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Biomedical subjects

D Scott

Publications and source records attributed to D Scott.

At least 73 records · Page 4Linked to original sources
PubMed2000

Sialochemical markers of salivary gland involvement with Sjögren's syndrome secondary to rheumatoid arthritis and primary biliary cirrhosis.

Sjögren's syndrome is an autoimmune condition affecting the lacrimal and salivary glands and can be associated with rheumatoid arthritis and primary biliary cirrhosis. Parotid salivas collected from patients and normal controls were analysed for lactoferrin, IgA and beta2-microglobulin (measured by ELISA), and cystatin (measured by a enzyme inhibition assay). Output data provided less variable means, whilst expressing results as a proportion of the total protein provided greater specificity as markers for Sjögren's syndrome. Levels of specificity for IgA, lactoferrin and beta2-microglobulin were all high (100, 95 and 100%, respectively). Sensitivity levels of these markers (but not cystatin) tended to be similar for Sjögren's syndrome secondary to primary biliary cirrhosis (IgA, 25%; lactoferrin, 63%; and beta2-microglobulin, 50%), compared to Sjögren's syndrome secondary to connective tissue diseases such as rheumatoid arthritis (IgA, 50%; lactoferrin, 86%; and beta2-microglobulin; 38%).

Arthritis, Rheumatoid↗
PubMed2000

Acid resistance of Helicobacter pylori depends on the UreI membrane protein and an inner membrane proton barrier.

ureI encodes an inner membrane protein of Helicobacter pylori. The role of the bacterial inner membrane and UreI in acid protection and regulation of cytoplasmic urease activity in the gastric microorganism was studied. The irreversible inhibition of urease when the organism was exposed to a protonophore (3,3',4', 5-tetrachlorsalicylanide; TCS) at acidic pH showed that the inner membrane protected urease from acid. Isogenic ureI knockout mutants of several H. pylori strains were constructed by replacing the ureI gene of the urease gene cluster with a promoterless kanamycin resistance marker gene (kanR). Mutants carrying the modified ureAB-kanR-EFGH operon all showed wild-type levels of urease activity at neutral pH in vitro. The mutants resisted media of pH > 4.0 but not of pH < 4.0. Whereas wild-type bacteria showed high levels of urease activity below pH 4.0, this ability was not retained in the ureI mutants, resulting in inhibition of metabolism and cell death. Gene complementation experiments with plasmid-derived H. pylori ureI restored wild-type properties. The activation of urease activity found in structurally intact but permeabilized bacteria treated with 0.01% detergent (polyoxy-ethylene-8-laurylether; C12E8), suggested a membrane-limited access of urea to internal urease at neutral pH. Measurement of 14C-urea uptake into Xenopus oocytes injected with ureI cRNA showed acid activation of uptake only in injected oocytes. Acceleration of urea uptake by UreI therefore mediates the increase of intracellular urease activity seen under acidic conditions. This increase of urea permeability is essential for H. pylori survival in environments below pH 4.0. ureI-independent urease activity may be sufficient for maintenance of bacterial viability above pH 4.0.

Acids↗
PubMed2000

Chromosome instability in fibroblasts derived from Li-Fraumeni syndrome families without TP53 mutations.

The mean in vitro lifespan of dermal fibroblast strains derived from cancer-affected individuals belonging to families conforming to the classical Li-Fraumeni-syndrome or the Li-Fraumeni-like syndrome (LF strains), but in whom no TP53 mutation has been found, was not significantly different to that of normal strains. This was in contrast to LF strains that carry TP53 mutations. Cytogenetic observations of numerical and structural chromosome abnormalities were made on Giemsa stained metaphases prepared at different times during the lifespan of strains. Five strains from different LF families showed significantly increased frequencies of abnormal cells during the last 10% of their lifetime compared with seven normal strains and three other LF strains fell outside the normal range but did not reach significance. Two LF strains fell within the normal range indicating heterogeneity of the phenotype in this subset of LF fibroblasts. Numerical aberrations were the major aberration type observed. These observations of genetic instability are similar, but generally less strongly expressed, to those seen in LF strains with TP53 mutations. The basis for genetic instability in LF strains without TP53 mutations is not known, but appears not to involve defects in either the G(1)checkpoint or the checkpoint kinase hChk2.

Adolescent↗
PubMed2000

The use of cryopreserved lymphocytes in assessing inter-individual radiosensitivity with the micronucleus assay.

PURPOSE: The feasibility of using cryopreserved lymphocytes to detect inter-individual differences in chromosomal radiosensitivity was investigated. Typically, such studies are conducted with fresh blood samples but, in a clinical setting, when availability of samples is unpredictable, this is not always convenient. The sensitivity of 23 normal healthy donors, 11 breast cancer patients who had shown severe acute skin reactions to radiotherapy and seven ataxia telangiectasia (A-T) heterozygotes was determined. MATERIALS AND METHODS: Thawed lymphocytes were exposed to high (HDR) or low dose rate (LDR) gamma irradiation (3.5 Gy) in Go, stimulated with PHA, treated with cytochalasin-B 24 h later and then harvested at 90 h for the determination of micronucleus (MN) yields in binucleate cells. RESULTS: Each normal donor was tested one to three times. Mean MN yields were 76.1 +/- 9.3/100 cells at HDR and 44.5 +/- 5.3 at LDR, giving an LDR sparing effect of 39.6 +/- 9.3%. A relatively high proportion of tests failed to yield sufficient binucleate cells for analysis. Inter-experimental variability was also high and it was not possible to demonstrate inter-individual differences in sensitivity in spite of the use of an internal control sample from a single normal donor in each experiment. There was a small but significant increase in radiation-induced MN in the breast cancer patients compared with the normals at LDR (but not at HDR), but a complete overlap with the normal range. There was no increase in sensitivity in the A-T heterozygotes at HDR. The LDR samples failed because the LDR protocol reduced proliferation rates, and radiation-induced mitotic inhibition in this group was higher than in normals. CONCLUSIONS: In comparison with previous experience with fresh blood samples, the use of frozen lymphocytes is not as satisfactory because: (1) experimental failures are higher; (2) inter-experiment variability is higher: (3) dose-rate sparing is lower, suggesting poorer repair; and (4) the ability to discriminate between breast cancer cases and normals is probably lower.

Adult↗
PubMed2000

Heritability of chromosomal radiosensitivity in breast cancer patients: a pilot study with the lymphocyte micronucleus assay.

Of breast cancer patients, 30% are sensitive in a lymphocyte assay of radiation-induced chromosome damage (micronucleus induction) compared with 10% of healthy controls. Twenty-two first-degree relatives of 11 sensitive patients had an average micronucleus yield significantly higher than that of 68 controls. This suggests that radiosensitivity in this assay may be an inherited characteristic associated with predisposition to breast cancer.

Breast Neoplasms↗
PubMed2000

Intravenous immunoglobulin for ANCA-associated systemic vasculitis with persistent disease activity.

Intravenous immunoglobulin (IVIg) is a potential alternative treatment for anti-neutrophil cytoplasm antibody (ANCA)-associated systemic vasculitis (AASV) with less toxicity than conventional immunosuppressive agents. This randomized, placebo-controlled trial aimed to investigate the efficacy of a single course of IVIg (total dose 2 g/kg) in previously-treated AASV with persistent disease activity in whom there was an intention to escalate therapy. Vasculitic activity was monitored by the Birmingham vasculitis activity score (BVAS), C-reactive protein (CRP) and ANCA levels. Treatment response was defined as a reduction in BVAS of more than 50% after 3 months, and there was an intention to keep doses of concurrent immunosuppressive drugs unchanged during this period; follow-up continued to 12 months. Seventeen patients were randomized to receive IVIg and 17 to receive placebo. Treatment responses were found in 14/17 and 6/17 of the IVIg and placebo groups, respectively (p=0.015, OR 8.56, 95%CI 1.74-42.2). Following infusion of trial medication, greater falls in CRP were seen at 2 weeks (p=0.02) and 1 month (p=0.04) in the IVIg group. No differences were observed between ANCA levels or cumulative exposure to immunosuppressive drugs, and after 3 months there were no differences in CRP levels or disease activity between the IVIg and placebo groups. Seventeen adverse effects occurred after IVIg and six after placebo: they were mostly mild, although reversible rises in serum creatinine occurred in four from the IVIg group. A single course of IVIg reduced disease activity in persistent AASV, but this effect was not maintained beyond 3 months; mild, reversible side-effects following IVIg were frequent. IVIg is an alternative treatment for AASV with persistent disease activity after standard therapy.

Adult↗
PubMed2000

Comparison of central and peripheral pharmacologic effects of biperiden and trihexyphenidyl in human volunteers.

In this double-blind, randomized study, indices of central (memory, sedation) and peripheral (salivation, ratio of R-R interval on electrocardiogram) muscarinic function were evaluated in 14 healthy volunteers who received trihexyphenidyl, biperiden, and placebo. Additionally, serum drug levels were obtained 2 hours after oral administration. All subjects participated in three study sessions. During each session, subjects received two doses of biperiden (4 mg), trihexyphenidyl (5 mg), or placebo, and four series of tests were administered. The tests included the determination of cardiac response to standing (R-R ratio), mouth salivation, finger-tapping speed, digit span (forward and backward), a selective reminding task, and visual analog scales (VAS). On the VAS, subjects rated biperiden as significantly more sedating than either trihexyphenidyl or placebo, and both biperiden and trihexyphenidyl were associated with more dizziness than was placebo. Saliva production was significantly reduced by both trihexyphenidyl and biperiden compared with placebo. Digit span performance was significantly decreased in only the backward direction. The selective reminding task revealed highly significant decrements in the number of words recalled and consistent long-term retrieval after both biperiden and trihexyphenidyl. Delayed recall was significantly decreased by both active drugs. Both trihexyphenidyl and biperiden caused a significant increase in the R-R ratio comparison with placebo. With the exception of the VAS measurement of sedation, the effects caused by biperiden and trihexyphenidyl did not differ. The results of this study do not support the hypothesis that the side effect profile of biperiden is significantly different from that of trihexyphenidyl.

Adolescent↗
PubMed2000

Experimental evidence of electric inhibition in fast electron penetration and of electric-field-limited fast electron transport in dense matter

Fast electron generation and propagation were studied in the interaction of a green laser with solids. The experiment, carried out with the LULI TW laser (350 fs, 15 J), used K(alpha) emission from buried fluorescent layers to measure electron transport. Results for conductors (Al) and insulators (plastic) are compared with simulations: in plastic, inhibition in the propagation of fast electrons is observed, due to electric fields which become the dominant factor in electron transport.

Journal Article↗
PubMed2000

Detection of individual differences in radiation-induced apoptosis of peripheral blood lymphocytes in normal individuals, ataxia telangiectasia homozygotes and heterozygotes, and breast cancer patients after radiotherapy.

Quantification of radiation-induced apoptosis in peripheral blood lymphocytes (PBLs) has been proposed as a possible screening test for cancer-prone individuals and also for the prediction of normal tissue responses after radiotherapy. We have used the TUNEL assay (terminal transferase nick-end labeling) 24 h after irradiation with 4 Gy at high dose rate to assess interindividual differences in radiation-induced apoptosis between (1) a panel of normal individuals, (2) ataxia telangiectasia (AT) homozygotes and heterozygotes, and (3) breast cancer patients who had received radiotherapy 8-13 years ago, including a number of patients who had suffered adverse responses to radiation. With this protocol, we show clear differences in radiation-induced apoptosis between individuals, and good reproducibility in the assay. In agreement with previous reports using EBV-transformed lymphoblasts, we show a very poor induction of apoptosis in AT homozygotes and a reduced level in AT heterozygotes compared to normal individuals. A similar reduced level compared to normal individuals was seen in the breast cancer patients. Despite a wide range of values in the breast cancer patients and good reproducibility on repeat samples, there was no correlation of rates of apoptosis with the severity of breast fibrosis, retraction or telangiectasia. The reduced rate of apoptosis observed in the breast cancer cases may be associated with genetic predisposition to breast cancer; however, we conclude that assays of lymphocyte apoptosis are unlikely to be of use in predicting normal tissue tolerance to radiotherapy.

Adult↗
PubMed2000

Quantifying the qualitative: an empirical poetic approach.

Two studies are described which take a psychometric approach to a qualitative phenomenon. A computational analysis of poetry was conducted. Using a lexicon programme, patterns emerged generally supporting the idea of a poet's everchanging thematic preoccupations. Using a multimedia educational software package, presenting the poetical phrase accompanied by visual stimuli had a substantial effect on the appreciation of the poet's meaning. These novel methodological approaches might stimulate further work in this area.

Humans↗
PubMed1999

The Ovarian Tumor Index predicts risk for malignancy.

BACKGROUND: Prediction of ovarian malignancy by ultrasonographic findings and patient age in the scenario of clinically suspected adnexal masses is a desirable goal. METHODS: Prospective evaluation of clinically suspected adnexal masses was performed with transvaginal ultrasound using real-time, Doppler velocimetry, and color-flow mapping. Continuous ultrasound variables included ovarian volume, the Sassone morphology scale, and Doppler determination of angle-corrected systole, diastole, and time-averaged velocity, in addition to patient age. The Doppler pulsatility index (PI), vessel location, presence of a diastolic notch, and echogenic predominance of the lesion, suggestive of dermoid, also were assessed. RESULTS: Of 244 women with follow-up, 214 had nonmalignant findings (85 of which were benign neoplasms), and 30 had malignant neoplasms. Age and all ultrasound continuous variables except systole were found to be statistically significant (P < 0.05) between patients with both malignant (N = 30) and nonmalignant masses (N = 214), as well as those with benign (N = 85) and malignant (N = 30) neoplasms. By adding the continuous measures (age [in years], ovarian volume [mL], and Sassone morphology scale [1-15]) and weighting other variables ([-10] x PI, central or septal location [+10], peripheral location [-10], and echogenic [-10]), a receiver operating characteristic curve was generated (area under the curve = 0.91), which was found to be discriminating, predictive, and able to replicate the more complex logistic regression model. Prediction of malignancy was generated from the population-based data of the current study. CONCLUSIONS: The Ovarian Tumor Index, which combines patient age with specific ultrasonographic markers, is an accurate method for predicting ovarian malignancy in the clinical scenario of suspected adnexal masses.

Adolescent↗
PubMed1999

Dose-response effects of 32P radioactive stents in an atherosclerotic porcine coronary model.

BACKGROUND: Experimental studies have demonstrated that 32P radioactive stents reduce neointimal formation at 28 days in porcine iliac and coronary arteries. Our objective was to determine the long-term dose-response effects of 1.0- to 12.0-microCi 32P radioactive stents in a porcine atherosclerotic coronary model. METHODS AND RESULTS: Control (n=19) and 1.0- to 12.0-microCi 32P radioactive (n=43) stents (total, n=62) were implanted in the coronary arteries of 31 miniature swine at 28 days after creation of a fibrocellular plaque by overstretch balloon injury and cholesterol feeding. Angiography and histomorphometry were performed at 6 months. Stent thrombosis occurred in 3 radioactive (7.7%) and no control stents (P=0.54). On histology, the mean neointimal area and the percent in-stent stenosis correlated positively with increasing stent activity (r=0.64, P<0.001). The mean neointimal area (mm2) for the stents with >/=3.0 microCi 32P (3.57+/-1.21) was significantly greater than that for the nonradioactive stents (1.78+/-0.68, P<0.0001). The neointima of the stents with >/=3.0 microCi 32P was composed of smooth muscle cells, matrix proteoglycans, calcification, foam cells, and cholesterol clefts. CONCLUSIONS: Continuous low-dose-rate irradiation delivered by high-activity (32)P radioactive stents promotes the formation of an "atheromatous" neointima after 6 months in this experimental model. These data may be useful for predicting late tissue responses to radioactive stents in human coronary arteries.

Animals↗
PubMed1999

Evidence for and consequences of chronic heme deficiency in Belgrade rat reticulocytes.

The Belgrade rat has a microcytic, hypochromic anemia inherited as an autosomal recessive trait (gene symbol b). Transferrin-dependent iron uptake is defective because of a mutation in Nramp2 (now DMT1, also called DCT1), the protein responsible for endosomal iron efflux. Hence, Belgrade reticulocytes are iron deficient. We show that a chromatographic method is able to measure the amount of 'free' heme in reticulocytes. Most of the 'free' heme is the result of biosynthesis. Succinylacetone, an inhibitor of heme synthesis, decreases the level of 'free' heme and cycloheximide, an inhibitor of globin synthesis, increases the 'free' heme level. In a pulse-chase experiment with 59Fe-transferrin, the 'free' heme pool behaves as an intermediate, with a half-life of just over 2 h. Belgrade reticulocytes contain about 40% as much 'free' heme as do heterozygous or homozygous reticulocytes. This deficiency of 'free' heme slows initiation of translation in Belgrade reticulocytes by increasing the level of an inhibitor of initiation. Thus the Belgrade rat makes a whole animal model available with chronic heme deficiency.

Anemia, Hypochromic↗
PubMed1999

Characterization of the effect of high molecular weight hyaluronan on trans-synovial flow in rabbit knees.

1. The effect of a rooster comb hyaluronan (3.6-4.0 g l-1) of similar chain length to rabbit synovial fluid hyaluronan, on the trans-synovial escape of fluid from the joint cavity in the steady state ( 8d s) was studied in 29 rabbit knees at controlled intra-articular pressures (Pj). 2. Rooster hyaluronan caused the pressure-flow relation to flatten out as pressure was raised. At 10-20 cmH2O the slope of the quasi-plateau, 0.05 +/- 0.01 microliter min-1 cmH2O-1 (mean +/- s.e.m.), was 1/39th that for Ringer solution (1.94 +/- 0.01 microliter 2O-1 ). 3. Bovine synovial fluid had a similar effect to hyaluronan in Ringer solution. 4. The quasi-plateau was caused by increasing opposition to outflow; the pressure required to drive unit outflow increased 4.4-fold between 5 and 20 cmH2O. The increased opposition to outflow at 20 cmH2O was equivalent to an effective osmotic pressure of 13-17 cmH2O at the interface. Since the infusate's osmotic pressure was only 0.9 cmH2O, this implied concentration polarization to 15-18 g l-1 hyaluronan at the interface. 5. Mechanical perforation of the lining, or enzymatic degradation of the interstitial matrix by chymopapain, abolished the quasi-plateau. Hydrational expansion of the matrix by approximately 2-fold did not. The increased opposition to outflow was reversible by washing out the hyaluronan, or by reducing Pj. It was unaffected by interruption of tissue blood flow or synoviocyte oxidative metabolism. These properties are compatible with a concentration polarization mechanism, i.e. flow-induced concentration of hyaluronan at the synovial interface due to molecular reflection. 6. A concentration polarization theory was developed for a partially reflected solute. Numerical solutions supported the feasibility of this osmotic explanation of the quasi-plateau. Additional mechanisms may also be involved. 7. It is concluded that native-size hyaluronan helps to retain synovial fluid in the joint cavity when pressure is raised and acts, at least in part, by exerting osmotic pressure at the interface between synovial matrix and a concentration polarization layer.

Animals↗
PubMed1999

The effect of surface roughness on the stress adaptation of trabecular architecture around a cylindrical implant.

The effect of implant-bone bonding and the effect of implant surface roughness on bone remodeling near the bone-implant interface were studied by using a surface remodeling theory and the boundary element method. The study has shown that implant attachment plays an important role in bone remodeling near the implant. It has been observed in animal experiments and in clinical situations that the remodeled trabecular bone architecture around a cylindrical implant could vary, on one hand, from a hub surrounding the implant with a set of external spokes to, on the other hand, a hubless situation in which a set of spokes attach directly to the implant. It is shown here that the difference in these structures may be attributed to differences in implant attachment. The results show that the bone with perfect bonding or roller boundary condition without a gap remodeled to a hubless spoke trabecular bone architecture. On the other hand, the roller boundary condition with a specified gap yielded a spoke trabecular architecture with a hub or ring surrounding the implant. These quantitative results mirror the experimental and clinical observations. It is concluded that the hub is a consequence of the gap and not a consequence of the lack of friction between the implant and the bone.

Humans↗
PubMed1999

Expression of oestrogen and progesterone receptors in gastric cancer: a flow cytometric study.

Increased expression of oestrogen (ER) and progesterone (PR) receptors have been reported in gastric adenocarcinoma, although results have been variable. Immunohistochemical staining methodologies, in particular in the detection of ER, have been inconsistent with many tumours being classified ER-negative. In this study we have used flow cytometry to quantify expression of ER and PR in gastric adenocarcinoma and examine their relationships with established prognostic indicators. Cytokeratin-positive cells obtained from tumour biopsies of 50 patients with gastric cancer and ten control patients were labelled with biotinylated ER or PR antibodies followed by streptavidin PE. Flow cytometry was seen to increase the detection of ER levels in gastric cancer with more receptor-positive patients in this study than in results published to date. We believe this is related to the sensitivity of the flow cytometric assay with the detection of small shifts in ER level detected using cytokeratin gating. On analysis, the data showed no significant correlations with tumour stage and grade, and no differences were seen between normal mucosa and gastric cancer samples.

Adenocarcinoma↗