New insights into the pharmacokinetics and pharmacodynamics of natalizumab treatment for patients with multiple sclerosis, obtained from clinical and in vitro studies.

BACKGROUND The monoclonal antibody natalizumab (NAT) inhibits the migration of lymphocytes throughout the blood-brain barrier by blocking very late antigen (VLA)-4 interactions, thereby reducing inflammatory central nervous system (CNS) activity in patients with multiple sclerosis (MS). We evaluated the effects of different NAT treatment regimens. METHODS We developed and optimised a NAT assay to measure free NAT, cell-bound NAT and VLA-4 expression levels in blood and cerebrospinal fluid (CSF) of patients using standard and prolonged treatment intervals and after the cessation of therapy. RESULTS In paired CSF and blood samples of NAT-treated MS patients, NAT concentrations in CSF were approximately 100-fold lower than those in serum. Cell-bound NAT and mean VLA-4 expression levels in CSF were comparable with those in blood. After the cessation of therapy, the kinetics of free NAT, cell-bound NAT and VLA-4 expression levels differed. Prolonged intervals greater than 4 weeks between infusions caused a gradual reduction of free and cell-bound NAT concentrations. Sera from patients with and without NAT-neutralising antibodies could be identified in a blinded assessment. The NAT-neutralising antibodies removed NAT from the cell surface in vivo and in vitro. Intercellular NAT exchange was detected in vitro. CONCLUSIONS Incorporating assays to measure free and cell-bound NAT into clinical practice can help to determine the optimal individual NAT dosing regimen for patients with MS.

A domestic priority [microform] : overcoming family poverty in America : hearing before the Select Committee on Children, Youth, and Families, House of Representatives, One Hundredth Congress, second session, hearing held in Washington, DC, September 22, 1988.

CIS Microfiche Accession Numbers: CIS 89 H961-13

Latchkey children [microform] : hearing before the Subcommittee on Education and Health of the Joint Economic Committee, Congress of the United States, One Hundredth Congress, second session, March 11, 1988.

CIS Microfiche Accession Numbers: CIS 89 J841-13

Literature review on recent international activity in cooperative vehicle-highway automation systems /

This literature review supports the report, Recent International Activity in Cooperative Vehicle-Highway Automation Systems. It reviews the published literature in English dating from 2007 or later about non-U.S.-based work on cooperative vehicle-highway automation systems. This review covers work performed in Europe and Japan, with application to transit buses, heavy trucks, and passenger cars. In addition to fully automated driving of the vehicles (without human intervention), it also covers partial automation systems, which automate subsets of the total driving process. Recent International Activity in Cooperative Vehicle Highway Automation Systems is published separately as FHWA-HRT-12-033.

Leached zone : dissolution of values using heat treated feeds /

"U.S. AEC Contract AT(49-1)-545."

Manual de teoría y práctica notarial /

Contiene: T. I (XII, 13-543 p.)

Collection complète des ouvrages : publiés sur le gouvernement représentatif et la constitution actuelle de la France, formant une espèce de cours de politique constitutionelle /

Pie de imp. v.7-8: Paris : Béchet aîné ; Rouen : Béchet fils, 1820 (Imprimerie de J.-L- Chanson)

Latin American Seminar on the Prevention of Crime and the Treatment of Offenders, Rio de Janeiro, 6 to 19 April 1953.

"United Nations publications. Sales number: 1954.iv.3."

Studies of inheritance in rabbits,

"Contributions from the Zoölogical laboratory of the Museum of comparative zoölogy at Harvard college. E. L. Mark, director. no. 199."

Nouveau manuel complet du cultivateur français : ou L'art de bien cultivier les terres, de soigner les bestiaux et de retirer des unes et des autres le splus de bénéfices possibles /

Contiene: T. I (XI, 13-295 p.) -- T. II (276 p., 2 h. de lám. pleg.)

Annual report /

"Developed in cooperation with the U. S. Small Business Administration and the Illinois Department of Commerce and Community Affairs as a service to small businesses under cooperative agreement #SB-2M-00097-13."--Cover p. [4].

Business assistance directory for minority, women and disabled business owners.

"Developed in cooperation with the U. S. Small Business Administration and the Illinois Dept. of Commerce and Community Affairs as a service to small businesses under cooperative agreement #SB-2M-00097-13."--Cover p. [4].

A discourse on the duty of sustaining the laws occasioned by the burning of the Ursuline Convent : delivered at the First Church in Medford, Sunday, August 24, 1834 /

"Published by request."

A statement of the penal laws, which aggrieve the Catholics of Ireland: with commentaries. In two parts.

The table of contents of pt. 1 is for another edition, with xviii, xii, [13]-148 p.

Samlade skrifter /

Edited by John Lindquist.