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Biomedical subjects

J Cameron

Publications and source records attributed to J Cameron.

At least 37 records · Page 2Linked to original sources
PubMed1996

Human immunodeficiency virus, type 1 protease substrate specificity is limited by interactions between substrate amino acids bound in adjacent enzyme subsites.

The specificity of the retroviral protease is determined by the ability of substrate amino acid side chains to bind into eight individual subsites within the enzyme. Although the subsites are able to act somewhat independently in selection of amino acid side chains that fit into each pocket, significant interactions exist between individual subsites that substantially limit the number of cleavable amino acid sequences. The substrate peptide binds within the enzyme in an extended anti-parallel beta sheet conformation with substrate amino acid side chains adjacent in the linear sequence extending in opposite directions in the enzyme-substrate complex. From this geometry, we have defined both cis and trans steric interactions, which have been characterized by a steady state kinetic analysis of human immunodeficiency virus, type-1 protease using a series of peptide substrates that are derivatives of the avian leukosis/sarcoma virus nucleocapsid-protease cleavage site. These peptides contain both single and double amino acid substitutions in seven positions of the minimum length substrate required by the retroviral protease for specific and efficient cleavage. Steady state kinetic data from the single amino acid substituted peptides were used to predict effects on protease-catalyzed cleavage of corresponding double substituted peptide substrates. The calculated Gibbs' free energy changes were compared with actual experimental values in order to determine how the fit of a substrate amino acid in one subsite influences the fit of amino acids in adjacent subsites. Analysis of these data shows that substrate specificity is limited by steric interactions between pairs of enzyme subsites. Moreover, certain enzyme subsites are relatively tolerant of substitutions in the substrate and exert little effect on adjacent subsites, whereas others are more restrictive and have marked influence on adjacent cis and trans subsites.

Amino Acid Sequence↗
PubMed1996

Detrimental effects of reward. Reality or myth?

Based on seemingly overwhelming empirical evidence of the decremental effects of reward on intrinsic task interest and creativity, the use of reward to alter human behavior has been challenged in literature reviews, textbooks, and the popular media. An analysis of a quarter century of research on intrinsic task interest and creativity revealed, however, that (a) detrimental effects of reward occur under highly restricted, easily avoidable conditions; (b) mechanisms of instrumental and classical conditioning are basic for understanding incremental and decremental effects of reward on task motivation; and (c) positive effects of reward on generalized creativity are easily attainable using procedures derived from behavior theory.

Adult↗
PubMed1996

Hypodontia of the permanent dentition. Case reports.

Hypodontia has been observed as one of the most common human dental developmental anomalies. It may be defined as agenesis of one or more teeth. The prevalence in the permanent lower central and lateral incisor region is low, ranging from 0.23 percent to 0.08 percent, respectively. This is compared with an overall incidence of hypodontia of 3.49 percent. However, significant racial variation occurs. Treatment options generally available are: no treatment, closure of spaces orthodontically, or prosthetic replacement. Aetiology, associated anomalies, and factors involved in treatment choice are discussed. A report of four cases of hypodontia of the permanent lower anterior teeth and their orthodontic management is presented.

Anodontia↗
PubMed1995

Dietary calcium supplementation restores pressure natriuresis responses in Dahl-S rats.

Calcium supplementation prevents hypertension in Dahl S (DS) rats. Because abnormal pressure natriuresis may contribute to the development of hypertension, we examined the effect of calcium on pressure natriuresis. DS and Dahl R (DR) rats maintained on a 4% sodium diet containing either 0.5% or 2% calcium for 4 weeks were anesthetized; sodium excretion, renal blood flow, and inulin clearance were determined at perfusion pressures of 100, 125, and 156 mm Hg. Inulin clearance and renal blood flow were not different between groups. Sodium excretion increased with increasing renal perfusion pressure in all groups. The slope of the line relating renal perfusion pressure to sodium excretion was greater (P < .05) in DR rats than in DS rats on normal calcium intakes. High calcium intake normalized the slope of the line relating renal perfusion pressure to sodium excretion in DS rats, but had no effect on DR rats. Thus, dietary calcium supplementation normalizes the blunted pressure natriuresis response in the DS rat and may contribute to the prevention of hypertension.

Anesthesia↗
PubMed1995

Directional coronary atherectomy for lesions of the proximal left anterior descending artery: initial clinical results, complications and histopathological findings.

BACKGROUND: Directional coronary atherectomy is a percutaneous technique which extends the role of balloon angioplasty to bulky eccentric coronary lesions. AIMS: To report the early experience, clinical results, complications and histopathological findings of directional coronary atherectomy (DCA) in proximal left anterior descending artery (LAD) stenosis. METHODS: Study of 25 lesions in 24 patients on whom directional atherectomy was performed on the proximal LAD artery with the Simpson coronary atherectomy device. RESULTS: Twenty-five procedures were performed on 24 patients with stenosis in the proximal LAD artery. There were 21 males and three females with a mean age of 56.5 years. Sixteen patients presented with stable angina and eight with unstable angina. Eight patients had previous myocardial infarction (MI). Angiographic success was obtained in 24 of 25 lesions (96%). The mean lesion length was 13.1 +/- 3.7 mm and the mean LAD artery diameter was 3.6 +/- 0.5 mm. Minimal luminal diameter improved from 0.9 +/- 0.4 mm to 3.0 +/- 0.5 mm and the percentage diameter stenosis reduced from 75 +/- 12% to 16 +/- 9%. Complications included acute occlusion in one patient, non-Q MI in three patients, local vascular complications in one patient and side-branch loss in one patient. Histology demonstrated fibrous cap of atherosclerotic plaque in 100%, media and internal elastic lamina in 28% and intimal hyperplasia in 100% of restenotic lesions and 27% of native lesions. Restenosis rates in angiographically restudied patients was 27%. The mean minimal luminal diameter at follow-up was 2.3 +/- 0.9 mm and the mean percentage diameter stenosis was 35 +/- 21%. CONCLUSION: From this initial study, we conclude that DCA is an effective and safe procedure for the treatment of large proximal LAD lesions. DCA provides a large luminal diameter and "smoother' angiographic appearance compared to coronary angioplasty. Acute complication rates are low and restenosis rates were comparable with percutaneous transluminal coronary balloon angioplasty.

Adult↗
PubMed1995

Development of HIV-1 resistance to (-)2'-deoxy-3'-thiacytidine in patients with AIDS or advanced AIDS-related complex.

OBJECTIVE: To determine the rate of development of in vitro HIV resistance to (-)2'-deoxy-3'-thiacytidine (3TC) and relate the effect of dose to emergence of resistance. METHODS: HIV-infected men and non-pregnant women, aged > or = 18 years, with a CD4 count < or = 300 x 10(6)/l cells were followed in a Phase I/II study, in which they were evaluated for tolerance to 3TC and effect of this agent with regard to viral susceptibility. Peripheral blood and plasma samples were collected at regular intervals for analysis. HIV was isolated using umbilical cord blood mononuclear cells as targets. These cells were also used in determinations of median inhibitory drug concentration. Specific amplification of the 184 mutation site, associated with HIV resistance to 3TC, was performed by polymerase chain reaction, using specific primer pairs, on DNA harvested from infected peripheral blood mononuclear cells (PBMC) of donors or, alternatively, on DNA that had been reverse transcribed from plasma-associated HIV RNA. RESULTS: Phenotypic resistance was detected in approximately one-third of individuals studied, who were followed between 8 and 56 weeks. Development of 3TC resistance occurred independently of dose, although time of first appearance of resistant HIV-1 variants appeared reduced at high 3TC doses. Amino-acid changes at codon 184 in HIV-1 reverse transcriptase were associated with, and preceded, the development of phenotypic 3TC resistance. Most commonly, a Met to Ile substitution appeared transiently before being superceded by a Val substitution at codon 184. CONCLUSIONS: In vitro resistance to 3TC developed in a high proportion of subjects who received prolonged monotherapy with this drug. The development of resistance to 3TC was associated with appearance of mutated viral forms and the disappearance of wild-type virus, with regard to codon 184, in both patient plasma and PBMC.

AIDS-Related Complex↗
PubMed1994

Outcome five years after percutaneous transluminal coronary angioplasty or coronary artery bypass grafting for significant narrowing limited to the left anterior descending coronary artery.

Percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) are both used widely for angina but information about their comparative efficacy is limited. This study compared the outcome of 358 consecutive patients undergoing initial revascularization for significant narrowing of the left anterior descending artery (LAD) by PTCA (n = 254) or CABG (n = 104) from 1987 to 1989. PTCA was successful in 93% but complicated by urgent CABG in 3%. A left internal mammary graft was used in 88% of those having elective CABG. There was 1 perioperative death. Follow-up data were obtained after a median interval of 5.5 years (maximum 7.1). Rates for freedom from death (97% PTCA vs 93% CABG, p = 0.06) were similar, but CABG patients had greater rates for freedom from chest pain recurrence (74% CABG vs 48% PTCA, p < 0.0001), myocardial infarction (98% vs 92%, p = 0.04), and from need for further revascularization (99% vs 67%, p < 0.0001). Both groups achieved similar status, with 81% of PTCA and 90% of CABG patients having angina no worse than functional class I. Quality-of-life index was high for both groups (0.983 +/- 0.034/1.000 vs 0.987 +/- 0.032/1.000, p = 0.3). Both PTCA and CABG result in excellent survival, functional ability, and quality of life, but patients undergoing PTCA require more procedures to achieve this.

Adult↗
PubMed1994

Percutaneous transluminal coronary angioplasty: clinical and quality of life outcomes one year later.

BACKGROUND: The quality of life status of patients prior to and following percutaneous transluminal coronary angioplasty (PTCA) has not been comprehensively investigated. AIM: This study was carried out to determine the effect that PTCA has on patients' quality of life. METHODS: Data on 209 patients were collected one day pre-PTCA and at a mean of two and 11 months post-PTCA. Data on symptomatic status, functional capacity, life satisfaction and psychological well-being were analysed quantitatively. Clinical outcomes, patient perception of PTCA and employment status wee analysed by descriptive statistics. RESULTS: Highly significant improvement in all quality of life measures was found at the early follow-up (p < .001). This improvement was sustained at the late follow-up. At the late follow-up, 58% of patients felt that PTCA had been very beneficial to their health and well-being, and 79% of workers had returned to work. PTCA was primarily successful in 91% of vessels dilated. There were no procedural-related deaths, 12 patients (6%) developed acute occlusion and three patients (1.5%) experienced myocardial infarction (MI). A symptomatic restenosis rate of 16% was found, including 19 patients (9%) requiring repeat PTCA and 14 (7%) undergoing coronary artery bypass grafting (CABG). CONCLUSION: These findings suggest that, after PTCA, the majority of patients experienced improved quality of life which was sustained one year later.

Angioplasty, Balloon, Coronary↗
PubMed1994

Experience with the Gianturco-Roubin stent for abrupt vessel closure complicating percutaneous transluminal coronary angioplasty.

BACKGROUND: Emergency coronary artery bypass grafting (CABG) has previously been the only option in the treatment of refractory abrupt vessel closure complicating percutaneous transluminal coronary angioplasty (PTCA), and has been associated with high rates of morbidity and mortality. Intracoronary stenting now provides an alternative to emergency CABG. AIM: To assess our initial experience with emergency coronary artery stenting as a new technique. METHODS: Retrospective case study review with clinical and angiographic follow-up. RESULTS: The Gianturco-Roubin (GR) stent was deployed in 13 patients in whom PTCA was complicated by abrupt vessel closure refractory to standard balloon techniques. Indications for PTCA were unstable angina (six), stable angina (six) and acute myocardial infarction (MI) (one). The arteries stented included left anterior descending (LAD) artery lesions (eight) and right coronary artery lesions (five). Two patients required urgent CABG, one due to failed stent deployment and one for inadequate control of vessel dissection. In seven of the stented patients the creatine kinase rose to greater than twice the upper limit or normal. Three patients had subacute thrombotic occlusion at seven to 19 days post stent deployment, managed with intravenous thrombolysis or repeat PTCA. At seven months follow-up, 11 patients were free of angina, two patients had Canadian Heart Association class II angina and there were no deaths. Eleven patients had repeat angiography at mean six months post stent. Five patients had evidence of restenosis managed with repeat PTCA in four and CABG in one. CONCLUSIONS: The GR stent is an effective alternative to urgent CABG in the treatment of refractory abrupt vessel closure complicating PTCA.

Angioplasty, Balloon, Coronary↗
PubMed1994

The effect of vitamin A on the proliferation of oral epithelium in the rat.

This study assessed the effect of topical and systemic 13-cis-retinoic acid on rat palatal epithelial proliferation with bromodeoxyuridine labelling and silver stained nucleolar organizer regions. Sixty male Wistar rats were assigned randomly to a control group or treatment groups of topical orabase, RA in orabase, 5 times/week or twice weekly systemic doses of 12 mg RA in coconut oil. The rats were treated for 1, 2, 4 or 8 weeks and killed 1 h post-injection of 40 mg/kg BrdUrd. The palatal mucosae were processed, using immunoperoxidase staining or silver stain to visualize BrdUrd utilization or AgNORs, respectively. The number of BrdUrd positive nuclei/mm overlying epithelium and number and area of AgNORs in the basal cells were assessed using image analysis. ANOVA indicated there was no significant effect of treatment on LN/mm or the numbers or areas of AgNORs. The LN/mm for the 8 w group (29.5) was significantly lower than the other groups. RA did not influence rat palatal epithelial proliferation, but across all groups increased age was associated with decreased proliferation. It would appear that the proliferation of normal oral mucosa may not be subject to altered proliferation when treated with therapeutic doses of topical or systemic RA.

Administration, Oral↗
PubMed1994

Identification of a mutation at codon 65 in the IKKK motif of reverse transcriptase that encodes human immunodeficiency virus resistance to 2',3'-dideoxycytidine and 2',3'-dideoxy-3'-thiacytidine.

The technique of in vitro selection was used to generate variants of the human immunodeficiency virus type 1 that are resistant to 2',3'-dideoxycytidine (ddC). Most of the pol regions of such viruses, including the complete reverse transcriptase open reading frame and portions of flanking protease and integrase genes, were cloned and sequenced, using PCR-based procedures. Mutations were variously detected at amino acid site 65 (Lys-->Arg; AAA-->AGA) and at a previously reported codon, site 184 (Met-->Val; ATG-->GTG). We introduced the site 65 mutation into the pol gene of infectious, cloned HxB2-D DNA by site-directed mutagenesis in order to confirm by viral replication assay the importance of this site in conferring resistance to ddC. The recombinant virus possessed greater than 10-fold resistance against this compound in comparison with parental HxB2-D. Cross-resistance of approximately 20- and 3-fold, respectively, was detectable against the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine and 2',3'-dideoxyinosine but not against 3'-azido-3'-deoxythymidine. Combinations of the site 65 and 184 mutations did not yield levels of resistance higher than those attained with the site 65 mutation alone. The presence of the site 65 mutation was confirmed by PCR analysis of peripheral blood mononuclear cells from patients on long-term ddC therapy in 4 of 11 cases tested. Viruses that possessed a ddC resistance phenotype were isolated from subjects whose viruses contained the site 65 mutation in each of four instances. Four of these clinical samples were also demonstrated to possess the Met-184-->Val mutation, and one of them possessed both the Lys-65-->Arg and Met-184-->Val substitutions. Direct cloning and sequencing revealed the site 65 mutation in viruses isolated from these individuals.

Amino Acid Sequence↗
PubMed1994

Prediction of reproductive status in women with bulimia nervosa by past high weight.

It is not understood why disturbed menstrual function occurs in as many as 50% of women with bulimia nervosa who are at normal weight. The authors measured luteinizing hormone (LH), estradiol, and progesterone in 13 women with bulimia nervosa who were at normal weight and six normal comparison subjects. They found that the women with bulimia nervosa were likely to have abnormal 24-hour luteinizing hormone (LH) secretion if their current weight was less than 85% of their past high weight.

Adolescent↗
PubMed1994

EFFECT OF THE EXTERNAL CONCENTRATION OF CALCIUM ON THE POSTMOULT UPTAKE OF CALCIUM IN BLUE CRABS (CALLINECTES SAPIDUS)

The rate of calcium uptake in blue crabs (Callinectes sapidus Rathbun) acclimated to 2 sea water with a calcium concentration of 1.4 mmol l-1 was dependent on the magnitude and direction of the electrochemical gradient for calcium. When transferred to water with a high calcium concentration (6 mmol l-1), the electrochemical gradient for calcium favoured diffusive influx, and calcium uptake and apparent H+ excretion increased by approximately 50 %. When transferred to water with a low calcium concentration (0.10 mmol l-1), where the electrochemical gradient for calcium strongly favoured diffusive efflux, calcium uptake ceased but apparent H+ excretion continued at a reduced rate. Crabs regulated the free calcium concentration in their blood at approximately 8 mmol l-1 when the external concentration of calcium was 1.4 mmol l-1 or higher, but the concentration of free calcium in the blood decreased to 5.6 and 4.6 mmol l-1, respectively, at external concentrations of calcium of 0.25 and 0.10 mmol l-1. Crabs transferred to water with 0.10 mmol l-1 calcium for the first 2 days after moult accumulated only 2.5 g calcium kg-1 wet mass, about one-quarter of the mass normally accumulated. Seawater-acclimated crabs transferred to 2 salinity at 1 day postmoult took up calcium at a reduced rate, indicating that a period of acclimation is necessary for a component of the active transport system to increase its capacity, for diffusive efflux to be reduced, or for both to occur.

Journal Article↗