-degree atrioventricular block, a very quiet closing sound increased markedly in intensity with the onset of ventricular pacing. The mechanism for these changes is described using a technique which at brief intervals throughout the cardiac cycle permitted documentation of simultaneously recorded phonocardiogram, electrocardiogram, and pulse tracings with a visible image of the prosthesis. In the usual patient with a prosthetic valve auscultatory changes should arouse a suspicion of malfunction; however, in the relatively uncommon patient with a prosthesis and an artificial pacemaker, it should be recognized that auscultatory changes may well have a physiologic explanation.

Adult↗