Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.1.1.6 (CAD)
4,420 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exercise myocardial-thallium scintigraphy plays a fundamental role in the diagnosis of coronary artery disease. Once exercise is not always feasible, pharmacological stress became a possible alternative. The authors review the mechanism of action, administrations protocols, indications and side effects of the drugs used for this purpose: dipyridamole, adenosine and dobutamine. Dipyridamole causes coronary hyperemia by increasing the interstitial levels of endogenous adenosine. Perfusion defects result from the mismatch of coronary reserve in different coronary territories. The drug administration is classically performed with a 0.142 mg/kg/min dosage e.v. for 4 minutes, total of 0.56 mg/kg. It is possible to use a greater dose of 0.84 mg/kg e.v. for 10 minutes, increasing sensitivity without loss of specificity for diagnosis of coronary artery disease. Oral dipyridamole protocols with 300 and 400 mg were used with similar results for sensitivity and specificity. The oral protocol has the disadvantage of delayed onset and longer action. Including several dipyridamole studies, 87% was obtained for sensitivity and 84% for specificity, in the diagnosis of CAD. Dipyridamole scintigraphy has been applied to myocardial infarction risk stratification, cardiac risk evaluation of patients proposed to noncardiac surgery and therapeutic efficacy evaluation of reperfusion techniques (angioplasty and surgery). The secondary effects of dipyridamole are frequent, however mild and well tolerated. They occur in half the patients, the most frequent, facial flushing (2%), dizziness (5%), nausea (4%), vomiting (1%), headaches (11%) and chest pain (26%). Some important complications were reported although rare: myocardial infarction, ventricular fibrillation and bronchospasm.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Role of pharmacologic stimulation with myocardial perfusion scintigraphy in the evaluation of patients with ischemic cardiopathy]. 129 Jun 55

This review covers the properties of dental ceramics. Castable systems, bioactive glass, PMF systems, CAD/CAM, and ceramic brackets in orthodontics are briefly discussed. Many of the advances made between 1960 and 1975 were directed toward the understanding, controlling, and developing of new ceramic processes. New and deeper understanding of the structure of non-crystalline solids, structural imperfections, sintering physics, and other physical phenomena related to the melting and solidification processes has brought ceramics from the near-total art form process of the mid-century to the status of a highly sophisticated science it enjoyed in the 1980's.
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PMID:Dental ceramics: the state of the science. 129 67

Although the prevalence of caries has decreased markedly in children, adolescents, and young adults in most industrialized countries, caries continues to be the main reason for tooth loss, particularly among the high risk segment of the population. In many developing countries, where traditional dietary patterns have changed to include sugar-containing foods and beverages, caries prevalence has increased and will continue to do so in the immediate future. Accordingly, it would be a serious mistake to be complacent about caries prevention. In future industrialized countries will see computers playing a significant role in cariology, finding applications not only in research and practice administration but directly in clinical practice as well. They will be used in every operatory in the assessment of caries risk, the recording of caries prevalence, the direct storing of radiographic information, and the restoration of carious teeth, assisted by computer-aided design and computer-aided manufacture (CAD/CAM) technology. Fluoride therapy, both systemic and topical, will continue to be the basis of caries prevention. Dental sealants, which are highly effective in protecting pits and fissures when applied soon after the teeth erupt, will be more widely used in the future when insurance plans will pay for prevention. Substitution of sucrose and syrups by non-fermentable sweetening agents can also reduce caries increments, but most agents are more expensive than sucrose and require consumer education to pay for the additional cost. Caries, as an infectious and transmissible disease, is amenable to prevention by interfering with the chain of transmission or by suppressing the putative pathogens, the mutans streptococci, in infected patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dental caries in the future: a global view. 129 66

Dental CAD-CAM has become a clinical reality. It holds great promise to help provide a higher level of service to the patient, while allowing the dentist to spend more time on patient needs than on the mechanics of restoration production. Still, this technology is not suited for every dental office. This paper discusses the technique of CAD-CAM, its potential and its limitations so the dentist can better evaluate the appropriateness of this new modality for his or her own office.
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PMID:The reality of dental CAD-CAM: hype or hope? 130 29

The subperiosteal implant has long been regarded as the most successful, predictable, and versatile of all implant systems. In some cases, however, anatomic morphology and surgical technique present certain limitations for the subperiosteal procedure. Through CAD/CAM multiplanar diagnostic imaging, not only have we been able to eliminate the first stage of the surgical procedure, but we have expanded the capabilities and versatility of the subperiosteal procedure. In addition, coating the subperiosteal implant frame with hydroxyapatite has allowed the achievement of bony union, thus increasing the long-range prognosis of the individual case.
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PMID:Long-term retrospective studies on the CT-scan, CAD/CAM, one-stage surgery hydroxyapatite-coated subperiosteal implants, including human functional retrievals. 131 Jun 63

1. We studied the effects of chronic calcium antagonist (calcium entry blocker, CEB; nifedipine, verapamil, diltiazem) treatment on beta-adrenoceptor density (assessed by (-)-[125I]-iodocyanopindolol [ICYP] binding) and subtype distribution in right atria from 65 patients without apparent heart failure undergoing elective coronary artery bypass grafting (CAD-patients) and from 13 patients with moderate heart failure (NYHA class III to class III-IV) undergoing mitral valve replacement (MVD-patients). 2. In CAD-patients atrial beta-adrenoceptor density was 79.3 +/- 7.9 fmol ICYP bound mg-1 protein (n = 18), the beta 1:beta 2-adrenoceptor ratio 69:31%. Chronic CEB-treatment did not affect either atrial beta-adrenoceptor density or beta 1:beta 2-adrenoceptor ratio. 3. In contrast, in CAD-patients chronically treated with beta 1-adrenoceptor antagonists (atenolol, bisoprolol, metoprolol) and CEB, atrial beta-adrenoceptor density was significantly increased (108.6 +/- 10.5 fmol ICYP bound mg-1 protein, n = 21); this increase was due to a selective increase in beta 1-adrenoceptors. 4. In MVD-patients atrial beta-adrenoceptor density (55.5 +/- 8.7 fmol ICYP bound mg-1 protein, n = 7) was significantly lower (P less than 0.05) than in CAD-patients; beta 1:beta 2-adrenoceptor ratio, however, was not changed (67:33%). Chronic CEB-treatment of MVD-patients did not prevent the decrease in atrial beta-adrenoceptors. 5. We conclude that chronic CEB-treatment does not affect human right atrial beta-adrenoceptor density, either in patients without apparent heart failure or in patients with moderate heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lack of effect of chronic calcium antagonist treatment on beta 1- and beta 2-adrenoceptors in right atria from patients with or without heart failure. 131 61

In this article we have focused on the evolving pattern of nutritional management of the person with diabetes. Before the advent of insulin in 1922, it was sufficient to identify a meal plan that would keep people alive until they could be rescued from mortality due to diabetic ketoacidosis (the major killer of the era) by pharmacologic means. Now, the life expectancy of people with diabetes is close to that of the general population and focus has turned to combating the new threats of macrovascular disease and kidney failure. Over recent years the susceptibility of NIDDM patients to macrovascular events has been established and the twofold increase in risk of a heart attack in diabetic men is outshadowed by the four- to fivefold risk in diabetic women and the 13- to 17-fold greater risk in diabetics under the age of 30 years compared with their nondiabetic counterparts. The mechanism behind the susceptibility to macrovascular disease has generated a veritable plethora of investigations focusing on the atherogenic profile of diabetic dyslipidemia. Hyperinsulinemia, insulin resistance, and overtreatment of the diabetic with insulin have been claimed as contributors to the development of premature atherosclerosis. The hallmark of the diabetic dyslipidemia is the tendency to elevated VLDL triglyceride levels and the closely linked reduction in HDL cholesterol. Although there is some controversy on the relationship between triglyceride levels and the incidence of CAD, there is no doubt that HDL is an independent risk factor. It can now be safely said that elevated triglycerides are a risk factor in women and that in men elevated triglycerides constitute a risk factor if accompanied by a reduced HDL level. For these reasons, any approach to nutritional management of the diabetic must attempt not only to normalize glycemia but to make every effort to reduce the atherogenic profile. In the accompanying algorithm (Fig. 4), we consider the risk factors conducive to a reduction in life expectancy and offer a meal plan that is appropriate for the individual with diabetes. For the 80% of NIDDM patients who are obese, a diet with a reduction of 500 to 1000 kcal is in order and this may be achieved by a periodic VLCD. We examined carefully the controversy related to yo-yo dieting and support the notion that its effects in humans are not all that harmful. Ingestion of simple sugars in the high carbohydrate diet has negative effects both on carbohydrate and lipid metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The good, the bad, and the ugly in diabetic diets. 131 32

Patterns of RFLP association were studied, to identify gene regions influencing quantitative variation in lipid and lipoprotein traits (coronary artery disease [CAD] risk factors or metabolically related traits). Subjects (118 female and 229 male; age 20-59 years) were selected for health. Multiple RFLPs were used to sample variability in regions around genes for apolipoprotein (apo) B (restriction enzymes HincII, PvuII, EcoRI, and XbaI), apo AI-CIII-AIV (BamHI, XmnI, TaqI, PstI, SstI, and PvuII) and cholesterol ester transfer protein (TaqI). Separate analyses were done by gender. The sample was truncated at mean +/- 4 SD, to remove extreme outliers. There was no significant gender difference in RFLP genotype frequency distribution. After trait-level adjustment to maximize removal of concomitant variability, analysis of variance was used to estimate the percentage trait phenotypic variance explained by measured variability in the gene regions studied. Fewer gene regions were involved in men, with less influence on quantitative trait variation than in women, in whom hormone use affected association patterns. Gender differences imply that pooling genders or adjusting data for gender effects removes genetic information and should be avoided. The association patterns show that variability around the candidate genes modulates trait levels: the genes are contributors to the genetics of CAD risk variables in a healthy sample.
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PMID:Patterns of association between genetic variability in apolipoprotein (apo) B, apo AI-CIII-AIV, and cholesterol ester transfer protein gene regions and quantitative variation in lipid and lipoprotein traits: influence of gender and exogenous hormones. 134 81

We have previously reported the isolation and characterization of mutant Chinese hamster ovary (CHO-K1) cells of the Urd-A complementation group, which require uridine for growth, are deficient in the activities of the first three enzymes of de novo UMP biosynthesis, and produce markedly reduced amounts of a truncated form of the multifunctional protein CAD, which contains these three enzyme activities. We report here that a single base change of G to A at a highly conserved RNA splice acceptor site is responsible for the phenotype of this mutant. In addition to a small amount of apparently normal CAD mRNA, this mutation causes production of two alternative forms of CAD mRNA in the mutant, one that includes the intron just prior to the mutation and one that excludes the exon just after the mutation. The affected splice site is located at the intron-exon boundary just preceding the exon that encodes the beginning of the aspartate transcarbamylase (ATCase) domain of the CAD protein. Both intron inclusion and exon exclusion during RNA processing introduce a translation stop codon upstream of the region encoding this domain, resulting in the production of the truncated CAD protein seen in the Urd-A mutant. This mutation also results in markedly decreased levels of CAD mRNA and protein in the mutant.
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PMID:A single base change at a splice acceptor site leads to a truncated CAD protein in Urd-A mutant Chinese hamster ovary cells. 134 64

CAD is a multidomain protein that catalyzes the first three steps in mammalian de novo pyrimidine biosynthesis. The 243-kDa polypeptide consists of four functional domains; glutamine amidotransferase (GLNase), carbamyl phosphate synthetase (CPSase), aspartate transcarbamylase (ATCase), and dihydroorotase (DHOase). Controlled proteolysis of hamster CAD was found to cleave the molecule into 18 fragments which successively accumulate and disappear during the course of digestion. Each fragment was isolated and partially sequenced to determine its location in the polypeptide chain. Proteolysis was found to usually occur at the junctions between the domains and sub-domains identified by sequence homology. All proteases of low to moderate specificity cleaved the molecule in a similar fashion. The rate of proteolysis widely varied and the interdomain regions were not always accessible to proteases. Each of the major functional domains is postulated to consist of subdomains. The duplicated halves of the CPSase domain (116 kDa) have a homologous structure consisting of 11-, 25-26-, and 21-22-kDa subdomains. Prolonged digestion cleaved the DHOase domain (36.6 kDa) into two stable species suggesting that this region is comprised of 11.5- and 15.0-kDa subdomains. Similarly, proteolysis of the 21-kDa catalytic subdomain of the GLNase domain (40 kDa) indicated a bilobal structure consisting of 12.3- and 8.5-kDa chain segments. The connecting region between the two ATCase subdomains (16.4 and 18 kDa) was not cleaved. Copurification of many of the domains showed that they remain associated by noncovalent interactions even after the connecting segments have been cleaved. The chain segments, the linkers, which connect the domains and subdomains were conserved in length but not in sequence, were predicted to be relatively hydrophilic and flexible but did not show a tendency to assume a particular secondary structure. These studies provide a more detailed map of the structural organization of the CAD polypeptide.
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PMID:The structural organization of the hamster multifunctional protein CAD. Controlled proteolysis, domains, and linkers. 134 59


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