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Biomedical subjects

A Campbell

Publications and source records attributed to A Campbell.

At least 109 records · Page 6Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Iodine-131 in breast milk following therapy for thyroid carcinoma.

UNLABELLED: This study evaluates breast milk secretion of 131I following therapeutic administration of 4000 MBq of 131I-iodide during lactation. METHODS: Breast milk 131I activity concentration was measured over a 32-day period. Dosimetry calculations were undertaken to estimate the period for discontinuation of breast feeding and the equivalent dose to the breasts. RESULTS: To achieve an infant effective dose < 1 mSv and an infant thyroid dose < 10 mSv, breast feeding would need to be discontinued for at least 52 days. The estimated equivalent dose to the breasts was 1.6 Gy. CONCLUSION: It is suggested that 131I-iodide administration is not undertaken during lactation and that breast feeding is discontinued several days prior to administration.

Adenocarcinoma, Follicular↗

Hydrodynamic performance of Carbomedics valves in double valve replacement.

Most patients undergoing double valve replacements have reduced myocardial capacity. However, little is known about the influence of valve sizes on myocardial energy consumption in double valve replacement. This study was designed to supply hydrodynamic data for the proper selection of sizes in double valve replacement. A mock loop system was used to measure the energy consumption of CarboMedics valves at conditions resembling rest (5 L/min) and moderate exercise (9 L/min). All combinations of aortic valves size #21 to #27 with mitral prosthesis sizes #25 to #29 were tested separately. Larger size aortic prostheses revealed remarkably less energy consumption up to size #27. Under high flow (9 L/min) this effect was more pronounced. In contrast, mitral valve prosthesis sizes #25 to #29 had similar hydrodynamic data. At low flow conditions (5 L/min) no significant benefit was found with the use of a larger mitral valve. Only a reduction of less than 10 percent of total energy consumption could be achieved with the use of a mitral valve larger than #25 at 9 L/min flow. In conclusion there is no hydrodynamic reason for using a valve larger than #25 in the mitral position for patients who exercise moderately. Continuous reduction of cardiac work can be expected with the use of the largest possible aortic prosthesis up to size #27 at rest and at moderate exercise.

Aortic Valve↗

Feasibility of on-line transesophageal echocardiography during balloon mitral valvulotomy: experience with 93 patients.

Percutaneous balloon mitral valvulotomy (PBMV) has become an established method of treating symptomatic patients with rheumatic mitral stenosis. PBMV is performed with fluoroscopic guidance alone in most centres. However, even experienced operators can be misled by radiographic anatomic landmarks. Transesophageal echocardiography (TEE) provides high-quality images of the atrial septum, left atrium, mitral valve, and surrounding structures and has a number of unique advantages that make it a useful adjunct to fluoroscopy for guidance and monitoring of patients during PBMV. The aim of this study was to demonstrate the feasibility, safety, and utility of on-line TEE during PBMV on awake patients. TEE was performed on 93 consciously sedated, awake patients in the cardiac catheterisation laboratory during PBMV. Ninety five patients were successfully intubated in the supine position. Two patients were excluded from PBMV based on mobile thrombi near the mouth of the left atrial appendage. The TEE was well-tolerated in the 93 patients who underwent PBMV, and no complications of TEE were detected. Major complications of PBMV were detected in 7 patients (severe MR, n = 3; tamponade, n = 1; large ASD, n = 3). We conclude that on-line TEE during PBMV is feasible, safe, and well tolerated. TEE-guidance facilitates transseptal catheterization and proper positioning of balloon catheters across the mitral orifice. TEE can help monitor the adequacy of PBMV and help decide whether or not subsequent dilatations are necessary. TEE can rapidly detect complications and thereby guide appropriate management of these complications.

Adolescent↗

Altered spontaneous behavior and sensitivity to apomorphine in rats following pretreatment with S(+)-aporphines or fluphenazine.

Rats were pretreated for 2 weeks with similarly effective doses of the typical neuroleptic fluphenazine (FPZ) or the experimental weak partial D2 agonists S(+)N-n-propylnorapomorphine (NPA) and S(+)11-hydroxy-N-n-propylnoraporphine (11-OH-NPa). Spontaneous and dopamine (DA) agonist (apomorphine; APO) stimulated stereotyped behaviors or locomotion, and interactions with APO were evaluated over the following 2 weeks. While FPZ induced marked supersensitivity in APO stereotype, (+)NPA showed no significant change, and (+)11-OH-NPa produced only a small, transient increase in response; NPA also lacked a supersensitizing effect on locomotor arousal induced by APO. The time-course of stereotyped responses to APO following pretreatment with FLZ included a marked increase following FPZ that became maximal at day 5 and normalized by day 9; there was a parallel reduction of acute antisteotypy efficacy of FPZ. (+)11-OH-NPa had similar, but much lesser and shorter-lived effects. Spontaneous locomotion was markedly depressed following FPZ, recovered in 1 week, exceeded controls at day 9, and returned to baseline by day 11; (+)11-OH-NPa, again, had similar but smaller effects. Acute effects of FPZ to reduce spontaneous or APO-induced locomotion were greater after FPZ pretreatment and normalized within a week; (+)11-OH-NPa had a similar but smaller effect. Locomotor arousal by APO was altered inconsistently in the week after pretreatment with FPZ or (+)11-OH-NPa. Thus, FPZ appeared to induce tolerance and supersensitivity in central DA systems, most clearly seen following a several-day period to eliminate the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗