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Showing papers by "University of Lausanne published in 1994"


Journal ArticleDOI
K. Hagiwara, Ken Ichi Hikasa1, Koji Nakamura, Masaharu Tanabashi1, M. Aguilar-Benitez, Claude Amsler2, R. M. Barnett3, Patricia R. Burchat4, C. D. Carone5, C. Caso, G. Conforto6, Olav Dahl3, Michael Doser7, Semen Eidelman8, Jonathan L. Feng9, L. K. Gibbons10, Maury Goodman11, Christoph Grab12, D. E. Groom3, Atul Gurtu13, Atul Gurtu7, K. G. Hayes14, J. J. Herna`ndez-Rey15, K. Honscheid16, Christopher Kolda17, Michelangelo L. Mangano7, David Manley18, Aneesh V. Manohar19, John March-Russell7, Alberto Masoni, Ramon Miquel3, Klaus Mönig, Hitoshi Murayama20, Hitoshi Murayama3, S. Sánchez Navas12, Keith A. Olive21, Luc Pape7, C. Patrignani, A. Piepke22, Matts Roos23, John Terning24, Nils A. Tornqvist23, T. G. Trippe3, Petr Vogel25, C. G. Wohl3, Ron L. Workman26, W-M. Yao3, B. Armstrong3, P. S. Gee3, K. S. Lugovsky, S. B. Lugovsky, V. S. Lugovsky, Marina Artuso27, D. Asner28, K. S. Babu29, E. L. Barberio7, Marco Battaglia7, H. Bichsel30, O. Biebel31, Philippe Bloch7, Robert N. Cahn3, Ariella Cattai7, R. S. Chivukula32, R. Cousins33, G. A. Cowan34, Thibault Damour35, K. Desler, R. J. Donahue3, D. A. Edwards, Victor Daniel Elvira, Jens Erler36, V. V. Ezhela, A Fassò7, W. Fetscher12, Brian D. Fields37, B. Foster38, Daniel Froidevaux7, Masataka Fukugita39, Thomas K. Gaisser40, L. Garren, H.-J. Gerber12, Frederick J. Gilman41, Howard E. Haber42, C. A. Hagmann28, J.L. Hewett4, Ian Hinchliffe3, Craig J. Hogan30, G. Höhler43, P. Igo-Kemenes44, John David Jackson3, Kurtis F Johnson45, D. Karlen, B. Kayser, S. R. Klein3, Konrad Kleinknecht46, I.G. Knowles47, P. Kreitz4, Yu V. Kuyanov, R. Landua7, Paul Langacker36, L. S. Littenberg48, Alan D. Martin49, Tatsuya Nakada7, Tatsuya Nakada50, Meenakshi Narain32, Paolo Nason, John A. Peacock47, Helen R. Quinn4, Stuart Raby16, Georg G. Raffelt31, E. A. Razuvaev, B. Renk46, L. Rolandi7, Michael T Ronan3, L.J. Rosenberg51, Christopher T. Sachrajda52, A. I. Sanda53, Subir Sarkar54, Michael Schmitt55, O. Schneider50, Douglas Scott56, W. G. Seligman57, Michael H. Shaevitz57, Torbjörn Sjöstrand58, George F. Smoot3, Stefan M Spanier4, H. Spieler3, N. J. C. Spooner59, Mark Srednicki60, A. Stahl, Todor Stanev40, M. Suzuki3, N. P. Tkachenko, German Valencia61, K. van Bibber28, Manuella Vincter62, D. R. Ward63, Bryan R. Webber63, M R Whalley49, Lincoln Wolfenstein41, J. Womersley, C. L. Woody48, O. V. Zenin 
Tohoku University1, University of Zurich2, Lawrence Berkeley National Laboratory3, Stanford University4, College of William & Mary5, University of Urbino6, CERN7, Budker Institute of Nuclear Physics8, University of California, Irvine9, Cornell University10, Argonne National Laboratory11, ETH Zurich12, Tata Institute of Fundamental Research13, Hillsdale College14, Spanish National Research Council15, Ohio State University16, University of Notre Dame17, Kent State University18, University of California, San Diego19, University of California, Berkeley20, University of Minnesota21, University of Alabama22, University of Helsinki23, Los Alamos National Laboratory24, California Institute of Technology25, George Washington University26, Syracuse University27, Lawrence Livermore National Laboratory28, Oklahoma State University–Stillwater29, University of Washington30, Max Planck Society31, Boston University32, University of California, Los Angeles33, Royal Holloway, University of London34, Université Paris-Saclay35, University of Pennsylvania36, University of Illinois at Urbana–Champaign37, University of Bristol38, University of Tokyo39, University of Delaware40, Carnegie Mellon University41, University of California, Santa Cruz42, Karlsruhe Institute of Technology43, Heidelberg University44, Florida State University45, University of Mainz46, University of Edinburgh47, Brookhaven National Laboratory48, Durham University49, University of Lausanne50, Massachusetts Institute of Technology51, University of Southampton52, Nagoya University53, University of Oxford54, Northwestern University55, University of British Columbia56, Columbia University57, Lund University58, University of Sheffield59, University of California, Santa Barbara60, Iowa State University61, University of Alberta62, University of Cambridge63
TL;DR: This biennial Review summarizes much of Particle Physics using data from previous editions, plus 2205 new measurements from 667 papers, and features expanded coverage of CP violation in B mesons and of neutrino oscillations.
Abstract: This biennial Review summarizes much of Particle Physics. Using data from previous editions, plus 2205 new measurements from 667 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We also summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics. This edition features expanded coverage of CP violation in B mesons and of neutrino oscillations. For the first time we cover searches for evidence of extra dimensions (both in the particle listings and in a new review). Another new review is on Grand Unified Theories. A booklet is available containing the Summary Tables and abbreviated versions of some of the other sections of this full Review. All tables, listings, and reviews (and errata) are also available on the Particle Data Group website: http://pdg.lbl.gov.

5,143 citations


Journal ArticleDOI
TL;DR: It is reported that glutamate, in addition to its receptor-mediated actions on neuronal excitability, stimulates glycolysis--i.e., glucose utilization and lactate production--in astrocytes and is consistent with data obtained from functional brain imaging studies indicating local nonoxidative glucose utilization during physiological activation.
Abstract: Glutamate, released at a majority of excitatory synapses in the central nervous system, depolarizes neurons by acting at specific receptors. Its action is terminated by removal from the synaptic cleft mostly via Na(+)-dependent uptake systems located on both neurons and astrocytes. Here we report that glutamate, in addition to its receptor-mediated actions on neuronal excitability, stimulates glycolysis--i.e., glucose utilization and lactate production--in astrocytes. This metabolic action is mediated by activation of a Na(+)-dependent uptake system and not by interaction with receptors. The mechanism involves the Na+/K(+)-ATPase, which is activated by an increase in the intracellular concentration of Na+ cotransported with glutamate by the electrogenic uptake system. Thus, when glutamate is released from active synapses and taken up by astrocytes, the newly identified signaling pathway described here would provide a simple and direct mechanism to tightly couple neuronal activity to glucose utilization. In addition, glutamate-stimulated glycolysis is consistent with data obtained from functional brain imaging studies indicating local nonoxidative glucose utilization during physiological activation.

2,521 citations


Journal ArticleDOI
03 Feb 1994-Nature
TL;DR: The ion-selective permeability, the gating properties and the pharmacological profile of the channel formed by coexpressing the three subunits in oocytes are similar to that of the native channel.
Abstract: The amiloride-sensitive epithelial sodium channel constitutes the rate-limiting step for sodium reabsorption in epithelial cells that line the distal part of the renal tubule, the distal colon, the duct of several exocrine glands, and the lung. The activity of this channel is upregulated by vasopressin and aldosterone, hormones involved in the maintenance of sodium balance, blood volume and blood pressure. We have identified the primary structure of the alpha-subunit of the rat epithelial sodium channel by expression cloning in Xenopus laevis oocytes. An identical subunit has recently been reported. Here we identify two other subunits (beta and gamma) by functional complementation of the alpha-subunit of the rat epithelial Na+ channel. The ion-selective permeability, the gating properties and the pharmacological profile of the channel formed by coexpressing the three subunits in oocytes are similar to that of the native channel.

1,935 citations


Journal ArticleDOI
04 Nov 1994-Cell
TL;DR: It is demonstrated that Liddle's syndrome is caused by mutations in the beta subunit of the epithelial sodium channel and have implications for the regulation of this epithelial ion channel as well as blood pressure homeostasis.

1,174 citations


Journal ArticleDOI
25 Aug 1994-Nature
TL;DR: Two complementary, specific cytotoxic mechanisms are functional in CTLs, one based on the secretion of lytic proteins and one which depends on cell-surface ligand–receptor interaction, which is triggered upon T-cell receptor occupancy and directed to the cognate target cell.
Abstract: The recent generation of perforin knock-out mice has demonstrated a crucial role for the pore-forming perforin in cytolytic T-lymphocyte (CTL)-mediated cytolysis. Perforin-deficient mice failed to clear lymphocytic choriomeningitis virus in vivo, yet substantial killing activity still remained in perforin-free CTLs in vitro, indicating the presence of (a) further lytic pathway(s). Fas is an apoptosis-signalling receptor molecule on the surface of a number of different cells. Here we report that both perforin-deficient and Fas-ligand-deficient CTLs show impaired lytic activity on all target cells tested. The killing activity was completely abolished when both pathways were inactivated by using target cells from Fas-receptor-deficient lpr mice and perforin-free CTL effector cells. Fas-ligand-based killing activity was triggered upon T-cell receptor occupancy and was directed to the cognate target cell. Thus, two complementary, specific cytotoxic mechanisms are functional in CTLs, one based on the secretion of lytic proteins and one which depends on cell-surface ligand-receptor interaction.

1,065 citations


Journal ArticleDOI
TL;DR: Measurement of the combined local synthesis of antibodies against measles, rubella, and/or varicella zoster could represent a significant advance if it offers higher specificity (not sensitivity) for identifying chronic rather than acute inflammation.
Abstract: The Committee of the European Concerted Action for Multiple Sclerosis (Charcot Foundation) organised five workshops to discuss CSF analytical standards in the diagnosis of multiple sclerosis. This consensus report from 12 European countries summarises the results of those workshops. It is hoped that neurologists will confer with their colleagues in clinical chemistry to arrange the best possible local practice. The most sensitive method for the detection of oligoclonal immunoglobulin bands is isoelectric focusing. The same amounts of IgG in parallel CSF and serum samples are used and oligoclonal bands are revealed with IgG specific antibody staining. All laboratories performing isoelectric focusing should check their technique at least annually using "blind" standards for the five different CSF and serum patterns. Quantitative measurements of IgG production in the CNS are less sensitive than isoelectric focusing. The preferred method for detection of blood-CSF barrier dysfunction is the albumin quotient. The CSF albumin or total protein concentrations are less satisfactory. These results must be interpreted with reference to the age of the patient and the local method of determination. Cells should be counted. The normal value is no more than 4 cells/microliters. Among evolving optional tests, measurement of the combined local synthesis of antibodies against measles, rubella, and/or varicella zoster could represent a significant advance if it offers higher specificity (not sensitivity) for identifying chronic rather than acute inflammation. Other tests that may have useful correlations with clinical indices include those for oligoclonal free light chains, IgM, IgA, or myelin basic protein concentrations.

617 citations


Journal ArticleDOI
TL;DR: This work focuses on intraspecific variability in the distribution of reproduction within animal societies, and the available data suggest that this variability might be greater than previously suspected.
Abstract: A key feature differentiating cooperative animal societies Is the apportionment of reproduction among individuals. Only recently have studies started to focus on intraspecific variability in the distribution of reproduction within animal societies, and the available data suggest that this variability might be greater than previously suspected. How can one account for intra-and interspecific variability in partitioning of reproduction? This Is one of the most intriguing problems in the study of social behaviour, and understanding the factors underlying this variability is one of the keys to understanding the properties of complex animal societies.

501 citations


Journal ArticleDOI
C Duc1, N Farman1, C M Canessa1, J P Bonvalet1, Bernard C. Rossier1 
TL;DR: The data indicate that alpha, beta, and gamma subunit mRNAs and proteins are co-expressed in the distal nephron (excepting IMCD), a localization that correlates with the previously described physiological expression of amiloride-sensitive electrogenic sodium transport.
Abstract: A highly selective, amiloride-sensitive, epithelial sodium channel from rat colon (rENaC), composed of three homologous subunits termed alpha, beta, and gamma rENaC, has been cloned by functional expression and was proposed to mediate electrogenic sodium reabsorption in aldosterone-responsive epithelia. To determine whether rENaC could account for sodium absorption in vivo, we studied the cellular localization of the sodium channel messenger RNA subunits by in situ hybridization and their cellular and subcellular distribution by immunocytochemistry in the kidney, colon, salivary, and sweat glands of the rat. In the kidney, we show that the three subunit mRNAs are specifically co-expressed in the renal distal convoluted tubules (DCT), connecting tubules (CNT), cortical collecting ducts (CCD), and outer medullary collecting ducts (OMCD), but not in the inner medullary collecting ducts (IMCD). We demonstrate co-localization of alpha, beta, and gamma subunit proteins in the apical membrane of a majority of cells of CCD and OMCD. Our data indicate that alpha, beta, and gamma subunit mRNAs and proteins are co-expressed in the distal nephron (excepting IMCD), a localization that correlates with the previously described physiological expression of amiloride-sensitive electrogenic sodium transport. Our data, however, suggest that another sodium transport protein mediates electrogenic amiloride-sensitive sodium reabsorption in IMCD. We also localized rENaC to the surface epithelial cells of the distal colon and to the secretory ducts of the salivary gland and sweat gland, providing further evidence consistent with the hypothesis that the highly selective, amiloride-sensitive sodium channel is physiologically expressed in aldosterone-responsive cells.

372 citations


Journal ArticleDOI
TL;DR: The association of passive smoking exposure with dyspnea, wheeze, and asthma showed evidence of a dose-dependent increase with hours per day of exposure, whereas association with symptoms of bronchitis was stronger with years of exposure.
Abstract: The association between passive exposure to tobacco smoke and respiratory symptoms was examined in a sample of 4,197 never-smoking adults. They constituted the never-smoking subsample of a random sample of 9,651 adults (age, 18 to 60 yr) in eight areas in Switzerland. Information on passive smoking exposure and standardized questions on respiratory symptoms were obtained via a questionnaire administered by trained examiners. After controlling for age, sex, body mass index (BMI), study area, atopy, and parental and sibling history, passive smoking exposure was associated with an elevated risk of wheezing apart from colds (odds ratio [OR] = 1.94, 95% CI = 1.39 to 2.70), an elevated risk of bronchitis symptoms (OR = 1.59, 95% CI = 1.17 to 2.15), an elevated risk of symptoms of chronic bronchitis (OR = 1.65, 95% CI = 1.28 to 2.16), an elevated risk of dyspnea (OR = 1.45, 95% CI = 1.20 to 1.76), and an elevated risk of physician diagnosed asthma (OR = 1.39, 95% CI = 1.04 to 1.86). It was not associated with any increased risk of allergic rhinitis including hayfever. Adding a variable for low educational level, excluding subjects whose mother ever smoked or subjects with end-expiratory CO levels > or = 7 ppm, and controlling for paternal smoking during childhood or occupational exposure had little impact on the association. The association of passive smoking exposure with dyspnea, wheeze, and asthma showed evidence of a dose-dependent increase with hours per day of exposure, whereas association with symptoms of bronchitis was stronger with years of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

311 citations


Journal ArticleDOI
TL;DR: The highly selective amiloride-sensitive epithelial sodium channel is formed of three homologous subunits termed alpha-, beta-, and gamma-rENaC, and all three subunits are glycosylated in a cell-free translation assay, demonstrating that they share in vitro a common pattern of membrane insertion.
Abstract: The highly selective amiloride-sensitive epithelial sodium channel is formed of three homologous subunits termed alpha-, beta-, and gamma-rENaC. Each subunit has two putative transmembrane domains (M1 and M2), yielding a protein with a large (approximately 50 kDa) hydrophilic loop (between M1 and M2) and short hydrophilic NH2- and COOH-termini (9 and 10 kDa). All three subunits are glycosylated in a cell-free translation assay, demonstrating that they share in vitro a common pattern of membrane insertion. The membrane topology of the alpha-rENaC subunit in intact cells was studied in Xenopus laevis oocytes. We demonstrate that 1) all six potential N-linked glycosylation sites (N190, N259, N320, N339, N424, and N538) of the large hydrophilic loop are used in intact cells; 2) the glycosylation of alpha-rENaC does not play a significant role in the functional expression of the channel; and 3) the two hydrophobic domains M1 (A109-F131) and M2 (S588-L612) serve in intact cells as start- and stop-transfer signals, respectively. We conclude that alpha-rENaC spans the membrane twice with the short NH2- and COOH-terminal ends on the cytoplasmic side and a large hydrophilic loop in the extracellular space.

306 citations


Journal ArticleDOI
TL;DR: Current evidence strongly supports the idea that perichromatin fibrils are the in situ form of hnRNA transcripts and sites of pre-mRNA processing steps such as splicing and polyadenylation.

Journal ArticleDOI
TL;DR: The MLP method presented here can be used as a third field in CoMFA studies, as illustrated with two series of α1 ligands, allowing insights into ligand-receptor interactions.
Abstract: A new method is presented to calculate the Molecular Lipophilicity Potential (MLP). The method is validated by showing that the MLP thus generated on the solvent-accessible surface can be used to back-calculate log P. Because the MLP is shown to be sensitive to conformational effects, the MLP/log P relation is best sought by taking all conformers into account. The MLP method presented here can be used as a third field in CoMFA studies, as illustrated with two series of alpha 1-adrenoceptor ligands. In the first series, the steric, electrostatic and lipophilic fields are highly intercorrelated, and taken separately yield comparable models. In the second series of ligands, the best model is obtained with the lipophilic field alone, allowing insights into ligand-receptor interactions.

Journal ArticleDOI
TL;DR: Oral immunization with H. pylori urease protects mice against H. felis infection and it is unclear whether protection depends on the development of a mononuclear inflammatory response in the gastric corpus.

Journal ArticleDOI
TL;DR: In this article, it was shown that the cross-polarization efficiency in the rotating frame can be improved by sweeping the radiofrequency amplitude adiabatically through the Hartmann-Hahn condition.

Journal ArticleDOI
TL;DR: It is suggested that endocytosis and basolateral sorting can be mediated by both tyrosine‐ and di‐leucine‐based signals and confirmed the close relationship between the two determinants already observed for ‘classical’ tyosine‐dependent motifs.
Abstract: An important function of the low affinity IgG Fc receptor FcRII-B2 (FcR) on macrophages is the internalization of soluble antigen-antibody complexes for lysosomal degradation. Most endocytic receptors possess tyrosine-containing cytoplasmic determinants required for endocytosis. In many proteins, signals which overlap with the endocytosis determinant and share the same critical tyrosine residue also mediate basolateral sorting in the trans-Golgi network of epithelial cells. Despite the presence of two tyrosine residues in the FcR cytosolic domain, neither one is absolutely required for coated pit localization or basolateral targeting. Nevertheless, a short domain of 13 residues containing one of the non-critical tyrosine residues mediates endocytosis and basolateral delivery. Alanine scan mutagenesis of this region now revealed a critical role of a leucine-leucine motif in both events. These findings suggest that endocytosis and basolateral sorting can be mediated by both tyrosine- and di-leucine-based signals and confirm the close relationship between the two determinants already observed for 'classical' tyrosine-dependent motifs.

Journal ArticleDOI
TL;DR: It is demonstrated here that a decrease of DNA-DNA repulsion by increasing concentrations of counterions causes a higher fraction of the linking number deficit to be partitioned into writhe.

Journal ArticleDOI
TL;DR: The PPAR alpha gene is an early response gene of glucocorticoids that control its expression at the transcriptional level, and it is demonstrated that the expression of the peroxisome proliferator-activated receptor alpha (PPAR alpha) is regulated by glucOCorticoid hormones in hepatocytes.

Journal ArticleDOI
TL;DR: It is concluded that perforin is a crucial effector molecule in T cell- and NK cell-mediated cytolysis, however, alternative per forin-independent lytic mechanisms also exist.
Abstract: Lymphocyte-mediated cytotoxicity has been proposed to consist of the polarized secretion of granule-stored perforin leading to target-cell lysis. Nevertheless, perforin-independent pathways were postulated to explain the cytolytic activity of apparently perforin-free lymphocytes and the DNA degradation found in dying target cells. To evaluate the role of perforin, we used gene targeting in embryonic stem cells to produce mice lacking perforin. Mice homozygous for the disrupted gene have no perforin mRNA. The mice are healthy. Activation and granzyme A secretion of perforin-free cytolytic T cells are unaltered. The killing activity of cytolytic T cells as well as natural killer (NK) cells, however, is impaired but not abolished. Approximately one-third of the killing activity remains when lysis of 3T3 fibroblast targets and the apoptotic cell death of YAC-1 NK targets are analyzed. We conclude that perforin is a crucial effector molecule in T cell- and NK cell-mediated cytolysis. However, alternative perforin-independent lytic mechanisms also exist.

Journal ArticleDOI
TL;DR: In the early Palaeogene period of the Tertiary orogeny, the main Ternian nappe emplacement resulted from a NW-thrusting of the Austroalpine, Penninic and Helvetic nappes as discussed by the authors.

Journal ArticleDOI
TL;DR: In this article, the design and construction of the silicon strip microvertex detector (SMD) of the L3 experiment at LEP are described and the sensors, readout electronics, data acquisition system, mechanical assembly and support, displacement monitoring systems and radiation monitoring system of the recently installed double-sided, double-layered SMD.
Abstract: The design and construction of the silicon strip microvertex detector (SMD) of the L3 experiment at LEP are described. We present the sensors, readout electronics, data acquisition system, mechanical assembly and support, displacement monitoring systems and radiation monitoring system of the recently installed double-sided, double-layered SMD. This detector utilizes novel and sophisticated techniques for its readout.

Journal ArticleDOI
01 Jan 1994-Gut
TL;DR: The results indicate that duodenal bacterial overgrowth of both oral and faecal type bacteria occurs often in ambulatory patients treated with omeprazole and further studies are needed to determine the clinical significance of these findings.
Abstract: The extent of duodenal bacterial overgrowth during the pronounced inhibition of acid secretion that occurs with omeprazole treatment is unknown. The bacterial content of duodenal juice of patients treated with omeprazole was therefore examined in a controlled prospective study. Duodenal juice was obtained under sterile conditions during diagnostic upper endoscopy. Aspirates were plated quantitatively for anaerobic and aerobic organisms. Twenty five outpatients with peptic ulcer disease were investigated after a 5.7 (0.5) weeks (mean (SEM)) treatment course with 20 mg (nine patients) or 40 mg (16 patients). The control group consisted of 15 outpatients referred for diagnostic endoscopy without prior antisecretory treatment. No patient in the control group had duodenal bacterial overgrowth. In the omeprazole group bacterial overgrowth (> or = 10(5) cfu/ml) was found in 14 (56%) patients (p = 0.0003). The number of bacteria (log10) in duodenal juice in patients treated with omeprazole was distinctly higher (median 5.7; range < 2-8.7) when compared with the control group (median < 2; range < 2-5.0; p = 0.0004). As well as orally derived bacteria, faecal type bacteria were found in seven of 14 and anaerobic bacteria in three of 14 patients. Bacterial overgrowth was similar with the two doses of omeprazole. These results indicate that duodenal bacterial overgrowth of both oral and faecal type bacteria occurs often in ambulatory patients treated with omeprazole. Further studies are needed to determine the clinical significance of these findings, particularly in high risk groups during long term treatment with omeprazole.

Journal ArticleDOI
TL;DR: This article showed that with increased competition resulting from closer economic integration, the hump-shaped pattern summarizing the relationship between economic performance and the degree of centralization in wage bargaining flattens out, and the importance of where a particular economy stands on the wage bargaining scale diminishes.
Abstract: It is widely believed that the integration of European economies will have little impact on labor mobility. This does not mean, however, that European labor markets will be unaffected by the process of economic integration. In this paper, the authors show that, with increased competition resulting from closer economic integration, the hump-shaped pattern summarizing the relationship between economic performance and the degree of centralization in wage bargaining flattens out. As a consequence, the importance of where a particular economy stands on the wage bargaining scale diminishes. Copyright 1994 by Royal Economic Society.

Journal ArticleDOI
TL;DR: It is shown here that membrane attachment is not required for the survival activity of bcl-2 alpha, and evidence is provided for motifs at the NH2 and COOH terminus of bCl-2, which are crucial for its activity.
Abstract: Bcl-2 is a mitochondrial- and perinuclear-associated protein that prolongs the lifespan of a variety of cell types by interfering with programmed cell death (apoptosis). Bcl-2 seems to function in an antioxidant pathway, and it is believed that membrane attachment mediated by a COOH-terminal hydrophobic tail is required for its full activity. To identify critical regions in bcl-2 alpha for subcellular localization, activity, and/or interaction with other proteins, we created, by site-directed mutagenesis, various deletion, truncation, and point mutations. We show here that membrane attachment is not required for the survival activity of bcl-2 alpha. A truncation mutant of bcl-2 alpha lacking the last 33 amino acids (T3.1) including the hydrophobic COOH terminus shows full activity in blocking apoptosis of nerve growth factor-deprived sympathetic neurons or TNF-alpha-treated L929 fibroblasts. Confocal microscopy reveals that the T3 mutant departs into the extremities of neurites in neurons and filopodias in fibroblasts. Consistently, T3 is predominantly detected in the soluble fraction by Western blotting, and is not inserted into microsomes after in vitro transcription/translation. We further provide evidence for motifs (S-N and S-II) at the NH2 and COOH terminus of bcl-2, which are crucial for its activity.

Journal Article
TL;DR: The results demonstrate the possibility of broadening and improving the efficiency of tumor immunophotodiagnosis by coupling to a MAb directed against SCC, a fluorescent dye absorbing and emitting at higher wavelength than fluorescein, and thus having deeper tissue penetration and lower tissue autofluorescence.
Abstract: We have recently shown that immunophotodetection of human colon carcinomas in nude mice and in patients is possible by using anti-carcinoembryonic antigen monoclonal antibodies (MAb) coupled to fluorescein. The most common clinical application of photodiagnosis has been for the detection of squamous cell carcinomas (SCC) in the upper respiratory tract, but the free dyes used have a poor tumor selectivity. We selected the known MAb E48 directed against SCC and coupled it to a fluorescent dye: indopentamethinecyanin (indocyanin). This dye has an advantage over fluorescein in that it emits a more penetrating fluorescent red signal at 667 nm after excitation with a laser ray of 640 nm. In vitro, an conjugate with an indocyanin:MAb molar ratio of 2, and an additional trace labeling with 125I, showed more than 80% of binding to cells from the SCC line A431. In vivo, when injected i.v. into nude mice bearing xenografts of the same carcinoma line, the MAb E48-(indocyanin)2 conjugate was almost as efficient as the unconjugated MAb E48 in terms of specific tumor localization: 15% of the injected dose per g of tumor at 24 h after injection and a tumor:overall normal tissue ratio of 6-8. There was no selective tumor localization of an irrelevant IgG1-(indocyanin)2 conjugate. Immunophotodetection of the s.c. SCC xenografts on mice given injections of 100 micrograms of MAb E48-(indocyanin), conjugate (representing 1 microgram of indocyanin) was performed at 24 h. Upon laser irradiation, clearly detectable red fluorescence from the indocyanin-MAb conjugate was observed specifically in the SCC xenografts across the mouse skin. In comparison, injection of 100 micrograms of a MAb E48 coupled to 2 micrograms of fluorescein gave a specific green fluorescence signal in the tumor xenografts, which was detectable, however, only after removing the mouse skin. Injection i.v. of a 15 times higher amount of free indocyanin (15 micrograms) gave a diffuse red fluorescence signal all over the mouse body with no definite increase in intensity in the tumor, indicating a lack of tumor selectivity of the free dye. The results demonstrate the possibility of broadening and improving the efficiency of tumor immunophotodiagnosis by coupling to a MAb directed against SCC, a fluorescent dye absorbing and emitting at higher wavelength than fluorescein, and thus having deeper tissue penetration and lower tissue autofluorescence. Such a demonstration opens the way to a new form of clinical immunophotodiagnosis and possibly to the development of a more specific approach to phototherapy of early bronchial carcinomas.

Journal ArticleDOI
TL;DR: The biophysical properties, the cell distribution, and the regulation of this channel will be reviewed, with emphasis on its expression in the kidney, colon, and lung, where the clinical implications are most relevant.
Abstract: The highly selective amiloride-sensitive epithelial sodium channel is expressed in the distal part of the nephron, the distal colon, and the lung. It plays a critical role in the control of sodium balance, extracellular volume, blood pressure, and of fluid reabsorption in the lung. The primary structure of the rat epithelial sodium channel has recently been determined. It is a heteromultimeric protein made up of three homologous subunits (alpha, beta, and gamma). The biophysical properties, the cell distribution, and the regulation of this channel will be reviewed, with emphasis on its expression in the kidney, colon, and lung, where the clinical implications are most relevant. The epithelial sodium channel is a member of a novel gene superfamily that encodes cation channels involved in the control of cellular and extracellular volume and in the control of distinct functions such as taste transduction and mechanotransduction.

Journal ArticleDOI
TL;DR: In this paper, an empirical calibration for the quartz-calcite thermometer was derived from measured Δ18O(qz-cc) values from greenschist-facies marbles, veins composed of cogenetic quartz and calcite and various low-grade metamorphic rocks.

Journal ArticleDOI
TL;DR: To identify the phosphorylation sites, the alpha 1-subunit of Bufo marinus is mutated in a highly conservative PKA and in 20 different PKC consensus sequences and serine 943 (Ser-943) was identified as a unique target site for PKA, but none of thePKC consensus serine or threonine residues are implicated in PKC phosphorylated residues.

Journal ArticleDOI
TL;DR: The direct evidence reported here for significant alterations of the discharge properties of auditory neurons in the thalamus and cortex resulting from low dose administration of K and/or P emphasizes difficulties in comparing data derived from experiments conducted in various conditions of anesthesia or in the awake state.

Journal ArticleDOI
TL;DR: It seems that the causal relationship underlying this association is that the number of matings by queens depends on thenumber of queens present in the colony, which supports the GV hypotheses together with the assumption that mating has costs.
Abstract: Several hypotheses have been put forward to explain the adaptive significance of interspecific variation in mating frequencies by eusocial hymenopteran queens. Four of these hypotheses assert that polyandry is advantageous to queens because of the resultant increase in genetic variability within colonies (referred to as the "GV" hypotheses). Here we compare the frequency of polyandry between monogynous (single-queen) and polygynous (multiple-queen) ant species to test the hypotheses that (1) multiple mating functions primarily to increase intracolonial genetic variability, and (2) mating has costs (such as increased energetic losses or risk of predation or venereal disease). If one of the GV hypotheses is true and mating is costly, the frequency of polyandry should be lower in polygynous species (in which the presence of multiple queens results in low relatedness among workers) than in monogynous species. As predicted by the GV hypotheses, polyandry is less common among polygynous than among monogynous species. Furthermore, it seems that the causal relationship underlying this association is that the number of matings by queens depends on the number of queens present in the colony (rather than the number of queens being influenced by the number of matings), which also supports the GV hypotheses together with the assumption that mating has costs.

Journal ArticleDOI
10 May 1994
TL;DR: In this paper, a portable data logger is designed to record body accelerations during human walking, and two neural networks are used to estimate the incline and the speed of walking.
Abstract: A portable data logger is designed to record body accelerations during human walking. Five subjects walk first on a treadmill at various speeds on the level, and at positive and negative inclines. Then, the subjects performed a self-pace walking on an outdoor test circuit involving roads of various inclines. The recorded signals are parameterized, and the pattern of walking at each gait cycle is found. These patterns are presented to two neural networks which estimate the incline and the speed of walking. The results show a good estimation of the incline and the speed for all of the subjects. The correlation between predicted and actual inclines is r=0.98, and the maximum of speed-predicted error is 16%. To the best of our knowledge these results constitute the first speed and incline estimation of level and slope-unconstrained walking. >