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CD23, the low-affinity IgE receptor, is up-regulated on interleukin (IL)-4-stimulated B cells and monocytes, with a concomitant increase in the release of soluble fragments of CD23 (sCD23) into the medium by proteolytic processing of the surface-bound intact CD23. The effect of inhibition of the processing of CD23 on IgE production in human and mouse cells and in a mouse model in vivo was evaluated. CD23 processing to sCD23 from RPMI 8866 (a human Epstein-Barr virus-transformed B cell line) cell membranes was inhibited by a broad-spectrum matrix-metalloprotease inhibitor, batimastat, with an IC50 of 0.15 microM. Batimastat also inhibited CD23 processing in whole RPMI 8866 cells as well as in IL-4-stimulated purified human monocytes with similar IC50. Batimastat inhibited IgE production from IL-4/anti-CD40-stimulated human tonsil B cells as well as mouse splenic B cells in a manner consistent with inhibition of CD23 processing. Release of soluble fragments of CD23 in the cell supernatants of tonsil B cells was inhibited over the concentration range of 1-10 microM batimastat and intact cell surface CD23 was increased on mouse splenic B cells in the presence of these concentrations of batimastat. IgE production of IL-4-stimulated human peripheral blood mononuclear cells was also blocked by 1-10 microM batimastat, again with comparable inhibition of sCD23 release over the same concentration range. Finally, in a mouse model of IgE production, batimastat inhibited IgE production in response to ovalbumin challenge as determined by serum IgE levels. Taken together, the data support a role of CD23 in IgE production and point to CD23 processing to sCD23 as a therapeutically relevant control point in the regulation of IgE synthesis.

The material below has been excerpted from Alfred Kazin's journals now held in the Berg Collection of the New York Public Library. Kazin, who has always regarded his journal writing as indispensable to his work as writer and critic, has described his journal variously as: a "private lie-detector," a "way of ascertaining authenticity" (26 Sept. 1966), a "place where one can turn an idea over for its own sake alone-where one can talk to oneself in perfect privacy of heart" (23 Jan. 1950), a place to discover "the inner voice [. . .] the soundness of the private personality as against the innumerable temptations to facility, convention and untruth" (16 Sept. 1956), "a new way of seeing" (25 May 1976). In a 1963 interview Kazin cited his journal as his "great resource as a writer," "a travel report into my thought and experience," a necessary exercise "for getting at my thought about anything and everything" (103). More recently he has credited his journal writing for his success in moving beyond literary criticism to "personal history," an autobiographical "form of my own," whose "passion and beat come from my life in history recorded since I was a boy ... in a voluminous daily journal or sketchbook into which went everything that I felt like describing and thinking about" (Contemporaries 412; "The Past" 4). Yet, Kazin insists, the greatest value of his journal has always been the sheer private pleasure of adding to it. "What I liked most about this intimate record was writing in it, first thing in the morning, in complete spontaneity and naturalness, lifelike and at the quick, as the French say. It represented some effort to think my life out. It also got me away from editors and their subjective dogmas of public taste and capacity; this, at least, was all for myself' ("The Past" 4).

A graphical computer based upon five automatic curve followers, two integrators, nine adding amplifiers, and a pen recorder was built for the transformation and combination of curves and for a simple analog computer to plot curves from equations. Heavily inked curves on 14‐in. × 17‐in. moving tables are tracked by photoelectric followers which continuously set potentiometers so that their output voltage is proportional to the curve height. The tables are positioned by voltages so that they may be made to move at a constant rate or may be individually controlled by some variable voltage. The follower output voltages may be transformed in various ways or combined algebraically with each other and used directly or indirectly through amplifiers to drive a recorder, a table, or an integrator. By this means curves may be changed in scale (linearly or nonlinearly) on either axis. Curves may be added, subtracted, multiplied, divided, or otherwise combined or operated upon in accordance with simple equations, and the result plotted in about a minute with an accuracy under favorable conditions of about ±0.02 in. Complex curves can be analyzed by fitting with algebraic combinations of simpler curves. The apparatus may be used to fit integral or differential equations to experimental data by trial adjustment of the constants. A low ac voltage increasing linearly with time represents the independent variable; the form of the equation is determined by the way in which the various units are connected and the values of constants are set by potentiometers.

Two fragment pools, one of MW > 10 000 and the other of MW between 1 000 and 10 000, were prepared by the sequential treatment of rye grass pollen extract with cyanogen bromide (cleavage at Met-X) and 2-nitro-5-thiocyanobenzoic acid (cleavage at X-Cys). Electrophoretic analysis of the two pools showed that none of the major components of the whole extract remained intact. Characterisation of the two fragment pools by radioimmunoassay showed that whilst they both lost the ability to bind to human anti-rye IgE antibodies, they largely retained their reactivity towards both human and mouse anti-rye IgG antibodies. In addition, the higher molecular weight pool retained its ability to stimulate extract-specific T cells, after accessory cell processing. This separation of the immunological properties of rye grass pollen extract by chemical cleavage is seen as a basis for the development of novel immunotherapy agents.