Effect of donor brain-death duration on graft outcome.
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Brain Death↗
Biomedical subjects
J Martinez
Publications and source records attributed to J Martinez.
Application of the 15N technique to determine the contributions of nitrification and denitrification to the flux of nitrous oxide from aerated pig slurry.
In order to elucidate and quantify nitrogen transformations occurring during aerobic treatment of pig slurry, two laboratory experiments were carried out with contrasting levels of aeration, high level (experiment 1) and low level (experiment 2) of aeration. During these experiments, after reaching steady-state conditions, a single pulse of NO3(-)-15N tracer was added directly to the reactor. When nitrification conditions were prevailing (experiment 1), no transformation of added NO3(-)-15N occurred (98.7% 15N-recovery as nitrates in the liquid slurry). Moreover, the unlabelled nitrous oxide (N2O) measured (7.4% of the total nitrogen content of the raw slurry) strongly demonstrated that the source of N2O emitted was nitrification. During simultaneous nitrification and denitrification conditions (experiment 2), the added NO3(-)-15N was found in gaseous nitrogen forms (N2O-15N: 27%; N2-15N: 18%) and in the liquid (TN-15N: 54%). From this result, it was evident that N2O was mainly emitted by denitrification process. Using the decrease of the isotopic excess of the NO3(-)-15N we calculated that 92% of NO2(-)-N was directly denitrified (as gaseous forms) without any previous oxidation to nitrate.
Aerobiosis↗
Argentine Randomized Study: Coronary Angioplasty with Stenting versus Coronary Bypass Surgery in patients with Multiple-Vessel Disease (ERACI II): 30-day and one-year follow-up results. ERACI II Investigators.
OBJECTIVE: The purpose of this study was to compare percutaneous transluminal coronary revascularization (PTCR) employing stent implantation to conventional coronary artery bypass graft surgery (CABG) in symptomatic patients with multivessel coronary artery disease. BACKGROUND: Previous randomized studies comparing balloon angioplasty versus CABG have demonstrated equivalent safety results. However, CABG was associated with significantly fewer repeat revascularization procedures. METHODS: A total of 2,759 patients with coronary artery disease were screened at seven clinical sites, and 450 patients were randomly assigned to undergo either PTCR (225 patients) or CABG (225 patients). Only patients with multivessel disease and indication for revascularization were enrolled. RESULTS: Both groups had similar clinical demographics: unstable angina in 92%; 38% were older than 65 years, and 23% had a history of peripheral vascular disease. During the first 30 days, PTCR patients had lower major adverse events (death, myocardial infarction, repeat revascularization procedures and stroke) compared with CABG patients (3.6% vs. 12.3%, p = 0.002). Death occurred in 0.9% of PTCR patients versus 5.7% in CABG patients, p < 0.013, and Q myocardial infarction (MI) occurred in 0.9% PTCR versus 5.7% of CABG patients, p < 0.013. At follow-up (mean 18.5 +/- 6.4 months), survival was 96.9% in PTCR versus 92.5% in CABG, p < 0.017. Freedom from MI was also better in PTCR compared to CABG patients (97.7% vs. 93.4%, p < 0.017). Requirements for new revascularization procedures were higher in PTCR than in CABG patients (16.8% vs. 4.8%, p < 0.002). CONCLUSIONS: In this selected high-risk group of patients with multivessel disease, PTCR with stent implantation showed better survival and freedom from MI than did conventional surgery. Repeat revascularization procedures were higher in the PTCR group.
Aged↗
Static secondary ion mass spectrometry to monitor solid-phase peptide synthesis.
Insights into the direct monitoring of supported peptide synthesis were realized through the design of time of flight static secondary ion mass spectrometry (TOF-S-SIMS) experiments. The mass spectrometric method was carried out at the resin bead level and was found reproducible (intra- and inter-day assays), sensitive (femtomol level) and non-destructive (only 0.01% of the peptides were destroyed by the primary ion beam bombardment). The nature of the peptide-resin linkage governed the recovery of ions characterizing the whole peptide sequence. A S-SIMS cleavable bond was thus required solely in that position to achieve the release of the growing structures from the insoluble support into the gas phase without any fragmentation. Results are presented with standard solid-phase resins allowing linkage through an amide or an ester bond. The latter was orthogonally broken upon the bombardment and thus constituted a convenient S-SIMS cleavable bond.
Mass Spectrometry↗
Effects of LY354740, a novel glutamatergic metabotropic agonist, on nonhuman primate hypothalamic-pituitary-adrenal axis and noradrenergic function.
The search for novel anxiolytics and antidepressants has focused on compounds with the potential to reduce excessive hypothalamic-pituitary-adrenal (HPA) axis activity. L-glutamate, an excitatory neurotransmitter ubiquitously present within the central nervous system, conceivably plays an important role in activating the neural sites involved in stress modulation. Deactivation of the HPA axis by glutamatergic neurotransmission modulation may represent a novel therapeutic approach. Accordingly, the acute intravenous effects of the novel metabotropic (mGlu2/3) agonist LY354740 were tested on bonnet macaques (Macaca radiata) undergoing acute infusions of yohimbine, a noradrenergic stimulant. Dependent measures were the magnitude of the increase of plasma cortisol and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) customarily elicited by yohimbine. Next, the effects of 6 weeks of chronic oral administration of LY354740 on baseline (postcapture) plasma cortisol and MHPG levels in comparison to the identical measure in untreated controls were assessed. Subjects chronically treated with LY354740 received yohimbine infusions which were compared to yohimbine infusions and saline infusions in non-LY354740-treated subjects. Preliminary evidence supports the view that acute LY354740 infusion resulted in a marked diminution of yohimbine-induced stress response, as manifest by a substantial attenuation of cortisol and MHPG response observed in comparison to the saline-treated yohimbine condition. Chronic oral administration of LY354740 led to postcapture baseline cortisol levels which were markedly reduced (approximately 50 percent) in comparison to untreated control subjects; however, there were no significant parallel differences in MHPG levels. Yohimbine infusions elicited an increase in cortisol and MHPG levels in both LY354740-treated and non-LY354740-treated subjects, in comparison to declines in cortisol values observed following vehicle infusions (group X time interaction; P<.0001). Chronic LY354740-treated subjects failed to achieve cortisol levels comparable in range to those of untreated subjects primarily because of their low baseline cortisol levels. In contrast, despite equivalent baselines, yohimbine-induced MHPG values were increased overall in the chronically treated group compared to the saline and yohimbine-alone groups. Thus, LY354740 markedly reduced the acute corticoid and noradrenergic response elicited by yohimbine infusion. Chronic administration of LY354740 appears to present a safe and effective mechanism to markedly down-modulate the HPA axis while retaining noradrenergic responsivity.
Journal Article↗
IgM antibodies identified by a DTT-ameliorated positive crossmatch do not influence renal graft outcome but the strength of the IgM lymphocytotoxicity is associated with DR phenotype.
A positive crossmatch that is rendered negative by treating the serum with the IgM-reducing agent dithiothreitol (DTT) is generally reported not to influence short-term renal graft outcome. Its effect on long-term (> or = 3 years) cadaveric and live-donor transplant function, however, is less clear. We evaluated the effect of IgM antibodies in a DTT-ameliorated positive crossmatch (DTT-APXM) on long-term renal graft outcome in 1,290 consecutive cadaveric renal transplants (8-year survival) and 384 live-donor renal transplants (7-year survival) from patients transplanted between 1990 and 1999. The data show that 1- and 8-year graft survival for cadaveric renal transplants in patients with IgM antibodies (n=72) (DWFG censored = 91% and 65%; DWFG not censored = 90% and 60%) was not significantly different from the group without IgM antibodies (n = 1,218) (DWFG censored = 92% and 71%; DWFG not censored = 87% and 55%) (log-rank = 0.25 for DWFG censored, log-rank = 0.92 for DWFG not censored). The one- and seven-year graft survival for live-donor renal transplants in patients with IgM antibodies seen in a DTT-APXM (n = 22) (DWFG censored = 95% and 83%; DWFG not censored = 95% and 66%) was not significantly different from the group without IgM antibodies (n = 362) (DWFG censored = 94% and 81%; DWFG not censored = 92% and 73%) (log-rank = 0.61 for DWFG censored, log-rank = 0.89 for DWFG not censored). DR phenotype was found to be associated with the strong (>40% cell death) IgM reactivity in both black and white patients. In white patients, DR2 was more frequently seen with a strong IgM crossmatch (48.2%) than in molecularly typed controls (28.5%) (P < 0.03) and concomitant with that DR increase, DR4 was decreased in white patients (6.8%) compared with controls (25.5%) (P < 0.02). In black patients with strong IgM reactivity, DR6 was increased in patients (46.1%) compared with controls (20.5%) (P = 0.07) and concomitant with that DR6 increase, DR5 was decreased in frequency in black patients (7.6%) compared with controls (41%) (P < 0.03). These data show that long-term graft survival in renal transplantation is not negatively influenced by the presence of donor-reactive lymphocytotoxic antibodies in the crossmatch ameliorated by serum DTT treatment. They also suggest that the strength of the IgM antibody response is regulated in part by certain gene (s) of the DR region.
Adult↗
Biotransformation in vitro of the 22R and 22S epimers of budesonide by human liver, bronchus, colonic mucosa and skin.
The pharmacological effects of glucocorticoids are greatly influenced by their pharmacokinetic properties. In the present report, the in vitro biotransformation of the 22R and 22S epimers of the topical steroid budesonide was studied in the S-9 fraction of human liver, bronchus, skin and colonic mucosa. The disappearance of unchanged epimers of budesonide was measured during 90 min of incubation by high performance liquid chromatography. The rate of disappearance was high in human liver while little biotransformation occurred in bronchial tissue and colonic mucosa, and none was detected in the skin. A marked decay of the initial concentration of unchanged budesonide epimers was noticed after 2 h incubation in cultured human hepatocytes, while only a small decrease was observed after 24 h incubation in cultured human airway smooth muscle cells and BEAS-2B cells. The 22R epimer of budesonide suffered greater in vitro biotransformation than the 22S epimer in human hepatic, bronchial and colonic tissues. These findings extend those of other studies, and confirm that the high therapeutic ratio of budesonide is due to negligible local biotransformation combined with high level of liver metabolism for locally absorbed budesonide.
Administration, Topical↗
Nonmyeloablative conditioning allows for more rapid T-cell repertoire reconstitution following allogeneic matched unrelated bone marrow transplantation compared to myeloablative approaches.
Nonmyeloablative pretransplantation conditioning regimens have resulted in durable engraftment of allogeneic hematopoietic stem cells. In contrast to conventional fully myeloablative approaches, nonmyeloablative regimens are associated with a marked reduction of morbidity and mortality in the early posttransplantation period. Consequently, such reduced-intensity transplantation approaches can be used in older and frailer patients who would not tolerate fully ablative regimens. However, it is currently unclear how this radically different transplantation strategy affects immunological reconstitution. To address this important issue, we used T-cell receptor Vbeta spectratype analysis to examine the distribution of complementarity-determining region 3 (CDR3)-size bands as a measure of the complexity of the redeveloping T-cell repertoire. For this study, we evaluated the T-cell repertoire of 9 patients receiving T-cell replete, matched unrelated donor transplants following fully ablative or nonmyeloablative conditioning regimens. All 4 of the myeloablative and 2 of the nonmyeloablative patients received bone marrow, whereas 3 other nonmyeloablative patients received peripheral blood stem cells. The results of the spectratype analysis demonstrated that the patients who received nonmyeloablative conditioning together with either bone marrow or peripheral blood stem cells exhibited more rapid reconstitution of T-cell repertoire complexity.
Adult↗
Chemoenzymatic synthesis of surfactants from carbohydrates, amino acids, and fatty acids.
The chemoenzymatic synthesis of new surfactants is reported; they were prepared from unprotected carbohydrates, amino acids, and fatty acids. This study pointed out the factors that govern the possibility to enzymatically bind the carbohydrate to the amino acid.
Amides↗
[Dimethyl 3-benzyl-2-(4-methyl-2,5-dioxoimidazolidin-1-yl)butanedioate].
There are two symmetry-independent formula units of the title compound, dimethyl 3-benzyl-2-(4-methyl-2,5-dioxoimidazolidin-1-yl)butanedioate, C17)H20N2O6, per cell. The two symmetry-independent molecules differ in their configuration and are diastereomers. This structural study confirms a new side reaction during the synthesis of seven-membered cyclopeptides. The stereochemistry of both diastereomers has been established.
English Abstract↗
Interaction of fibrin with VE-cadherin.
The conversion of fibrinogen into fibrin and the association of fibrin(ogen) with activated platelets play a fundamental role in hemostasis because their interaction with the injured vessel prevents blood extravasation. Platelet aggregates and fibrin also participate in the occlusion of the vascular lumen in pathological conditions. Fibrin II also promotes the formation of new blood vessels, for example, during wound healing and tumor growth. Using an in vitro assay, we have studied the mechanism by which fibrin II induces formation of capillaries. Generation of fibrin II on top of an endothelial cell monolayer rapidly rearranged the ECs into a capillary network. In contrast, neither fibrin I nor fibrin 325 induced these morphogenetic changes, indicating that exposure of the N-terminal peptide beta 15-42 is involved in this process. Binding studies, using the N-terminal fragment of fibrin (NDSK II), showed that NDSK II binds to EC with high affinity, but neither NDSK nor NDSK325 bound specifically. Binding of NDSK II to endothelial cells was blocked with an antibody to VE-cadherin. Direct association of NDSK II and VE-cadherin was also demonstrated in a VE-cadherin antibody capture assay. NDSK II bound specifically with the captured VE-cadherin but NDSK or NDSK 325 did not associate with VE-cadherin. Moreover, fibrin II associated with EC VE-cadherin and this interaction triggered the formation of capillary-like structures. A better understanding of the cellular responses to fibrin, identification of the fibrin binding site within VE-cadherin and the intracellular signaling that follows this interaction, could yield important information that may translate into better control of the angiogenic process.
Antigens, CD↗
Agonism, inverse agonism, and neutral antagonism at the constitutively active human neurotensin receptor 2.
Two G protein-coupled neurotensin (NT) receptors, termed NTR1 and NTR2, have been identified so far. In contrast to the NTR1, which has been extensively studied, little is known about the pharmacological and biological properties of the NTR2. In the course of characterizing NT analogs that exhibited binding selectivity for the NTR2, we discovered that this receptor constitutively activated inositol phosphate (IP) production. Here, we report on the constitutive activity of the human NTR2 (hNTR2) transfected in COS cells and on compounds that exhibit agonism, inverse agonism, and neutral antagonism at this receptor. IP levels increased linearly with time, whereas they remained constant in mock-transfected cells. Furthermore, IP production was proportional to the amount of hNTR2 present at the cell membrane. SR 48692, a nonpeptide antagonist of the NTR1, stimulated IP production, whereas levocabastine, a nonpeptide histamine H1 antagonist that binds the NTR2 but not the NTR1, behaved as a weak partial inverse agonist. NT analogs modified at position 11 of the NT molecule, in particular by the introduction of bulky aromatic D amino acids, exhibited binding selectivity at the hNTR2 and also behaved as partial inverse agonists, reversing constitutive IP production up to 50%. Finally, NT barely affected constitutive IP production but antagonized the effects of both agonist and inverse agonist compounds, thus behaving as a neutral antagonist. The unique pharmacological profile of the hNTR2 is discussed in the light of its sequence similarity with the NTR1 and the known binding site topology of NT and SR 48692 in the NTR1.
Amino Acid Sequence↗
Comparison of two commercial microimmunofluorescence kits and an enzyme immunoassay kit for detection of serum immunoglobulin G antibodies to Chlamydia pneumoniae.
We compared the MRL and the Labsystems Chlamydia pneumoniae microimmunofluorescence (MIF) immunoglobulin G (IgG) kits and the Labsystems enzyme immunoassay (EIA) kit in a blinded study of 83 serum samples in which we evaluated titers, cross-reactivity to other species, and reproducibility. There was no statistically significant difference between the MRL and the Labsystems MIF kits in the endpoint titers of IgG antibody to C. pneumoniae. The correlation between the results obtained with these two MIF kits was excellent (r = 0.95; P = 0.001). The cross-reactivity of the C. pneumoniae-positive sera with C. trachomatis- and C. psittaci-positive sera was assessed for each MIF kit. For C. pneumoniae-positive sera with titers of > or =32, the Labsystems MIF kit exhibited more cross-reactivity to C. psittaci than the MRL kit did. The values obtained with the Labsystems EIA kit represented single dilutions of serum specimens expressed as enzymeimmuno units on a continuous scale. The results obtained with the Labsystems EIA kit correlated moderately well with those obtained with each MIF kit when they were compared for their abilities to detect IgG antibodies to C. pneumoniae (for the MRL MIF kit, r = 0.79 [P = 0.001]; for the Labsystems MIF kit, r = 0.78 [P = 0.001]). The results obtained with the commercial MRL and Labsystems MIF kits and the Labsystems EIA kit tested were reproducible; and the kits were standardized, had quality control reagents, and are suitable for detection of C. pneumoniae antibodies in serum and for use in interlaboratory studies. Validation of the use of these kits for clinical diagnosis still needs further evaluation.
Antigens, Bacterial↗
Variations in dystrophin complex in red and white caudal muscles from Torpedo marmorata.
We present an up-to-date study on the nature, at the protein level, of various members of the dystrophin complex at the muscle cell membrane by comparing red and white caudal muscles from Torpedo marmorata. Our investigations involved immunodetection approaches and Western blotting analysis. We determined the presence or absence of different molecules belonging to the dystrophin family complex by analyzing their localization and molecular weight. Specific antibodies directed against dystrophin, i.e., DRP2 alpha-dystrobrevin, beta-dystroglycan, alpha-syntrophin, alpha-, beta-, gamma-, and delta-sarcoglycan, and sarcospan, were used. The immunofluorescence study (confocal microscopy) showed differences in positive immunoreactions at the sarcolemmal membrane in these slow-type and fast-type skeletal muscle fibers. Protein extracts from T. marmorata red and white muscles were analyzed by Western blotting and confirmed the presence of dystrophin and associated proteins at the expected molecular weights. Differences were confirmed by comparative immunoprecipitation analysis of enriched membrane preparations with anti-beta-dystroglycan polyclonal antibody. These experiments revealed clear complex or non-complex formation between members of the dystrophin system, depending on the muscle type analyzed. Differences in the potential function of these various dystrophin complexes in fast or slow muscle fibers are discussed in relation to previous data obtained in corresponding mammalian tissues. (J Histochem Cytochem 49:857-865, 2001)
Animals↗
Mass spectrometry and combinatorial chemistry: new approaches for direct support-bound compound identification.
Mass spectrometry is a powerful analytical tool allowing rapid and sensitive structural elucidation of a wide range of molecules issued from solution-, solid- and liquid-phase syntheses. Therefore, mass spectrometry has become the most widely used tool to probe combinatorial libraries. A significant portion of the reported combinatorial data are being produced using solid phase organic synthesis. In contrast to indirect strategies where the tethered structures were released from the support into solution to undergo standard mass spectrometric analyses, static - secondary ion mass spectrometry (S-SIMS) has enabled the identification of support-bound molecules without any chemical treatment of the resin bead. Such non-destructive characterization was applied at the bead level and facilitated the step-by-step monitoring of solid-phase peptide syntheses. Side-reactions were also detected. The relevance of S-SIMS in the rehearsal phase of combinatorial chemistry is demonstrated by comparison with infrared and nuclear magnetic resonance (NMR) spectroscopies, the two other techniques investigated in that field. An alternative to solid-phase synthesis consists of assembling molecules on a soluble polymer. This methodology is termed liquid-phase synthesis. Compound characterization is facilitated since the derivatized support is soluble in spectroscopic solvents used in NMR or in electrospray ionization mass spectrometry. The advantages and drawbacks of this approach will be discussed in terms of the direct monitoring of supported reactions during chemistry optimization and rehearsal library validation.
Chemistry, Organic↗
Novel design of peptides to reverse the anticoagulant activities of heparin and other glycosaminoglycans.
Patients undergoing anticoagulation with unfractionated heparin, low molecular weight heparin, or danaparoid may experience excess bleeding which requires reversal of the anticoagulant agent. Protamine is at present the only agent available for reversal of unfractionated heparin. Protamine is not effective in patients who have received low molecular weight heparin or danaparoid. We have developed a series of peptides based on consensus heparin binding sequences (Verrecchio et al., J Biol Chem 2000; 275: 7701-7707) that are capable of neutralizing the anti-thrombin activity of unfractionated heparin in vitro, the antifactor Xa activity of unfractionated heparin, Enoxaparin (Lovenox) and danaparoid (Orgaran) in vitro and the anti-Factor Xa activity of Enoxaparin in vivo in rats. These peptides may serve as alternatives for Protamine reversal of UFH and may be useful for neutralization of enoxaparin and danaparoid in humans.
Amino Acid Sequence↗
[Socio-professional acclimation of children operated on for cardiac disease].
In order to assess the socio-professional insertion of children operated for cardiac disease, 177 patients over 20 years of age completed a questionnaire about their scholastic achievements, training and socio-professional categories. This formation was compared with that of the French population based on the statistics of the "Institut national de la Statistique et des Etudes Economiques" (INSEE). The cardiac patients were more likely to have technical occupations than the general population and their level of scholastic achievement reflected this tendency. They attained better professional situations than commonly thought. The analysis of the conditions of surgical treatment indicated that a single, curative and early operation is the best guarantee for future achievements. However, the foundation of a family is much more difficult for operated cardiac patients than for the general French population. Failure of socio-professional insertion is far from being a fatality and psychological problems play an important role, implicating the practitioner at three levels: patient, family and society. In order to be totally convincing, the study of the future of operated patients requires analysis of many different factors.
Adolescent↗
[Association of consumers for better care].
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Consumer Organizations↗