John F. Flanagan

The yeast SWI/SNF complex is required for expression of many genes and for the full functioning of several transcriptional activators. Genetic and biochemical studies indicate that SWI/SNF uses the energy of ATP hydrolysis to antagonize chromatin-mediated transcriptional repression. We have tested the possibility that SWI/SNF might also play a role in DNA replication. A mitotic minichromosome stability assay was used to investigate the replication efficiency of a variety of autonomous replication sequences (ARSs) in the presence and absence of SWI/SNF. The stability of minichromosomes that contain ARS1, ARS309 or ARS307 is not altered by lack of SWI/SNF, whereas the functioning of ARS121 is crippled when SWI/SNF is inactivated. The SWI/SNF dependence of ARS121 does not require the replication enhancer factor, ABF1, and thus, it appears to be a property of a minimal ARS121 origin. Likewise, a minimal derivative of ARS1 that lacks the ABF1 replication enhancer acquires SWI/SNF dependence. Replacing the ABF1 binding site at ARS1 with a binding site for the LexA-GAL4 chimeric activator also creates a SWI/SNF-dependent ARS. Our studies suggest that the SWI/SNF chromatin remodeling complex can play a role in both replication and transcription and, furthermore, that SWI/SNF dependence of ARS elements is a property of both an ARS-specific replication enhancer and the overall organization of ARS sequence elements.

Anterior cruciate ligament (ACL) reconstruction is associated with significant postoperative pain, usually requiring parenteral narcotics. A prospective study of arthroscopically assisted autograft patellar tendon ACLR was initiated using Winnie's "three-in-one" femoral nerve block (FNB) as the primary means of postoperative pain control. Patient satisfaction and absence of parenteral narcotic use indicated clinical success. Of 24 patients studied, 92% had no parenteral narcotics administered following FNB. Ninety-five percent of patients believed FNB was beneficial and would request another. The average duration of pain control was 29 hours and the majority of patients (79%) believed discharge was possible within 23 hours. There were two patients who failed to respond to FNBs (8%) and no major complications. FNB is a safe, reliable, and effective form of analgesia following ACLR, eliminating the need for parenteral narcotics.

The role of the gastrointestinal tract as a major source of blood ammonia has been extensively studied in animals and in patients with liver dis-ease. Less information is available concerning the relative contribution to the blood ammonia by other organs, such as muscle, liver, brain and kid-ney, which are known to be concerned with am-monia metabolism (1). The renal release of am-monia into the systemic circulation was first demonstrated by the observations of Nash and Benedict in 1921 (2). Although the magnitude of this ammonia release and its effect on the arterial ammonia concentration have not been determined, factors affecting the quantity of ammonia excreted into urine have engendered considerable investiga-tion. Current evidence indicates that changes in urine pH are important determinants of urinary ammonia excretion, lesser amounts of ammonia appearing in alkaline than in acid urines (3-8). Studies in unilaterally nephrectomized dogs sug-gest that total renal ammonia production may re-main unchanged following acute alterations in urine pH (9). Of particular interest in this re-gard have been the observations of significant in-creases in arterial ammonia concentrations of cir-rhotic patients given Diamox (acetazolamide) (10-12), an agent which is known to increase urine pH. The present investigation is concerned with the release of ammonia into the renal vein of patients with liver disease, with particular empha-sis on the effect of intravenous acetazolamide. METHODS Eleven patients with liver disease were studied. All were hospitalized males, ranging in age from 32 to 63 * This investigation was supported (in part) by a re-