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R J Thomas

Publications and source records attributed to R J Thomas.

At least 55 records · Page 3Linked to original sources
PubMed1998

Gene organization and alternative splicing of human prohormone convertase PC8.

The mammalian Ca2+-dependent serine protease prohormone convertase PC8 is expressed ubiquitously, being transcribed as 3.5, 4.3 and 6.0 kb mRNA isoforms in various tissues. To determine the origin of these various mRNA isoforms we report the characterization of the human PC8 gene, which has been previously localized to chromosome 11q23-24. Consisting of 16 exons, the human PC8 gene spans approx. 27 kb. A comparison of the position of intron-exon junctions of the human PC8 gene with the gene structures of previously reported prohormone convertase genes demonstrated a divergence of the human PC8 from the highly conserved nature of the gene organization of this enzyme family. The nucleotide sequence of the 5'-flanking region of the human PC8 is reported and possesses putative promoter elements characteristic of a GC-rich promoter. Further supporting the potential role of a GC-rich promoter element, multiple transcriptional initiation sites within a 200 bp region were demonstrated. We propose that the various mRNA isoforms of PC8 result from the inclusion of intronic sequences within transcripts.

Alternative Splicing↗
PubMed1998

Colorectal cancer: a survey of community beliefs and behaviours in Victoria.

OBJECTIVE: To document self-reported beliefs and behaviours in relation to colorectal cancer (CRC) and screening for CRC. DATA COLLECTION: A stratified random sample was selected from the telephone directory, and structured telephone interviews were conducted using a computer-assisted telephone interviewing system. PARTICIPANTS: 500 men and 500 women aged 40-60 years, 70% randomly selected from the Melbourne metropolitan area and 30% from rural Victoria. The response rate to the initial telephone invitation of 1569 eligible people was 63.7%. OUTCOME MEASURES: Awareness of and experience with CRC; knowledge of CRC risk, risk reduction behaviour, and screening tests for CRC; willingness to have screening tests for CRC; and test preferences. RESULTS: The people surveyed were relatively unaware of their personal risk of CRC, despite 61% (95% CI, 57%-65%) knowing someone who had CRC. Although 51% (95% CI, 48%-54%) could not name any CRC screening test, 68% (95% CI, 65%-71%) knew of the value of a high fibre diet in prevention. However, 67% (95% CI, 64%-70%) thought it was unlikely they would have a screening test for CRC in the next two years, but 64% (95% CI, 61%-67%) considered that some person could influence their decision to have a test, 60% (95% CI, 56%-64%) stating that they would be influenced by a doctor. Faecal occult blood testing and sigmoidoscopy were equally acceptable. In general, women were more knowledgeable than men. There were no systematic age or urban/rural differences. CONCLUSIONS: There is a variable understanding of CRC in the community. Although prevention is well understood, this is not true of screening. General practitioners are likely to be influential in the uptake of any screening programs.

Adult↗
PubMed1998

Increased levels of phosphatidylinositol 3-kinase activity in colorectal tumors.

BACKGROUND: Phosphatidylinositol 3-kinase (PI 3-kinase), an enzyme that phosphorylates inositol phospholipids at the D-3 position of the inositol ring, has been implicated in the signaling pathways regulating cell growth by virtue of its activation in response to various mitogenic stimuli. In spite of the considerable attention PI 3-kinase has received with regard to its possible role in the mitogenic pathways in hematopoietic malignancies, there are few reports of investigations into PI 3-kinase activity in solid tumors. METHODS: Colorectal tumor tissue and normal-appearing colonic mucosa from the same patients were homogenized and solubilized and adjusted to equal protein levels. PI 3-kinase then was immunoprecipitated from 200 microg of the solubilized tissue using a polyclonal antibody to the p85 subunit of PI 3-kinase. PI 3-kinase activity was assessed using phosphatidylinositol as the substrate and the assay product analyzed by thin-layer chromatography. Phosphorylation of phosphatidylinositol in the D-3 position was confirmed by high performance liquid chromatography analysis of deacylated and deglycerated products. RESULTS: Thirty-two of the 37 tumors tested (86%) demonstrated increased PI 3-kinase activity compared with normal-appearing mucosa from the same patients (overall mean increase+/-standard error of the mean=3.8+/-0.6-fold; P < 0.05, Student's t test for paired data). The frequency and extent of increased PI 3-kinase enzyme activity in tumors did not correlate with clinical parameters or the presence of oncogenic ras mutations. CONCLUSIONS: In this study colorectal tumors exhibited enhanced PI 3-kinase activity compared with normal colonic mucosa, raising the possibility that PI 3-kinase may be a potential target for new strategies for the treatment of colorectal carcinoma.

Colorectal Neoplasms↗
PubMed1998

Varied presentations of unilateral lung hypoplasia and agenesis: a report of four cases.

Unilateral lung hypoplasia or agenesis can be asymptomatic or present with recurrent respiratory symptoms. The latter may be amenable to surgical treatment in selected cases. Of four children in this report, two are being managed without surgery. A third was relieved of his symptoms by pneumonectomy. The fourth presented with acute foreign-body inhalation into the healthy right main bronchus, and coexistent left pulmonary agenesis was discovered at bronchoscopy. Bronchoscopy and computed tomography were found to be the most useful investigations in management.

Child, Preschool↗
PubMed1998

Asymptomatic sexually transmitted disease prevalence in four military populations: application of DNA amplification assays for Chlamydia and gonorrhea screening.

The prevalence of asymptomatic chlamydial and gonococcal infections in male and female military populations was determined using urine-based ligase chain reaction DNA amplification assays (DAAs). Cross-sectional surveys in four military settings revealed an overall prevalence of asymptomatic chlamydial infection of 4.2% (56/1338). This included 3.4% (21/618) of Western Pacific shipboard US Marine Corps enlisted men; 5.2% (21/406) of male marines shore-based in Okinawa, Japan; 2.7% (5/183) of female enlisted US Navy subtender personnel in dry dock; and 6.9% (9/131) of shore-based female naval personnel in San Diego. No gonococcal infections were detected. All subjects were treated within 2 weeks of screening; none of them had progressed to symptomatic disease. General population-based screening for asymptomatic sexually transmitted diseases, and in particular chlamydial infection, can be successfully implemented using urine-based DAA tests. Benefits are maximized in a population in which compliance for follow-up therapy is high.

Adult↗
PubMed1998

Seven-year change in graded exercise treadmill test performance in young adults in the CARDIA study. Cardiovascular Risk Factors in Young Adults.

PURPOSE: Most studies of physical fitness change have been relatively small, not population-based, and lacking in women and nonwhites. The purpose of this analysis was to evaluate the 7-yr change in physical fitness in a biracial (black and white) population of young men and women. METHODS: We evaluated change in exercise treadmill test performance in a biracial (black and white) population of 1,962 young adults, ages 18-30 yr at baseline, who completed symptom-limited graded exercise treadmill tests at the baseline (1985-1986) and year 7 (1992-1993) examinations of the CARDIA study. RESULTS: Mean test duration decreased 58 s (9.5%) over 7 yr (black men, 13.6% decrease, white men, 7.4%; black women, 11.1%; white women, 7.0%). Mean time to heart rate 130 (WL130), a measure of submaximal performance, decreased 31 s (11.3%) (black men, 16.9%; white men, 10.0%; black women, 12.3%; white women, 6.1%). Baseline body mass index (BMI) and physical activity were not statistically significant predictors of test duration change in any race-gender group, but change in BMI and activity were. Seven-year weight gain >20 lbs (31% of cohort) was associated with a large decrease in fitness (18.5% decrease in mean duration, 21.8% decrease in WL130). CONCLUSION: These data suggest that fitness declines during young adulthood in blacks and whites and that fitness changes are related to changes in weight and physical activity.

Adult↗
PubMed1998

Rising incidence of oesophageal adenocarcinoma in men in Australia.

Adenocarcinomas of the oesophagus and of the gastric cardia have been reported to be increasing in incidence in many countries, while the incidence of squamous cell carcinoma of the oesophagus is stable and non-cardia gastric cancers are decreasing in incidence. Age-standardized incidence rates for the years 1982-1993 for oesophageal adenocarcinoma and non-adenocarcinoma, and gastric cardia and non-cardia cancers were calculated based on state cancer registry incidence data. Time trends in the age-standardized rates were assessed using linear regression. A consistent increasing trend in the incidence of oesophageal adenocarcinoma in men was seen in all states of Australia and was statistically significant in all states except South Australia. There were no consistent nationwide trends in the incidence of oesophageal adenocarcinoma in women, although a trend towards an increase in the incidence of this cancer reached statistical significance (P < 0.05) in three states (New South Wales, Victoria, Queensland). There were no important trends in the incidence of oesophageal non-adenocarcinoma in either men or women. There were no consistent nationwide changes in the incidence of gastric cardia cancer in either men or women, although this cancer was significantly increasing in Tasmania in both men and women. The incidence of cancer of the stomach not arising at the gastric cardia was significantly decreasing in men in all states and was also decreasing in women in all states, although in women this decrease was statistically significant only in New South Wales, Victoria and Western Australia. There has been a dramatic increase in the incidence of oesophageal adenocarcinoma in men in Australia. The incidence of this cancer in men is now approximately equal with that of non-adenocarcinoma of the oesophagus. The incidence of non-cardia stomach cancer continues to fall.

Adenocarcinoma↗
PubMed1998

Community (mis)understanding of colorectal cancer treatment.

BACKGROUND: A study was undertaken to assess community understanding of colorectal cancer symptoms and colorectal cancer treatment. METHODS: A computer-assisted telephone survey was undertaken to interview 1000 men and women aged 40-60 years. RESULTS: Overall there was a considerable lack of information in the community about colorectal cancer symptoms and treatment. Men were less knowledgeable than women, and 28% of men were unable to name any symptoms of bowel cancer. Although surgery was mentioned by 53% of the sample, a third could not name any treatments. Most responses to questions about the effects of treatment related to chemotherapy-related disturbances and the possibility of having a colostomy bag postoperatively. CONCLUSIONS: There is inaccurate information in the community about colorectal cancer symptoms and treatment. This may inhibit involvement in screening programmes or delay presentation for therapy, as a result of undue concern about the prospects of treatment.

Adult↗
PubMed1998

Parathyroid hormone-related protein (PTHrP) mRNA splicing and parathyroid hormone/PTHrP receptor mRNA expression in human placenta and fetal membranes.

During human pregnancy, parathyroid hormone-related protein (PTHrP) and parathyroid hormone (PTH)/PTHrP receptor are produced by the uterus, placenta, fetal membranes (amnion and chorion) and developing fetus. PTHrP alternative 3' mRNA splicing results in transcripts which encode three PTHrP isoforms and have been identified in amnion. Uteroplacental PTHrP expression is greatest in amnion and increases dramatically during late pregnancy. The aims of this study were to determine PTH/PTHrP receptor mRNA expression at preterm and term gestations and to determine 3' alternative splicing patterns in placenta, amnion and choriodecidua at preterm and term gestations. Using semiquantitative reverse transcription-polymerase chain reaction, PTHrP and PTH/PTHrP receptor transcripts were identified in preterm (n=5) and term (n=7) gestational tissues. PTH/PTHrP receptor mRNA expression did not differ between tissue types or change with advancing gestation. In contrast, PTHrP expression in the same tissues increased with advancing gestation and was significantly greater in amnion than in placenta and choriodecidua. Thus PTHrP, although produced predominantly in amnion, may act in amnion and other tissues including placenta, choriodecidua and myometrium. In amnion over placenta, transcripts encoding PTHrP 1-139 and 1-173 were detected in some preterm and all term samples and those encoding PTHrP 1-141 were detected in all samples. Similar results were obtained for reflected amnion. In placenta and choriodecidua, PTHrP 1-139 and 1-173 transcripts were undetectable or of low abundance. PTHrP 1-141 transcripts were detected in some placenta and choriodecidua samples. In summary, transcripts encoding PTHrP 1-141 appeared to be more abundantly expressed than those encoding PTHrP 1-139 or 1-173. However, the up-regulation of PTHrP expression in amnion at term may involve each of the alternative 3' mRNA splicing pathways since transcripts for each isoform appeared to be more consistently expressed at term.

Alternative Splicing↗
PubMed1998

Achalasia cardia in infancy and childhood: an Indian experience.

Seven children with achalasia cardia, six of them infants, were seen over a 10-year period. In infantile achalasia, respiratory symptoms predominate and vomiting may easily be mistaken for gastroesophageal reflux (GER). Vomiting of uncurdled milk is characteristic of achalasia. Six children underwent esophagocardiomyotomy with good results in five. The procedure was transthoracic in two and transabdominal combined with an anterior fundoplication in the others. There was one post-operative death. Achalasia and alacrima were associated in two infants. One baby with this association also had a neurogenic bladder.

Child, Preschool↗
PubMed1997

Calcitonin receptors, bone sialoprotein and osteopontin are expressed in primary breast cancers.

Several human breast cancer cell lines express the calcitonin receptor (CTR), but this has not been demonstrated previously in clinical breast cancers. We examined 18 primary breast cancers by reverse transcription-PCR, for expression of CTR and of the bone proteins osteopontin (OPN) and bone sialoprotein (BSP). OPN and CTR were expressed by each of the tumours, and 7 (39%) additionally expressed an alternate form of CTR, whilst BSP was expressed by 13 tumours (72%). In situ hybridisation confirmed that expression of OPN and CTR was confined to the tumour cells. Expression of CTR, BSP and OPN may prove to be a useful marker for breast cancers, and their role in the homing of breast cancer cells to bone remains to be investigated.

Breast Neoplasms↗
PubMed1997

Seizures and epilepsy in the elderly.

Seizures and epilepsy in the elderly are an important and increasingly common clinical problem. Major known causes include cerebrovascular disease, brain tumor, degenerative disorders such as Alzheimer disease and cerebral amyloid angiopathy, and toxic-metabolic syndromes such as nonketotic hyperglycemia, postcardiac arrest, and drug-induced seizures. Recognition of seizures may be complicated by relatively unique clinical presentations and differential diagnosis. Nonconvulsive status epilepticus may present as recurrent episodes of confusion. The electroencephalogram is less useful than in the pediatric age group, but has a role in the evaluation of a first seizure and may rarely show characteristic patterns, such as poststroke periodic lateralized epileptiform discharges. Convulsive status, especially that associated with drug toxicity, is associated with increased mortality in the elderly. Pharmacological treatment is complicated by age-related changes in pharmacokinetics and pharmacodynamics and drug-drug and drug-disease interactions. Some of the new antiepileptic drugs may offer advantages for use in the elderly. Oxcarbazepine has fewer drug interactions than carbamazepine, and gabapentin has one, a reduction of felbamate renal elimination. Vigabatrin causes little cognitive dysfunction, while drugs that reduce excitatory amino acid neurotransmission, such as lamotrigine and felbamate, have potentially protective effects in patients with ischemic cerebrovascular disease. The use of barbiturates, primidone, the benzodiazepine clobazam, and the calcium blockers flunarizine and cinnarizine should preferably be avoided in the elderly.

Aged↗
PubMed1997

Phosphotyrosine phosphatase activity in the macrophage is enhanced by lipopolysaccharide, tumor necrosis factor alpha, and granulocyte/macrophage-colony stimulating factor: correlation with priming of the respiratory burst.

Tyrosine phosphorylation is now recognised as a key event in the activation of the macrophage respiratory burst. Since vanadate, a phosphotyrosine phosphatase (PTP) inhibitor is able to enhance the respiratory burst, we proposed that agents which prime the macrophage for enhance respiratory burst activity may do so by suppressing cellular PTP activity. The level of PTP activity in murine bone marrow-derived macrophages (BMM) was assessed by the ability of cell lysates to dephosphorylate 32P-labelled RR-src peptide. In contrast to our hypothesis, pretreatment of BMM with bacterial lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF alpha) or granulocyte/macrophage-colony stimulating factor (GMCSF), agents which prime for enhanced respiratory burst activity, was found to dramatically increase the level of cellular PTP activity. The time-course for this increase correlated well with the time course of priming by these agents. In addition, colony stimulating factor-1, a cytokine which does not prime the macrophage respiratory burst, did not enhance PTP levels. The physiological relevance of the increased PTP activity was further supported by confirming it was active against endogenous tyrosine phosphorylated substrates. Interestingly, phorbol myristate acetate and zymosan, agents which trigger the macrophage respiratory burst, were found to inhibit the PTP activity of BMM. Our results demonstrate the regulation of cellular PTP activity by priming agents and further highlight the importance of tyrosine phosphorylation and dephosphorylation events in the regulation of macrophage function.

Animals↗
PubMed1997

Longitudinal relaxation and diffusion measurements using magnetic resonance signals from laser-hyperpolarized 129Xe nuclei.

Methods for T1 relaxation and diffusion measurements based on magnetic resonance signals from laser-hyperpolarized 129Xe nuclei are introduced. The methods involve optimum use of the perishable hyperpolarized magnetization of 129Xe. The necessary theoretical framework for the methods is developed, and then the methods are applied to measure the longitudinal relaxation constant, T1, and the self-diffusion constant, D, of hyperpolarized 129Xe. In a cell containing natural abundance 129Xe at 790 Torr, the T1 value was determined to be 155 +/- 5 min at 20 degrees C and at 2.0 T field. For a second cell at 896 Torr, at the same field and temperature, the T1 value was determined to be 66 +/- 2 min. At a higher field of 7.05 T, the T1 values for the two cells were found to be 185 +/- 10 and 88 +/- 5 min, respectively. The 129Xe self-diffusion constant for the first cell was measured to be 0.057 cm2/ s and for the second cell it was 0.044 cm2/s. The methods were applied to 129Xe in the gas phase, in vitro; however, they are, in principle, applicable for in vivo or ex vivo studies. The potential role of these methods in the development of newly emerging hyper-polarized 129Xe MRI applications is discussed.

Animals↗
PubMed1997

Frequency and clinico-pathological associations of ras mutations in colorectal cancer in the Victorian population.

BACKGROUND: Mutations in the oncogene ras occur in 20-50% of colorectal cancers. The presence of these mutations allows screening tests to be developed based on the identification of mutant DNA in cells derived from cancers. A study of the prevalence and clinicopathological associations of ras mutations was undertaken. METHODS: The frequency of mutations in codons 12 and 13 of the K-ras gene was investigated in 103 colorectal carcinomas using restriction fragment length polymorphism. RESULTS: Mutations were detected in 32% (33/103) of the tumours, predominantly in codon 12 (25/33). No mutations were detected in normal-appearing mucosa from the same patients. CONCLUSIONS: Analysis of the frequency of ras mutations compared with various independent clinical variables revealed a sex-linked relationship between the presence of a ras mutation and nodal status but no correlation with any other clinical parameter was found. The findings suggest that screening tests based on ras mutation detection may lack sensitivity because of the presence of mutations in only 32% of tumours.

Aged↗