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Biomedical subjects

W Wright

Publications and source records attributed to W Wright.

At least 19 recordsLinked to original sources
PubMed1999

Rapid thinning of parts of the southern greenland ice sheet

Aircraft laser-altimeter surveys over southern Greenland in 1993 and 1998 show three areas of thickening by more than 10 centimeters per year in the southern part of the region and large areas of thinning, particularly in the east. Above 2000 meters elevation the ice sheet is in balance but thinning predominates at lower elevations, with rates exceeding 1 meter per year on east coast outlet glaciers. These high thinning rates occur at different latitudes and at elevations up to 1500 meters, which suggests that they are caused by increased rates of creep thinning rather than by excessive melting. Taken as a whole, the surveyed region is in negative balance.

Journal Article↗
PubMed1999

PRINTS prepares for the new millennium.

PRINTS is a diagnostic collection of protein fingerprints. Fingerprints exploit groups of motifs to build characteristic family signatures, offering improved diagnostic reliability over single-motif approaches by virtue of the mutual context provided by motif neighbours. Around 1000 fingerprints have now been created and stored in PRINTS. The September 1998 release (version 20.0), encodes approximately 5700 motifs, covering a range of globular and membrane proteins, modular polypeptides and so on. The database is accessible via the DbBrowser Web Server at http://www.biochem.ucl.ac.uk/bsm/dbbrowser /. In addition to supporting its continued growth, recent enhancements to the resource include a BLAST server, and more efficient fingerprint search software, with improved statistics for estimating the reliability of retrieved matches. Current efforts are focused on the design of more automated methods for database maintenance; implementation of an object-relational schema for efficient data management; and integration with PROSITE, profiles, Pfam and ProDom, as part of the international InterPro project, which aims to unify protein pattern databases and offer improved tools for genome analysis.

Amino Acid Sequence↗
PubMed1998

Social class and health: the puzzling counter-example of British South Asians.

British South Asians (with ancestry from the Indian subcontinent) provided a puzzling exception to the British class gradient in mortality during the 1970s. On the assumption that class gradients in health are produced mainly by gradients in standard of living, this might be due to a break in the relation of class to standard of living (change in class structure), or by a break in the relation of standard of living to patterns of health behaviour and health risk (change in class lifestyles). Data on these characteristics are available from the West of Scotland Twenty-07 Study, where 159 South Asians aged 30-40 (mean age 35) were sampled alongside 319 of the general population in Glasgow. As regards changes in class structure, results indicate that the underclass thesis, which suggests that ethnic minorities are forced into less eligible jobs or into a separate labour market or into unemployment, resulting in a standard of living below that of the general population, still holds good for British South Asians in categories from social class III non-manual downwards. It does not hold good for owners of small businesses, where Sikhs and Hindus in particular have a standard of living equivalent to general population counterparts. However, prosperity is not predictable from levels of education in the subcontinent and from this and other signs it appears that a wholesale redistribution of class chances is occurring among British South Asians, disrupting inter-and intra-generational continuities in the relation between class and standard of living. There is little sign of change in class lifestyles, i.e. in the relation between standard of living and health behaviour or health risk. As yet, though, the new distribution of standard of living is affecting patterns of health behaviour and health risk more strongly than symptom experience or chronic illness, suggesting that a class gradient in health will re-emerge.

Adult↗
PubMed1997

Human gene therapy for melanoma: CT-guided interstitial injection.

OBJECTIVE: Our intent is to describe the role of CT in the intratumoral injection of Allovectin-7 (Vical, San Diego, CA), an allogeneic class I major histocompatibility complex antigen, HLA-B7, formulated with cationic lipid, in the treatment of metastatic malignant melanoma. MATERIALS AND METHODS: Ten patients with metastatic malignant melanoma were treated with gene therapy in which we used CT-guided intratumoral injection of plasmid DNA containing the HLA-B7 gene. This therapy was part of a phase I gene therapy trial in patients with metastatic melanoma. CT guidance was chosen as an accurate way to direct gene delivery in patients with deep, impalpable lesions. Tumor locations included pulmonary, mediastinal, hepatic, adrenal, and paracaval sites. Patients in the CT protocol underwent baseline CT studies. Examinations were repeated 2, 4, and 8 weeks after gene therapy and thereafter at 3-month intervals. Both injected and noninjected tumors were measured. CT-guided injections of 10, 50, or 250 micrograms of plasmid DNA were performed with 22-gauge spinal needles. Injection volumes were between 1.0 and 4.0 ml, depending on tumor size. CT-guided core biopsy specimens were obtained (with 18- or 20-gauge needles) from the selected tumor before therapy and 2, 4, and 8 weeks after therapy to assess HLA-B7 plasmid DNA and gene expression. Peripheral blood was analyzed for cytotoxic T lymphocytes directed against HLA-B7. RESULTS: CT-guided intratumoral injections were successful in delivering genetic material to all patients with impalpable tumors. Significant responses (as defined by a decrease of 25% or more in the product of the length and width of the injected tumor) were observed in six of the 10 patients. One of these six patients who had a solitary lesion remains free of disease 19 months after gene therapy. HLA-B7 protein expression was detected in 89% of biopsy specimens, and plasmid DNA and messenger RNA were detected in 56% and 22% of biopsy specimens, respectively. CONCLUSION: CT provides a safe, accurate, and efficacious way to monitor and assess tumor progression and response, and it provides guidance for biopsies and intratumoral injections during gene therapy. Significant responses in injected tumors of six of the 10 patients in our study suggest that further clinical trials of this gene therapy are warranted.

Adult↗
PubMed1995

Conformational analysis of molecular chains using nano-kinematics.

We present algorithms for 3-D manipulation and conformational analysis of molecular chains, when bond lengths, bond angles and related dihedral angles remain fixed. These algorithms are useful for local deformations of linear molecules, exact ring closure in cyclic molecules and molecular embedding for short chains. Other possible applications include structure prediction, protein folding, conformation energy analysis and 3D molecular matching and docking. The algorithms are applicable to all serial molecular chains and make no assumptions about their geometry. We make use of results on direct and inverse kinematics from robotics and mechanics literature and show the correspondence between kinematics and conformational analysis of molecules. In particular, we pose these problems algebraically and compute all the solutions making use of the structure of these equations and matrix computations. The algorithms have been implemented and perform well in practice. In particular, they take tens of milliseconds on current workstations for local deformations and chain closures on molecular chains consisting of six or fewer rotatable dihedral angles.

Algorithms↗
PubMed1995

A skeletal muscle-specific enhancer regulated by factors binding to E and CArG boxes is present in the promoter of the mouse myosin light-chain 1A gene.

The mouse myosin light-chain 1A (MLC1A) gene, expressed in the atria of the adult heart, is one of the first muscle genes to be activated when skeletal as well as cardiac muscles form in the embryo. It is also transcribed in skeletal muscle cell lines at the onset of differentiation. Transient transfection assays of mouse skeletal muscle cell lines with DNA constructs containing MLC1A promoter fragments fused to the chloramphenicol acetyltransferase (CAT) gene show that the first 630 bp of the promoter is sufficient to direct expression of the reporter gene during myotube formation. Two E boxes located at bp -76 and -519 are necessary for this regulation. MyoD and myogenin proteins bind to them as heterodimers with E12 protein and, moreover, transactivate them in cotransfection experiments with the MLC1A promoter in nonmuscle cells. Interestingly, the effect of mutating each E box is less striking in primary cultures than in the C2 or Sol8 muscle cell line. A DNA fragment from bp -36 to -597 confers tissue- and stage-specific activity to the herpes simplex virus thymidine kinase promoter in both orientations, showing that the skeletal muscle-specific regulation of the MLC1A gene is under the control of a muscle-specific enhancer which extends into the proximal promoter region. At bp -89 is a diverged CArG box, CC(A/T)6AG, which binds the serum response factor (SRF) in myotube nuclear extracts, as does the wild-type sequence, CC(A/T)6GG. Both types of CArG box also bind a novel myotube-enriched complex which has contact points with the AT-rich part of the CArG box and adjacent 3' nucleotides. Mutations within the CArG box distinguish between the binding of this complex and binding of SRF; only SRF binding is directly involved in the specific regulation of the MLC1A gene in skeletal muscle cell lines.

Animals↗
PubMed1992

Initial characterization of heat-induced excess nuclear proteins in HeLa cells.

Exposure of mammalian cells to hyperthermia is known to cause protein aggregation in the nucleus. The presence of such aggregates has been detected as the relative increase in the protein mass that is associated with nuclei isolated from heated cells. We have characterized these excess nuclear proteins from the nuclei of heated HeLa cells by two-dimensional gel electrophoresis. The abundance of cytoskeletal elements which co-purify with the nuclei did not increase with exposure to hyperthermia, indicating that these proteins are not part of the excess nuclear proteins. In contrast, several specific polypeptides become newly bound or increase in abundance in nuclei isolated from heated cells. Members of the hsp 70 family were identified as a major component of the excess nuclear proteins. Among the other excess nuclear proteins we identified ten that had apparent molecular weights of 130, 95, 75, 58, 53, 48, 46, 37, 28, and 26 kilodaltons. Since hsp 70 is mainly cytoplasmic in non-heated cells, its association with nuclei in heated cells indicates that one mechanism accounting for the heat-induced excess nuclear proteins is the movement of cytoplasmic proteins to the nucleus. We also obtained evidence that increased binding of nuclear proteins is another mechanism for this effect. No overall increase or decrease in the phosphorylation of nuclear proteins was found to be associated with such altered binding or movement from the cytoplasm to the nucleus.

Cytoskeletal Proteins↗
PubMed1992

Clinical microleakage evaluation of a cavity varnish.

This clinical study evaluated the microleakage effectiveness of a cavity varnish when used in combination with two types of amalgam: a spherical particle and a dispersed phase alloy. Calcium hydroxide was utilized as the microleakage detection agent. Copalite showed a reduction in microleakage when it was employed with the spherical particle alloy used in this study. This study clinically demonstrated that Copalite is not totally effective in eliminating microleakage.

Bicuspid↗
PubMed1991

Propranolol pretreatment reduces cardiorespiratory toxicity due to plain, but not epinephrine-containing, intravenous bupivacaine in rats.

The purpose of this study was to evaluate the effects of pretreatment with propranolol on the cardio-respiratory toxicity of bupivacaine, either plain or with epinephrine 1:200,000 (5 micrograms.ml-1) added. Adult male Sprague Dawley rats, anaesthetized with intraperitoneal pentobarbital, were divided into four groups. Groups I and III were pretreated with iv propranolol 150 micrograms.kg-1, and Groups II and IV received iv NS as a placebo. Three minutes later, rats in Groups I and II received plain 0.5% bupivacaine, 4 mg.kg-1, and Groups III and IV received 4 mg.kg-1 of 0.5% bupivacaine with epinephrine, 5 micrograms.ml-1 iv. Five of eight rats pretreated with propranolol survived (Group I), compared with uniform fatality with NS pretreatment (Group II) (P less than 0.05). Addition of epinephrine to the bupivacaine eliminated the protective effect of propranolol. All rats pretreated with propranolol (Group III) or NS (Group IV) died when given bupivacaine with epinephrine. In conclusion, acute propranolol pretreatment reduced the fatal cardiotoxicity due to iv bupivacaine in male Sprague Dawley rats, but the addition of epinephrine 5 micrograms.ml-1 to bupivacaine eliminated the protective effect of propranolol.

Animals↗
PubMed1990

Nicardipine reduces the cardio-respiratory toxicity of intravenously administered bupivacaine in rats.

The purpose of our study was to examine the effect of intravenous (IV) nicardipine pretreatment (30 micrograms.kg-1), given three minutes before an IV bolus of bupivacaine to determine its effect on the incidence of fatal bupivacaine cardio-respiratory toxicity in adult male Sprague Dawley rats anaesthetized with intraperitoneal pentobarbital. Fifty rats were divided into four groups. Groups I and II (n = 10 each) received 3.5 mg.kg-1 0.5 per cent bupivacaine and Groups III and IV (n = 15 each) received 5.0 mg.kg-1, 0.5 per cent bupivacaine. Groups I and III received pretreatment with normal saline before bupivacaine, whereas Groups II and IV were given pretreatment with nicardipine, 30 mg.kg-1. There was no difference in the incidence of survival between the nicardipine pretreatment group and the saline placebo pretreatment group given 3.5 mg.kg-1, 0.5 per cent bupivacaine (no fatalities in either group). However, there was significant protection by nicardipine pretreatment in the group given 5 mg.kg-1, 0.5 per cent bupivacaine (13 of 15 survived, compared with only 4 of 15 in the saline pretreatment group, P less than 0.001). In conclusion, our data demonstrate that in rats given 0.5 per cent bupivacaine, 5 mg.kg-1, nicardipine pretreatment protected against fatal cardio-respiratory toxicity.

Analysis of Variance↗
PubMed1990

Effect of inhaled preservatives on asthmatic subjects. I. Sodium metabisulfite.

Sodium metabisulfite (MBS) is used as a preservative in food and wine and frequently triggers attacks of asthma. To determine the characteristics of responses to inhaled MBS, 30 asthmatic subjects and 16 nonasthmatic subjects inhaled MBS, in concentrations of 6.2, 12.5, 50, and 100 mg/ml, from a DeVilbiss No. 40 nebulizer (DeVilbiss Co., Somerset, PA) in doses ranging from 0.1 to 12.8 mumol. Response was measured as the dose that caused a 20% fall in FEV1 (PD20FEV1). All the asthmatic subjects responded; one of the atopic, nonasthmatic subjects responded and none of the nonatopic, nonasthmatic subjects responded. The response occurred within 1 min, and most subjects recovered to within 10% of baseline after 30 to 40 min. Dose-response curves to MBS were steep and were reproducible, within a 7-day period, to within one doubling dose, with mean PD20FEV1 values of 2.17 and 2.11 mumol in 11 subjects. There was no correlation between PD20FEV1 values to MBS and histamine, and inhalation of MBS did not enhance responses to subsequent challenge with histamine (mean PD20FEV1 to histamine was 0.65 mumol and to histamine 1 h after MBS was 0.74 mumol). Challenge with MBS (mean PD20FEV1 4.07 mumol) did not cause refractoriness to a second challenge 1 h later (mean PD20FEV1 5.39 mumol). Of 20 subjects tested, prior inhalation of 8 mg nedocromil sodium blocked the response to MBS in 15 subjects and reduced it in two others. Cromolyn sodium (4 mg) blocked the response to MBS in three subjects but did not alter the mean PD20FEV1 in the remaining 17 subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Epinephrine and phenylephrine increase cardiorespiratory toxicity of intravenously administered bupivacaine in rats.

We studied the effects of epinephrine and phenylephrine on the cardiorespiratory toxicity of intravenously injected bupivacaine in Sprague-Dawley rats. Our data show that both epinephrine and phenylephrine significantly increased cardiorespiratory toxicity of intravenously injected bupivacaine (P less than 0.007, X2 analyses with Yates' correction). Our data suggest that epinephrine or phenylephrine added to bupivacaine may be more toxic to cardiorespiratory systems than plain bupivacaine or epinephrine alone or phenylephrine alone when injected intravenously in rats.

Animals↗
PubMed1986

Effect of die spacer on the seating of complete cast gold crowns with grooves.

Fifty crowns were constructed with an indirect technique for a standardized Ivorine tooth preparation to determine whether casting relief would improve the seating of complete cast crowns with zinc phosphate cement. The variables were two grooves in the preparations and die spacer casting relief of approximately 20 to 40 micron. The tooth preparations of two groups had no grooves, but castings were made with internal relief for only one group. Three groups had buccal and lingual grooves in the preparation. One group had no relief, a second group had complete relief, and a third group had relief but not in the grooves. The discrepancies noted before and after cementation of the castings were measured. The average discrepancy for each group and the significance between groups was determined. Results of this study demonstrated the following. Die relief significantly improved the seating of complete cast-gold crowns with or without grooves. Omitting die spacer from grooves did not reduce the benefits of relieving the remainder of the die. Partial internal relief was better than no relief. The grooves did not disrupt seating when die spacer application was complete or specifically omitted from the grooves alone.

Crowns↗