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Biomedical subjects

R J Thomas

Publications and source records attributed to R J Thomas.

At least 37 records · Page 2Linked to original sources
PubMed2000

Methylation of exon 2 of p16 is associated with late stage oesophageal cancer.

Methylation of the p16 gene was studied in 16 oesophageal tumours. Five (31%) of the tumours were found to be methylated in exon 1 and eight (50%) were methylated in exon 2. The loss of p16 protein correlated with methylation of exon 1 (P = 0.005). However, methylation of exon 2, but not exon 1, was found to be associated with late stage tumours (P = 0.01). We conclude that the methylation of exon 2 of p16 may have effects on the progression of oesophageal tumours that are independent of the expression of the p16 protein.

Adenocarcinoma↗
PubMed2000

A pilot study on the effects of exercise in patients with systemic lupus erythematosus.

OBJECTIVE: A pilot study was designed to assess the efficacy and safety of different exercise therapies on patient-reported fatigue and functional status. METHODS: Ten patients with systemic lupus erythematosus (SLE) were randomly placed in either an aerobic exercise group (group 1: n = 5) or a range of motion/muscle strengthening (ROM/MS) exercise group (group 2: n = 5). Outcome measures assessed at baseline and the end of the study were fatigue, functional status, disease activity, cardiovascular fitness, isometric strength, bone mineral density (BMD) of the lumbar spine and femoral neck, and parathyroid hormone and osteocalcin as representative bone biochemical markers for bone resorption and bone formation, respectively. RESULTS: Both aerobic and ROM/MS types of exercise were safe and did not worsen SLE disease activity. Patients in both exercise groups showed some improvement in fatigue, functional status, cardiovascular fitness, and muscle strength. Both groups showed increased bone turnover, but BMD was unchanged. Eighty percent of the patients met the compliance standard for the study. CONCLUSIONS: This pilot study shows the feasibility of exercise for SLE patients. The potential value of this approach shows promise in the routine management of these patients.

Activities of Daily Living↗
PubMed2000

Results of laparoscopic fundoplication where atypical symptoms coexist with oesophageal reflux.

BACKGROUND: Laparoscopic Nissen fundoplication (LNF) has been increasingly performed for gastro-oesophageal reflux disease. The outcomes of LNF for patients with concurrent symptoms other than heartburn are unclear. The purpose of the present paper was to review the outcomes of LNF performed by one surgeon over 4 years and compare the outcomes of patients with reflux symptoms with those of patients having reflux symptoms plus atypical symptoms. METHODS: The records of a consecutive series of 90 patients were reviewed. Preoperative symptoms were defined as typical (heartburn and reflux) or atypical (other symptoms, e.g. cough, atypical chest pain, choking). At the time of follow up an independent observer interviewed patients, and collected data on current symptoms and patient satisfaction. A questionnaire of current symptoms and patient satisfaction was completed. A satisfaction score from 1 to 10 was given by patients, with 1 being very unsatisfied and 10 being very satisfied. RESULTS: Of the 90 patients, 97% had typical symptoms and 56% had concurrent atypical symptoms. Eighty-three of 90 patients were contacted; typical reflux symptoms improved in 95% of patients whereas atypical symptoms improved in only 54%. Overall, the mean satisfaction score was 8.7. Patients with atypical symptoms had a lower satisfaction score of 8.0 versus a satisfaction score of 9.0 for patients with only typical symptoms (P < 0.05). Patients with a satisfaction score < 8.0 had a higher rate of atypical symptoms (75%) than patients with a satisfaction score > or = 8 (50%). CONCLUSION: Laparoscopic Nissen fundoplication controlled typical reflux symptoms very well but atypical symptoms were improved in only approximately 50%. A lower satisfaction score was associated with preoperative atypical symptoms.

Adolescent↗
PubMed2000

Nuclear and nucleolar localization of parathyroid hormone-related protein.

Parathyroid hormone-related protein (PTHrP) was first discovered as the factor causing hypercalcaemia produced by solid tumours frequently associated with the head and neck, breast, lung and kidney. The homology of its amino-terminus to parathyroid hormone (PTH; eight of the first 13 residues are identical), enables it to share the same receptor and perform similar biological functions to PTH. The sequences of PTHrP C-terminal to its PTH-like region confer functions such as transplacental calcium transport, renal bicarbonate excretion and in vitro osteoclast inhibition. Recent findings have shown that PTHrP is a nuclear/nucleolar protein in certain tissues and that this localization is cell cycle-regulated, mediated by the middle portion of the molecule, and involves the nuclear import receptor importin beta1. The present review discusses what is known about the pathway by which PTHrP localizes to the nucleus/nucleolus and the putative roles it may have there.

Amino Acid Motifs↗
PubMed2000

Comparison of macular versus paramacular retinal sensitivity to femtosecond laser pulses.

Single 130 fs laser pulses in the near-IR (800 nm) were used to create ophthalmoscopically viewed minimum visible lesions (MVLs) within the macular and paramacular regions in rhesus monkey eyes. MVL thresholds at 1 and 24 h are reported as the 50% probability for damage (ED50) together with their fiducial limits at the 95% confidence level. These measured thresholds are compared with previously reported thresholds for near-IR and visible wavelengths for both macular and paramacular areas. Threshold doses were lower at the 24 h reading than at the 1 h reading for both retinal regions and the ED50s for the macula were slightly lower than for the paramacula. We measured the 24 h MVL ED50 thresholds to be 0.35 and 0.55 microJ for the macular and paramacular areas, respectively. The combined data for both areas yielded a threshold of 0.45 microJ.

Animals↗
PubMed2000

Sodium butyrate-induced differentiation of human LIM2537 colon cancer cells decreases GSK-3beta activity and increases levels of both membrane-bound and Apc/axin/GSK-3beta complex-associated pools of beta-catenin.

Analysis of the glycogen synthase kinase-3beta (GSK-33) activity in several colon cancer cell lines suggested a correlation between comparatively low enzyme activity and moderate to high differentiation status. Treatment of LIM2537 cells, a poorly differentiated colon cancer cell line, with the potent differentiating agent sodium butyrate resulted in 34% reduction in GSK-3beta activity in the treated cells (P < 0.028, n = 3). Decreases in GSK-3beta activity were paralleled by stabilization of cytoplasmic beta-catenin, a hallmark of Wnt signaling. However, in contrast to Wnt signaling, expression of the beta-catenin/ TCF target genes c-myc and cyclin D1 did not appear to be increased in the sodium butyrate-treated cells. Interestingly, expression of membrane-bound beta-catenin was increased in the sodium butyrate-treated cells. This suggests that, in the context of cellular differentiation, increases in beta-catenin expression may be sequestered at the cell membrane and suggests that a possible role of sodium butyrate in promoting differentiation may be via increasing the levels of beta-catenin available for cell adhesion.

Alkaline Phosphatase↗
PubMed2000

The CardioVision 2020 baseline community report card.

OBJECTIVE: To establish baseline data for the CardioVision 2020 program, a collaborative project in Olmsted County, Minnesota, organized to reduce cardiovascular disease rates by altering 5 health-related items: (1) eliminating tobacco use and exposure, (2) improving nutrition, (3) increasing physical activity, (4) lowering serum cholesterol level, and (5) controlling blood pressure. SUBJECTS AND METHODS: Data about tobacco use, diet, and physical activity were collected by random digit dial interview and follow-up questionnaire from a sample of the population. Blood pressure data were collected from medical records at Mayo Clinic, and serum cholesterol data were derived from the Mayo Clinic laboratory database. Data were stratified into 6 age groups. RESULTS: A total of 624 women and 608 men responded to the questionnaire. Population blood pressure data were available for 1,956 women and 1,084 men. Population serum cholesterol data were available for 17,042 women and 12,511 men. Except for women in the 30- to 39-year-old age group, less than 10% of the population sampled met 4 or 5 goals. Conversely, about 90% of the population met at least 1 goal, and about 80% met 1, 2, or 3 of the goals. CONCLUSION: The data from the Olmsted County population indicate considerable opportunity to reduce this population's burden of cardiovascular disease.

Adult↗
PubMed2000

Microsatellite instability in gastrointestinal tract tumours.

Although a number of studies have documented microsatellite instability (MSI) in gastrointestinal tumours, the clinical significance is uncertain. In this study the MSI status and clinicopathological features were examined in gastric and colorectal tumours. Eighty-four gastrointestinal tumours were examined for MSI. Normal and tumour DNA isolated from the same patients were analysed at five different microsatellite loci. Clinical features of these patients were also collated and compared with MSI status. High level MSI (MSI-H) (as defined by instability in 2 or more microsatellites) was detected in 6 out of 47 (13%) colon tumours and 6 of 37 (16%) gastric tumours. The frequency of MSI-H between these groups was not statistically significant (P = 0.36). There was no significant correlation with patient age or gender, UICC stage, or degree of differentiation of the tumour. This was true both when analysed as a group, as well as when divided into colon and gastric sites. Our results confirm that a proportion of sporadic tumours from the colon and stomach exhibit an MSI-H phenotype. However, there was no significant relationship between the presence of MSI and any of the clinicopathological characteristics studied.

Colonic Neoplasms↗
PubMed1999

Lipopolysaccharide-induced priming of the human neutrophil is not associated with a change in phosphotyrosine phosphatase activity.

The activation of the neutrophil respiratory burst is a two-step process involving an initial 'priming' phase followed by a 'triggering' event. The biochemical mechanisms which underlie these events are yet to be fully elucidated, but the evidence suggests a crucial role for stimulus-induced tyrosine phosphorylation. The enhanced tyrosine phosphorylation observed upon triggering primed cells may reflect an increase in tyrosine kinase activity or a reduction in the levels of the opposing phosphotyrosine phosphatases (PTPases). We have investigated the latter by examining the possibility that lipopolysaccharide (LPS)-induced priming of the neutrophil respiratory burst involves the suppression of cellular PTPase activity. Purified human neutrophils were incubated for 60 min with and without LPS. Priming of the respiratory burst was confirmed by fMet-Leu-Phe-induced cytochrome c reduction. The level of PTPase activity was assessed by dephosphorylation of [32P]RR-src peptide as substrate. Pretreatment of human neutrophils with 200 ng/ml LPS induced a 2.9 +/- 0.3 (mean +/- SEM, n = 3, P = 0.022) fold increase in the fMet-Leu-Phe-triggered respiratory burst. In the same cells, LPS did not induce a significant change in the total cellular PTPase activity (1.02 +/- 0.02-fold, mean +/- SEM, n = 3, P = 0.63). Similarly, stimulation of neutrophils with fMet-Leu-Phe or phorbol myristate acetate did not significantly affect the cellular PTPase activity (P = 0.94 and 0.68, respectively). Our results suggest that suppression of PTPase activity is not the mechanism underlying the priming and/or triggering of the neutrophil respiratory burst.

Dose-Response Relationship, Drug↗
PubMed1999

Localization of RANKL (receptor activator of NF kappa B ligand) mRNA and protein in skeletal and extraskeletal tissues.

RANKL (receptor activator of NFkappaB ligand) is a membrane-associated osteoblastic molecule, and along with macrophage-colony-stimulating factor, is crucial for osteoclast formation. RANKL is known to be strongly expressed in osteoblasts and lymphoid tissues. We have sought to determine the skeletal and extraskeletal sites of production of RANKL mRNA and protein using the techniques of in situ hybridization and immunohistochemistry. Expression of RANKL mRNA and protein were determined in the developmental progression of endochondral bone formation in mouse, intramembranous bone formation in a rabbit model (mRNA only), in human giant cell tumors of bone, and at extraskeletal sites in the mouse. RANKL mRNA was expressed in prehypertrophic and hypertrophic chondrocytes at day E15 embryonic mouse long bone, and its expression was maintained at these sites throughout development. In newborn and adult mice, high levels of RANKL mRNA were expressed in mesenchymal cells of the periosteum and in mature osteoblasts, while megakaryocytes within the marrow microenvironment expressed RANKL mRNA from 1 week of age. Immunohistochemical analysis revealed a similar localization pattern of RANKL protein at the sites described. In the intramembranous bone formation model, RANKL mRNA was expressed in mesenchymal cells and in actively synthesizing osteoblasts, but not in flattened lining osteoblasts or late osteocytes. Expression of RANKL mRNA and protein in osteoclasts was variable with those within resorption lacunae showing the strongest signal/staining. Likewise, expression varied in osteoclasts from giant cell tumor of bone with a minority of tartrate-resistant acid phosphatase-positive multinucleated cells having no detectable RANKL mRNA or protein. In extraskeletal tissues, RANKL mRNA and protein were detected in the brain, heart, kidney, skeletal muscle, and skin throughout mouse development, suggesting the possibility of several other functions of the molecule. RANKL was also developmentally regulated, as evidenced by its expression in the intestine, liver, and lung at E15 and newborn mouse but not in the adult.

Amino Acid Sequence↗
PubMed1999

Breast cancer cells interact with osteoblasts to support osteoclast formation.

Breast cancers commonly cause osteolytic metastases in bone, a process that is dependent upon osteoclast-mediated bone resorption. Recently the osteoclast differentiation factor (ODF), better termed RANKL (receptor activator of NF-kappaB ligand), expressed by osteoblasts has been cloned as well as its cognate signaling receptor, receptor activator of NFkappaB (RANK), and a secreted decoy receptor osteoprotegerin (OPG) that limits RANKL's biological action. We determined that the breast cancer cell lines MDA-MB-231, MCF-7, and T47D as well as primary breast cancers do not express RANKL but express OPG and RANK. MCF-7, MDA-MB-231, and T47D cells did not act as surrogate osteoblasts to support osteoclast formation in coculture experiments, a result consistent with the fact that they do not express RANKL. When MCF-7 cells overexpressing PTH-related protein (PTHrP) were added to cocultures of murine osteoblasts and hematopoietic cells, osteoclast formation resulted without the addition of any osteotropic agents; cocultures with MCF-7 or MCF-7 cells transfected with pcDNAIneo required exogenous agents for osteoclast formation. When MCF-7 cells overexpressing PTHrP were cultured with murine osteoblasts, osteoblastic RANKL messenger RNA (mRNA) levels were enhanced and osteoblastic OPG mRNA levels diminished; MCF-7 parental cells had no effect on RANKL or OPG mRNA levels when cultured with osteoblastic cells. Using a murine model of breast cancer metastasis to bone, we established that MCF-7 cells that overexpress PTHrP caused significantly more bone metastases, which were associated with increased osteoclast formation, elevated plasma PTHrP concentrations and hypercalcaemia compared with parental or empty vector controls.

Animals↗
PubMed1999

Spectrally resolved white-light interferometry for measurement of ocular dispersion.

Spectrally resolved white-light interferometry was used to measure the wavelength dependence of refractive index (i.e., dispersion) for various ocular components. Verification of the technique's efficacy was substantiated by accurate measurement of the dispersive properties of water and fused silica, which have both been well-characterized in the past by single-wavelength measurement of the refractive index. The dispersion of bovine and rabbit aqueous and vitreous humors was measured from 400 to 1100 nm. In addition, the dispersion was measured from 400 to 700 nm for aqueous and vitreous humors extracted from goat and rhesus monkey eyes. An unsuccessful attempt was also made to use the technique for dispersion measurement of bovine cornea and lens. The principles of white-light interferometry, including image analysis, measurement accuracy, and limitations of the technique, are discussed. In addition, alternate techniques and previous measurements of ocular dispersion are reviewed.

Animals↗