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Biomedical subjects

A Campbell

Publications and source records attributed to A Campbell.

At least 19 recordsLinked to original sources
PubMed1996

Spontaneously increased production of nitric oxide and aberrant expression of the inducible nitric oxide synthase in vivo in the transforming growth factor beta 1 null mouse.

Transforming growth factor beta 1 null mice (TGF-beta 1-/-) suffer from multifocal inflammation and die by 3-4 wk of age. In these mice, levels of nitric oxide (NO) reaction products in serum are elevated approximately fourfold over levels in controls, peaking at 15-17 d of life. Shortterm treatment of TGF-beta 1-/- mice with NG-monomethyl-L-arginine suppressed this elevated production of NO. Expression of inducible NO synthase (iNOS) mRNA and protein is increased in the kidney and heart of TGF-beta 1-/- mice. These findings demonstrate that TGF-beta 1 negatively regulates iNOS expression in vivo, as had been inferred from mechanistic studies on the control of iNOS expression by TGF-beta 1 in vitro.

Amino Acid Sequence↗
PubMed1996

In situ comparison of phenotypical and functional activity of infiltrating cells in ulcerative colitis mucosa.

The production of reactive oxygen species may have an important role in the pathogenesis of inflammatory bowel disease, yet the cells responsible in colonic mucosa have not been clearly defined. We studied 28 patients with ulcerative colitis and 13 controls to determine the cells generating reactive oxygen species, using a combined method for determining nitroblue tetrazolium reducing activity and immunohistochemical characterization. In contrast to the proportion of EBM11-positive cells (tissue macrophages), which did not increase in inflamed mucosa, the proportions of PMN-13F6 positive cells, CD11b-positive cells, and eosinophils were significantly increased in inflamed mucosa. PMN-13F6 positive cell and eosinophil counts were significantly correlated with CD11b positivity. Eosinophils, however, showed a stronger correlation with CD11b positivity than PMN-13F6-positive cells. The majority of CD11b-positive cells were eosinophils. Although some nitroblue tetrazolium reducing leukocytes were positively stained with EBM11 or PMN-13F6, eosinophils were the major subset of nitroblue tetrazolium reducing leukocytes. Recruitment and activation of eosinophils may play an important role in the pathogenesis of ulcerative colitis.

Adult↗
PubMed1996

Hydrodynamic function of tilting disc prostheses and bileaflet valves in double valve replacement.

OBJECTIVE: To determine the energy loss attributable to prosthetic valve size and design in double valve replacement, energy consumption of mitral valves (size #25 to #29), of two different designs (Bjork Shiley tilting disc and Carbomedics bileaflet valves), in combination with a small (#21) and large sized (#27) aortic prosthesis, were analyzed in a flow simulator. METHODS: A pulsatile flow simulator was used to reproduce physiological ventricular dynamics and to match the input and output impedances of the human left ventricle. Hydrodynamic performance was determined as stroke work, closing work and leak work for each combination of valves at low flow (5 liters per minute) and high flow (9 liters per minute) conditions. RESULTS: At low flow no decrease of energy requirement was found with the use of a mitral valve larger than #25. At high flow the #27 and #29 mitral valves required less energy compared to a #25 mitral valve, in combination with a large aortic prosthesis. The #29 mitral prosthesis revealed similar results as the #27. With the use of a large aortic prosthesis a remarkable reduction of total flow work was shown. These results were found in both designs. In comparison of the two designs, tilting disc valves required more energy for stroke and closure of the valve, although less energy for leakage. In total, energy requirements were higher for tilting disc valves. COMMENTS: A hydrodynamic advantage for the use of a mitral valve larger than #25 was found only with the combination of a large aortic prosthesis and high flow. Hydrodynamic data favor the use of bileaflet prosthesis especially for a patient who is expected to exercise.

Aortic Valve↗
PubMed1996

Health check-ups in general practice: a patient perspective.

One of the strategies identified by the NHS to achieve improvements in the health status of the Scottish population is to implement health promotion programmes through the general medical practitioner service. Grampian Local Health Council undertook a survey of Grampian residents to identify factors which might encourage greater public participation in such programmes. The results which are analysed and discussed in this paper show that factors identified by the public include: a preference for doctors to carry out health checks; the need for public education on the roles of different health professionals; the need for information on health checks and their benefits to be supplied in advance; a choice of appointment times and the offer of a follow-up appointment to discuss test results. These results are of interest to health professionals as they are likely to contribute to higher levels of patient involvement in health promotion programmes.

Adult↗
PubMed1996

Pitfalls and outcomes from accelerated wear testing of mechanical heart valves.

In 1990 Sorin Biomedica introduced a new bileaflet heart valve called the Bicarbon valve. This design was reported to eliminate wear in the hinge mechanism. Clinical quality Sorin Bicarbon, CarboMedics, St. Jude Medical, Duromedics and Jyros valves were obtained to test this claim and to compare the wear in the pivot of this new valve to other available heart valves. The valves were visually inspected then subjected to 4,000 cycles at a physiological beat rate in vitro. The valves were re-inspected then subjected to 400 million cycles in a Reul type accelerated wear tester. Scanning electron microscope photographs were taken of all contact areas at 40, 80, 120, 160, 200, 240, 280 and 400 million cycles. Wear marks on the inflow side of the Sorin, CarboMedics and St. Jude leaflets were measured and compared. Orifice wear was not quantified because of difficulty with measuring inside complex depressions. After 4,000 cycles of testing at a physiological beat rate the CarboFilmTM coating on the Sorin orifice showed signs of erosion. The other valve components only exhibited minor burnishing after 4,000 cycles. Following completion of 400 million cycles in an accelerated wear tester, approximately ten years in vivo, all valves showed significant wear. The inflow face of the pivot on the Sorin Bicarbon leaflets exhibited the deepest wear marks. The CarboFilm coating on the Sorin Bicarbon orifices was removed from most areas of leaflet contact. The transition between the remaining coating and the eroded areas created a rough edge. The tips of the Sorin leaflets contacted the bottom of the orifice pivot, in contrast to the St. Jude Medical and CarboMedics designs, which had minimal contact between the leaflet and the orifice.

Biocompatible Materials↗
PubMed1995

A mutation affecting signal peptidase inhibits degradation of an abnormal membrane protein in Saccharomyces cerevisiae.

Signal peptidase removes amino-terminal signal peptides from precursor proteins during or immediately following their translocation to the lumen of the endoplasmic reticulum (ER) and may participate in ER degradation, a poorly defined process whereby abnormal proteins are rapidly degraded early in the secretory pathway. Here, the involvement of signal peptidase in ER degradation is examined through the use of two chimeric membrane proteins that lack amino-terminal signal peptides: A189invHD, which contains sequences derived from arginine permease and histidinol dehydrogenase, and AHDK2, containing the ER-resident protein Kar2p fused to the carboxyl terminus of A189invHD. Degradation of approximately 95% of A189invHD is observed in yeast cells expressing enzymatically active signal peptidase, whereas only 60% undergoes rapid degradation in a sec11 mutant bearing a temperature-sensitive mutation in the gene encoding the 18-kDa subunit (Sec11p) of the signal peptidase complex. AHDK2 is proteolyzed in a reaction yielding at least two fragments in wild-type cells and in the sec11 mutant containing a plasmid bearing the SEC11 gene. The proteolytic reaction is catalyzed in a temperature-dependent manner in the sec11 mutant, with AHDK2 remaining stable at the nonpermissive temperature. Using conditional mutants defective in protein translocation into and out of the ER and in vitro protease protection studies, the site of degradation for AHDK2 is localized to the ER lumen. The data therefore indicate (i) A189invHD is degraded through both signal peptidase-dependent and independent processes; (ii) signal peptidase, specifically the Sec11p subunit, is required for the proteolysis of AHDK2; and (iii) the Kar2 fragment at the carboxyl terminus of AHDK2 permits detection of proteolytic intermediates.

Alcohol Oxidoreductases↗
PubMed1995

Silicone breast implants and autoimmunity: causation, association, or myth?

In vivo and in vitro studies, case reports and population studies show that: (1) silicone is immunogenic; (2) silicone is biodegradable and transported via the reticuloendothelial system to distant locations; (3) silicone breast implants "leak" and in turn silicone migrates outside the breast tissue; (4) case reports and population studies document an autoimmune reaction and immunological dysfunction in patients with silicone breast implants; (5) these immunological abnormalities and symptoms are reversible upon removal of the breast implants (in 50-70% of cases). The criteria to establish medical causation are defined, and based on those criteria it is concluded that silicone breast implants cause immunological disease.

Animals↗
PubMed1995

Demonstration of antiphospholipid antibody heterogeneity by phospholipid column chromatography and salt gradient elution techniques.

Antiphospholipid (aPL) antibodies are associated with thrombosis, recurrent abortions and thrombocytopenia. Studies to determine the mechanisms of action of these antibodies have been hindered by their heterogeneity and limited availability of techniques to isolate and characterize subgroups of the antibodies. We report a new phospholipid affinity chromatography method which enables separation of antiphospholipid positive sera into more than one antibody subpopulation. Sera from five patients with complications of the antiphospholipid syndrome (APS) were studied. Each serum was applied to chromatography columns prepared by coating polystyrene beads (diameter 100 A) with phosphatidylserine (PS) or cardiolipin (CL). A linear salt gradient (0.03-1.0 M NaCl) was used for elution. Eluates were analyzed for phospholipid binding and for inhibition of the prothrombin-thrombin conversion reaction. Each sample yielded two to three peaks for CL and PS affinity columns. Molarities at which peaks were eluted differed between samples. For individual samples, molarities at which peaks were eluted differed between CL and PS columns. These data suggest that aPL antibodies are heterogenous, with differences existing between patients and even within single serum samples. Subpopulations differed in their avidities for CL and PS but generally all had prothrombinase inhibitory activity.

Adult↗
PubMed1995

Adhesion molecule expression on vascular endothelium and nitroblue tetrazolium reducing activity in human colonic mucosa.

BACKGROUND: Expression of adhesion molecules is increased in inflamed colonic mucosa, but little is known about their functional activity in vascular endothelium. METHODS: We studied in situ nitroblue tetrazolium reducing activity and expression of E-selectin, ICAM-1, CD31, and VCAM-1 by immunohistochemistry in the same biopsy specimen in controls and patients with ulcerative colitis (UC). RESULTS: VCAM-1 expression was negative in mucosal vessels. E-selectin-positive vessels were significantly increased in endoscopically active colitis compared with normal mucosa. ICAM-1-positive vessels were consistently found in normal, quiescent UC and active UC. CD31-positive vessels were not significantly increased in quiescent UC and active UC compared with control. Only E-selectin significantly correlated with the histologic grade of inflammation. Nitroblue tetrazolium reducing vessels were increased in inflamed mucosa, and these vessels expressed ICAM-1 and CD31. E-selectin positivity in association with nitroblue tetrazolium reduction was mainly seen in the large mucosal vessels, but capillaries showing nitroblue tetrazolium reduction were rarely positive for E-selectin. CONCLUSIONS: Phenotypic and functional activation of vascular endothelium might be involved in the recruitment of leukocytes and tissue destruction of inflamed colonic mucosa.

Adult↗
PubMed1994

Crystallization of recombinant hemoglobins with basic amino acid substitutions (Lys and Arg) at the beta 6 position.

We have produced recombinant hemoglobins (rHbs) alpha 2 beta 2(6Glu-->Lys) (rHb beta E6K) and alpha 2 beta 2(6Glu-->Arg) (rHb beta E6R) using a yeast expression system coupled with a polymerase chain reaction (PCR)-based mutagenesis strategy for studies focused on defining determinants that facilitate crystallization of Hb C (alpha 2 beta 2(6Lys)). rHb beta E6K had the same electrophoretic mobility as native human Hb C, whereas rHb beta E6R migrated slightly slower than Hb C on cellulose acetate electrophoresis. The carbonmonoxy (CO) forms of rHb beta E6K and rHb beta E6R formed tetrahedral crystals in vitro in 2.3 mol/L phosphate buffer just like native Hb C. The Hb concentration required for crystallization of CO-rHb beta E6R was lower than that of CO-rHb beta E6K, suggesting that stronger basic amino acids at the beta 6 position accelerate crystallization of Hb. However, the size of rHb beta E6R crystals was smaller than that of rHb beta E6K. Crystallization of native Hb C and both rHbs was inhibited by Hb F. These results suggest that alpha 2 beta gamma-heterohybrids that have basic amino acids at the beta 6 position behave similarly and are unable to crystallize like Hb C.

Amino Acid Sequence↗
PubMed1994

Effects of aporphine isomers on rat prolactin.

S(+)-aporphines are partial agonists at D2 dopamine receptors. High selectivity of anti-dopaminergic action in limbic vs. extrapyr amidal regions of rat brain and lack of induction of dopaminergic supersensitivity have suggested their potential as atypical antipsychotic drugs. Now, in testing for effects on circulating prolactin, a typical D2 antagonist haloperidol elevated, and potent agonist R(-)-11-hydroxy-N-propylnoraporphine lowered, serum prolactin levels in gentled male rats, while S(+)-N-propylnorapomorphine and its 11-monohydroxy analog had little or no effect, even at high doses. Lack of hyperprolactinemia adds to characteristics of S(+)-aporphines that are desirable in improved antipsychotics.

Animals↗
PubMed1994

Transcriptional analysis of the Escherichia coli bio operon.

Using primer extension, two in vivo transcription start points (tsp) were identified for rightward transcription of the Escherichia coli biotin operon, at nucleotides (nt) +20 and +29. The strongest leftward transcript begins at +9, with a tenfold less abundant transcript starting at +3. The activity of segments cloned into promoter probe vectors locates the major leftward promoter between nt +1 and +105, as expected for the +9 tsp. Although the activity of a chromosomal operator is reduced about 300-fold by point mutation in either arm of the palindrome extending from nt -20 to +20, either a half-operator segment or a full operator bearing the same point mutation in one arm is substantially repressed when cloned into pKB2000, as though cellular location strongly affects the operator's affinity for the repressor.

Base Sequence↗
PubMed1994

Time to discontinue the use of solutions A and B as a cyanide 'antidote'.

Solutions A and B (15.8% ferrous sulfate in 0.3% citric acid and 6% sodium carbonate, respectively) have been available as a first-aid treatment for cyanide ingestion for many decades. Controversy surrounding the efficacy of solutions A and B has existed for much of that time, the main protagonists being in the UK. The current opinion in the UK is that solutions A and B should no longer be used as a first-aid measure in the management of cyanide poisoning. Similarly, oral sodium thiosulfate or activated charcoal should not be used. The recommended first-aid treatment of symptomatic cyanide poisoning is 100% oxygen and amyl nitrite, irrespective of the route of exposure.

Antidotes↗
PubMed1994

Sex differences in aggression: social representation and social roles.

Previous research suggests that men hold an instrumental social representation of aggression in which aggression is viewed as a functional interpersonal act aimed at imposing control over other people while women view aggression in expressive terms as a breakdown of self-control over anger. The present study examines the relative contribution of gendered personality differences (communality-agency) and occupational role in accounting for these differences. Men and women in the armed forces and nursing profession completed the Personal Attributes Questionnaire (PAQ: Spence & Helmreich, 1976) together with a psychometric measure of their tendency to view aggression as expressive rather than instrumental (Expagg: Campbell, Muncer & Coyle, 1992). The results indicate that occupational role and sex are both important correlates of individuals' representations of aggression. Though agency showed a significant negative zero-order correlation with expressive aggression, the impact of gendered personality traits was diminished when occupation and sex were taken into account. The data strongly support social role theory's emphasis upon contemporaneous occupational factors in explaining sex differences in the understanding of aggression but are less supportive of the role of masculine and feminine personality traits.

Aggression↗
PubMed1994

Comparative molecular biology of lambdoid phages.

Lambdoid phages are natural relatives of phage lambda. As a group, they are highly polymorphic in DNA sequence and biological specificity. Specificity differences have played a key role in identifying the specific sequences recognized by the N and Q antitermination proteins, the initiator O for DNA synthesis, the terminase system Nv1-A for cutting DNA during packaging, and the cI repressor protein. Variations that go beyond specificity differences are seen in packaging mechanism (headful in P22, specific cutting in lambdoid coliphages), in early control (terminator protein and phage-independent antitermination in HK022, phage-specific antitermination in lambda), in repression control (antirepressor operon in P22, absent in other lambdoid phages) and murein-degrading enzymes (transglycosylase in lambda, lysozyme in other lambdoid phages). Sequence comparisons indicate that recombination among lambdoid phages is frequent in nature.

Bacteriophage lambda↗