Biomedical subjects

J Prescott

Publications and source records attributed to J Prescott.

At least 19 recordsLinked to original sources

PubMed2005

Oncogene-dependent tumor suppression: using the dark side of the force for cancer therapy.

Cancers arise by an evolutionary process that involves the protracted acquisition by somatic cells of suites of interlocking mutations that uncouple proliferation, survival, migration, and damage responses from the mechanisms (selective pressures) that normally restrain or restrict them in time and space. The relative rareness of cancer cells within the soma, in the face of huge numbers of available cell targets, substantial rates of mutation, and an abundance of proto-oncogenes and tumor suppressor gene targets, indicates that the evolutionary space available to incipient tumor cells is highly restricted. The principal way in which this is achieved is through intrinsic tumor suppression pathways-innate growth arrest and apoptotic programs that fulfill an essentially analogous functional role to checkpoints in the cell cycle machinery by antagonizing the tumorigenic potential of oncogenic mutations. Using switchable transgenic and knockin mouse models, it is possible to identify these various tumor suppressor programs and establish where, when, how, and why they act to forestall neoplasia in each tissue type and, consequently, how and why their failure leads to cancer.

Animals↗

PubMed2005

Response of the tendon during limb lengthening.

Little is known about the increase in length of tendons in postnatal life or of their response to limb lengthening procedures. A study was carried out in ten young and nine adult rabbits in which the tibia was lengthened by 20% at two rates 0.8 mm/day and 1.6 mm/day. The tendon of the flexor digitorum longus (FDL) muscle showed a significant increase in length in response to lengthening of the tibia. The young rabbits exhibited a significantly higher increase in length in the FDL tendon compared with the adults. There was no difference in the amount of lengthening of the FDL tendon at the different rates. Of the increase in length which occurred, 77% was in the proximal half of the tendon. This investigation demonstrated that tendons have the ability to lengthen during limb distraction. This occurred to a greater extent in the young who showed a higher proliferative response, suggesting that there may be less need for formal tendon lengthening in young children.

Aging↗

PubMed2004

Responses of PROP taster groups to variations in sensory qualities within foods and beverages.

Despite increasing evidence that variations in sensitivity to the bitterness of 6-n-propylthiouracil (PROP) are also reflected in responses to other tastes in solution, there has been little research examining the impact of PROP sensitivity on responses to sensory qualities in foods or beverages. The present studies examined responses of PROP taster groups to systematic variations in tastes and oral irritation in different foods and beverages. In Experiment 1, PROP groups were asked to discriminate variations in bitterness, sweetness, or sourness within two foods (yogurt and cream cheese) and a beverage (orange juice). In most cases, tasters and especially supertasters (STs) were able to discriminate smaller variations in tastant concentration than PROP nontasters (NTs). Differences were most evident with variations in bitterness and sourness. In Experiment 2, PROP taster groups rated the sweetness, sourness, and oral irritation in carbonated fruit drinks that systematically varied in citric acid (CA) and CO2 concentrations. Ratings of sourness and irritation were highest for STs and lowest for NTs, although there were no group differences for sweetness ratings. These data are some of the first to show PROP taster group differences in tastes and irritation within foods and provide a basis for reported differences of PROP groups in their hedonic responses to foods.

Adult↗

PubMed2004

Incidental learning and memory for three basic tastes in food.

Forty three subjects were invited under the pretence that they would take part in an experiment on hunger feelings. They came without having eaten anything that morning and received a standard breakfast containing orange juice, cream cheese on crackers and yoghurt. These products were later (when subjects returned after scoring hunger feelings during the day) used as targets amidst a set of distractors varied by adding or subtracting different amounts of two basic tastes. Orange juice was varied in sweetness and bitterness, cream cheese in sourness and bitterness and yoghurt in sweetness and sourness. The changes were made comparable by using just noticeable differences, determined in preliminary experiments with other subjects, as units of change. Two measurements of memory were compared, an absolute (indicating which were the targets) and a relative one (indicating whether the targets and distractors were more, less or equally pleasant, sweet, sour, bitter or salty as the item eaten at breakfast). Both methods showed incidental learning, but relative memory was superior. Memory differed between tastes and was partly product dependent. These experiments suggest that taste memory is tuned to detect novel and potentially dangerous stimuli rather than to remember features of earlier experienced stimuli with great precision.

Adult↗

PubMed2003

A one-quarter reduction in the salt content of bread can be made without detection.

OBJECTIVE: To determine if it is possible to deliver a one-quarter reduction in the sodium content of bread without detection. DESIGN: Single-blind, randomized, controlled trial. SETTING: The Royal North Shore Hospital in Sydney, Australia. PARTICIPANTS: One-hundred and ten volunteers from the hospital staff that completed 94% of scheduled assessments. INTERVENTION: Six consecutive weeks of bread with usual sodium content or six consecutive weeks of bread with cumulating 5% reductions in sodium content each week. MAIN OUTCOME MEASURE: The proportion of participants reporting a difference in the salt content of the study bread from week to week. RESULTS: The intervention group were no more likely than the control group to report a difference in the salt content of the bread from week to week (P=0.8). Similarly, there were no differences between randomized groups in the scores for flavour (P=0.08) or liking of the bread (P=0.95) over the study follow-up period. However, the saltiness scores recorded on a visual analogue scale did decline in the intervention group compared with the control group (P=0.01) CONCLUSIONS: A one-quarter reduction in the sodium content of white bread can be delivered over a short time period, while maintaining consumer acceptance. Over the long term, and particularly if achieved for multiple foods, a decrease in sodium content of this magnitude would be expected to reduce population levels of blood pressure and the risks of stroke and heart attack.

Adult↗

PubMed2001

Altering telomere structure allows telomerase to act in yeast lacking ATM kinases.

BACKGROUND: Telomerase is a ribonucleoprotein that copies a short RNA template into telomeric DNA, maintaining eukaryotic chromosome ends and preventing replicative senescence. Telomeres differentiate chromosome ends from DNA double-stranded breaks. Nevertheless, the DNA damage-responsive ATM kinases Tel1p and Mec1p are required for normal telomere maintenance in Saccharomyces cerevisiae. We tested whether the ATM kinases are required for telomerase enzyme activity or whether it is their action on the telomere that allows telomeric DNA synthesis. RESULTS: Cells lacking Tel1p and Mec1p had wild-type levels of telomerase activity in vitro. Furthermore, altering telomere structure in three different ways showed that telomerase can function in ATM kinase-deleted cells: tel1 mec1 cells senesced more slowly than tel1 mec1 cells that also lacked TLC1, which encodes telomerase RNA, suggesting that tel1 mec1 cells have residual telomerase function; deleting the telomere-associated proteins Rif1p and Rif2p in tel1 mec1 cells prevented senescence; we isolated a point mutation in the telomerase RNA template domain (tlc1-476A) that altered telomeric DNA sequences, causing uncontrolled telomeric DNA elongation and increasing single strandedness. In tel1 mec1 cells, tlc1-476A telomerase was also capable of uncontrolled synthesis, but only after telomeres had shortened for >30 generations. CONCLUSION: Our results show that, without Tel1p and Mec1p, telomerase is still active and can act in vivo when the telomere structure is disrupted by various means. Hence, a primary function of the ATM-family kinases in telomere maintenance is to act on the substrate of telomerase, the telomere, rather than to activate the enzymatic activity of telomerase.

Ataxia Telangiectasia Mutated Proteins↗

PubMed2001

Binary taste mixture interactions in prop non-tasters, medium-tasters and super-tasters.

It is generally assumed that the mutual, but asymmetric, suppression of the components in binary taste mixtures is an invariant property of the human psychophysical response to such mixtures. However, taste intensities have been shown to vary as a function of individual differences in sensitivity, indexed by the perceived bitterness of 6-n-propylthiouracil (PROP). To determine if these variations in taste perception influence taste mixture interactions, groups of PROP super-, medium- and non-tasters assessed four binary taste mixtures: sweet-bitter [sucrose/quinine hydrochloride (QHCl)], sweet-sour (sucrose/citric acid), salty-bitter (NaCl/QHCl) and salty-sour (NaCl/citric acid). In each experiment, subjects received factorial combinations of four levels of each of two tastants and rated individual taste intensities and overall mixture intensity. For each taste quality, super-tasters typically gave higher ratings than either medium- or non-tasters, who tended not to differ. There were also group differences in the interactions of the mixtures' components. Super-tasters rated the overall intensity of the mixtures, most likely reflecting integration of the taste components, as greater than medium- and non-tasters, who again showed few differences. In sweet-bitter mixtures, non-tasters failed to show the suppression of sweetness intensity by the highest QHCl concentration that was evident in super- and medium-tasters. These data show that the perception of both tastes and binary taste mixture interactions varies as a function of PROP taster status, but that this may only be evident when three taster groups are clearly distinguished from one another.

Adolescent↗

PubMed2000

Responses to repeated oral irritation by capsaicin, cinnamaldehyde and ethanol in PROP tasters and non-tasters.

Both increases (sensitization) and decreases (desensitization) in oral irritation have been reported in response to repeated short-term stimulation by compounds such as capsaicin, zingerone and menthol. It is unclear why one irritant would show sensitization and another desensitization, and this is further complicated by substantial inter-individual variation in response patterns. These variations may be the result of individual differences such as that represented by sensitivity to 6-n-propylthiouracil (PROP), which has been associated with variation in the overall intensity of irritation. In addition, comparisons between irritants have almost always involved inter-study comparisons, entailing different subject groups and frequently different methods. In the studies reported here, responses to three irritants-capsaicin, cinnamaldehyde and ethanol-were examined as a function of PROP taster status. A common core of subjects also received all three irritants, allowing an assessment of the extent to which different response patterns between irritants seen previously were the result of different properties of the irritants themselves. Over a series of ten stimuli presented at 1 min intervals, PROP taster status differentiated subject responses on the basis of overall intensity, but not the pattern of responses over repeated stimulation. The group response to ethanol and cinnamaldehyde was desensitization, a pattern also shown by most of the individual subjects. In contrast, the group response to capsaicin was neither clear sensitization nor desensitization, reflecting much greater individual variability in response patterns. It is suggested that the time course to a single irritant stimulus largely determines between irritant response variations, while the inter-stimulus interval (ISI) used for a given irritant will have critical values for showing predominantly sensitization or desensitization.

Acrolein↗

PubMed2000

Molecular manifestations and molecular determinants of telomere capping.

Multiple interacting components of the telomere, together with telomerase (and sometimes recombination), determine whether a telomere will be functional, allowing cell proliferation. The various components reinforce each other, providing for a robust and resilient system of protection and replenishment of telomeres. A characteristic of a telomere is that its structural features elicit responses that allow it to be dynamically recapped. Eliciting a DNA damage response through uncapping of a telomere appears to be one way in which telomerase action at that telomere is stimulated. Thus, as long as a timely and appropriate recapping of the telomere is possible, regulated uncapping of a telomere appears to be not only normal, but even required for optimal telomere maintenance. Telomere length and the presence of telomerase provide an example of a pair of interacting components that determine telomere capping function. Telomerase is dispensable in cells with sufficiently long telomeres; but in cells with short telomeres lacking telomerase, cells lose the ability to proliferate, and in some cell types, telomere fusions are increased. However, expressing telomerase can make even very short telomeres functional. Many interesting questions remain as to the mechanisms of these biological effects.

Animals↗

PubMed2000

Coprescribing proton pump inhibitors with other medications.

Proton pump inhibitors, the treatment of choice for acid-related disorders, are often coadministered with other medications, sometimes with potentially adverse interactions. Although all agents studied may potentially interact with one proton pump inhibitor or another, a literature review documented adverse interactions for 10 medications in particular. Furthermore, 44% of people using proton pump inhibitors received another gastrointestinal drug. Although documented interactions involving these agents have been reported infrequently, the authors advise that physicians and pharmacists should recognize this possibility and watch for potentially problematic combination therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1999

The fatty acid distribution in low density lipoprotein in diabetes.

Atherosclerosis is commonly found in diabetes. There is an association between small dense low density lipoprotein (LDL) phenotype, which is more prevalent in the diabetic state, and atherosclerosis. Small dense LDL is more easily oxidised and it is possible that fatty acid compositional changes, particularly an increase in polyunsaturated fatty acids, could underlie this association. However, there is little information about fatty acids in the different LDL phenotypes in the literature. This study examined LDL subfraction composition in 18 non-insulin-dependent diabetic (NIDDM) patients and 11 control subjects. LDL was isolated and fractionated into LDL 1, 2 and 3 by density gradient ultracentrifugation. NIDDM patients had significantly more fatty acids in all LDL subfractions than control subjects (P<0.01). Palmitic and linoleic acid were significantly greater in all subfractions in the diabetic patients compared to control subjects (P<0.01) and palmitoleic and oleic acids were also greater in LDL1 and LDL2 in diabetic patients (P<0.01). We conclude that in NIDDM fatty acids are increased in all LDL subfractions and this may be the reason for the increased atherosclerosis in diabetes irrespective of phenotype.

Aged↗

PubMed1999

Cleavage of double-stranded copy RNA by RNase 1 and RNase T1 provides a robust means to detect p53 gene mutations in clinical specimens.

Detecting somatic mutations in patient specimens is challenging because of the wide variation in quality and quantity of genomic DNA in clinically derived material. In cancer specimens, the challenge of detecting mutations is usually compounded by the presence of large numbers of nonmutated normal cells that dampen the relative signal that can be obtained from employing any mutation detection strategy. In the case of somatic mutations in the gene encoding the tumor suppressor, p53, a clinically useful mutation detection assay must be able to detect a wide variety of types of mutations scattered over five coding exons and their flanking intron sequences. This study examined the ability of a mutation detection strategy, termed NIRCA, to identify single-base mutations in the clinically relevant domain of the p53 gene. This strategy relies on RNase digestion-mediated cleavage of double-stranded copy RNA transcribed in vitro from polymerase chain reaction (PCR)-amplified genomic templates to detect mismatched base pairs resulting from hybridization of complimenting mutant and wild-type copy RNA strands. This assay system was found to robustly detect all twelve possible mismatches and the plus one and minus one frame shifts. Furthermore, the assay could detect mutations in clinical specimens when the mutant alleles composed as few as 4% of the total population of alleles isolated in bulk specimen genomic DNA. This mutation detection strategy worked efficiently in bladder, breast, colon and lung tumors as well as sediments from bladder cytology specimens.

Humans↗

PubMed1999

The generalizability of capsaicin sensitization and desensitization.

Studies using capsaicin-saturated filter papers have shown that the intensity of oral irritation tends to grow over successive samples, a phenomenon known as sensitization. If a hiatus of 5-15 min is then introduced, the intensity of irritation produced by a subsequent capsaicin stimulus is much reduced, and desensitization is said to have occurred. The use of other methodologies such as whole-mouth rinses, either with capsaicin or the irritants menthol or zingerone, have not consistently shown this response pattern, casting doubt on the extent to which sensitization and desensitization are general phenomena. Experiment 1 addressed this issue by comparing responses to whole-mouth rinses of 0.6 and 3 ppm capsaicin with those to 3 ppm capsaicin filter papers. Over an initial series of 10 samples, sensitization was evident but only for the 3 ppm capsaicin stimuli. Following a 10-min hiatus, desensitization was observed for all stimulus types. An examination of the data of individual subjects revealed considerable variability in response patterns over the initial 10 samples between subjects and, within subjects, between the filter paper and rinse stimuli, and between the test replications. Desensitization to the posthiatus stimuli was more consistent. A second experiment examined whether the capsaicin sensitization and desensitization shown by stimulation with filter papers or solutions also occurred in the context of the consumption of foods containing capsaicin. Two foods--soup and chili con carne--were consumed under conditions in which the rate of consumption was timed, as in Experiment 1, or was self-paced. In neither of the two conditions or foods was there strong evidence of sensitization, although, again, desensitization following a hiatus was evident. Substantial individual variability in response patterns was again apparent. There is thus no evidence for sensitization occurring during normal food consumption.

Adult↗

PubMed1999

Confusing tastes and smells: how odours can influence the perception of sweet and sour tastes.

This study investigated the relationship between perception of an odour when smelled and the taste of a solution to which the odour is added as a flavorant. In Experiment 1 (E1) sweetness, sourness, liking and intensity ratings were obtained for 20 odours. Taste ratings were then obtained for sucrose solutions to which the odours had been added as flavorants. Certain odours were found to enhance tasted sweetness while others suppressed it. The degree to which an odour smelled sweet was the best predictor of the taste ratings. These findings were extended in Experiment 2 (E2), which included a second tastant, citric acid, and employed four odours from E1. The most sweet smelling odour, caramel, was found to suppress the sourness of citric acid and, as in E1, to enhance the sweetness of sucrose. Again, odours with low sweetness suppressed the sweetness of tasted sucrose. The study demonstrated that the effects of odours on taste perception are not limited to sweetness enhancement and apply to sour as well as sweet tastes. The overall pattern of results is consistent with an explanation of the taste properties of odours in terms of prior flavour-taste associations.

Adult↗

PubMed1999

Gastroesophageal reflux disease.

The data indicate that gastroenterologists have higher (P < .05) utilization, covered charges, and prescription drug utilization per PTE than FPs/GPs with regard to patients with lowest-severity GERD. The data show that patients treated by an FP/GP have significantly lower PTE duration when compared with patients treated by gastroenterologists. Average overall charges for FPs/GPs are also significantly lower than average overall charges for gastroenterologists. Additionally, average prescription drug charges per PTE are lower for FPs/GPs than for gastroenterologists. An important consideration is the variation of practice patterns in the treatment of GERD. This analysis is not based on a controlled study; therefore, adjustments for patients demographic and geographic factors are necessary in order to provide further reliable analysis. Additional research in this area is worthwhile and may include a controlled comparison of practice patterns among PCPs and specialists in relation to the quality of care and cost effectiveness of treatments prescribed for GERD.

Adolescent↗

PubMed1998

Genome-wide search for asthma susceptibility loci in a founder population. The Collaborative Study on the Genetics of Asthma.

Founder populations offer many advantages for mapping genetic traits, particularly complex traits that are likely to be genetically heterogeneous. To identify genes that influence asthma and asthma-associated phenotypes, we conducted a genome-wide screen in the Hutterites, a religious isolate of European ancestry. A primary sample of 361 individuals and a replication sample of 292 individuals were evaluated for asthma phenotypes according to a standardized protocol. A genome-wide screen has been completed using 292 autosomal and three X-Y pseudoautosomal markers. Using the semi-parametric likelihood ratio chi2 test and the transmission-disequilibrium test, we identified 12 markers in 10 regions that showed possible linkage to asthma or an associated phenotype (likelihood ratio P < 0.01). Markers in four regions (5q23-31, 12q15-24.1, 19q13 and 21q21) showed possible linkage in both the primary and replication samples and have also shown linkage to asthma phenotypes in other samples; two adjacent markers in one additional region (3p24.2-22) showing possible linkage is reported for the first time in the Hutterites. The results suggest that even in founder populations with a relatively small number of independent genomes, susceptibility alleles at many loci may influence asthma phenotypes and that these susceptibility alleles are likely to be common polymorphisms in the population.

Adolescent↗

PubMed1998

Salmonella typhimurium DT104: a virulent and drug-resistant pathogen.

Salmonella typhimurium phage type (PT) or definitive type (DT) 104 is a virulent pathogen for humans and animals, particularly cattle. It has been isolated increasingly from humans and animals in the United Kingdom and several other European countries and, more recently, in the United States and Canada. Humans may acquire the infection from foods of animal origin contaminated with the infective organism. Farm families are particularly at risk of acquiring the infection by contact with infected animals or by drinking unpasteurized milk. The symptoms in cattle are watery to bloody diarrhea, a drop in milk production, pyrexia, anorexia, dehydration and depression. Infection may result in septicemic salmonellosis and, upon necropsy, a fibrinonecrotic enterocolitis may be observed. The infection occurs more commonly in the calving season than at other times. Feedlot cattle and pigs may also be affected. Prolonged carriage and shedding of the pathogen may occur. Symptoms in humans consist of diarrhea, fever, headache, nausea, abdominal pain, vomiting, and, less frequently, blood in the stool. Salmonella typhimurium DT104 strains are commonly resistant to ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline.

Agricultural Workers' Diseases↗

PubMed1997

Functionally interacting telomerase RNAs in the yeast telomerase complex.

The ribonucleoprotein (RNP) enzyme telomerase from Saccharomyces cerevisiae adds telomeric DNA to chromosomal ends in short increments both in vivo and in vitro. Whether or not telomerase functions as a multimer has not been addressed previously. Here we show, first, that following polymerization, the telomerase RNP remains stably bound to its telomeric oligonucleotide reaction product. We then exploit this finding and a previously reported mutant telomerase RNA to demonstrate that, unexpectedly, the S. cerevisiae telomerase complex contains at least two functionally interacting RNA molecules that both act as templates for DNA polymerization. Here, functional telomerase contains at least two active sites.

Base Sequence↗