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Biomedical subjects

W Wright

Publications and source records attributed to W Wright.

At least 19 recordsLinked to original sources
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↗
PubMed1985

Haemorrhage from smooth muscle tumours of the upper gastro-intestinal tract.

Eight patients with haemorrhage from smooth muscle tumours of the upper gastro-intestinal tract were treated during a 10 year period from 1973 to 1982. Seven of the tumours were benign and one a malignant leiomyoblastoma. Seven tumours were sited in the stomach and there was one duodenal lesion. Endoscopy was performed in all eight cases and made the diagnosis definitively in four. In two cases the diagnosis was confirmed on barium meal and in the other two, diagnosis was eventually made at laparotomy. Two patients were shocked on admission and required emergency surgery. In one case a diameter greater than 10 cm suggested malignant potential and wide local resection was performed. In one other case with a tumour in the antrum, a distal partial gastrectomy was performed, and in the case with leiomyoblastoma a proximal gastrectomy was performed. One case was lost to follow-up. The mean follow-up in six cases free of disease with benign tumour was 2.6 years. The patient with a tumour of greater than 10 cm in diameter remains well at 18 months follow-up and the patient with a malignant leiomyoblastoma died 2 years after surgery.

Aged↗
PubMed1985

Ability of specific monoclonal antibodies and conventional antisera conjugated to hematoporphyrin to label and kill selected cell lines subsequent to light activation.

A variety of cell lines have been prepared by fusion of the murine WEH1 3B cell line with peripheral blood leukocytes from a patient with chronic granulocytic leukemia. Fusion products were selected for their ability to produce a leukemia-associated antigen (CAMAL) previously described. One such line which originally produced CAMAL subsequently lost this ability and was used as a negative control. A number of antibodies were conjugated to hematoporphyrin (HP) and tested for their ability to bind to cell lines as detected by either fluorescence or by their ability to kill cells after light activation. The antibodies used were: rabbit anti-Hu (a conventional rabbit antiserum raised to membrane preparations from normal human peripheral blood leukocytes which served as a positive control); CAMAL-1 (a monoclonal gamma 1 antibody with specificity for the CAMAL antigen); and L1210 (an irrelevant monoclonal gamma 1 antibody). HP was conjugated to the antibodies by a carbodiimide procedure. When labeled cells were examined by fluorescence microscopy, it was apparent that both the rabbit antibody and CAMAL-1:HP showed positive labeling. The ability of the antibody:HP conjugates to kill labeled cells following light activation was tested. It was shown that rabbit anti-Hu:HP and CAMAL-1:HP conjugates were capable of killing significant numbers of cells when HP concentrations were as low as 1.2 ng/10(6) cells, whereas similarly treated cells exposed to either L1210:HP or HP alone did not exhibit significant killing until concentrations reached 240 and 120 ng/10(6) cells, respectively. Further experiments in which other cell lines were tested, all at HP concentrations of 12 ng/10(6) cells, demonstrated that those lines producing CAMAL were killed, whereas negative lines were not.

Animals↗
PubMed1984

Use of paint-on die spacers in preparations with grooves.

Film thickness of paint-on die spacer materials was measured on axial walls and in grooves. Two different materials and two different modes of application were tested. From the data presented, the following conclusions can be drawn: There are potentially significant differences in film thickness produced with different die spacing materials. The technique used to apply die spacer can affect the film thickness produced. Careful application of Pactra airplane dope will not result in significant accumulation of die spacer in the groove. Tru-fit die spacer produced generally erratic film thickness and demonstrated a potentially significant amount of pooling in the groove base. Further study is warranted to determine if use of die spacer in grooves will improve the seating of castings.

Chemical Phenomena↗
PubMed1983

The hormonal and cellular control of Sertoli cell secretion.

Sertoli cells synthesize and secrete a number of cell-specific products including androgen binding protein (ABP), as well as "serum proteins" such as transferrin. The secretion of these proteins is regulated by extra-testicular hormones such as FSH and insulin; Leydig cell-produced steroids and proopiomelano-cortin-derived peptides; and the presence of peritubular myoid cells and/or factors secreted by these cells. Many of the Sertoli cell proteins are secreted in a cyclic fashion during the different stages of the spermatogenic cycle suggesting communication between Sertoli cells and developing germ cells. The availability of quantitative measurements for Sertoli cell-specific proteins such as ABP make it feasible to follow Sertoli cell function in vivo by measuring these products in serum. A bidirectional secretion of proteins by Sertoli cells is proposed to explain the presence of specific peptides in the male reproductive tract and blood.

Androgen-Binding Protein↗
PubMed1982

Asbestos exposure and lymphomas of the gastrointestinal tract and oral cavity.

An epidemiological case-control study of non-Hodgkin's lymphomas revealed an excess of male patients with large-cell lymphomas primary to the gastrointestinal tract and oral cavity who had evidence of substantial exposure to asbestos. Between 1977 and 1981, 28 men with large-cell lymphomas primary to these sites were interviewed about previous environmental exposure. Pathology slides from 26 of these cases were reviewed by haematopathologists, who confirmed each to be non-Hodgkin's lymphoma of large-cell type. Neighbourhood controls were matched to patients for age, race, and sex. 13 matched pairs were discordant for asbestos exposure, and in 12 of these the exposed individual was a lymphoma patient. 10 patients and 1 control also reported a history of malaria.

Adult↗