Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In patients with glycogen storage disease type Ia (glucose-6-phosphatase deficiency), serum triglyceride concentrations are markedly raised, whereas phospholipids and cholesterol levels are only moderately elevated. In addition, both VLDL and LDL lipoprotein fractions are raised. Despite these abnormalities, endothelial vascular dysfunction and atherosclerosis seem to be rare in such patients. In view of the crucial role of apolipoprotein E (apoE) in lipid metabolism, we studied both apoE polymorphism (40 patients) and serum concentration (20 patients) in patients with glycogen storage disease type Ia. The distribution of each allele at the apoE locus was similar to that reported in the general population, whereas serum apoE concentrations were raised in our patients. Raised apoE levels in the serum could play an important role in counterbalancing the at-risk-for-atherosclerosis lipid profile of patients with glycogen storage disease type Ia. Moreover, E3 and E4 polymorphisms, predominant in our patients, have a high triglyceride binding capacity and are thus able to increase triglyceride clearance. However, the origin of raised concentrations of apoE is not completely clear though, bearing in mind previous reports regarding serum protein concentrations in such patients, increased hepatic synthesis is likely.
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PMID:Apolipoprotein E polymorphism and serum concentrations in patients with glycogen storage disease type Ia. 1080 Oct 51

An interest in the ageing process has increased greatly with increasing the population of the aged. The goal of this interest is to improve the quality of life(QOL) in the aged. In this paper, the presidential address "Ageing Society and Laboratory Medicine" at the 46th annual meeting of JSCP in Kumamoto'99 was summarized on the important research for ageing in the past decades. The paper presented was age- and gene-related changes, the latent variation of serum constituents and lipids abnormality in the ageing process. Concerning to the definition of reference value of healthy populations and the subjects who had no combined ailments, the reference interval of individuals(intra-personal), followed 5 years categorized by age, sex, and social conditions, gave a narrow range of variation than did a larger mixed populations(inter-personal). The reference intervals set would be a more sensitive reference than is the customary "normal range" for values occurring in inter-personal. Concerning to the study of the relationship between laboratory test and activity of daily living(ADL), the higher serum levels for TP, Alb, Hb, Glu, TC were observed in the higher ADL. The basic research techniques were also evaluated in the paper. The serum lipoperoxides were correlated with serum lipoprotein free radicals which caused atherosclerosis. The higher frequency of cerebral- and myocardial-infarction in the aged were observed in the higher serum LDL-C and lower serum level of arachidonic acid(AA), eicosapentaenoic acid(EPA), and AA/EPA ratio were observed in AMI patients with lower HDL-C groups than the healthy aged. Although Alzheimer(AD)'s disease had a progressive memory loss and immobile dementia and was reported the decrease of acetyltransferase activity in the brain, decrease of serum level of free choline, lyso-phosphatidylcholine, phosphatidylcholine(PC) and sphingomyelin(SM)/PC ratio were observed in spite of keeping normal serum level of SM. The decreased serum levels of pseudocholin esterase and albumin, especially mercaptoalbumin were observed in the healthy aged with advancing age. The early diagnosis and prediction of prognosis for the latent ailments in the aged was stressed. As to the study of variations of serum protein levels in the healthy aged, variations of serum proteins were classified into three types, 1) mainly acute phase reactant proteins such as alpha 1AT increased with advancing age, 2) transporting proteins such an albumin decreased and 3) proteins with no significant variation these were useful proteins for the early finding of latent ailments. The higher increase of alpha 1AT/beta 2III in the healthy aged over 60 y.o. was suspected to become severe in near future.
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PMID:[Ageing society and laboratory medicine]. 1105 92

Elevated blood viscosity is a predictor of cardiovascular disease. The major determinants of blood viscosity are hematocrit and plasma viscosity. Plasma triglycerides elevate plasma viscosity; however, the contribution of plasma triglycerides to blood viscosity after adjustment for other major covariates has not been reported. This cross-sectional study of 257 adult subjects evaluated the associations between fasting plasma lipids, fibrinogen, total serum protein, hematocrit and blood viscosity. Blood viscosity was measured at 37 degrees C with a coaxial cylinder microviscometer at shear rates of 100 and 1 s(-1). Blood viscosity values are reported both as uncorrected measurements and measurements corrected to a hematocrit of 45% by a regression equation. Uncorrected blood viscosity at a shear rate of 100 s(-1) was significantly associated with triglycerides, fibrinogen, high density lipoprotein (HDL) cholesterol, total serum protein, and hematocrit using stepwise multivariate regression analysis. When corrected blood viscosity at 100 s(-1) was the dependent variable, there were statistically significant associations with triglycerides, HDL cholesterol, and total serum protein. Corrected blood viscosity at 1 s(-1) was significantly associated with triglycerides, fibrinogen, total serum protein, and an indicator variable for diabetes mellitus. This study supports an additional mechanism whereby triglycerides may contribute to cardiovascular risk.
Atherosclerosis 2002 Apr
PMID:Hypertriglyceridemia is associated with an elevated blood viscosity Rosenson: triglycerides and blood viscosity. 1188 28

The present report describes application of advanced analytical methods to establish correlation between changes in human serum proteins of patients with coronary atherosclerosis (protein metabolism) before and after moderate beer consumption. Intrinsic fluorescence, circular dichroism (CD), differential scanning calorimetry and hydrophobicity (So) were used to study human serum proteins. Globulin and albumin from human serum (HSG and HSA, respectively) were denatured with 8 m urea as the maximal concentration. The results obtained provided evidence of differences in their secondary and tertiary structures. The thermal denaturation of HSA and HSG expressed in temperature of denaturation (Td, degrees C), enthalpy (DeltaH, kcal/mol) and entropy (DeltaS kcal/mol K) showed qualitative changes in these protein fractions, which were characterized and compared with fluorescence and CD. Number of hydrogen bonds (n) ruptured during this process was calculated from these thermodynamic parameters and then used for determination of the degree of denaturation (%D). Unfolding of HSA and HSG fractions is a result of promoted interactions between exposed functional groups, which involve conformational changes of alpha-helix, beta-sheet and aperiodic structure. Here evidence is provided that the loosening of the human serum protein structure takes place primarily in various concentrations of urea before and after beer consumption (BC). Differences in the fluorescence behavior of the proteins are attributed to disruption of the structure of proteins by denaturants as well as by the change in their compactability as a result of ethanol consumption. In summary, thermal denaturation parameters, fluorescence, So and the content of secondary structure have shown that HSG is more stable fraction than HSA.
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PMID:Structure characterization of human serum proteins in solution and dry state. 1190 9

This paper describes a ProteinChip technology for the identification and quantification of apolipoprotein profiles in crude biological samples. Expression levels of apoA-I and apoA-II and their glycosylated products were accomplished using single 1 microL plasma samples. In the present studies, strong anionic and weak cationic exchanger ProteinChips (SAX2 and WCX2 chip surfaces) were tested, and the WCX2 chip was found to be selective for specific apolipoproteins. Using the WCX2 chip and analysis via surface-enhanced laser desorption ionization mass spectrometry (SELDI-MS), apoA-I and apoA-II were separated as sharp peaks at 28 and 17 kD and did not overlap with other serum protein peaks. Since these assays can be completed on a large number of clinical samples in approximately 1 h, further development of this technique will facilitate both epidemiological studies and therapeutic trials in assessing the role of the apolipoproteins and their glycosylated products in atherosclerosis.
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PMID:ProteinChip technology: a new and facile method for the identification and measurement of high-density lipoproteins apoA-I and apoA-II and their glycosylated products in patients with diabetes and cardiovascular disease. 1264 94

In clinical practice, diagnosis and risk prediction are usually based on the analysis of serum or plasma proteins whereas gene expression analysis is not used on a routine basis. In order to compare the diagnostic and predictive relevance of serum protein and peripheral blood mRNA levels, we determined cytokine levels of end-stage renal failure patients undergoing hemodialysis. These patients face a high mortality mainly due to acceleration of atherosclerosis and subsequent severe vascular events. mRNA expression of the pro-inflammatory cytokine TNF alpha was significantly elevated in hemodialysis patients and further increased after 2 h of dialysis treatment. In contrast, gene expression of the anti-inflammatory cytokine TGF beta was significantly decreased. Patients who died during the observation period of 36 months had significantly increased mRNA levels of TNF alpha and decreased TGF beta mRNA expression at baseline. Survival analysis indicated that increased TNF alpha mRNA levels (P < 0.02) and TNF alpha/TGF beta mRNA ratios (P < 0.001) predict mortality. The corresponding cytokines in serum showed some association with disease, but serum concentrations neither changed during hemodialysis nor predicted mortality. This study shows that gene expression patterns of circulating leukocytes may present an important new diagnostic tool to predict clinical outcome in patients with inflammatory vascular diseases.
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PMID:Evaluation of diagnostic relevance of mRNA levels in peripheral blood: predictive value for mortality in hemodialysis patients. 1530 46

Mannose binding lectin (MBL) is a serum protein with structure and functions similar to those of complement factor C1q, and is a key molecule in innate immunity. Interestingly, absence or extremely low concentration of serum MBL (MBL deficiency) seems to be a risk factor for occurrence of autoimmune diseases, in particular systemic lupus erythematosus. In addition, individuals with MBL deficiency are at risk of infection when in immunocompromised conditions. The concentration of serum MBL is greatly influenced by relatively common single nucleotide polymorphisms of the MBL gene. Therefore, typing of the MBL gene, or measurement of serum MBL may be valuable for determining the risk of infections in patients with systemic autoimmune diseases, who frequently undergo immunosuppressive therapies. MBL deficiency may also be a risk factor for atherosclerosis and arterial thrombosis, both being common complications of autoimmune diseases. On the other hand, MBL may be pathological in tissue injuries, and the precise roles of MBL in autoimmune diseases, and the value of MBL gene typing or serum MBL measurement in a clinical setting are yet to be clarified. Recently, presence of anti-MBL autoantibodies in sera of SLE patients has been reported. The significance of this autoantibody remains to be elucidated.
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PMID:Mannose binding lectin: genetics and autoimmune disease. 1608 Oct 27

Vascular calcification predicts an increased risk for cardiovascular events/mortality in atherosclerosis, diabetes, and ESRD. Serum concentrations of alpha(2)-Heremens-Schmid glycoprotein, commonly referred to as fetuin-A, are reduced in ESRD, a condition associated with an elevated circulating calcium x phosphate product. Mice that lack fetuin-A exhibit extensive soft tissue calcification, which is accelerated on a mineral-rich diet, suggesting that fetuin-A acts to inhibit calcification systemically. Western blot and immunohistochemistry demonstrated that serum-derived fetuin-A co-localized with calcified human vascular smooth muscle cells (VSMC) in vitro and in calcified arteries in vivo. Fetuin-A inhibited in vitro VSMC calcification, induced by elevated concentrations of extracellular mineral ions, in a concentration-dependent manner. This was achieved in part through inhibition of apoptosis and caspase cleavage. Confocal microscopy and electron microscopy-immunogold demonstrated that fetuin-A was internalized by VSMC and concentrated in intracellular vesicles. Subsequently, fetuin-A was secreted via vesicle release from apoptotic and viable VSMC. Vesicles have previously been identified as the nidus for mineral nucleation. The presence of fetuin-A in vesicles abrogated their ability to nucleate basic calcium phosphate. In addition, fetuin-A enhanced phagocytosis of vesicles by VSMC. These observations provide evidence that the uptake of the serum protein fetuin-A by VSMC is a key event in the inhibition of vesicle-mediated VSMC calcification. Strategies aimed at maintaining normal circulating levels of fetuin-A may prove beneficial in patients with ESRD.
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PMID:Multifunctional roles for serum protein fetuin-a in inhibition of human vascular smooth muscle cell calcification. 1609 53

Accelerated atherosclerosis in dialysis patients is characterized by severe vascular calcification, and the magnitude of vascular calcification is associated with increased cardiovascular mortality. Calcification-dependent arterial stiffness is considered to be a major determinant of cardiac failure in uremia. Fetuin-A/alpha(2)-Heremans-Schmid glycoprotein is an abundant serum protein with powerful calcification inhibitory properties. Fetuin-A deficiency was recently linked to cardiovascular mortality in dialysis patients. Fetuin-A knockout (fetuin-KO) mice spontaneously develop widespread soft tissue calcification, including significant myocardial calcification, whereas larger arteries are spared. Therefore, this investigation offers the unique opportunity to study the functional role of isolated myocardial calcification independent of arterial stiffness by assessing the hemodynamics of fetuin-KO mice. Cardiac output in fetuin-KO mice was lower than in wild-type mice (fetuin-KO 1.81 +/- 0.18 versus WT 2.45 +/- 0.29 ml/min per g; P < 0.005), and fetuin-KO mice were refractory to dobutamine stimulation. Left ventricular relaxation was significantly impaired in fetuin-KO hearts with the relaxation index reduced by 23% (P < 0.005). After ischemia, fetuin-KO hearts displayed a continuous decline in left ventricular developed pressure after the initial phase of reperfusion, resulting in 77 +/- 15% of preischemic left ventricular developed pressure (P < 0.05 versus wild-type). In fetuin-KO mice, dystrophic cardiac calcification, with myocardial calcium contents increased 60-fold, was associated with profound induction of profibrotic TGF-beta and downstream collagen and fibronectin mRNA synthesis. In conclusion, independent of arterial stiffness, calcification-associated "myocardial stiffness" characterized by cardiac fibrosis, diastolic dysfunction, impaired tolerance to ischemia, and catecholamine resistance thus may constitute an underestimated cardiovascular risk factor that contributes to cardiac failure in calcification-prone states.
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PMID:Myocardial stiffness, cardiac remodeling, and diastolic dysfunction in calcification-prone fetuin-A-deficient mice. 1617

In this paper titled "My Kumamoto Life of 19 Years; The Travel for Times", the memorial lecture on my retirement from Kumamoto National University Corporation Integrated Medical and Pharmaceutical Sciences, Department of Biomedical Informatics (Chairman) is summarized. As they say "Time flies", time extends from seconds to years. The lecture includes a summary of my short term research and long term studies, such as age-dependant and gene-related changes in ageing over 5 or more years in the healthy elderly. Short-term study mostly involved of newly evaluated assay methods for important substances such as the second level in the cell life span in the variation of lipid metabolite of cardiovascular diseases based on atherosclerosis, Alzheimer disease, and their evaluation by homogeneous assay of HDL-C, LDL-C, enzymatic assay for choline relating metabolites, and lipoperoxide as the results of free radical reactions. The intermediate-term studies were mainly on the development of total laboratory automation (TLA) for the management of the laboratory of the university hospital. The hospital has various degrees of sophistication in its laboratory services. Technicians were allowed to transport specimens immediately by using an air-shooter system after drawing blood, from the emergency room to the central laboratory. Routine specimens could be measured within 30 min and the results could be automatically sent to the physician's office. It greatly minimized reporting errors, decreased the exposure to biohazards, reduced labor expense, improved operation efficiency, and shortened turnaround time. Moreover, for the outpatients and emergency laboratories, we constructed a robotic measuring system which was assembled into a sequential method for the analysis of chemistry, hematology and urinalysis specimens by using a polyarticular robot. The robot arm extends to a bar-coded tube, picking up and placing test tubes on a turn table of autoanalyzers for analysis without manpower. This is the first known effective unmanned procedure for assay in the world of laboratory medicine. Also, our research on pathological informatics was begun. Our laboratory had 7 themes; the study of the reference intervals in the elderly as one of strategy of standardization on laboratory data (Drs. Uji Y, Sugiuchi H), the study of the activation mechanism of ribosomal proteins by the functions of blood cells (Drs. Shibuya Y, Senba U), the evaluation of diagnostic methods in latent ailments by gene analysis (Dr. Ando Y), the evaluation of a highly sensitive method for disseminated intravascular coagulopathy (Okajima K), the study of the neogenesis of blood vessels by physical invasion (Uchiba M), the study of the deposition mechanism of amyloid proteins and evaluation of the diagnostic methods in the autonomic system(Drs. Ando Y, Nakamura M), and the study of the function of blood stem cells in blood transfusion services (Drs. Yamaguchi K, Yonemura M, Tsunemi M). Finally, my long term work also included research into the early diagnosis and prediction of latent ailments and the variation of serum proteins levels in the healthy aged. The conclusion was that the reference value of healthy populations and individuals (intra-personal) who had no combined ailments, in follow-up for 5 years, categorized by age, sex, and social conditions, gave a narrower range of variation than did large mixed populations (inter-personal), in laboratory tests and activity of daily living (ADL). Concerning the early diagnosis and prediction studies for the latent ailments in the aged, variations of serum protein levels in the healthy aged were classified into 3 types: serum proteins levels increased with advancing age (alphaAT, mainly acute phase reactant proteins), those that decreased with advancing age (albumin mainly transporting proteins) and proteins with no significant variation. The higher increase of the alpha1AT/beta2 III ratio in the healthy aged over 60 years old is suspected to create symptoms in the near future. The papers presented concerning ageing studies were presented at the APCCC Symposium (India, 2002) and the IFCC Symposium (Kyoto, 2002), and the TLA study was also presented at the Symposium of XX World Congress of Pathology and Laboratory Medicine (San Paulo Brazil 1999).
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PMID:[My Kumamoto life of 19 years]. 1644 89


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