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D Barnes

Publications and source records attributed to D Barnes.

At least 73 records · Page 4Linked to original sources
PubMed1998

PTR3, a novel gene mediating amino acid-inducible regulation of peptide transport in Saccharomyces cerevisiae.

We have isolated and characterized the Saccharomyces cerevisiae PTR3 gene by functional complementation of a mutant deficient for amino acid-inducible peptide transport. PTR3 is predicted to encode a protein of 678 amino acids that exhibits no similarity to any other protein in the database. Deletion of the PTR3 open reading frame pleiotropically reduced the sensitivity to toxic peptides and amino acid analogues. Initial rates of radiolabelled dipeptide uptake demonstrated that elimination of PTR3 resulted in the loss of amino acid-induced levels of peptide transport. PTR3 was required for amino acid-induced expression of PTR2, the gene encoding the dipeptide/tripeptide transport protein, but was not necessary for nitrogen catabolite repression of peptide import or PTR2 expression. It was determined that PTR3 also modulates expression of BAP2, the gene encoding the branched-amino acid permease. Furthermore, we present genetic evidence that suggests that PTR3 functions within a novel regulatory pathway that facilitates amino acid induction of the PTR system.

Amino Acid Transport Systems↗
PubMed1998

Stromelysin 3: an independent prognostic factor for relapse-free survival in node-positive breast cancer and demonstration of novel breast carcinoma cell expression.

Stromelysin 3 (ST3) is a matrix metalloproteinase implicated in mammary carcinoma progression. To date, localization of ST3 expression in breast cancer by in situ hybridization and immunocytochemistry has shown that the expression of the enzyme is limited to only the stromal fibroblasts surrounding the cancer cells. We have immunostained a large group of ductal carcinoma in situ and invasive breast carcinomas using a monoclonal antibody (5ST-4A9) raised against the hemopexin-like domain of human ST3. We show that invasive lobular carcinomas express significantly less ST3 than invasive ductal carcinomas (IDCs) (P = 0.002). We also show, for the first time, that certain breast carcinoma cells that have undergone a degree of epithelial-to-mesenchymal transition, the so-called metaplastic carcinomas, can express ST3 mRNA and protein, which may in part explain the increased metastatic propensity seen in a number of these tumors. In addition, patients with IDC who had moderate to strong ST3 levels had significantly shorter disease-free survival than those with negative or weak ST3 levels (P = 0.02). Furthermore, in node-positive IDC patients, multivariate analysis revealed that ST3 level was a strong, independent prognostic parameter for disease-free survival (P = 0.005).

Adult↗
PubMed1998

Identification of missense and truncating mutations in the BRCA1 gene in sporadic and familial breast and ovarian cancer.

The cloning of the breast and ovarian cancer susceptibility gene, BRCA1, allows direct estimation of the proportion of these cancers in the general population which can be attributed to germline mutations in this gene. We have used a combination of SSCP, heteroduplex analysis, and chemical cleavage of mismatch to screen the BRCA1 gene for mutations in the germline of 42 patients with breast or ovarian cancer who either have a moderate family history of these cancers, or have no family history of malignancy but a very early onset of the disease. A total of 30 sequence variants were observed, eight of which have not been described previously. Three sequence changes detected by chemical cleavage or heteroduplex analysis were missed by SSCP. The variants included 13 missense mutations, which were assessed for their pathogenic implications. Two of these (M18T and A1708E) are nonconservative substitutions which are located in evolutionarily conserved regions of the gene: M18T lies just upstream of the RING finger motif, and A1708E abolishes the transcriptional transactivation activity of the carboxy-terminal region of BRCA1. Mutations were observed in eight patients overall (19.0%), and protein-truncating mutations occurred in five of 27 (18.5%) families with 1-3 cases of breast or ovarian cancer. The data suggest that a significant proportion of patients with a modest or no family history of these cancers may carry germline mutations in BRCA1.

Adult↗
PubMed1998

Medical readiness training exercise in El Salvador, Central America, 1996.

Medical Readiness Training Exercises (MEDRETEs) can be a valuable training tool for U.S. Army personnel in remote areas of deployment. We report our experience of the MEDRETE in El Salvador in 1996. Working with foreign physicians of the host country was a positive experience in which we learned local customs and mutual cooperation. Evaluation and treatment of nearly 6,000 patients increased goodwill in the community and provided an opportunity for teamwork for Army Reserve medical units, including increased discussions of public health issues. We also report on the field applicability of the advanced laboratory and pharmacy equipment we included in our training.

Adolescent↗
PubMed1997

Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis.

BACKGROUND: An intravenous rather than oral course of methylprednisolone is often prescribed for treating acute relapses in multiple sclerosis (MS) despite the lack of evidence to support this route of administration. Our double-blind placebo-controlled randomised trial was designed to compare the efficacy of commonly used intravenous and oral steroid regimens in promoting recovery from acute relapses in MS. METHODS: 42 patients with clinically definite relapse in MS received oral, and 38 intravenous, methylprednisolone. Clinical measurements at entry and at 1 week, 4 weeks, 12 weeks, and 24 weeks included Kurtzke's expanded disability status scale (EDSS), Hauser's Ambulatory Index, and an arm-function index. The primary outcome criterion was a difference between the two treatment groups of one or more EDSS grades at 4 weeks. FINDINGS: There were no significant differences between the two groups at any stage of the study in any measurement taken: the mean difference in EDSS at 4 weeks (adjusted for baseline level) was 0.07 grades more in those taking oral steroids (95% CI -0.46 to 0.60). The most optimistic outcome for intravenous therapy is an average benefit of less than half a grade improvement on EDSS over oral treatment. INTERPRETATION: Since our study did not show any clear advantage of the intravenous regime we conclude that it is preferable to prescribe oral rather than intravenous steroids for acute relapses in MS for reasons of patient convenience, safety, and cost.

Administration, Oral↗
PubMed1997

A randomized clinical trial of ursodeoxycholic acid as adjuvant treatment to prevent liver transplant rejection.

Acute rejection following orthotopic liver transplantation is a common problem despite current immunosuppressive regimens. Ursodeoxycholic acid (UDCA) has been shown in small, open-labeled studies to prevent rejection episodes, although its effects on complications such as infections, length of hospital stay, and survival have not been evaluated. We conducted a randomized, placebo-controlled, double-blind trial to determine if UDCA (10-15 mg/kg/d) added to a cyclosporine-based immunosuppressive regimen was associated with a decrease in the incidence of at least one episode of acute cellular rejection. Secondary end-points included determining differences in the total number of rejection episodes, the use of muromonab-CD3, the incidence of infections, length of hospital stay, and survival at 90 days and 1 year. Fifty-two patients were randomized, 28 to the treatment group and 24 to the placebo group. During the 3 months of the trial, there was no difference between the placebo and UDCA groups in the number of patients who were rejection-free; however, there were significantly fewer patients in the treatment group who had multiple episodes of acute rejection (0 vs. 6; P = .007). Patients in the treatment group experienced a significantly lower incidence of bacterial infections (4% vs. 29%; P = .02), shorter hospital stay (25 days vs. 34 days; P = .03), and better 90-day survival (100% vs. 83%; P = .04) and 1-year survival (93% vs. 79%). The addition of UDCA to a cyclosporine-based immunosuppressive regimen results in significantly fewer patients experiencing multiple episodes of rejection and improved survival at 90 days and at 1 year. The use of UDCA as adjuvant therapy for patients undergoing liver transplantation who are treated with a cyclosporine-based immunosuppressive regimen should be considered.

Adult↗
PubMed1997

Spinal rigidity following acute myelitis.

A patient with a 2(1/2)-year history of painful spasms and rigidity of both lower limbs is described. Symptoms began after an episode of acute myelitis. The spasms--which were spontaneous and stimulus sensitive and occurred on voluntary action--involved the repetitive grouped discharge of motor units. Continuous motor unit activity was present at rest in the muscles of both legs, and cutaneomuscular reflexes were abnormal. This patient is similar to those recently reported as having stiffness and spasms of the legs due to a possible chronic spinal interneuronitis and provides further evidence that this kind of movement disorder may be caused by spinal cord pathology.

Acute Disease↗
PubMed1997

Emergent conditional discriminations in children and adults: stimulus equivalence derived from simple discriminations.

This study examines whether trained and derived simple discriminations lead to conditional relations between discriminative stimuli of the same and opposite (S+, S-) functions. After being trained on an arbitrary X-Y task (X1-Y1, X2-Y2) and on two simple discrimination tasks (A1+/A2- and B1+/B2-), children (Experiment 1) and adults (Experiment 2) were tested on the formation of novel simple discriminations (A3+/A2- and B3+/B2-) and conditional stimulus relations between all directly and indirectly paired A stimuli and between all directly and indirectly paired B stimuli (A1-A2-A3, B1-B2-B3). Subjects who formed these sets also received A2-X1 and B1-X2 training followed by a series of probes to assess the formation of two five-member stimulus equivalence classes (A1-A2-A3-X1-Y1, B1-B2-B3-X2-Y2). A modest majority of the children matched the directly paired stimuli (A2-A1, B2-B1 and A1-A2, B1-B2; A2-A3, B2-B3 and A3-A2, B3-B2) with one another while only a few of them also matched the indirectly paired stimuli with one another (A1-A3, B1-B3 and A3-A1, B3-B1). Those who did also related all the A and B stimuli with the designated X and Y stimuli. By contrast, all normal adults matched all paired and conditionally linked stimuli with one another. Present findings and those of related studies on stimulus equivalence are discussed from a stimulus contiguity perspective.

Age Factors↗
PubMed1997

Functional equivalence in children: derived stimulus-response and stimulus-stimulus relations.

The present study investigated the simultaneous occurrence of emergent stimulus-response relations (functional equivalence) and stimulus-stimulus relations (stimulus equivalence). After being pretrained and tested on two symbolic match-to-sample tasks (X1-Y1, X2-Y2), 20 4- and 5-year-old children were trained to emit specified responses to pairs of stimuli (A1-R1, B1-R1, A2-R2, B2-R2) in one setting (original training) and to emit other responses to one member of each pair (A1-R3, A2-R4) in another setting (reassignment training). Of the 18 children who responded correctly on all trained tasks, 15 emitted the novel responses also in the presence of the nonreassigned stimuli (B1-R3, B2-R4). Eleven of these children also matched same-class stimuli with one another (A1-B1, A2-B2, and vice versa). Additional tests with four of these children documented the formation of conditional response-stimulus relations (R3-B1, R4-B2) in all four children, and of conditional response-response relations (R1-R3, R2-R4, and vice versa) in two of them. Children who did not show stimulus control transfer also failed to match same-class stimuli with one another. Present findings, together with those obtained in animal research, suggest that functional equivalence can imply but does not require stimulus equivalence.

Child, Preschool↗
PubMed1997

Effect of dietary dl-alpha-tocopherol on tissue alpha- and gamma-tocopherol and pulmonary hypertension syndrome (ascites) in broilers.

The objectives of this experiment were to determine the effects of high dietary levels of vitamin E on growth performance and pulmonary hypertension syndrome (PHS) mortality. Male broiler chicks (Cobb 500) were randomly assigned to one of four dietary treatments consisting of standard starter and grower diets supplemented with 0, 17, 46, and 87 mg dl-alpha-tocopherol acetate/kg. To encourage the development of PHS, air temperature in the house was 32 and 28 C for Weeks 1 and 2, dropped to 18 C during Week 3, and kept between 10 and 15 C during Weeks 4 through 7. Also, chicks were placed in floor pens on litter used for five previous flocks and ventilation reduced to increase dust and ammonia in the house. Ammonia levels increased from an initial 18 to 36 ppm on Day 42 with the increase in ammonia corresponding to an obvious increase in dust in the air. Lung and liver tissue obtained at 2, 5, and 7 wk of age were analyzed for tissue alpha- and gamma-tocopherol by liquid chromatography. Dietary vitamin E had no effect on body weight, feed intake, or feed efficiency. Cumulative PHS mortality through 7 wk of age was 21% and was also unaffected by dietary treatment. Liver and lung alpha-tocopherol concentrations exhibited a dose-response increase to dietary tocopherol and there was a high correlation between lung and liver tissue alpha-tocopherol (r = 0.72, P < 0.05). Whereas gamma-tocopherol concentrations in lung and liver were unaffected by dietary treatment, liver and lung exhibited age-dependent increases in both alpha- and gamma-tocopherol. Despite dose-dependent increases in tissue alpha-tocopherol, supplementation of diets with up to 87 mg dl-alpha-tocopherol acetate had no effect on growth performance or PHS mortality in broilers under the conditions used in this study.

Ammonia↗
PubMed1997

Characterization of dynamic 3-D PET imaging for functional brain mapping.

Methods for optimizing the acquisition, reconstruction and analysis of positron emission tomography (PET) images for functional brain mapping have been investigated. The scatter fraction and noise-equivalent count rate characteristics were measured for the ECAT 951/31R PET scanner operating in septa-extended two-dimensional (2-D) and septa-retracted three-dimensional (3-D) modes. The 3-D mode is shown to provide higher signal-to-noise images than the 2-D mode at specific activities less than 30 kBq/ml. To enable increased temporal resolution in dynamic 3-D PET activation studies, a parallel version of the 3-D reconstruction algorithm was developed. Implementation of the reprojection algorithm on an 88 processor 1860 supercomputer resulted in a more than tenfold increase in reconstruction speed compared to a single 1860 processor system. An investigation of the optimal duration for imaging brain activations was undertaken in 12 normal subjects using repeated H2(15)O slow infusions and a visually presented lexical decision task. The significance of change in regional cerebral blood flow (CBF) was determined using statistical parametric maps for images acquired during stimulation, immediately after stimulation, and commencing 1 min after cessation of the stimulus. Regions of CBF change were detected in all three images. Dynamic 3-D, or four-dimensional (4-D), PET activation scanning is shown to be practical and likely to further improve the sensitivity of PET for detection of subtle regional CBF changes in functional brain mapping research.

Adult↗
PubMed1997

Studies to assess if pizotifen prophylaxis improves migraine beyond the benefit offered by acute sumatriptan therapy alone.

Two multi-centre studies-one double-blind, placebo-controlled (study 1) and one open (study 2)-were set up to assess if pizotifen prophylaxis improved migraine beyond the benefit offered by acute sumatriptan therapy alone. Eighty-eight patients completed the blinded study and 63 patients completed the open study. Both studies were of crossover design with patients undertaking a 4 week run-in period prior to a 12-week treatment period. Following a 4-week washout period patients commenced a second 12-week treatment period on the alternative treatment regimen. All breakthrough attacks were treated with 100 mg oral sumatriptan with an optional 2 doses available to treat any recurrence within 24 h of taking dose 1. Pizotifen was built up to a final daily dose of 1.5 mg over a 2-week period and patients remained on this dose for a further 10 weeks. Patients in the blinded study were given matching placebo tablets for one of the two treatment periods. The efficacy of sumatriptan was not affected by pizotifen. The median of the monthly attack rate experienced by patients was slightly lower whilst patients were on pizotifen and sumatriptan than while on placebo prophylaxis and sumatriptan or sumatriptan alone; study 1, 3.5 vs 3.9 attacks per month (p = 0.008); study 2, 2.9 vs. 3.2 attacks per month (p = 0.23). Also, while on pizotifen and sumatriptan more patients had a greater proportion of their time in the study migraine-free. From the results of these studies it does not appear that pizotifen reduces migraine severity; regardless of the treatment regimen the initial headache severity of most attacks was moderate. Weight gains experienced by patients while on pizotifen and sumatriptan were greater than the weight gains experienced while on placebo prophylaxis and sumatriptan or sumatriptan alone (period 1); study 1, 2.6 vs. 1.0 kg (p = 0.002); study 2, 1.6 vs. -0.8 kg (p < 0.0001). The combination of pizotifen and sumatriptan did not result in any additional adverse events other than those usually seen with each medication alone. In these studies, where the average number of migraine attacks was around 4 per month, the benefits conferred by pizotifen were at the expense of the adverse events associated with the drug, particularly weight gain. Therefore the clinical benefit of treatment with pizotifen for patients who have less than 4 attacks per month should be carefully reviewed as acute treatment with sumatriptan may be the most appropriate treatment. Pizotifen may be better reserved for those patients who have 4 of more attacks per month.

Adolescent↗
PubMed1997

An investigation into the temperature dependence of the rheological synergy between xanthan gum and locust bean gum mixtures.

The interaction between xanthan gum (XG) and locust bean gum (LBG) in water has been investigated using texture analysis, thermorheological analysis and high sensitivity differential scanning calorimetry. For the batches of XG and LBG used in the present study and at a total polymer concentration of 1% w/v, texture analysis indicated that the greatest synergy occurred at approximately 10% w/w XG, while the technique also allowed measurement of the increase in strength resulting from heating the mixes to 70 and 80 degrees C and cooling to room temperature. Thermorheological studies showed a maximum in viscosity for the xanthan gum gels at approximately 45 degrees C; this maximum became less pronounced as the concentration of XG decreased. High sensitivity differential scanning calorimetry indicated that XG undergoes two transitions at approximately 30 and 80 degrees C on heating, but on cycling a single transition is seen at approximately 74 degrees C. It was also noted that the transitions were diminished or were absent in the presence of LBG.

Calorimetry, Differential Scanning↗
PubMed1997

A transformation of respondently conditioned stimulus function in accordance with arbitrarily applicable relations.

Adult male subjects saw a sexual film clip paired with a nonsense syllable (C1). Similarly, an emotionally neutral film clip was paired with a second nonsense syllable (C3). Responses to the nonsense syllables were recorded as skin resistance responses. Subjects were also trained in a series of related conditional discriminations, using the C1 and C3 stimuli, from which the following equivalence relations were predicted; A1-B1-C1, A2-B2-C2, and A3-B3-C3. Some subjects were given matching-to-sample (equivalence) tests after the conditional discrimination training (Experiment 1), whereas others were not (Experiment 2). Subjects were tested for a transformation of eliciting functions by presenting the A1 and A3 stimuli, which were related through equivalence to C1 and C3, respectively. Five of the 6 subjects who showed significantly greater conditioned responses to C1 than to C3, also showed significantly greater skin resistance responses to A1 than to A3. Two additional subjects demonstrated a transformation of an eliciting stimulus function in accordance with five-member equivalence relations (Experiment 3), and another 5 subjects demonstrated similar effects in accordance with the relations of sameness and opposition (Experiment 4).

Adolescent↗
PubMed1997

Cloning, sequencing, and embryonic expression of an N-ras proto-oncogene isolated from an enriched zebrafish (Danio rerio) cDNA library.

An enriched zebrafish (Danio rerio) complementary DNA library was constructed for screening of ras-related genes, and a positive clone was isolated from one plate of 3 x 10(4) plaques. This clone, Zras-B1, carried an insert of 2592 base pairs (bp) with an open reading frame encoding a ras p21 protein of 188 amino acids. The deduced amino-terminal 86 amino acid residues and the carboxy-terminal CAAX binding motif are identical to mammalian ras. The full-length Zras-B1-encoded protein is most closely related to human N-ras (91% identity), with lesser homology to Ha-ras (84%) and Ki-ras (85%). Preliminary screening data also indicate other ras genes in zebrafish, at least one of which is also transcribed in adults. A Zras-B1-related 3.1-kb transcript was found to be abundant in embryos from zygote through gastrulation, and may be maternally derived.

Amino Acid Sequence↗