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A Brack

Publications and source records attributed to A Brack.

At least 55 records · Page 3Linked to original sources
PubMed1997

Salt-dependent conformational diversity of alternating poly (Glu-Leu).

Alternating poly(Glu-Leu) was synthesized by the condensation of the corresponding dipeptide p-nitrophenyl ester at high concentration. It exhibits a random coil structure in pure water at neutral pH. Addition of monovalent cations, such as NH4+ to a final 0.1 M solution, induces a transition to a water soluble beta-structure. The salt effect is quite selective since no transition was observed with Li+, Na+ or Cs+ ions. Addition of 0.5 equiv of calcium, cobalt or manganese chlorides per glutamyl residue induces similar coil to beta-sheet transitions. No polymer precipitation was observed at these very low salt concentrations. Addition of 0.5 equiv. of Cu2+ or 0.15 equiv. of Fe3- induces a coil to alpha-helix transition. Molecular modeling has been used to understand tentatively the main factors controlling the different conformations observed with the various metal ions.

Ammonia↗
PubMed1997

Giant cell vasculitis is a T cell-dependent disease.

BACKGROUND: Giant cell arteritis (GCA) is a systemic vasculitis that preferentially targets medium-sized and large arteries. The etiopathogenesis of the syndrome is not known, and because of the paucity of information concerning the mechanisms of blood vessel wall damage, treatment options are limited. Clues to pathogenic events in this arteritis may derive from understanding the function of tissue-infiltrating cells. Arterial injury in GCA is associated with the formation of granulomas that are composed of T cells, activated macrophages, and multinucleated giant cells. To examine the role of T cells, we implanted inflamed temporal arteries from patients with GCA into severe combined immunodeficiency (SCID) mice and studied whether the vascular lesions were T cell-dependent. MATERIALS AND METHODS: Temporal artery specimens from patients with GCA were engrafted into SCID mice. The histomorphologic appearance of fresh arteries and grafts retrieved from the mice was compared by two-color immunohistochemistry, and the functional profile of tissue-infiltrating cells was analyzed by semiquantifying cytokine transcription with a polymerase chain reaction (PCR)-based assay system. The repertoire of tissue-infiltrating T cells was assessed for the presence of dominant T cell populations by using T cell receptor beta-chain-specific PCR followed by sequencing. To investigate the role of T cells in the activation of tissue-infiltrating macrophages, T cells were depleted from the arterial grafts by treating the mice with T cell-specific antibodies and the production of monokines was monitored. To demonstrate the disease relevance of T cells expanding in the implants, T cells were isolated from tissue segments and adoptively transferred into mice implanted with syngeneic arteries. The in situ production of lymphokines was then determined. RESULTS: The inflammatory infiltrate penetrating all layers of the arterial wall persisted in the xenotransplants, indicating that the inflammatory foci represent independent functional units. Similar quantities of T cell- and macrophage-derived cytokines were detected in fresh and engrafted tissue. However, the diversity of tissue-infiltrating T cells decreased following implantation. T cells with identical T cell receptors were expanded in different mice that had been engrafted with tissue fragments from the same patient, indicating that T cell survival in the arterial wall was a nonrandom process. To confirm the disease relevance of these T cells, T cell depletion and reconstitution experiments were performed. Antibody-mediated elimination of T cells from the xenotransplants resulted in the attenuation of the production of the monokines, IL-1 beta and IL-6. Adoptive transfer of syngeneic tissue-derived T cells, but not of peripheral blood T cells, into engrafted SCID mice enhanced the transcription of IL-2 and IFN-gamma in the implanted arteries. CONCLUSIONS: The vascular lesions of GCA are maintained in human artery-mouse chimeras, indicating that all cellular and noncellular components necessary for the disease are present in the temporal artery. Activation of tissue-infiltrating T cells and macrophages depends upon an infrequent subpopulation of lesional T cells that have a survival advantage in the xenotransplants. The selective proliferation of these T cells in the arteries suggests that there is recognition of a locally expressed antigen. Therefore, these T cells should be candidate targets for the development of novel therapeutic strategies in GCA.

Adoptive Transfer↗
PubMed1996

Deletion of glycoprotein gE reduces the propagation of pseudorabies virus in the nervous system of mice after intranasal inoculation.

A pseudorabies virus (PrV) mutant, deficient in the nonessential glycoprotein E (gE) and expressing the LacZ gene (gE- beta gal+ PrV), and its rescued virus were inoculated intranasally in mice. The median lethal dose of gE- beta gal+ PrV was similar to that of the parental Kaplan strain, but mice survived longer and did not develop symptoms of pseudorabies. In the nasal mucosa, gE- beta gal+ PrV replicated less efficiently than rescued virus. gE- beta gal+ PrV could infect first-order trigeminal and sympathetic neurons innervating the nasal mucosa. However, transneuronal transfer to second-order cells groups did not occur in trigeminal pathways and was severely reduced in sympathetic pathways. The mutant was also unable to propagate in the parasympathetic system. In contrast, gE-rescued virus was transferred transneuronally in trigeminal, sympathetic, and parasympathetic pathways, like wild-type PrV. These findings provide further evidence that deletion of gE specifically affects transneuronal transfer of PrV more than penetration and multiplication of the virus in first-order neurons.

Administration, Intranasal↗
PubMed1996

[Problems and limits in noninvasive oxygen monitoring].

Recently, professional anaesthesiologists organizations, have set up recommendations for intraoperative monitoring. These recommendations are based upon the assumption that anaesthesia-related deaths are largely preventable and that extensive monitoring will reduce mortality. Hypoxaemia appears to be an important pathophysiological mechanism, and this is why oxygen monitoring is given a high priority in safety standards in anaesthesia. However, no reduction in mortality has been definitively shown to follow the use of any monitoring device in randomized, controlled trials. Four techniques of oxygen monitoring are discussed and evaluated. Oxygen monitoring during inspiration can be recommended, although its implementation will probably prevent only a few anaesthesia-related deaths. Pulse oximetry is certainly highly recommended, but also has some deficiencies which are not sufficiently well known considering the popularity of this technique. Transcutaneous PO2 is considered mainly for historical reasons. Near infrared spectrometry is a new technique offering noninvasive and continuous monitoring of intracerebral oxygenation.

Anesthesiology↗
PubMed1996

Why exobiology on Mars?

Processing of organic molecules by liquid water was probably an essential requirement towards the emergence of terrestrial primitive life. According to Oparin's hypothesis, organic building blocks required for early life were produced from simple organic molecules formed in a primitive reducing atmosphere. Geochemists favour now a less reducing atmosphere dominated by carbon dioxide. In such an atmosphere, very few building blocks are formed. Import of extraterrestrial organic molecules may represent an alternative supply. Experimental support for such an alternative scenario is examined in comets, meteorites and micrometeorites. The early histories of Mars and Earth clearly show similarities. Liquid water was once stable on the surface of Mars attesting the presence of an atmosphere capable of decelerating C-rich micro-meteorites. Therefore, primitive life may have developed on Mars, as well. Liquid water disappeared from the surface of Mars very early, about 3.8 Ga ago. The Viking missions did not find, at the surface of the Martian soil, any organic molecules or clear-cut evidence for microbial activities such as photosynthesis, respiration or nutrition. The results can be explained referring to an active photochemistry of Martian soil driven by the high influx of solar UV. These experiments do not exclude the existence of organic molecules and fossils of micro-organisms which developed on early Mars until liquid water disappeared. Mars may store below its surface some well preserved clues of a still hypothetical primitive life.

Earth, Planet↗
PubMed1996

Homochirality as the signature of life: the SETH Cigar.

A characteristic hallmark of life is its homochirality: all biomolecules are usually of one hand, e.g. on Earth life uses only L-amino acids for protein synthesis and not their D mirror images. It is therefore suggested that a search for extra-terrestrial life can be approached as a Search for Extra-Terrestrial Homochirality (SETH). A novel miniaturized space polarimeter, called the SETH Cigar, is described which could he used to detect optical rotation as the homochiral signature of life on other planets. Moving parts are avoided by replacing the normal rotating polarizer by multiple fixed polarizers at different angles as in the eye of the bee. It is believed that homochirality will be found in the subsurface layers on Mars as a relic of extinct life.

Astronomy↗
PubMed1996

The inflammatory infiltrate in giant cell arteritis selects against B lymphocytes.

OBJECTIVE: To understand mechanisms regulating the cellular composition of the inflammatory infiltrate in giant cell arteritis (GCA) and to explore whether B lymphocytes, such as neoplastic B cells in chronic lymphocytic leukemia (CLL), can infiltrate the inflamed arterial wall of GCA. METHODS: A Mayo Clinic database search was conducted to identify patients that developed GCA after the onset of CLL between 1950 and 1994. Inflammatory infiltrates were analyzed immunohistochemically for T cells, B cells, and plasma cells. RESULTS: Five patients with CLL were identified who subsequently developed clinical findings suggestive of GCA. Three of the 5 patients had biopsy proven disease, presented with typical clinical and histomorphological features of GCA, and responded promptly to corticosteroid treatment. Leukemic B cells known for their ability to diffusely seed organs were absent in the inflammatory lesions in the temporal artery. Plasma cells that contribute to the vasculitic infiltrate in patients without CLL were markedly reduced in the GCA lesions of patients with CLL. Two other patients had symptoms suggestive of GCA. Their temporal artery specimens were remarkable for small adventitial lymphocytic infiltrates but lacked typical panarteritis. CONCLUSION: The inflammatory infiltrate of GCA is tightly regulated, and cell accumulation in the granulomas is an active, not a passive, mechanism. The inflammatory pathway in GCA is focused on T cells and macrophages and excludes B cells.

Antibodies, Monoclonal↗
PubMed1995

Amyloid peptides are toxic via a common oxidative mechanism.

beta-Amyloid protein (A beta) is a member of a small group of proteins that accumulate as amyloid deposits in various tissues. It has recently been demonstrated that the toxicity of A beta toward some neural cells is caused by oxidative damage. Since all of the amyloid diseases are characterized by protein deposited in the antiparallel beta-sheet conformation, it was asked whether there is a common toxic mechanism. It is shown here that the protein components of other human amyloidoses, including amylin, calcitonin, and atrial natriuretic peptide, are all toxic to clonal and primary cells. The toxicity is mediated via a free radical pathway indistinguishable from that of A beta. Experiments with synthetic peptides suggest that it is the amphiphilic nature of the peptides generated by their beta structure rather than their beta structure per se that causes toxicity. These results tend to rule out the alternative that amyloid toxicity is exclusively mediated via specific cell surface receptors.

Amino Acid Sequence↗
PubMed1995

Were micrometeorites a source of prebiotic molecules on the early Earth?

"Interplanetary Dust Particles" with sizes approximately 10 micrometers collected in the stratosphere (IDPs), as well as much larger "giant" micrometeorites retrieved from Antarctic ice melt water (AMMs), are mostly composed of unequilibrated assemblages of minerals, thus being related to primitive unequilibrated meteorites. Two independent evaluations of the mass flux of micrometeorites measuring approximately 50 micrometers to approximately 200 micrometers, recovered from either the Greenland or the Antarctic ice sheets have been reported (approximately 20,000 tons/a). A comparison with recent evaluation of the flux of meteorites reaching the Earth's surface (up to masses of 10,000 tons), indicates that micrometeorites represent about 99.5% of the extraterrestrial material falling on the Earth's surface each year. As they show carbon concentrations exceeding that of the most C-rich meteorite (Orgueil), they are the major contributors of extraterrestrial C-rich matter accreting to the Earth today. Moreover they are complex microstructured aggregates of grains. They contain not only a variety of C-rich matter, such as a new "dirty" magnetite phase enriched in P, S, and minor elements, but also a diversity of potential catalysts (hydrous silicates, oxides, sulfides and metal grains of Fe/Ni composition, etc.). They could have individually functioned on the early Earth, as "micro-chondritic-reactors" for the processing of prebiotic organic molecules in liquid water. Future progress requires the challenging development of meaningful laboratory simulation experiments, and a better understanding of the partial reprocessing of micrometeorites in the atmosphere.

Antarctic Regions↗
PubMed1994

Conformational study of sequential Lys and Leu based polymers and oligomers using vibrational and electronic CD spectra.

Vibrational CD (VCD) and electronic CD (ECD) spectra of some sequential Lys and Leu based oligo- and polypeptides were studied as a function of added salt and (for ECD) as a function of concentration in aqueous solution. For these samples, the VCD spectra can only be measured at relatively high concentrations under which the well-known salt-induced transition to a beta-sheet form can be observed for the KL based species, but only the end-state alpha-helical conformation is obvious for the LKKL based samples. ECD concentration dependence demonstrates that, at high concentration with no added or with added salt, LKKL based oligomers and polymers give alpha-helical spectra. These data provide evidence of aggregation induced secondary structure formation in an exceptionally simple peptide system. Similarly, the KL based oligomers and polymers give beta-sheet like spectra at high concentration or at high salt. These systems further provide model systems under "normal" aqueous conditions that yield VCD band shapes that correlate to the major secondary structural types of polypeptides. They are in substantial agreement with those spectra obtained on homopolypeptides and on proteins, confirming the relative independence of the VCD technique from side-chain and solvent effects.

Chemical Phenomena↗
PubMed1993

Liquid water and the origin of life.

Liquid water has many peculiarities which confer special properties. The most important among them probably are the ability to establish hydrogen bonds, a high polarity and a high dielectric constant. In the presence of liquid water, large organic molecules have to manage the conflict between hydrophobic groups and hydrophilic groups. This duality can generate interesting prebiotic situations such as the stereoselective aggregation of short peptide sequences of alternating hydrophobic-hydrophilic residues into thermostable beta-sheets endowed with chemical activity. Liquid water is also a powerful hydrolytic agent. As such, it allows pathways which would have few chances to occur in an organic solvent.

Amino Acids↗
PubMed1992

Physical and biological properties of a new synthetic amino acid copolymer used as wound dressing.

A new synthetic amino acid copolymer has been evaluated as wound covering. It is permeable to water vapor in the region of 4.1 kg/m2/24 h, it does not allow microbial proliferation after in vitro inoculation, it is impermeable to bacteria, and is stable and flexible. In vivo experiments were designed to provide qualitative and quantitative evaluation on its possible use as a skin substitute in full-thickness skin excision in the guinea pig. Two excisions, approximately 12-14 cm2 were performed on each side of the spine, leaving the panniculus carnosus. One site was treated with the membrane, the other with gauze. Each animal served as its own control. Photographs with a fixed focal-length camera were taken in identical conditions for all wounds immediately and 7, 14, and 21 days after excision. They were analyzed by planimetry. Histological studies were performed at 7, 14, and 21 days. The rate of healing between 0 and 21 days of the wounds treated with the copolymer membrane was significantly accelerated in comparison with wounds covered with a dry dressing (p less than 0.05). This increased epithelialization rate was confirmed by histology, which also suggested a reduction of the inflammatory response of the wound. In vivo biodegradation studies were also performed by subcutaneous implantation in the rat followed at 15, 30, 60, and 90 days by histology and physicochemical analyses. The results demonstrate that the membrane is not biodegradable.

Animals↗
PubMed1991

Hydrolysis of oligoribonucleotides by alpha-helical basic peptides.

Poly(Leu-Lys-Lys-Leu) increases markedly the rate of hydrolysis of oligoribonucleotides. The polypeptide adopts and alpha-helical conformation in water in the presence of salt. Non-helical poly(Pro-Lys-Lys-Leu) is much less active. Ac-Leu-Lys-Lys-Leu-NHEt has no hydrolytic activity. Oligotetrapeptides Ac-(Leu-Lys-Lys-Leu)n-NHEt with increasing chain-length have been prepared by solid phase synthesis to evaluate the critical chain-length required for the hydrolytic activity. It is possible to correlate the activity to the propensity to form alpha-helices.

Acid-Base Equilibrium↗
PubMed1990

Chemical activity of simple basic peptides.

Alternating all-L poly(leucyl-lysyl) increases markedly the rate of hydrolysis of oligoribonucleotides. Pure D poly (leucyl-lysyl) is as active as the all-L polymer. The homochiral polypeptides adopt a beta-sheet structure when complexed to the oligonucleotides. Alternating poly(D,L-Leu-D,L-Lys) made of racemic amino acids is much less efficient and is unable to adopt a beta-sheet structure. A set of alternating poly (leucyl-lysyl) ranging from the racemic to the homochiral all-L polymer has been checked. Their conformations can be described as a mixture of random coil and beta-sheet conformations, the amount of beta-sheet increasing with the optical purity of the polymer. The hydrolytic activity follows the proportion of beta-sheets, suggesting that the chemical activity is related to the geometry of the chain. Short peptides were prepared in order to evaluate the critical chain length required for the hydrolytic activity. A decapeptide is long enough to present 90% of the activity of the corresponding polypeptide.

Amino Acid Sequence↗
PubMed1987

Selective emergence and survival of early polypeptides in water.

Oligopeptides essential to primitive cells could not be obtained just by raising the background noise of organic compounds produced by a prebiotic chemistry working at random. Selection pathways were required. Experimental evidence is given for selective condensation of amino acids in water as well as for selective resistance to degradation. It is shown that N-carboxyanhydrides are good candidates for chemical selection in water. They are formed when active esters of amino acids are left in the presence of bicarbonate ions or when N,N'-carbonyldiimidazole is used as condensing agent. Polymerization of a mixture of proteinaceous and non-proteinaceous amino acids leads to an enrichment in the proteinaceous ones plus alpha-aminobutyric acid. Selective resistance toward degradation of beta-pleated sheet conformation is used to exemplify a possible accumulation of homochiral sequences made of hydrophilic and strong hydrophobic residues. Amino acids with branched aliphatic side-chains are selected but those having short linear aliphatic side-chains such as alpha-aminobutyric acid or norvaline are not.

Bicarbonates↗