Proton Inhibition of Sodium Channels: Mechanism of Gating Shifts and Reduced Conductance

Extracellular acidosis affects both permeation and gating of the expressed rat skeletal muscle Na⁺ channel (μ1). Reduction of the extracellular pH produced a progressive decrease in the maximal whole-cell conductance and a depolarizing shift in the whole-cell current-voltage relationship. A smaller depolarizing shift in the steady-state inactivation curve was observed. The pK of the reduction of maximal conductance was 6.1 over the pH range studied. An upper limit estimate of the pK of the shift of the half-activation voltage was 6.1. The relative reduction in the maximal whole-cell conductance did not change with higher [Na⁺] _o . The conductance of single fenvalerate-modified Na⁺ channels was reduced by extracellular protons. Although the single-channel conductance increased with higher [Na⁺] _o , the maximal conductances at pH 7.6, 7.0 and 6.0 did not converge at [Na⁺] _o up to 280 mm, inconsistent with a simple electrostatic effect. A model incorporating both Na⁺ and H⁺ binding in the pore and cation binding to a Gouy-Chapman surface charge provided a robust fit to the single-channel conductance data with an estimated surface charge density of 1e⁻/439?². Neither surface charge nor proton block alone suffices to explain the effects of extracellular acidosis on Na⁺ channel permeation; both effects play major roles in mediating the response to extracellular pH. Received: 14 May 1996/Revised: 19 September 1996     

Neurological and electroencephalographic changes in newborns treated with prostaglandins E2 and E2

Six newborns with obstructive right heart lesions were examined neurologically and electroencephalographically during treatment with prostaglandin (PG) E₁ or E₂ given to maintain patency of the ductus arteriosus and to increase pulmonary blood flow. PG was administered intravenously or intraarterially in the aortic isthmus proximal to the ductus arteriosus. Besides a rise in arterial oxygen saturation, all patients had some sign of central nervous system involvement. The electroencephalogram showed minor changes suggestive of sedation. In addition, three patients in whom PG given intravenously presented various combinations of neurological abnormalities (“myoclonic jerks”, apnoeic spells, hiccup) of subcortical origin. Side-effects subsided after stopping the treatment anf posed no problem in the management of the patients. These findings confirm the usefulness and safety of the PG therapy and indicate that the intraaortic route of administration is preferable.     

Delayed hypersensitivity and Ig level in 210 patients with chronic myeloid leukemia

Summary Serum immunoglobulin concentration and skin reactivity to at least three recall antigens were determined in 210 patients with chronic myeloid leukemia (CML). Immunoglobulin concentration was normal in the great majority of the patients. Skin tests were negative in 50 of 210 cases (24%). No relationship could be demonstrated between skin reactivity, age, time since diagnosis, WBC, lymphocyte count, and splenectomy. Prior antileukemic therapy was a major factor in determining the response to skin tests.S. Tura (Chairman) and M. Baccarani (Secretary), Cattedra di Ematologia dell'Università e Servizio di Ematologia dell'Ospedale S. Orsola, Bologna; G. de Sandre, G. Perona, G. Cetto, G. Pizzolo, Istituto di Patologia Medica e Cattedra di Ematologia dell'Università, Verona; P. Rambotti, B. Falini, Clinica Medica dell'Università, Perugia; T. Chisesi, G. Capnist, Divisione di Ematologia, Ospedale Civile, Vicenza; A. Cajozzo, P. Citarella, Cattedra di Ematologia dell'Università, Palermo; G. Broccia, Sezione di Ematologia, Ospedale Armando Businco, Cagliari; V. Liso, G. Troccoli, Clinica Medica II dell'Università, Bari; L. Bruzzese, G. Nappi, A. Abbadessa, Clinica Medica (I Facoltà) dell'Università, Napoli; A. Porcellini, C. Delfini, Divisione di Ematologia, Ospedali Riuniti, Pesaro; E. Cacciola, R. Giustolisi, R. Musso, V. Raimondi, Cattedra di Ematologia dell'Università, Catania; G. Torlontano, L. Geraci, Cattedra di Ematologia dell'Università, Chieti, e Divisione di Ematologia, Ospedale Civile, Pescara; F. Mandelli, G. Mariani, B. Monarca, N. Petti, Cattedra di Ematologia dell'Università, Roma; R. di Guglielmo, A. Miliani, Clinica Medica dell'Università, Firenze; C. Bernasconi, M. Lazzarino, G. Castelli, Divisione di Ematologia, Ospedale S. Matteo, Pavia; A. Alberti, S. Magro, Servizio di Ematologia, Ospedale Generale Regionale, Catanzaro; A. Neri, P. Iacopino, Divisione di Ematologia, Ospedali Riuniti, Reggio Calabria; R. Delsignore, M. C. Baroni, Istituto di Patologia Medica dell'Universita, Parma; E. Bajetta, S. Monfardini, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano; S. Tognella, Istituto Scientifico di Medicina Interna, Cattedra di Clinica Medica 2R, Università, Genova.     

Chromosome constitution of in vitro segregated haploid and diploid cells of the mouse

The composition in segregated haploid sets of paternal and maternal chromosomes has been studied in order to verify whether their composition is uniparental of mixed, fixed or variable. Primary cultures where prepared using kidneys from hybrids of strains of Mus musculus in which the parental chromosomes are distinguishable; the maternal set consists of 20 teleocentric chromosomes, the paternal set of 9 metacentric chromosomes, derived by Robertsonian fusion and 2 telocentrics. Applying Seabright's banding technique, an analysis of segregated haploid and diploid cells, which have originated spontaneously through polyploidisation-segregation processes was carried out. It was concluded that the haploid sets have a variable composition of paternal and maternal chromosomes.     

« Spirulina labyrinthiformis » Gomont: prima segnalazione nelle Terme di Segesta (Sicilia)

Abstract

First report of the presence of Spirulina labyrinthiformis Gomont in Thermae of Segesta (Sicily). – The study on the algal ecology of thermal waters in Segesta shows for the first time the occurrence of Spirulina labyrinthiformis Gomont. It is interesting to note the high population density of Spirulina against the other components of the algal microflora, represented by the species of Cyanophyceae and Bacillariophyceae and that of photosynthetic bacteria.     

Micro‐ and nano‐scale mineralogical characterization of Fe(II)‐oxidizing bacterial stalks

Neutrophilic, microaerobic Fe(II)‐oxidizing bacteria (FeOB) from marine and freshwater environments are known to generate twisted ribbon‐like organo‐mineral stalks. These structures, which are extracellularly precipitated, are susceptible to chemical influences in the environment once synthesized. In this paper, we characterize the minerals associated with freshwater FeOB stalks in order to evaluate key organo‐mineral mechanisms involved in biomineral formation. Micro‐Raman spectroscopy and Field Emission Scanning Electron Microscopy revealed that FeOB isolated from drinking water wells in Sweden produced stalks with ferrihydrite, lepidocrocite and goethite as main mineral components. Based on our observations made by micro‐Raman Spectroscopy, field emission scanning electron microscopy and scanning transmission electron microscope combined with electron energy‐loss spectroscopy, we propose a model that describes the crystal‐growth mechanism, the Fe‐oxidation state, and the mineralogical state of the stalks, as well as the biogenic contribution to these features. Our study suggests that the main crystal‐growth mechanism in stalks includes nanoparticle aggregation and dissolution/re‐precipitation reactions, which are dominant near the organic exopolymeric material produced by the microorganism and in the peripheral region of the stalk, respectively.     

Gene Expression Analysis of PTEN Positive Glioblastoma Stem Cells Identifies DUB3 and Wee1 Modulation in a Cell Differentiation Model

The term astrocytoma defines a quite heterogeneous group of neoplastic diseases that collectively represent the most frequent brain tumors in humans. Among them, glioblastoma multiforme represents the most malignant form and its associated prognosis is one of the poorest among tumors of the central nervous system. It has been demonstrated that a small population of tumor cells, isolated from the brain neoplastic tissue, can reproduce the parental tumor when transplanted in immunodeficient mouse. These tumor initiating cells are supposed to be involved in cancer development and progression and possess stem cell-like features; like their normal counterpart, these cells remain quiescent until they are committed to differentiation. Many studies have shown that the role of the tumor suppressor protein PTEN in cell cycle progression is fundamental for tumor dynamics: in low grade gliomas, PTEN contributes to maintain cells in G1 while the loss of its activity is frequently observed in high grade gliomas. The mechanisms underlying the above described PTEN activity have been studied in many tumors, but those involved in the maintenance of tumor initiating cells quiescence remain to be investigated in more detail. The aim of the present study is to shed light on the role of PTEN pathway on cell cycle regulation in Glioblastoma stem cells, through a cell differentiation model. Our results suggest the existence of a molecular mechanism, that involves DUB3 and WEE1 gene products in the regulation of Cdc25a, as functional effector of the PTEN/Akt pathway.