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Showing papers by "University of Geneva published in 1988"



Journal ArticleDOI
TL;DR: Investigation of the influence of transforming growth factor beta, platelet-derived growth factor on the ability of fibroblasts to contract a collagen matrix in an in vitro system suggests that TGF-beta released from platelets and inflammatory cells at sites of tissue injury stimulates fibroblast to contract the provisional wound matrix and that this effect contributes to the ability to accelerate wound healing.
Abstract: An important event during wound healing is the contraction of newly formed connective tissue (granulation tissue) by fibroblasts. The role of polypeptide growth factors in the process of wound contraction was investigated by analyzing the influence of transforming growth factor beta (TGF-beta), platelet-derived growth factor on the ability of fibroblasts to contract a collagen matrix in an in vitro system. TGF-beta, but not the other growth factors tested, markedly enhanced the ability of BHK-21,3T3-L1, and human foreskin fibroblasts to contract collagen gels. These results suggest that TGF-beta released from platelets and inflammatory cells at sites of tissue injury stimulates fibroblasts to contract the provisional wound matrix and that this effect contributes to the ability of TGF-beta to accelerate wound healing.

560 citations


Journal ArticleDOI
15 Jul 1988-Cell
TL;DR: It is reported that NSF is needed for membrane fusion, and it is suggested that this reflects the stepwise assembly of a multisubunit "fusion machine" following vesicle attachment.

371 citations


Journal ArticleDOI
15 Apr 1988-Science
TL;DR: Results demonstrate that the alpha 2 subunit of rat neuronal nicotinic acetylcholine receptors differs from other known agonist-binding alpha-subunits of nAChRs in its distribution in the brain and in its pharmacology.
Abstract: A new type of agonist-binding subunit of rat neuronal nicotinic acetylcholine receptors (nAChRs) was identified. Rat genomic DNA and complementary DNA encoding this subunit (alpha 2) were cloned and analyzed. Complementary DNA expression studies in Xenopus oocytes revealed that the injection of messenger RNAs (mRNAs) for alpha 2 and beta 2 (a neuronal nAChR subunit) led to the generation of a functional nAChR. In contrast to the other known neuronal nAChRs, the receptor produced by the injection of alpha 2 and beta 2 mRNAs was resistant to the alpha-neurotoxin Bgt3.1. In situ hybridization histochemistry showed that alpha 2 mRNA was expressed in a small number of regions, in contrast to the wide distribution of the other known agonist-binding subunits (alpha 3 and alpha 4) mRNAs. These results demonstrate that the alpha 2 subunit differs from other known agonist-binding alpha-subunits of nAChRs in its distribution in the brain and in its pharmacology.

340 citations


Journal ArticleDOI
TL;DR: The detection of this previously unsuspected stromal cell phenotype in non-malignant mammary tissues might help in characterizing the variant morphological aspects designated under the label “fibrocystic disease” and in understanding the biology of pre‐malignant or early malignant lesions of the breast.
Abstract: A mouse monoclonal antibody (MAb) recognizing α-smooth-muscle actin has been used to study smooth-muscle differentiation features in the stromal cells of desmoplastic reactions accompanying mammary tumors. We have studied, by the same immunohistochemical technique, a series of malignant and non-malignant human breast tissues. Cells composing the desmoplastic reaction were found to express α-smooth-muscle actin in all the 11 breast carcinomas examined, whereas no immunostain was demonstrated in the stromal cells of 7 breast tissue samples histologically defined as normal. Three of 9 cases of fibrocystic disease showed a minority of positively stained stromal cells, generally in association with epithelial hyperplasia. All the 7 cases of sclerosing adenosis, 3 of 4 cases of diffuse papillomatosis and all 3 intraductal papillomas exhibited a majority of immunoreactive stromal cells. Numerous stromal cells in 3 of 11 circumscribed fibroadenomas analyzed expressed low amounts of α-smooth-muscle actin. The factor(s) responsible for smooth-muscle differentiation in stromal cells are presently unknown, but the detection of this previously unsuspected stromal cell phenotype in non-malignant mammary tissues might help in characterizing the variant morphological aspects designated under the label “fibrocystic disease” and in understanding the biology of pre-malignant or early malignant lesions of the breast.

329 citations


Book ChapterDOI
01 Jan 1988
TL;DR: In a recent review of classic theories of emotion and the disputes among adherents of competing traditions, this paper was struck by the remarkable lack of concern with the antecedent or eliciting conditions for emotional reactions.
Abstract: In reviewing classic theories of emotion and the disputes among adherents of competing traditions, one is struck by the remarkable lack of concern with the antecedent or eliciting conditions for emotional reactions. Most of the past and current controversies, e.g. central vs. peripheral control of feeling, universal vs. culturally specific affect states, unspecific arousal vs. discrete emotions, seem to have been orientated toward the different reaction components of the emotion process (physiological arousal, motor expression, subjective feeling) and the nature of their interrelationships. This is all the more surprising since it would seem that the analysis of the specificity of the emotional response systems requires an investigation into the specificity of the respective eliciting conditions.

327 citations


Journal ArticleDOI
TL;DR: The rapid recovery of AA and GSH levels after O3 exposure suggests a prominent role for these enzymes in cell protection against oxidative damage.

239 citations


Journal ArticleDOI
17 Jun 1988-Cell
TL;DR: It is proposed that the molecular defect in this congenital HLA class II regulatory deficiency is a lack of RF-X and that this factor plays an important role in the normal regulation of MHC class II gene expression.

234 citations


Journal ArticleDOI
TL;DR: Four genes encode the related protein subunits that assemble to form the nicotinic acetylcholine receptor (nAChR) at the motor endplate of vertebrates and probably exists in all vertebrates since their counterparts have also been identified in the rat genome.
Abstract: Four genes encode the related protein subunits that assemble to form the nicotinic acetylcholine receptor (nAChR) at the motor endplate of vertebrates. We have isolated from the chicken genome four additional members of the same gene family whose protein products, termed alpha 2, alpha 3, alpha 4 and n alpha (non-alpha) probably define three distinct neuronal nAChR subtypes. The neuronal nAChR genes have identical structures consisting of six protein-coding exons and specify proteins that are best aligned with the chicken endplate alpha subunit, whose gene we have also characterized. mRNA transcripts encoding alpha 4 and n alpha are abundant in embryonic and in adult avian brain, whereas alpha 2 and alpha 3 transcripts are much scarcer. The same set of neuronal genes probably exists in all vertebrates since their counterparts have also been identified in the rat genome.

225 citations


Journal ArticleDOI
23 Dec 1988-Cell
TL;DR: Surprisingly, sister chromatids have predominantly opposite helical handedness; that is, they are related by mirror symmetry.

221 citations


Journal ArticleDOI
TL;DR: It was concluded that the induction of glucokinase resulted primarily from a burst in the transcriptional activity of the gene, leading to a short-term accumulation of gluckinase mRNA.

Journal ArticleDOI
TL;DR: In this article, inelastic neutron scattering experiments performed on single crystals of the heavy fermion compounds CeRu2Si2 and CeCu6 were performed on both compounds.

Journal ArticleDOI
TL;DR: In this study, after enzymic amplification of a specific segment of the HIV genome, a simple slot-blot hybridisation procedure allowed unequivocal identification of HIV DNA in all seropositive subjects tested.

Journal Article
TL;DR: The presence of alpha-smooth muscle actin in 1 case of rhabdomyosarcoma suggests that this actin isoform may be expressed during skeletal muscle differentiation, and this antibody further allowed the recognition of pleomorphic variants and morphologically atypical forms of r HabdomyOSarcomas.
Abstract: A series of 15 rhabdomyosarcomas was examined by light microscopy, transmission electron microscopy, two-dimensional gel electrophoresis (2D-GE) and indirect immunofluorescence, the latter using monoclonal or affinity-purified polyclonal antibodies to desmin, vimentin, alpha-smooth muscle and alpha-sarcomeric (alpha-sr) actins. By light microscopy, the authors diagnosed 1 botrioid, 1 alveolar, and 7 embryonal rhabdomyosarcomas, 4 pleomorphic spindle cell sarcomas, and 2 spindle cell sarcomas, one nondistinct, the other with a hemangiopericytomatous pattern. By transmission electron microscopy, 13 neoplasms disclosed rhabdomyoblastic differentiation; the remaining 2, myogenic differentiation. By immunofluorescence microscopy, all neoplasms expressed vimentin and alpha-sr actin, 12 expressed, in addition, desmin, and 1 expressed alpha-smooth muscle actin. Among the 11 neoplasms studied by means of 2D-GE, 7 demonstrated an alpha-actin spot, while 4 showed only beta and gamma spots. One tumor disclosed, in addition to alpha, beta, and gamma spots, a spot with a molecular weight corresponding to actin, but more acidic than alpha-actins. This study demonstrates that alpha-sr actin antibody represents a valuable marker for the diagnosis of rhabdomyosarcoma, because it was present in all neoplasms, including the one negative for desmin. This antibody further allowed the recognition of pleomorphic variants and morphologically atypical forms of rhabdomyosarcomas. The presence of alpha-smooth muscle actin in 1 case of rhabdomyosarcoma suggests that this actin isoform may be expressed during skeletal muscle differentiation.

Journal ArticleDOI
TL;DR: In this paper, the structure of orthorhombic YBa2Cu3O7 was refined in the temperature interval 5-320K, to an accuracy higher by a factor of about two compared to previous refinements.

Book ChapterDOI
01 Jan 1988
TL;DR: Wound healing consists schematically of acute inflammation followed by formation of granulation tissue, a transitional tissue able to retract the wound space, and finally scar formation.
Abstract: The process of wound repair is of vital importance for animals as well as for plants (Shigo, 1985), since a wound perturbs body homeostasis and may result in infection by microorganisms. A wound may occur without or with tissue loss (Robbins et al, 1984). In both cases, but more clearly in the second case, wound healing consists schematically of acute inflammation followed by formation of granulation tissue, a transitional tissue able to retract the wound space, and finally scar formation.

Journal ArticleDOI
TL;DR: The findings show that the program regulating actin isoform expression in sarcomeric muscle development is complex and that α-smooth muscle actin participates in this process.

Journal ArticleDOI
05 Aug 1988-Science
TL;DR: Injection of antisense RNA complementary to 103 nucleotides of its extreme 3' untranslated region was sufficient to prevent the polyadenylation, translational activation, and destabilization of t-PA mRNA.
Abstract: Primary mouse oocytes contain untranslated stable messenger RNA for tissue plasminogen activator (t-PA). During meiotic maturation, this maternal mRNA undergoes a 3'-polyadenylation, is translated, and is degraded. Injections of maturing oocytes with different antisense RNA's complementary to both coding and noncoding portions of t-PA mRNA all selectively blocked t-PA synthesis. RNA blot analysis of t-PA mRNA in injected, matured oocytes suggested a cleavage of the RNA.RNA hybrid region, yielding a stable 5' portion, and an unstable 3' portion. In primary oocytes, the 3' noncoding region was susceptible to cleavage, while the other portions of the mRNA were blocked from hybrid formation until maturation occurred. Injection of antisense RNA complementary to 103 nucleotides of its extreme 3' untranslated region was sufficient to prevent the polyadenylation, translational activation, and destabilization of t-PA mRNA. These results demonstrate a critical role for the 3' noncoding region of a dormant mRNA in its translational recruitment during meiotic maturation of mouse oocytes.

Journal ArticleDOI
TL;DR: Examination of the relative molar amounts of the C′, P and C proteins found in vivo suggests that an ACG in an otherwise favorable context is almost as efficient for ribosome initiation as an ATG in a less favored context, but only 10‐20% as efficient as an AtG in the more favored context.
Abstract: The Sendai virus P/C mRNA expresses the P and C proteins from alternate reading frames. The C reading frame of this mRNA, however, is responsible for three proteins, C', C and Y, none of which appear to be precursors to each other in vivo. Using site-directed and deletion mutagenesis of the P/C gene cloned in SP6 and in vitro translation of the mRNAs, we show that the 5' most proximal initiation codon of the mRNA is an ACG at position 81, responsible for C' synthesis. The succeeding initiation codons, all ATGs, are responsible for the P protein (position 104), the C protein (position 114) and the Y protein(s) (either positions 183 or 201). Examination of the relative molar amounts of the C', P and C proteins found in vivo suggests that an ACG in an otherwise favorable context is almost as efficient for ribosome initiation as an ATG in a less favored context, but only 10-20% as efficient as an ATG in a more favored context. The judicious choice of increasingly more favorable initiation codons in the P/C gene allows multiple proteins to be made from a single mRNA.

Journal ArticleDOI
TL;DR: In this article, it was shown that the notion of algebraic closure is also useful over an arbitrary perfect field k for studying the fc-birational properties of singular cubic surfaces, and of certain other singular surfaces defined below.
Abstract: The study of singular cubic surfaces is quite an old subject, since their classification (over C) goes back to Schlafli [39] and Cay ley [8]. However, a recent account by Bruce and Wall [6] has shown that modern singularity theory can give much insight into this classification. One of the main themes of the present paper is that this approach is also useful over an arbitrary perfect field k for studying the fc-birational properties of singular cubic surfaces, and of certain other singular surfaces which are defined below. Recall that an absolutely irreducible algebraic variety V, defined over k, is said to be k-rational (respectively, k-unirational) if its function field k(V) is (respectively, is contained in) a purely transcendental extension of k. Throughout this paper k denotes an algebraic closure of k, and V = Vxkk. We say that V is rational if V is ^-rational, and we write P" for P£. Unless stated otherwise, the notation V <= P£ implies that V is a projective sub variety of P£, defined over k. In Part I we prove:

Book ChapterDOI
01 Jan 1988
TL;DR: Tissue repair takes place in well-characterized steps and tissue remodeling implicates extracellular matrix degradation, decrease of cellularity, and constitution of the scar.
Abstract: Following tissue injury, tissue repair takes place in well-characterized steps. After clot formation, inflammatory cells, essentially mononuclear cells and granulocytes, invade the injured tissue; then, fibroblasts migrate, proliferate, and synthesize extracellular matrix components, participating in the formation of granulation tissue. Finally, following reepithelialization and wound closure, tissue remodeling implicates extracellular matrix degradation, decrease of cellularity, and constitution of the scar.

Journal ArticleDOI
TL;DR: The cellular composition of aortic atherosclerotic plaques was analyzed by immunocytochemistry using cell type-specific monoclonal antibodies to suggest that T cell-smooth muscle interactions occur during atherogenesis.

Journal ArticleDOI
TL;DR: The results suggest that in vivo the synthesis of actin isoforms in arterial SMC depends on the mRNA levels and changes after injury in early G0/G1 whether or not the cells subsequently proliferate.
Abstract: Quiescent smooth muscle cells (SMC) in normal artery express a pattern of actin isoforms with alpha-smooth muscle (alpha SM) predominance that switches to beta predominance when the cells are proliferating. We have examined the relationship between the change in actin isoforms and entry of SMC into the growth cycle in an in vivo model of SMC proliferation (balloon injured rat carotid artery). alpha SM actin mRNA declined and cytoplasmic (beta + gamma) actin mRNAs increased in early G0/G1 (between 1 and 8 h after injury). In vivo synthesis and in vitro translation experiments demonstrated that functional alpha SM mRNA is decreased 24 h after injury and is proportional to the amount of mRNA present. At 36 h after injury, SMC prepared by enzymatic digestion were sorted into G0/G1 and S/G2 populations; only the SMC committed to proliferate (S/G2 fraction) showed a relative slight decrease in alpha SM actin and, more importantly, a large decrease in alpha SM actin mRNA. A switch from alpha SM predominance to beta predominance was present in the whole SMC population 5 d after injury. To determine if the change in actin isoforms was associated with proliferation, we inhibited SMC proliferation by approximately 80% with heparin, which has previously been shown to block SMC in late G0/G1 and to reduce the growth fraction. The switch in actin mRNAs and synthesis at 24 h was not prevented; however, alpha SM mRNA and protein were reinduced at 5 d in the heparin-treated animals compared to saline-treated controls. These results suggest that in vivo the synthesis of actin isoforms in arterial SMC depends on the mRNA levels and changes after injury in early G0/G1 whether or not the cells subsequently proliferate. The early changes in actin isoforms are not prevented by heparin, but they are eventually reversed if the SMC are kept in the resting state by the heparin treatment.

Journal ArticleDOI
TL;DR: Structural conservation of domains of the deduced protein and of intron/exon boundaries indicate that the Drosophila gene encodes an nAChR alpha‐like subunit (ALS), which most resembles the neuronal set of vertebrate nA ChRs alpha‐subunits.
Abstract: Nicotinic acetylcholine receptors (nAChR) are found both in vertebrate and insect central nervous systems. We have isolated a Drosophila gene by crosshybridization with a vertebrate probe. Structural conservation of domains of the deduced protein and of intron/exon boundaries indicate that the Drosophila gene encodes an nAChR alpha-like subunit (ALS). That the Drosophila gene product most resembles the neuronal set of vertebrate nAChRs alpha-subunits is also indicated by the failure of an ALS-beta-galactosidase fusion protein to bind alpha-bungarotoxin on blots in contrast to vertebrate endplate alpha-subunit constructions. The ALS encoding gene exceeds 54 kb in length and the transcript has a very long and unusual 5' leader. As we found previously for a gene whose product is also involved in cholinergic synapses, acetylcholinesterase, the leader encodes short open reading frames, which might be involved in translation control. We also note the presence of opa repeats in the gene, as has been found for various Drosophila genes expressed in the nervous system.

Journal ArticleDOI
TL;DR: To try to understand the function of NC and of each of its Cys-His boxes during the viral life cycle, particularly in viral RNA packaging, synthetic oligonucleotides are used to delete precisely either the proximal or the distal box, or both Cys -His boxes.
Abstract: Rous sarcoma virus nucleocapsid protein p12 (NC) contains two conserved amino acid motifs, the Cys-His boxes, which constitute potential metal-binding domains. To try to understand the function of NC and of each of its Cys-His boxes during the viral life cycle, particularly in viral RNA packaging, we have used synthetic oligonucleotides to delete precisely either the proximal or the distal box, or both Cys-His boxes. The mutant DNAs were transfected into chicken embryo fibroblasts, and the virions produced in a transient assay were characterized biochemically for production of viral proteins and particles, RNA packaging, and infectivity. The results indicated the following. (i) The deletion of either the proximal or the distal box decreases the amount of viral RNA packaged in the particles and results in incomplete 70S dimer formation. (ii) The deletion of both boxes inhibits viral RNA packaging. (iii) The deletion of the proximal, but not the distal, box suppresses any detectable infectivity, while the deletion of the distal, but not the proximal, box lowers infectivity 100 to 200 times.

Journal ArticleDOI
TL;DR: It is demonstrated that cloned DNA fragments containing SAR sequences bind to nuclear scaffolds in vitro with the same specificity as have genomic SAR fragments, which appear to be evolutionarily conserved.

Journal ArticleDOI
TL;DR: In regions where malaria is endemic the prevalence of hypohaptoglobinaemia could be as useful an indicator as the parasitic index but would be much easier to establish and to monitor.

Journal ArticleDOI
TL;DR: Readily available chiral tridentate ligand 8 catalyzes the highly Si-face selective addition of diethyl-, di-n-propylzinc and, more significantly, of divinylzinc to aromatic and aliphatic aldehydes whereas bidentates 11 and 12 exert a topologically reversed catalytic bias as mentioned in this paper.

Journal ArticleDOI
TL;DR: In this paper, the release of two very soluble beta adrenergic blockers namely: metoprolol tartrate and alprenolol HCl from cellulose matrices containing hydroxypropylcellulose (HPC) or sodium carboxymethylcelluloses (Na CMC) or methylcellulosa (MC), or MC + Na CMC or HPC + NaCMC in different ratios was studied in distilled water using USP dissolution apparatus 2.
Abstract: Release of two very soluble beta adrenergic blockers namely: metoprolol tartrate and alprenolol HCl from cellulose matrices containing hydroxypropylcellulose (HPC) or sodium carboxymethylcellulose (Na CMC) or methylcellulose (MC), or MC + Na CMC or HPC + Na CMC in different ratios was studied in distilled water using USP dissolution apparatus 2. Increase in the ratio of total polymer to drug has decreased the release rate in a nonlinear manner. When only one polymer (HPC or Na CMC) was used, the release profiles were of first-order or sigmoidal in nature respectively. MC matrices disintegrated in < 1 h. By mixing the drug with an optimum amount of the nonionic (HPC or MC) and anionic (Na CMC) polymers, zero-order release profiles with excellent reproducibility were obtained. Rate of erosion of the matrix was 2.5 times higher when drug, Na CMC and HPC were present compared to the matrix containing only drug and HPC. This indicates that the diffusional pathlength for the drug increases with time whe...

Journal ArticleDOI
TL;DR: The maintenance of the scaffold-DNA interaction in metaphase indicates that lamin proteins are not involved in the attachment site for at least a subset of Drosophila SARs, consistent with a fundamental role for these fragments in the organization of the genome into looped domains.