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Biomedical subjects

J Coulter

Publications and source records attributed to J Coulter.

17 recordsLinked to original sources
PubMed2000

Progressive increases in de novo methylation of CpG islands in bladder cancer.

We conducted a quantitative analysis of the extent of de novo methylation of four CpG islands in human urinary transitional cell carcinomas of different stages and grades to determine how frequently these CpG islands became methylated in transition cell carcinomas during progression. The CpG islands included exon 5 of PAX6, exon 2 of p16, the 5' end of the deleted in bladder cancer gene, and the 5' end of transmembrane protein containing epidermal growth factor and follistatin domains. These sequences were not methylated in normal urothelial tissues; however, 48 of the 54 tumors examined (89%) showed methylation levels in excess of 20% for at least one of the markers. The number of markers concurrently methylated in individual tumors increased with the stage of the tumor, with several of the more aggressive invasive cancers showing hypermethylation of all four markers compared with the less aggressive invasive cancers. However, considerable methylation defects were present in superficial, preinvasive, papillary tumors. These data demonstrate that 89% of bladder cancers have increased methylation of CpG islands relative to their normal counterparts and suggest the occurrence of a hypermethylator phenotype in which multiple independent CpG islands become concurrently methylated in individual tumors in a process associated with tumor progression.

Carcinoma, Transitional Cell↗
PubMed2000

Immunoreactivity of recombinant squamous cell carcinoma antigen and leupin/SCCA-2: implications for tumor marker detection.

OBJECTIVES: Squamous cell carcinoma antigen (SCCA) is a member of the serpin superfamily, and has been used as a serological tumor marker for cervical squamous cell carcinomas. We have identified a closely related serpin gene, leupin (SCCA-2), which may be the fraction previously thought to be the acidic isoform of SCCA. The purpose of this study is to isolate the individual recombinant proteins, to examine their reactivity with current immunological detection methods, and to use a gene-specific method to examine their expression in the uterine cervix. METHODS: We have expressed and purified recombinant forms of SCCA and leupin individually. The proteins were characterized with respect to their isoelecric points and their reactivity with the monoclonal antibody from the current tumor marker diagnostic immunoassay (IMx SCC). Reverse transcription polymerase chain reaction (RT-PCR) with gene-specific primers was used to examine expression of both genes. RESULTS: Isoelectric focusing shows that leupin is the more acidic antigen with a determined pI for recombinant leupin (rLeupin) of 6.01, with rSCCA having a pI of 6.17. The IMx SCC monoclonal antibody recognized both rSCCA and rLeupin in immunoassays and immunoblots and both genes are expressed in normal cervix and in cervical carcinoma tissue. CONCLUSIONS: The findings from this study suggest that all previous clinical studies examining SCCA expression have used methodology that detects two gene products. The confirmation that leupin or SCCA-2 is the more acidic protein and that its expression is significantly elevated in cervical cancer suggests that this gene product may be the more important tumor marker.

Antibodies, Monoclonal↗
PubMed2000

Frequency of fruit and vegetable consumption and blood antioxidants in the Caerphilly cohort of older men.

OBJECTIVE: To assess the number of portions of fruit and vegetables consumed daily by a large representative sample of older men, and to determine how blood antioxidant (vitamins E, A and carotenoids) concentrations vary with fruit and vegetable consumption. DESIGN: Cross-sectional study of free-living men. SUBJECTS: Men aged 55-69 y (dietary data, n=1957; blood data, n=1874) participating in Phase III (1989-1993) of the Caerphilly and Speedwell Collaborative Heart Disease Studies. METHODS: Dietary data were obtained by semi-quantitative food-frequency questionnaire and blood samples were analysed for antioxidant vitamins. Men were subdivided into groups on the basis of portions per day of fruit and vegetables. Within these sub-groups, mean and 95% ranges of intakes and of blood antioxidant levels were obtained. Log transformations were performed where appropriate. RESULTS: Only 4.3% of the men met the recommended target of five portions, while 33.3% of the men consumed one or fewer portions of fruit and vegetables per day. Those men who consumed the poorest diets with respect to fruit and vegetable intakes were more likely to be from lower socio-economic classes, drink more alcohol and be current smokers. Fruit and vegetable intake reflected plasma concentrations of antioxidants, which showed a dose-response relationship to frequency of consumption. CONCLUSIONS: Older men in the UK consume much less fruit and vegetables than current recommendations. Major difficulties are likely to be encountered in trying to meet a dietary target that is clearly much higher than the fruit and vegetable consumption of large sections of the older population in the UK. SPONSORSHIP: This work was supported by the Medical Research Council.

Aged↗
PubMed1999

Antioxidant enzymes, inflammatory indices and lifestyle factors in older men: a cohort analysis.

We examined the relationship between blood antioxidant enzyme activities, indices of inflammatory status and a number of lifestyle factors in the Caerphilly prospective cohort study of ischaemic heart disease. The study began in 1979 and is based on a representative male population sample. Initially 2512 men were seen in phase I, and followed-up every 5 years in phases II and III; they have recently been seen in phase IV. Data on social class, smoking habit, alcohol consumption were obtained by questionnaire, and body mass index was measured. Antioxidant enzyme activities and indices of inflammatory status were estimated by standard techniques. Significant associations were observed for: age with alpha-1-antichymotrypsin (p < 0.0001) and with caeruloplasmin, both protein and oxidase (p < 0.0001); smoking habit with alpha-1-antichymotrypsin (p < 0.0001), with caeruloplasmin, both protein and oxidase (p < 0.0001) and with glutathione peroxidose (GPX) (p < 0.0001); social class with alpha-1-antichymotrypsin (p < 0.0001), with caeruloplasmin both protein (p < 0.001) and oxidase (p < 0.01) and with GPX (p < 0.0001); body mass index with alpha-1-antichymotrypsin (p < 0.0001) and with caeruloplasmin protein (p < 0.001). There was no significant association between alcohol consumption and any of the blood enzymes measured. Factor analysis produced a three-factor model (explaining 65.9% of the variation in the data set) which appeared to indicate close inter-relationships among antioxidants.

Acute-Phase Proteins↗
PubMed1999

Survival of patients with epithelial ovarian cancer and the effect of lymphadenectomy in those with stage 3 disease.

This study looks at the 10-year survival data in patients with epithelial ovarian carcinoma at the Mercy Hospital for Women, Melbourne. An ovarian cancer database was established at the hospital in 1980, since then 253 patients have been diagnosed with epithelial ovarian cancer. The 5-year survival rates for Stages 1 to 4 are 75%, 55%, 24% and 21% respectively. The 10-year survival rates are 65%, 55%, 16% and 15% respectively. One hundred and thirty patients have been diagnosed with Stage 3 disease. The Gynaecologic Oncology Department at the Mercy Hospital for Women was formalized in 1987. Patients treated for ovarian cancer by the unit since 1987 had a significantly better survival (median 47 months) than patients treated prior to 1987 (median 17 months), p = 0.03. There is much debate as to whether lymphadenectomy in patients with ovarian cancer is of therapeutic value. In this study the patients with Stage 3 disease and who had a lymphadenectomy performed had a better 5-year survival rate of 38% compared to 22% in the group who did not have a lymphadenectomy (p < 0.05). The Stage 3 patients who had negative retroperitoneal nodes had a 10-year survival rate of 51%. There was no difference in survival rate between patients with endometrioid and serous papillary carcinomas.

Australia↗
PubMed1998

Riboflavin and vitamin B-6 intakes and status and biochemical response to riboflavin supplementation in free-living elderly people.

Free-living elderly people aged > or = 65 y were recruited to assess riboflavin and vitamin B-6 intakes and status and the effect of riboflavin supplementation on biochemical indicators of these 2 vitamins. The status of riboflavin (erythrocyte glutathione reductase activation coefficient; EGRAC) and vitamin B-6 (plasma pyridoxal-5'-phosphate; PLP) were determined in a total sample of 92 subjects, from whom dietary intake data were obtained by using the diet history method (n = 83). Although dietary intakes of both vitamins were considered to be adequate according to current reference values, abnormal EGRAC and plasma PLP values were identified in 49% and 38% of subjects, respectively, with 21% having suboptimal status for both nutrients. A subgroup of subjects from the initial sample (n = 45) was assigned in a double-blind manner to receive either 1.6 or 25 mg riboflavin or placebo daily for 12 wk. In those subjects with a baseline EGRAC or plasma PLP value falling outside the currently accepted threshold value for adequacy, low-dose riboflavin supplementation improved status of the limiting nutrient significantly (P<0.0001 and P = 0.020 for EGRAC and plasma PLP responses, respectively). We conclude that a high proportion of healthy elderly people may have suboptimal status for these nutrients despite apparently adequate dietary intakes. Furthermore, we showed that riboflavin supplementation at physiologic doses corrects biochemical abnormalities of not only EGRAC, but also plasma PLP, confirming the biochemical interdependency of these vitamins and suggesting that riboflavin is the limiting nutrient.

Age Factors↗
PubMed1997

Thyroid hormones and selenium status in breast cancer.

Within a case-control study of postmenopausal breast cancer patients (n = 99) and matched healthy controls (n = 105), thyroid hormone levels were compared and correlated with toenail selenium concentrations. Plasma triiodothyronine (T3) was significantly lower in cases (1.4 +/- 0.4 nmol/l) than in controls (1.6 +/- 0.4 nmol/l), and a strong inverse relationship with breast cancer was observed with an odds ratio of 0.17 (95% CI = 0.08-0.36) in the highest compared with the lowest tertile of T3. Plasma thyroxine and thyroid-stimulating hormone concentrations were similar between cases and controls. Plasma T3 concentration was positively associated with toenail selenium in cases (age-adjusted regression coefficient = 0.049) and controls (age-adjusted regression coefficient = 0.036). Toenail selenium concentrations tended to be lower in cases than in controls, but the differences did not reach statistical significance. Although the disease process per se may explain the lower plasma T3 concentrations, it is also possible, inasmuch as these patients were in early-stage breast cancer, that selenium status may be influencing T3 levels via changes in the activity of the selenoenzyme type 1 iodothyronine deiodinase.

Aged↗
PubMed1997

Normal eruption of the maxillary canine quantified in three dimensions.

The normal eruption path of maxillary canine teeth was quantified on annual lateral and depressed postero-anterior cephalometric radiographs of 15 females and 15 males aged 5-15 years. The lateral view was rotated so that the horizontal coincided with the Frankfort plane on the depressed views, thus orientating the two views in space. Successive positions of canine cusps were marked on tracings of both views superimposed on the anterior outline of the zygomatic process. All positions of the canine cusps were digitized and the horizontal, vertical and lateral annual differences found by subtraction, taking the first position of the canine as the origin. The chronological data were corrected for enlargement and adjusted to increments of 12 months. Adjustments were also made to take into account varying ages of eruption. Posterior movement occurred between 7 and 13 years (all three years before eruption, the year of eruption and the following year). Vertical movement occurred between 5 and 13 years (all of the six years before eruption, the year of eruption and the following year). Lateral movement tended to be in a palatal direction up to 2 years before eruption followed by significant buccal movement in the year before eruption, the year of eruption and the following year. Data are given for eruption in three planes.

Adolescent↗
PubMed1993

Nerve regeneration across colorectal anastomoses after low anterior resection in a canine model.

The disappearance and subsequent return of the recto-anal inhibitory reflex following low anterior resection was investigated using manometric and histological studies. Ten female greyhound dogs were randomised into 2 groups. All underwent low anterior resection. Five had stapled EEA anastomosis of the rectum and 5 were handsewn. The recto-anal inhibitory reflex was measured before and after surgery using a microtransducer tipped catheter. Six months postoperatively the recto-anal inhibitory response was again measured and the animals sacrificed. The colorectal anastomoses were examined histologically using light microscopy to determine the pattern of innervation at the anastomotic site. Manometric studies showed the recto-anal inhibitory reflex present in all cases pre-operatively, in only 1 case on the tenth postoperative day and was present in eight cases after 6 months. Histological examination of longitudinal sections across the anastomoses showed clear evidence of regenerating nerve trunks at the anastomotic site in both stapled and handsewn groups. We conclude that the return of the recto-anal inhibitory reflex is associated with regeneration of intramural autonomic nerves across the anastomotic scar.

Anastomosis, Surgical↗
PubMed1992

Mechanism of sphincter impairment following low anterior resection.

It has been postulated that reduction in anal resting pressure following low anterior resection is due to intraoperative injury to the internal anal sphincter during transanal passage of the stapling device or damage to its nerve supply in the course of rectal mobilization. The aim of this study was to assess the relative importance of either mechanism. Fourteen dogs had a standard segment of colon and distal rectum excised. Colorectal reconstruction was performed using either a low stapled EEA (U.S. Surgical Corporation, Norwalk, CT) colorectal anastomosis (n = 7) or a handsewn anastomosis (n = 7). Anorectal manometry was performed preoperatively and again on the 10th postoperative day. Resting anal pressure was significantly reduced after EEA anastomosis (mean +/- SEM: before, 49 +/- 3 mm Hg; after, 20 +/- 4 mm Hg; P less than 0.001) and handsewn anastomosis (mean +/- SEM: before, 46 +/- 4 mm Hg; after, 35 +/- 4 mm Hg; P less than 0.01). Postoperative resting pressures were also significantly reduced (P less than 0.05) following EEA anastomosis when compared with the handsewn group. This study suggests that damage to the innervation of the internal anal sphincter during rectal mobilization and further direct injury to the sphincter during transanal instrumentation both contribute to the fall in anal resting pressure observed following low anterior resection.

Anal Canal↗
PubMed1989

A simple electronic volume cell sorter for clonogenicity assays.

A single-parameter electronic volume flow cell sorter that can be easily and inexpensively constructed using existing technology is described. The instrument is designed for ease and flexibility of operation, including such features as a large open area for recovering sorted cells into a variety of dishes or vessels; a remote, electrically activated fluidics system; a mechanism for heating or cooling samples during sorting; a simple arrangement for monitoring and adjusting the sorting control parameters; and an interface to a standard IBM personal computer for data acquisition, analysis, and control of the sorting windows. Several researchers in our laboratory now routinely use this sorter for plating precise numbers of cells directly into culture dishes in an aseptic manner for clonogenicity assays. The instrument can sort cells at rates of up to approximately 2,000 per second with greater than 80% sorting efficiency and no cytotoxicity. An advantage of this system is that the sorting windows can be set to exclude acellular debris and include either the entire cell volume distribution or a subset thereof. Applications of the instrument are detailed, including 1) precise cell plating for low-dose survival studies, 2) separation of cells into age compartments, and 3) rapid inoculation of single cells into multiwell dishes for cloning studies. Advantages of this technology for cell survival studies are detailed, along with some limitations to its applicability.

Animals↗