Molecular determinants of drug access to the receptor site for antiarrhythmic drugs in the cardiac Na+ channel.

The clinical efficacy of local anesthetic and antiarrhythmic drugs is due to their voltage- and frequency-dependent block of Na+ channels. Quaternary local anesthetic analogs such as QX-314, which are permanently charged and membrane-impermeant, effectively block cardiac Na+ channels when applied from either side of the membrane but block neuronal Na+ channels only from the intracellular side. This difference in extracellular access to QX-314 is retained when rat brain rIIA Na+ channel alpha subunits and rat heart rH1 Na+ channel alpha subunits are expressed transiently in tsA-201 cells. Amino acid residues in transmembrane segment S6 of homologous domain IV (IVS6) of Na+ channel alpha subunits have important effects on block by local anesthetic drugs. Although five amino acid residues in IVS6 differ between brain rIIA and cardiac rH1, exchange of these amino acid residues by site-directed mutagenesis showed that only conversion of Thr-1755 in rH1 to Val as in rIIA was sufficient to reduce the rate and extent of block by extracellular QX-314 and slow the escape of drug from closed channels after use-dependent block. Tetrodotoxin also reduced the rate of block by extracellular QX-314 and slowed escape of bound QX-314 via the extracellular pathway in rH1, indicating that QX-314 must move through the pore to escape. QX-314 binding was inhibited by mutation of Phe-1762 in the local anesthetic receptor site of rH1 to Ala whether the drug was applied extracellularly or intracellularly. Thus, QX-314 binds to a single site in the rH1 Na+ channel alpha subunit that contains Phe-1762, whether it is applied from the extracellular or intracellular side of the membrane. Access to that site from the extracellular side of the pore is determined by the amino acid at position 1755 in the rH1 cardiac Na+ channel.

Sobre la utilidad, seguridad y suavidad de la inoculación (1779). Discurso de Timoteo O'Scanlan (1726-1795) en la Real Academia de Medicina

Reconocido como una de las figuras clave en la difusión de la inoculación contra la viruela en España, el médico de origen irlandés Timoteo O'Scanlan dejó publicadas 3 obras y numerosos artículos de prensa en los que plasmó su pericia e interés por una práctica que se inició de forma tardía en nuestro país. Aceptado como miembro de la Real Academia Médica de Madrid en noviembre de 1778, leyó su discurso de ingreso en abril de 1779. El texto, que constituye la primera aproximación de O'Scanlan a la inoculación, que venía practicando con éxito desde 1771, fue incluido con algunas modificaciones y sin citar la fecha de redacción en la introducción de su primera obra, Práctica moderna de la inoculación (1784). El manuscrito se encuentra en el Archivo del Conde de Campomanes (Fundación Universitaria Española, Madrid).

"Certificate respecting the Rev. John Seccombe," 1795 August

One leaf (pages 301-302) of the August, 1795 issue of Massachusetts Magazine with an editorial regarding the authorship of Father Abbey's Will. The article identifies John Seccombe as the author based on information provided by "Thaddeus Mason, Esq. of Cambridge, the only surviving classmate, and very intimate friend of the Rev. John Seccombe."

Letter from William Croswell to Dr. Dingley, 1795 July 9

One-page letter from Croswell to Dr. Dingley in New York City, requesting information on teaching opportunities in the area.

Note from William Croswell to Mrs. Crocker, [1795] July 30

Note regarding the return of Mrs. Crocker's books.

Financial bills and receipts, 1795

This folder contains three receipts.

Plan for arranging library catalogues,1795-1800; 1822

This paper notebook contains six pages of financial entries made by Croswell between 1795 and 1800, followed by a bibliographical plan for the arrangement of the Harvard College Library, dated September 1822.

Notes about cases heard as Justice of the Peace, 1784-1795

This small paper-bound notebook contains notes Winthrop made concerning the cases he heard between 1784 and 1795 as a Justice of the Peace for Middlesex County. These notes provide insight into the nature of crimes being committed in Cambridge in the post-Revolutionary period, as well as the names and occupations of those accused and their victims. The cases involved the following individuals, among others: Samuel Bridge, Benjamin Estabrook, Joseph Jeffords, Cato Bordman, John Kidder, Spenser Goddin, Jacob Cromwell, Benjamin Stratton, Mary Flood, Bender Temple, John Willett, Joseph Hartwell, Nathaniel Stratton, Amos Washburn, Francis Moore, Thomas Malone, Thomas Cook, and Amboy Brown. The cases involved a range of offenses, and occasionally Winthrop decided that a case exceeded his jurisdiction and forwarded it to the General Court or the Supreme Judicial Court.