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Tions produced during trains of action potentials or voltage clamp pulses. The extent to which use-dependent block accumulates and is enhanced by increasing the amplitude of the depolarizing pulses is influenced partly by the voltage dependent component of the block, and can be described as the "voltage dependence" of use-dependent block. Many aspects of the nature of use-dependent block are not yet clarified. The voltage dependence of use-dependent block has been studied extensively in nerve membranes. Strichartz 1973 ; and Cahalan 1978 ; demonstrated that the strength of the block of Na current by local anesthetics can increase e-fold per 28-mV increase in the amplitude of membrane depolarization. This voltage dependence could arise in two ways: directly in that the electric field may affect the migration of drug molecules to their binding sites, or indirectly if either drug access or binding to the channel blocking site is influenced by the voltage dependence of the activation and or inactivation of the channel gating Hille, 1977; Cahalan, 1978; Starmer et al., 1984 ; . However, the voltage dependence of block is not always consistent with either of these possibilities. In addition, the slope and midpoint of the voltage dependence can be influenced by molecular structure and physico-chemical properties of the blocker Yeh, 1980; Wang et al., 1982 ; . Current flowing through Na channels can also modify the voltage dependence Cahalan and Shapiro, 1976; Shapiro, 1977; Cahalan and Almers, 1979a, b; Seyama et al., 1980; Yeh and Vijverberg, 1981 ; . Therefore, the structural and physical requirements of the molecule necessary to produce this dependence remain to be fully clarified. The dissipation of block during the resting phase after membrane repolarization usually is slower than the accumulation process and varies from several seconds to several minutes depending on the blocking molecule. Factors important in determining the time course of recovery such as molecular weight or size ; Courtney, 1980; Sada and Ban, 1980; Campbell, 1983 ; , lipid solubility Hille, 1977 ; , and stereo-specificity and the distribution of the molecule's charged groups have been recognized Yeh, 1980, 1982 ; . However, the structure-activity relationships of these factors have not yet been explored systematically. Using Norlace and 14 closely related derivatives, we investigated some of the physico-chemical and structural properties of molecules that can affect the use-dependent block of Na currents in voltage clamped, perfused squid giant axons internally exposed to these compounds. Use-dependent block was indeed found to be structure-dependent. Drug molecules with higher degrees of hydrophobicity exhibited only voltage dependent block; the voltage dependence parelleled that for channel activation, and removal of the inactivation process did not alter the character of the use-dependence of block. Drug molecules with lesser degrees of hydrophobicity showed current dependencies making the voltage dependence of block less steep in the range of membrane potential where inward Na current.

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Chairman, Indoor Air Quality Session, HAZMAT WEST Convention, Long Beach, California, November 8, 1990. "The Diagnosis and Treatment of Asthma and Allergies in Pregnancy", Sharp Memorial Hospital, ObstetricsGynecology Grand Rounds, December 13, 1990. "The Diagnosis and Treatment of Urticaria, Angioedema, and Anaphylaxis", Grand Rounds, Maui Memorial Hospital, Wailuku, Maui, Hawaii, December 28, 1990. "The Diagnosis and Treatment of Asthma and Allergies", Hilo Medical Society, Hilo, Hawaii, Hawaii, January 3, 1991. "The Effect of Asthma and Allergies on Childhood Performance", Pediatric Grand Rounds, Kapialani Medical Center, Honolulu, Oahu, Hawaii, January 7, 1991. Moderator, Postgraduate Education Course at the 1991 Annual American Academy of Allergy & Immunology Meeting, San Francisco: "The Relationship of the Indoor Environment to Health and Disease". "Impact of the Indoor Environment on Health", Annual American Academy of Allergy & Immunology Meeting, San Francisco, March 2, 1991. "Impact of the Indoor Environment on Health", International Facility Management Association, San Diego Chapter, March 13, 1991. "Latest Trends in the Pharmacotherapy of Allergic Rhinitis", Latter Day Saints Hospital, Salt Lake City, Utah, March 29, 1991. "Urticaria, Angioedema, and Anaphylaxis", St. Elizabeth's Hospital, Brighton, Massachusetts, August 22, 1991. "Advances in Allergy: Developments in Diagnosis and Management", Pacific Science Center, Seattle, Washington, October 12, 1991. "Novel Approaches for Treating Allergies & Asthma", Mission Bay Hospital, San Diego, February 20, 1992. Moderator of the session entitled "Antihistamines & Rhinitis" at meeting in Dana Point, California on "Cases in Allergy", February 20-21, 1992. Section 1. Eligible Employees Employees eligible for the Package are those active Boeing employees represented by one of the following International Association of Machinists and Aerospace Workers, AFL-CIO, Collective Bargaining Agreements: Aerospace Industrial District Lodge No. 751, District Lodge No. 70 and District Lodge No. 24. The employee is not eligible to enroll if he or she is working in a capacity that, at the sole discretion of the Plan Administrator, is considered contract labor or independent contracting. Section 2. Eligible Dependents Dependents eligible for the medical and dental plans are the employee's legal spouse and children natural children, adopted children, children legally placed with the employee for adoption and stepchildren ; who are under age 25, unmarried, and dependent on the employee for principal support, including children who are attending school. An employee may request coverage for the following dependents: 1. 2. A common-law spouse if the relationship meets the common-law requirements for the state in which the employee entered into the common-law relationship. A same-gender domestic partner if the employee and same-gender domestic partner meet all of the following requirements. The employee and partner must be: a. Of the same gender.

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