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M Roth

Publications and source records attributed to M Roth.

At least 109 records · Page 6Linked to original sources
PubMed1998

D2AM, a beamline with a high-intensity point-focusing fixed-exit monochromator for multiwavelength anomalous diffraction experiments.

D2AM is a french CRG beamline installed at the ESRF (European Synchrotron Radiation Facility) in Grenoble, with half of the time dedicated to biological macromolecule crystallography and half to materials science studies (diffraction, wide-angle and small-angle scattering). It is constructed at the front-end BM02 of the ESRF storage ring, using the X-ray beam from a 0.8 T bending magnet. D2AM entered into routine operation at the end of 1994, and is used either for single-wavelength or for multiwavelength anomalous diffraction studies. The beam is monochromated by an Si[111] two-crystal monochromator with a resolution of about 2 x 10(-4). The first crystal is water cooled. The X-ray photon energy covers the range between 6.5 keV (lambda approximately 1.9 A) and 17 keV (lambda approximately 0.7 A), a domain of energy with many K or L absorption edges of heavy atoms of interest for biological macromolecules studies and in materials science. The X-ray beam is focused in the vertical plane by two long curved mirrors and in the horizontal plane by the second crystal of the monochromator which is given an adjustable sagittal curvature. A spot size of 0.3 x 0.1 mm (FWHM) is measured at the sample position. Both mirrors are cut out of a 6"-diameter 1.1 m-long Si single crystal, polished and coated with a 400 A Pt thin film. The rugosity is better than 4 A r.m.s. and the longitudinal slope error is better than 5 x 10(-6) rad r.m.s. The first mirror is water cooled, the second is not. The beam intensity on the sample is about 10(11) photon s(-1) on a 0.3 x 0.3 mm focus area at 100 mA in the storage ring of the ESRF. The harmonic rejection ratio obtained with the two mirrors is better than 10(-5) for lambda/3. The combined optical system, mirror/monochromating-crystals/mirror, used on D2AM constitutes altogether a high-intensity point-focusing fixed-exit monochromator, which has the additional property that the energy resolution is not dependent on the beam divergence in use. Its stability and resolution are perfectly adapted to multiwavelength anomalous diffraction studies. The alignment of the mirrors and the monochromator is fully automated, taking 5 min, with the exception of the adjustment of the sagittal focusing. During multiwavelength diffraction experiments the wavelength is changed by a fast single monochromator rotation. Neither realignment of the mirrors nor readjustment of the beam focusing are necessary. The stability and reproducibility of the selected X-ray photon energy is better than 0.5 eV.

Journal Article↗
PubMed1998

Functional roles of conserved amino acid residues in DNA methyltransferases investigated by site-directed mutagenesis of the EcoRV adenine-N6-methyltransferase.

All DNA methyltransferases (MTases) have similar catalytic domains containing nine blocks of conserved amino acid residues. We have investigated by site-directed mutagenesis the function of 17 conserved residues in the EcoRV alpha-adenine-N6-DNA methyltransferase. The structure of this class of MTases has been predicted recently. The variants were characterized with respect to their catalytic activities and their abilities to bind to DNA and the S-adenosylmethionine (AdoMet) cofactor. Amino acids located in motifs X, I, and II are shown to be involved in AdoMet binding (Lys16, Glu37, Phe39, and Asp58). Some of the mutants defective in AdoMet binding are also impaired in DNA binding, suggesting allosteric interactions between the AdoMet and DNA binding site. Asp78 (motif III), which was supposed to form a hydrogen bond to the AdoMet on the basis of the structure predictions, turned out not to be important for AdoMet binding, suggesting that motif III has not been identified correctly. R128A and N130A, having mutations in the putative DNA binding domain, are unable to bind to DNA. Residues located in motifs IV, V, VI, and VIII are involved in catalysis (Asp193, Tyr196, Asp211, Ser229, Trp231, and Tyr258), some of them presumably in binding the flipped target base, because mutations at these residues fail to significantly interfere with DNA and AdoMet binding but strongly reduce catalysis. Our results are in substantial agreement with the structure prediction for EcoRV alpha-adenine-N6-methyltransferase and x-ray structures of other MTases.

Amino Acid Sequence↗
PubMed1998

The 1.7 A crystal structure of the regulator of chromosome condensation (RCC1) reveals a seven-bladed propeller.

The gene encoding the regulator of chromosome condensation (RCC1) was cloned by virtue of its ability to complement the temperature-sensitive phenotype of the hamster cell line tsBN2, which undergoes premature chromosome condensation or arrest in the G1 phase of the cell cycle at non-permissive temperatures. RCC1 homologues have been identified in many eukaryotes, including budding and fission yeast. Mutations in the gene affect pre-messenger RNA processing and transport, mating, initiation of mitosis and chromatin decondensation, suggesting that RCC1 is important in the control of nucleo-cytoplasmic transport and the cell cycle. Biochemically, RCC1 is a guanine-nucleotide-exchange factor for the nuclear Ras homologue Ran; it increases the dissociation of Ran-bound GDP by 10(5)-fold. It may also bind to DNAvia a protein-protein complex. Here we show that the structure of human RCC1, solved to 1.7-A resolution by X-ray crystallography, consists of a seven-bladed propeller formed from internal repeats of 51-68 residues per blade. The sequence and structure of the repeats differ from those of WD40-domain proteins, which also form seven-bladed propellers and include the beta-subunits of G proteins. The nature of the structure explains the consequences of a wide range of known mutations. The region of the protein that is involved in guanine-nucleotide exchange is located opposite the region that is thought to be involved in chromosome binding.

Amino Acid Sequence↗
PubMed1998

Data compression for diffraction patterns.

Efficient coding (lossless) and compression (lossy) of diffraction patterns is important in protein crystallography experiments because of storage and transmission limitations. The goal is to reduce the bit-rate significantly while keeping diffraction peak intensity distortion at an acceptable level. This paper presents an overview of coding and compression techniques more or less adapted to such problems. A large part of this study is dedicated to time-frequency-transform based compression algorithms and some of their extensions. Wavelet based software has been developed and tested. Results are compared with the discrete cosine transform (DCT) and other classical algorithms. These tools seem attractive and very promising for analyzing and compressing signals with singularities and transient phenomena such as diffraction peaks. Tests were performed on a standard protein crystallography data set coming from the CCD detector of D2AM beamline at the European Synchrotron Radiation Facility at Grenoble. These were compressed with DCT and wavelet-based algorithms. It appears that alterations of the result of the processing of restored images remain very weak for compression rates up to 10. These preliminary results indicate that the proposed wavelet method is a good standard technique for efficient compression of diffraction patterns.

Algorithms↗
PubMed1998

Highly efficient and consistent gene transfer into dendritic cells utilizing a combination of ultraviolet-irradiated adenovirus and poly(L-lysine) conjugates.

Dendritic cells (DCs) are capable of presenting tumor-associated antigens and subsequently play an essential role in T-cell activation. The aim of this study was to develop an efficient method for gene transfer into DCs. These genetically transduced DCs can then be used as potent inducers of specific cell-mediated immune response. When compared with physical methods for gene transfer (lipofection and calcium phosphate precipitation), adenovirus (AdV) vectors proved to be highly efficient for gene transfer into DCs. To overcome concomitant AdV gene expression and potential immunogenicity, AdVs were irradiated with UV. The UV dose was optimized to block AdV transcription without altering AdV receptor binding and endocytosis capacity. We subsequently used a polycationic amino acid compound, poly(L-lysine), to conjugate the irradiated AdVs to transgenes. The resulting complexes were found to mediate a highly efficient transfer of transgenes into DCs, without concomitant expression of AdV gene products. Low titers of irradiated AdVs were sufficient for a consistent gene transfer into DCs. This is the first study to demonstrate efficient, consistent, and practical gene transfer using an UV approach to irradiated AdV-poly(L-lysine) conjugates and should be useful for the development of DC-based tumor vaccine therapies.

Adenoviridae↗
PubMed1998

Kinetics of methylation and binding of DNA by the EcoRV adenine-N6 methyltransferase.

The EcoRV DNA methyltransferase (M.EcoRV) specifically methylates the first adenine within its recognition sequence GATATC. Methylation rates of DNA by this enzyme are strongly influenced by the length of oligonucleotide substrates employed. If substrates >20 bp compared to a 12mer substrate, the kcat/Km increases 100-fold, although the enzyme does not contact more than 12 base-pairs on the DNA. Single-turnover rates are higher than kcat values. M.EcoRV binding to DNA is fast but dissociation from the DNA is slow, demonstrating that the multiple-turnover rate is limited by the rate of product release. The kinetics of DNA binding by M.EcoRV are not in accordance with the thermodynamics binding constant, suggesting that the M.EcoRV-DNA complex is involved in a slow conformational change. The salt dependence of DNA binding is different for non-specific substrates (d ln(KAss)/d ln(cNaCl) = - 2, indicative of electrostatic interactions) and specific substrates (d ln(KAss)/d ln(cNaCl) = + 1, indicative of hydrophobic interactions). This result demonstrates that the M.EcoRV-DNA complex has a different conformation in both binding modes. M.EcoRV does not discriminate between hemimethylated and unmethylated substrates. Using the 20mer we have analyzed the temperature and pH dependence of the single-turnover rate constant of M.EcoRV-DNA methylation by M.EcoRV has an activation energy of 40 kJ/mol and its rate increases with increasing pH. The pH dependence reveals the presence of an ionizable residue with a pKa of 7.9, which must be unprotonated for catalysis. The rates of DNA methylation remain unchanged if an abasic site is introduced instead of the thymidine residue that is base-paired to the target adenine, demonstrating that flipping out the target adenine cannot contribute to the rate-limiting step of the enzymatic reaction.

Binding Sites↗
PubMed1998

The Flavobacterium okeanokoites adenine-N6-specific DNA-methyltransferase M.FokI is a tandem enzyme of two independent domains with very different kinetic properties.

The Flavobacterium okeanokoites adenine-N6-specific DNA-methyltransferase, M.FokI, modifies both adenine residues within its asymmetric recognition sequence 5'-GGATG/CATCC-3'. It is a fusion protein comprising two independent enzymes. We have cloned, overexpressed and purified full-length M.FokI as well as both individual domains and analyzed their kinetics of DNA methylation using unmethylated and hemimethylated oligodeoxynucleotide substrates. Our data show that both domains of M.FokI methylate DNA independently of each other but cooperate in DNA binding. In agreement to former studies, the N-terminal domain of M.FokI modifies the upper strand of the recognition sequence (GGATG). It strongly prefers hemimethylated (5'-GGATG/CmATCC-3'; mA = N6-methyladenosine) over unmethylated substrates. In contrast, the C-terminal domain prefers unmethylated DNA substrates. Surprisingly, in addition to methylating the lower strand of the recognition sequence (CATCC), M.FokI-(335-647) also modifies the upper strand (GGATG), albeit with a lower activity. In addition, methylation was detected at CACCC sites, but not at sites in which a central AT dinucleotide is flanked by at least one A x T or T x A base pair. These results suggests that M.FokI-(335-647) either has a very degenerate specificity for (G/C)AT(G/C) and sites similar to CATCC or GGATG or, alternatively, that it has a dual specificity for CATCC and GGATG.

Base Sequence↗
PubMed1998

[Nutritional deficiencies and complications in chronic inflammatory bowel diseases].

BACKGROUND: Deficiencies of vitamins and trace elements are frequent in inflammatory bowel disease. Aim of this study was to evaluate retrospectively the prevalence of these deficiencies and of liver complications in a large population. PATIENTS AND METHODS: The records from 392 out-patients, 279 with Crohn's disease (160 female, 119 male) and 113 with ulcerative colitis (56 female, 57 male) were analyzed. RESULTS: Deficiencies were found in 85% of patients with Crohn's disease vs 68% with ulcerative colitis during the course of the disease, predominantly a deficiency of iron and of calcium. Less frequently deficiencies of zinc, protein, cyanocobalamin, and folic acid were found. Elevated liver enzymes were seen in 38% of patients with Crohn's disease vs 27% with ulcerative colitis. In order of frequency: gamma-glutamyl-transferase, ALAT, AP, ASAT, and bilirubin. Gallstones were present in 12% of patients with Crohn's disease and 4% with ulcerative colitis. 6% of patients with Crohn's disease and 4% with ulcerative colitis had kidney stones. CONCLUSIONS: In view of the high frequency of deficiencies in patients with inflammatory bowel disease it seems to be important to check frequently for extraintestinal complications.

Adolescent↗
PubMed1998

Corticosteroids inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells.

The vascular endothelial growth factor (VEGF) is a specific mitogen for vascular endothelial cells and enhances vascular permeability and edemagenesis. VEGF is also a major regulator of angiogenesis and may be a key target for inhibiting angiogenesis in angiogenesis-associated diseases. Among the extensively studied angiostatic compounds are several corticosteroids when used alone or in combination with heparin. In this study we present evidence for an additional mechanism of action of hydrocortisone, cortisone and dexamethasone in inhibiting edemagenesis or angiogenesis. In cultures of aortic human vascular smooth muscle cells these corticosteroids (1 x 10(-8) to 1 x 10(-12) M) abolished the platelet-derived growth factor-induced (PDGF) expression of the VEGF gene in a dose-dependent manner. In contrast, two precursors of corticosteroids, desoxycorticosterone or pregnenolone, did not affect PDGF-induced VEGF expression. Our findings indicate that the capacity of corticosteroids to reduce edema or to prevent new blood vessel formation may be attributed, at least in part to the ability of these agents to abolish the expression of VEGF.

Anti-Inflammatory Agents↗
PubMed1998

Late paraphrenia: a variant of schizophrenia manifest in late life or an organic clinical syndrome? A review of recent evidence.

A large amount of research has been devoted during the past 15 years to the clinical and neurobiological aspects of the disorder named as 'late paraphrenia' (LP) in 1955. The symptomatology and diagnosis of the disorder, its prognosis, the cognitive functioning of those affected, the structural changes in the brain as revealed by modern techniques of brain imaging and its postmortem neuropathology have all been submitted to investigation. The results have been widely regarded as consistent with the concept of LP as an organic disease of the brain, but increased knowledge of the neurobiology of schizophrenia and of the age-related changes that occur in the brains of elderly people casts doubt on the validity of this interpretation. The findings are consistent with the view that LP is the form in which schizophrenia is manifest in old age. The proposal that LP has a closer kinship with affective disorder than with schizophrenia is part of a general theory of the sex differences in schizophrenia. In LP it becomes entangled with the organicity hypothesis, suggesting that neither of these explanations is adequate, and most of the evidence points to a unitary concept which views LP as a variant of a single disorder, namely schizophrenia, which, however, requires a broad definition. This concept has implications for fresh paths of enquiry.

Aged↗
PubMed1998

The differential distribution of hyaluronic acid in the layers of human atheromatic aortas is associated with vascular smooth muscle cell proliferation and migration.

Vascular smooth muscle cells (VSMC), under conditions of induced proliferation, similar to those involved in atherosclerosis, secrete an acidic glycan, 82% of which exhibits structural homology with hyaluronic acid (HA), has a molecular mass of 340 kDa (HA-340) and inhibits VSMC proliferation in vitro. In this study, the expression of glycans was investigated in human atheromatic aortas and evidence is presented that a HA molecule, similar to HA-340, is distinctly expressed in all aortic layers. The isolation of the glycans from human aortas was performed after homogenization of the individual aortic layers (atheromatic plaque, tunica intima, tunica media and tunica adventitia), by lipid extraction and extensive digestion with pronase and DNase. The total glycans were purified from the digestion products by gel filtration on Sephadex G-25 and fractionated on a Superose 6 column. Enzymatic treatment of the ensuing glycan fractions with all known glycosaminoglycan-degrading enzymes, followed by electrophoresis on polyacrylamide gradient gels and cellulose acetate membranes, revealed that, in addition to HA, the tunica intima and the atheromatic plaque also contained dermatan sulfate, while the tunica media and the tunica adventitia also contained chondroitin sulfates and heparan sulfate. The highest concentration of the human aorta HA was found in the tunica media, exhibiting a negative concentration gradient from the tunica media to the atheromatic plaque. Investigation of the biological function of the human aorta HA revealed that this molecule acts as a negative regulator on the PDGF-induced VSMC proliferation and as a positive regulator on the PDGF-induced VSMC migration. The differential expression of HA within the aortic layers correlates with the biological function attributed to this acidic glycan and associates it with key events in the progression of atherogenesis.

Adult↗
PubMed1998

The cellular immune responses induced in the follow-up of interferon-alpha treated patients with chronic hepatitis C may determine the therapy outcome.

BACKGROUND/AIMS: To study whether the host's immune response determines viral clearance in chronic hepatitis C, virological markers and antigen-specific T cell reactions were analysed in 30 chronic HCV carriers followed up during interferon-alpha therapy, 11 untreated anti-HCV positive individuals and 10 healthy controls. METHODS: Proliferative T helper cell responses to recombinant HCV core and non-structural antigens were monitored by 3H-thymidine uptake assay and compared to quantitative viraemia levels and HCV genotypes. RESULTS: Of the 30 treated patients, six had sustained complete responses (20%), another six were transient therapy responders (20%) and 18 were non-responders (60%). Viral clearance was associated with the HCV genotype 3 and low pretreatment viral load. In a substantial proportion of complete and transient therapy responders, increased NS3-, helicase- and NS4-antigen-specific T cell responses were observed during interferon-alpha therapy. In non-responders and in the later clinical courses of transient therapy responders, core and NS5-specific T cell responses dominated. In addition, 11 untreated anti-HCV antibody positive individuals were studied. Two HCV-RNA negative patients who might have recovered from HCV infection showed strong persistent lymphoproliferative responses to NS3, helicase and NS4 antigens, whereas seven of the nine viraemic patients reacted with HCV core or NS5 antigens. CONCLUSIONS: Interferon-alpha treatment enhances NS3-, helicase- and NS4-antigen-specific T helper cell responses in patients with viral clearance, whereas viral persistence was associated with increased T cell reactivities against core and NS5 antigens. Immunogenetical, immunological and virological factors that may influence differential T cell induction in chronic hepatitis C are discussed.

Adult↗
PubMed1998

Compartmentalization of pro-inflammatory cytokines in tuberculous pleurisy.

Increased levels of interleukin-6 (IL-6) and IL-8 are found in various immunologically mediated inflammatory disorders. Concentrations of IL-6, IL-8 and the soluble form of the IL-6 receptor (sIL-6R) were determined in serum and effusion fluid of 25 patients with tuberculous pleurisy utilizing enzyme linked immunosorbent assays (EIA). Serum IL-6 levels were only slightly increased in patients with tuberculous pleurisy in comparison to controls (11.1 +/- 2.1 vs 7.3 +/- 1.0 pg ml-1). IL-8 could not be detected in the serum of tuberculosis patients, but it was detected in the serum of healthy controls (8.0 +/- 1.5 pg ml-1). In comparison to serum, IL-6 and IL-8 were found in high concentrations in pleural effusions (IL-6: 932 +/- 70 vs 11.1 +/- 2.1 pg ml-1, P < 0.0001; IL-8: 450 +/- 85 vs 0 +/- 0 pg ml-1). In contrast, sIL-6R concentrations were much higher in serum compared to pleural effusion levels [30,477 +/- 1905 vs 9881 +/- 1177 pg ml-1, P < 0.0001 (mean +/- SEM)]. The authors conclude that elevated levels of IL-6 and IL-8 in pleural effusions are compartmentalized at the site of active disease. The low levels of sIL-6R in the presence of high levels of IL-6 in pleural effusions, and the high levels of sIL-6R in the presence of low levels of IL-6 in serum suggest that the expression or shedding of sIL-6R may be downregulated in the presence of excessive amounts of IL-6.

Adult↗
PubMed1998

Parenteral nutrition facilitates activation of coagulation but not of fibrinolysis during human endotoxemia.

Venous thrombosis and bacterial infections are common complications of parenteral nutrition. To test the hypothesis that infection facilitates activation of coagulation during parenteral nutrition, healthy subjects were intravenously injected with endotoxin (2 ng/kg) after they had received either 1 week of standard parenteral nutrition (n = 7) or normal enteral feeding (n = 8). Compared with enteral feeding, parenteral nutrition was associated with a selectively enhanced activation of the coagulation system (plasma levels of thrombin-antithrombin III complexes) during endotoxemia. Activation of the fibrinolytic system (plasminogen activator activity, tissue-type plasminogen activator, plasminogen activator inhibitor type 1) proceeded similarly in both study groups. In patients receiving parenteral nutrition, one common complication (bacterial infection) may facilitate the occurrence of another common complication (venous thrombosis) by synergistic stimulation of the coagulation system.

Adult↗
PubMed1998

A 340 kDa hyaluronic acid secreted by human vascular smooth muscle cells regulates their proliferation and migration.

The formation of atherosclerotic lesions is characterized by invasion of vascular smooth muscle cells (VSMC) into the tunica intima of the arterial wall and subsequently by increased proliferation of VSMC, a process apparently restricted to the intimal layer of blood vessels. Both events are preceded by the pathological overexpression of several growth factors, such as platelet-derived growth factor (PDGF) which is a potent mitogen for VSMC and can induce their chemotaxis. PDGF is generally not expressed in the normal artery but it is upregulated in atherosclerotic lesions. We have previously shown that PDGF-BB specifically stimulates proliferating VSMC to secrete a 340 kDa hyaluronic acid (HA-340). Here, we present evidence regarding the biological functions of this glycan. We observed that HA-340 inhibited the PDGF-induced proliferation of human VSMC in a dose-dependent manner and enhanced the PDGF-dependent invasion of VSMC through a basement membrane barrier. These effects were abolished following treatment of HA-340 with hyaluronidase. The effect of HA-340 on the PDGF-dependent invasion of VSMC coincided with increased secretion of the 72-kDa type IV collagenase by VSMC and was completely blocked by GM6001, a hydroxamic acid inhibitor of matrix metalloproteinases. HA-340 did not exert any chemotactic potency, nor did it affect chemotaxis of VSMC along a PDGF gradient. In human atheromatic aortas, we found that HA-340 is expressed with a negative concentration gradient from the tunica media to the tunica intima and the atheromatic plaque. Our findings suggest that HA-340 may be linked to the pathogenesis of atherosclerosis, by modulating VSMC proliferation and invasion.

Aorta↗
PubMed1998

HBW 023 (recombinant hirudin) for the acceleration of thrombolysis and prevention of coronary reocclusion in acute myocardial infarction: results of a dose-finding study (HIT-II) by the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte.

OBJECTIVE: To define an optimal dose of hirudin that would improve early coronary artery Thrombolysis in Myocardial Infarction grade 3 (TIMI 3) patency and prevent reocclusions in patients with acute myocardial infarction treated with front-loaded recombinant tissue-type plasminogen activator (rt-PA). METHODS: Recombinant hirudin (HBW 023) was tested in a sequential dose-escalating study as adjunct to front-loaded rt-PA in 143 patients with acute myocardial infarction. The sequential model was assigned two 'decision boundaries': it triggered an increase in dosage if the 60-min TIMI 3 flow rate in a dosage group was statistically not consistent with a target patency rate of 75%, or if the deterioration in coronary blood flow (of at least one TIMI grade, from TIMI 2 or 3, from one angiography to the next) exceeded 5%. RESULTS: The decision boundary for TIMI 3 flow grade at 60 min was crossed when 18 patients were treated with 0.1/0.06 mg/kg (bolus/infusion per hour over 48 h) r-hirudin (dosage group I), 42 patients treated with 0.2/0.1 mg/kg (dosage group II), and 83 patients with 0.4/0.15 mg/kg (dosage group III). TIMI 3 flow at 60 min was 50%, 58%, and 63% in dosage groups I-III, respectively (P = 0.15). Early, complete, and sustained patency (TIMI 3 flow at 60 min, 90 min and 48 h) were 44%, 55% and 64% (P = 0.07). Reocclusion between 90-min and 48-h angiograms or reinfarction occurred in 0 to 15, two of 36, and one of 72 patients, respectively (P = 0.5). Four patients (2.8%) died in hospital and 14 patients suffered a major bleeding event, but no intracranial bleeding was encountered. CONCLUSIONS: With increasing doses of hirudin, there was a trend towards greater early and complete patency, but no clear dose--response relationship was observed. A borderline significant effect was observed with respect to early, complete, and sustained patencies. In all groups, reocclusions or reinfarctions were rare. Neither clinical nor laboratory data predicted the imbalance in haemorrhagic events observed in a subsequent, prematurely terminated, phase III trial with hirudin and rt-PA.

Adult↗
PubMed1998

Serum concentration of calcium, 1,25 vitamin D and parathyroid hormone are not correlated with coronary calcifications. An electron beam computed tomography study.

BACKGROUND: The amount of coronary artery calcification, measured using electron beam computed tomography, is correlated with the volume of coronary artery atherosclerotic plaque, the severity of stenosis by angiography, and with the likelihood of future cardiovascular events. The deposition of calcium in atherosclerotic plaques may also be influenced by determinants of calcium metabolism, thus contributing to the variance of the relation between coronary artery calcification and extent of atherosclerosis. Our objective was to determine whether this variance could be explained by differences in the parameters of calcium metabolism. DESIGN AND METHODS: We measured serum concentrations of calcium, 1,25(OH)2 vitamin D and parathyroid hormone (PTH) in 50 subjects undergoing angiography for clinical indications, and evaluated the correlations between these concentrations and calcium deposition in the coronary arteries, and the ratio of calcium deposition to extent of atherosclerosis using coronary angiography. RESULTS AND CONCLUSIONS: Serum concentrations of calcium 1,25(OH)2 vitamin D and PTH were not correlated with coronary calcification or the ratio of coronary calcification to the extent of coronary stenosis. We conclude that, in subjects undergoing coronary angiography, the variance of the relationship between coronary atherosclerosis and coronary calcium is not a result of differences in serum concentrations of calcium, 1,25(OH)2 vitamin D or PTH.

Aged↗