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Biomedical subjects

C Martin

Publications and source records attributed to C Martin.

At least 631 records · Page 35Linked to original sources

[Sedation of patients with head injuries].

In severe head-injured patients, intravenous sedation is an integrant part of therapy. Its main objectives consist in facilitation of ventilation and other therapeutic procedures but also more specifically in the control of intracranial pressure and epileptic seizures. The ideal sedative drug must fulfil a number of criteria regarding pharmacokinetics, cerebral metabolism and hemodynamics. Opioids, midazolam and propofol are the most commonly used sedative drugs. The therapeutic response and the neurological status of the patients are the guidelines for the choice, the duration and the assessment of sedation.

Craniocerebral Trauma↗

Protection against cyclosporin-induced nephrotoxicity: 1. Effect of a PAF antagonist, BN50726.

The clinical usefulness of cyclosporin A (CsA) in organ transplantation is limited by its intrinsic nephrotoxicity, the mechanisms of which have not yet been completely elucidated. Various processes could be responsible for the CsA-induced nephrotoxicity including an interaction with glutathione metabolism, a lipoperoxidative process, or an interaction with platelet-activating factor (PAF). Therefore, the aim of this study was to assess the potential role of PAF in CsA-induced nephrotoxicity using a new PAF antagonist, BN50726. CsA alone provoked a significant increase in serum urea, urinary gamma-glutamyl transferase activity and oxidized glutathione level of kidney cortex in the rat. In contrast, when rats were treated with CsA plus BN50726, urinary gamma-glutamyltransferase activity was similar to that of controls and oxidized glutathione was significantly lower than that measured in rats treated with CsA alone. However, serum urea remained increased as it was in the CsA group. Our results suggest that BN50726 is able to prevent the damage of renal membranes probably by an antiperoxidative activity. These data indicate the potential therapeutic capacity of a PAF antagonist, BN50726, in reducing CsA nephrotoxicity and suggest interactions between PAF and CsA in the mechanism of renal injury.

Animals↗

Preservation of humidity and heat of respiratory gases in patients with a minute ventilation greater than 10 L/min.

OBJECTIVE: To compare the temperature and humidification output of one heated humidifier system (Bennett Cascade 2 Humidifier) and two heat and moisture exchangers (Pall Ultipor, BB 50, and Humid-Vent Filter) in intensive care unit (ICU) patients submitted to a minute ventilation of > 10 L/min. DESIGN: Prospective, controlled, randomized, unblinded study. SETTING: ICU of a university hospital. PATIENTS: Eleven sedated and paralyzed patients who required controlled mechanical ventilation with a minute ventilation of > 10 L/min for > 3 days. INTERVENTIONS: After a randomized selection process, the patients were ventilated for 24-hr periods with the humidifier and one of the heat and moisture exchangers. Both heat and moisture exchangers were first tested for 45 mins; then, the heat and moisture exchanger that demonstrated the best performance in terms of temperature and water preservation was tested for 24 hrs. MEASUREMENTS AND MAIN RESULTS: During the inspiration phase for each patient, the following measurements were performed: mean and minimum values of temperature, relative and absolute humidity of inspired gases. During the 45-min test period, the Humid-Vent Filter had a better temperature and humidification output than the Pall Ultipor Filter and thus was tested for 24 hrs. The Bennett Cascade 2 Humidifier and the Humid-Vent Filter had a better thermic capacity than the Pall Ultipor Filter (p < .001). No difference was ever observed between the Bennett Cascade 2 Humidifier and the Humid-Vent Filter regarding relative humidity. The Pall Ultipor Filter had a lower temperature and humidification output when compared with the other two systems (p < .007). Concerning absolute humidity of inspired gases, the Pall Ultipor Filter achieved a lower performance than any other tested systems (p < .02). A small but significant decrease in temperature and absolute humidity, but not in relative humidity, was seen after 24 hrs of use with the Humid-Vent Filter. However, with this heat and moisture exchanger, all patients had an absolute humidity of > 28 mg H2O/L and a relative humidity of > 93% after 24 hrs of use. CONCLUSIONS: In patients with a minute ventilation of > 10 L/min (> 10.5 to 16.0 L/min), the Humid-Vent Filter had a temperature and humidification output close to the reference system (the Bennett Cascade 2 Humidifier). The Pall Ultipor Filter had a significantly lower temperature and humidification output in these patients.

Acute Disease↗

Synthetic copolymer kit for radionuclide blood-pool imaging.

UNLABELLED: A synthetic blood pool imaging agent labeled with 99mTc is reported. METHODS: The agent, methoxypolyethylene glycol-poly-L-lysyl-diethylenetriaminepentaacetate monoamide was synthesized from a covalent graft copolymer of methoxypolyethylene glycol succinate (molecular weight 5.1 kD) and poly-L-lysine (molecular weight average 35.6 kD) with subsequent modification of the product with diethylenetriamineacetyl residues. The polymer was formulated into a kit that contained Sn(II) and sodium acetate for radiolabeling with 99mTc. Biodistribution studies were performed in rats. Blood-pool imaging and blood clearance determination was carried out in rabbits and in a rhesus monkey. RESULTS: The 99mTc-labeled agent [specific activity greater than 3.7 GBq/mg; radiochemical purity more than 98% by thin-layer and high-performance liquid chromatography (HPLC)] demonstrated remarkable stability in solution (pH 5.5-6.5) with no radioactive products of degradation detectable by HPLC even at 24 hr postlabeling. The agent exhibited prolonged circulation in the blood with a half-life of 31.5 hr in rabbits. Biodistribution in rats showed a lack of substantial accumulation of the agent in the reticuloendothelial system. Sequential acquisitions were performed in a rhesus monkey. The 99mTc-labeled polymer kit was compared with the 99mTc-red blood cells (RBCs) labeled in vitro. Both methods produced similar heart-to-lung ratios. The ratios remained essentially unchanged for up to 15 hr postinjection. CONCLUSION: The 99mTc-labeled methoxypolyethylene glycol-poly-L-lysyl-diethylenetriamine pentaacetate monoamide is an attractive alternative to radiolabeled RBCs for blood pool imaging applications.

Animals↗

Pivotal role of colony stimulating factor-1 in lupus nephritis.

Spontaneous autoimmune renal injury in MRL-lpr mice shares many features of human lupus nephritis. We noted a prominent increase of macrophages (M phi) in the glomerulus of MRL-lpr mice. Since colony stimulating factor-1 (CSF-1) regulates M phi growth and is a potent chemoattractant, we explored the possibility that there was an increase in CSF-1 in MRL-lpr mice. We detected a biphasic increase in circulating CSF-1 in MRL-lpr mice as compared to congenic MRL- ++ mice other strains with the lpr gene, and normal mice. There was an increase in CSF-1 steady state mRNA transcripts in the kidney but not in the liver, lung or bone marrow. By in situ hybridization our studies identified the glomeruli as the predominant source of renal CSF-1. Enhanced CSF-1 is expressed by the mesangial cells at the same time (4 weeks of age) that M phi begin to accumulate in the glomeruli, well in advance of the loss of renal function. We have isolated pure populations of glomerular M phi in culture from MRL-lpr mice. These glomerular M phi require CSF-1 to survive and proliferate. Therefore, these data suggest that CSF-1 is increased in the glomerulus prior to the influx and accumulation of M phi. We propose that CSF-1 expression in the kidney is pivotal in the attraction and accumulation of M phi and in turn responsible for initiating tissue destruction.

Animals↗

Potential topoisomerase II DNA-binding sites at the breakpoints of a t(9;11) chromosome translocation in acute myeloid leukemia.

We have examined a t(9;11)(p22;q23) chromosome translocation in an acute myeloid leukemia of an infant. The breakpoints on the two chromosomes occurred within introns of the involved genes: AF-9 on chromosome 9, and ALL-1 on chromosome 11. Sequence analysis identified heptamers flanking the breakpoints on both chromosomes 9 and 11, suggesting that the V-D-J recombinase was involved in the translocation. The presence of an N-region between the two chromosomes supports the hypothesis that a mistake in V-D-J joining was involved in the genesis of the translocation and indicates that terminal deoxynucleotidyl transferase was expressed in the cells from which this acute myeloid leukemia originated. In addition, potential topoisomerase II DNA-binding sites were found near the breakpoints of both chromosomes, suggesting the involvement of altered topoisomerase II activity in this translocation. Altered topoisomerase II activity in the presence of an active V-D-J recombinase may be a pathogenetic mechanism of acute myeloid leukemia with rearrangements at 11q23.

Amino Acid Sequence↗

The effect of local anaesthetics on the ryanodine receptor/Ca2+ release channel of brain microsomal membranes.

The effects of various local anaesthetics (LAs) on ryanodine binding of the sheep brain ryanodine receptor were tested. Tetracaine and dibucaine inhibit the binding with half-maximal inhibition (CI50) of 0.12 mM and 0.7 mM, respectively. Lidocaine and its analog QX-314, on the other hand, stimulate the binding up to 3-fold with half-maximal stimulation occurring with about 2 mM of the drugs. Lidocaine increases both the receptor affinity for ryanodine by about 5-fold and the rate of ryanodine association with its binding site by about 6-fold. Tetracaine and lidocaine also interact with the purified brain ryanodine receptor and produce inhibitory and stimulatory effects similar to those obtained with the membrane-bound receptor. The interaction of the LAs with the brain ryanodine receptor, as well as with the skeletal muscle receptor [J. Memb. Biol. 133 (1993) 171-182], suggest that ryanodine receptor possesses intrinsic binding site(s) for LAs.

Anesthetics, Local↗

Early and transient effects of neutron irradiation on dopamine receptors in the adult rat brain.

The early neurochemical effects of neutron-gamma radiation exposures were studied through ligand dopamine D1, D2 receptors binding experiments. The parameters of binding were investigated on crude preparations from striatum at different delays (from 2 to 72 hours) after irradiation. An early and transient increase in the total number of sites was seen after exposure, even at infra-lethal dose. This 'radiosensitivity' was higher for D1 than for D2 receptor. It is assumed that these modifications could participate in the early neuro-vegetative syndrome observed in irradiated persons.

Animals↗

First appearance, distribution, and origin of macrophages in the early development of the avian central nervous system.

A phagocytic cell system of hemopoietic origin exists in the early avian embryo (Cuadros, Coltey, Nieto, and Martin: Development 115:157-168, '92). In this study we investigated the presence of cells belonging to this system in the central nervous system (CNS) of chick and quail embryos by using both histochemical staining for acid phosphatase and immunolabelling with antibodies recognizing cells of quail hemangioblastic lineage. The origin of these cells was traced in interspecific chick-quail yolk sac chimeras. Hemopoietic cells were detected within the CNS from developmental stage HH15 on, and steadily increased in number at subsequent stages. Analysis of yolk sac chimeras revealed that most of these cells were of yolk sac origin, although some hemopoietic cells of intramebryonic origin were also found in the CNS. Immunocytochemical, histochemical, and ultrastructural characterization allowed us to identify hemopoietic cells in the CNS as macrophages. These cells were consistently found in the brain vesicles and spinal cord, appearing (1) between undifferentiated neuroepithelial cells at dorsal levels of the CNS; (2) in areas of cell death; (3) in the marginal layer in close relationship with developing axons; (4) in large extracellular spaces in the subventricular layer; (5) on vascular buds growing through the marginal and subventricular layers; and (6) in the ventricular lumen. Macrophages in different locations varied in morphology and ultrastructure, suggesting that in addition to their involvement in phagocytosis, they play a role in other processes in the developing CNS, such as axonal growth and vascular development. The first macrophages migrate to the CNS independently of its vascularization, apparently traversing the pial basal lamina to reach the nervous parenchyma. Other macrophages may enter the CNS together with vascular buds at subsequent stages during CNS vascularization.

Acid Phosphatase↗

The ClpE protein involved in biogenesis of the CS31A capsule-like antigen is a member of a periplasmic chaperone family in gram-negative bacteria.

The putative chaperone-like protein ClpE, required for biogenesis of the Escherichia coli capsule-like antigen CS31A, was compared with ten known periplasmic chaperones from E. coli, Klebsiella pneumoniae, Bordetella pertussis, Haemophilus influenzae and Yersinia pestis. The amino acid sequence alignment was superimposed onto the three-dimensional structure of the PapD chaperone of uropathogenic E. coli, and amino acid residues involved in maintaining the structure integrity of the suggested binding site were found identical in most of the 11 chaperones. Construction of a phylogenetic tree to investigate the relationship within the chaperone family has revealed interesting degrees of relatedness between the different proteins.

Amino Acid Sequence↗

The interaction of fluorescein isothiocyanate with the ryanodine receptor/Ca2+ release channel of sarcoplasmic reticulum.

Fluorescein 5'-isothiocyanate (FITC) markedly inhibited ryanodine binding to rabbit skeletal muscle junctional sarcoplasmic reticulum. Half-maximal inhibition was obtained with about 20 microM and complete inhibition by 80 microM FITC. Inhibition was enhanced in the presence of high salt and at alkaline pH. The pH dependence of the inactivation of ryanodine binding suggested that FITC bound to a very reactive lysine epsilon-amino group with a pK alpha of about 7.5 or above. Kinetic analysis of the time course of inactivation of ryanodine binding by various concentrations of FITC suggested that the inactivation resulted from the modification of 2 or more amino acid residues. The inhibition of ryanodine binding by FITC was partially prevented by ATP, ADP, adenyl imidodiphosphate, and 3-O-(benzoyl)-benzoyl-ATP (Bz-ATP) but not by AMP. FITC modification of sarcoplasmic reticulum membranes inhibited the photoaffinity labeling by [alpha-32P]Bz-ATP of the 450-kDa protein and the ryanodine receptor with half-maximal inhibition at about 100 microM. The results suggest that the inhibition of ryanodine binding is mainly due to FITC modification of sites which are not involved in ATP binding. The FITC moiety is bound to the 160-, 96-, 76-, and 60-kDa ryanodine receptor tryptic fragments, and the FITC site is apparently on the 21.5-, 18-, and 17-kDa fragments which are formed by the V8 protease. Covalent modification by FITC dramatically affected the activity of single Ca2+ release channels incorporated into planar lipid bilayers. FITC caused a marked increased in channel open probability mainly to a noisy approximately 60% subconductance state. FITC-modified channels were no longer affected by ryanodine but were still abolished by Mg2+ and ruthenium red. We suggest that FITC modifies reactive lysine residues involved in channel activation by transmembrane charge movement in the t-tubular system.

Adenine Nucleotides↗

The importance of starch biosynthesis in the wrinkled seed shape character of peas studied by Mendel.

The wrinkled-seed mutant (rr) of pea (Pisum sativum L.) arose through mutation of the gene encoding starch-branching enzyme isoform I (SBE1) by insertion of a transposon-like element into the coding sequence. Two isoforms of starch-branching enzyme have been documented in the developing pea embryo. The second isoform, SBEII, is expressed towards the later stages of embryo development while SBEI is expressed highly in the early stages. Due to mutation of SBEI the total amount of starch and the proportion of amylopectin, a branched starch polymer, are greatly reduced in the wrinkled (rr) line as compared to that in the wild-type, round (RR) line. Consequently, the level of sucrose in the rr line is nearly two fold that of the RR line. Increased sucrose concentration in the developing embryos of this mutant line causes increased uptake of water and thereby increases the cell size and fresh weight. During seed maturation in these mutant seeds a greater loss of water occurs. As a result, the wrinkled seed phenotype develops. Besides this morphological variation, the mutation also causes changes in the amount of lipid and of one storage protein, legumin. This review article discusses the role of the SBEI enzyme in causing such metabolic changes in the developing embryos with the implication that metabolism can play a central role in plant development.

1,4-alpha-Glucan Branching Enzyme↗

Differential expression of bean chitinase genes by virus infection, chemical treatment and UV irradiation.

Three chitinases have been shown previously to be induced upon various stresses of bean leaves. Time course studies of mRNA accumulation of two of them (P3- and P4-chitinases) have been studied upon virus infection, mercuric chloride treatment and UV irradiation. In alfalfa mosaic virus (AlMV)-infected plants both mRNAs, absent in uninfected bean leaves, become detectable 36 h after inoculation. A maximum level of mRNAs is reached 84 h after inoculation and, whereas the amount of P3-ch mRNA decreases soon after having reached the maximum, the amount of P4-ch mRNA remains at high levels for several days. In mercuric chloride-treated leaves P4-ch mRNA becomes detectable 1-1.5 h after onset of treatment and a maximum level is observed between 6 h and 24 h after treatment; P3-ch mRNA becomes detectable later than P4-ch mRNA in treated leaves and reaches a maximum as late as 18 h after treatment has been applied. UV light also induces the synthesis of both mRNAs but, here again, important differences are observed in the accumulation rate of the two transcripts. The relative amounts of each mRNA induced by the different stresses have been compared. The most effective inducer of P3-ch mRNA is AlMV. In contrast, mercuric chloride induces P4-ch mRNA more efficiently than AlMV or UV light. We have also determined the complete nucleotide sequence of the cDNA encoding P3-chitinase that has been isolated from a cDNA library by using the cucumber lysozyme-chitinase cDNA as a probe. The 1072 bp P3-ch cDNA encodes a mature protein of 268 amino acid residues and the 25 residue NH2-terminal signal peptide of the precursor. Because of its high structural homology to the cucumber and Arabidopsis acidic chitinases as well as to the N-terminal amino acid sequence of the bifunctional lysozyme-chitinase from P. quinquifolia, bean P3-chitinase can be considered to belong to the class III chitinases. Southern blot analysis of bean genomic DNA revealed that P3-chitinase is encoded by a single gene.

Amino Acid Sequence↗

Microsurgical anatomy of the ethmoid.

A description of the constant landmarks of the ethmoidal labyrinth is proposed, based on data from micro-dissection, endoscopy, computed tomography and histology in 12 subjects. In accord with surgical procedure, the identification of these landmarks follows the lateral orbital and superior cranio-frontal aspects. The uncinate process, ethmoidal bulla, middle nasal concha and their septal roots, and the upper wall of the ethmoidal labyrinth in continuity with that of the sphenoidal sinus, form the definitive landmarks for endonasal ethmoidectomy under endoscopic monitoring.

Endoscopy↗

Use of nonradioactive DNA probes to identify a Campylobacter jejuni strain causing abortion.

A case of human abortion due to a Campylobacter infection is reported. Cultures revealed two morphologically different isolates with large and small colonies respectively. Using conventional methods of identification, the large colonies were identified as Campylobacter jejuni and the small colonies as Campylobacter coli. Dot blot hybridization and determination of rDNA restriction fragment patterns revealed that both colony types were the same strain of Campylobacter jejuni. This observation illustrates the need to use methods other than phenotypic methods when identifying strains of Campylobacter.

Abortion, Spontaneous↗