Inactivation of tyrosine hydroxylase by nitration following exposure to peroxynitrite and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

The decrement in dopamine levels exceeds the loss of dopaminergic neurons in Parkinson’s disease (PD) patients and experimental models of PD. This discrepancy is poorly understood and may represent an important event in the pathogenesis of PD. Herein, we report that the rate-limiting enzyme in dopamine synthesis, tyrosine hydroxylase (TH), is a selective target for nitration following exposure of PC12 cells to either peroxynitrite or 1-methyl-4-phenylpyridiniun ion (MPP+). Nitration of TH also occurs in mouse striatum after MPTP administration. Nitration of tyrosine residues in TH results in loss of enzymatic activity. In the mouse striatum, tyrosine nitration-mediated loss in TH activity parallels the decline in dopamine levels whereas the levels of TH protein remain unchanged for the first 6 hr post MPTP injection. Striatal TH was not nitrated in mice overexpressing copper/zinc superoxide dismutase after MPTP administration, supporting a critical role for superoxide in TH tyrosine nitration. These results indicate that tyrosine nitration-induced TH inactivation and consequently dopamine synthesis failure, represents an early and thus far unidentified biochemical event in MPTP neurotoxic process. The resemblance of the MPTP model with PD suggests that a similar phenomenon may occur in PD, influencing the severity of parkisonian symptoms.

II. Benjamin Wadsworth's Index to College Books 1-6, created ca. 1736

This paper-bound index was created by Benjamin Wadsworth, probably around 1736. Although most entries are in his hand, additional entries have been made in other, unidentified hands. It is arranged alphabetically, though the keywords used to alphabetize topics are not always logical or intuitive. Each entry lists the College Book and page number where information on the given topic can be found.

List of books believed to be bequest of Thomas Hubbard, undated

A pencilled annotation in the hand of John Langdon Sibley reads: "Is not this the bequest of Thos. Hubbard in 1773-4." Thomas Hubbard, who served as Harvard's treasurer and as Commissary General of the Province of Massachusetts Bay, died in 1773.

II. Benjamin Wadsworth's Index to College Books 1-6, created ca. 1736

This paper-bound index was created by Benjamin Wadsworth, probably around 1736. Although most entries are in his hand, additional entries have been made in other, unidentified hands. It is arranged alphabetically, though the keywords used to alphabetize topics are not always logical or intuitive. Each entry lists the College Book and page number where information on the given topic can be found.

Winthrop, John, 1606-1676, autographed letter signed (copy) to Richard Odell; Pequot, Conn., 1 side (4 pages), 1652 November 27

Copy of correspondence responding to a November 16, 1652, letter from Odell regarding his daughter's illness, which Winthrop speculates is hemiplegia. According to Winthrop, "The cure depends upon the knowledge of the right cause, and not only that but the constand and due aplication of such things as may conduce them thereto, which is difficult to doe at a distance." Winthrop further writes that he did not at present have medicine to send for her condition, but recommends "some general things that might be helpfull." These included keeping the child warm with fox or rabbit furs, an ointment consisting of herbs, wax, castor oil, worm grease, fox grease, or an ointment of balsam. Winthrop writes he has sent an ointment, but does not specify its ingredients. His other suggestions for treatment include cupping without scarification, and an decoction containing sarsaparilla, guaiacum, and spirit of rosemary.

A catalogue of books relating to the discovery and early history of North and South America : forming a part of the library of E.D. Church /

Edition of 100 copies.

Classified list of books added to the circulating department of the ... library. Jan. 1, 1896 - July 1, 1900.

Mode of access: Internet.

General catalogue of mariners' charts and books : Cor. to April 1, 1919 /

Includes tables.

Index of the Rolls of honor (ancestor's index) in the Lineage books of the National society of the Daughters of the American revolution, volumes 1 to 160.

Vol. [2] has imprint: Washington, D.C., Press of Judd & Detweiler, inc., 1926.

Railroad employment protection : hearing[s] before a subcommittee of the Committee on Interstate and Foreign Commerce, House of Representatives, Seventy-fourth Congress, second session, on H.R. 11609, to foster and protect interstate commerce by authorizing the Interstate commerce commission to approve or disapprove of the consolidation or abandonment of carrier facilities of public service. March 30, 31, April 1 and 4, 1936.

Printed for the use of the Committee on interstate and foreign commerce.