Two-domain structure of the td intron-encoded endonuclease I-TevI correlates with the two-domain configuration of the homing site.

I-TevI, the T4 td intron-encoded endonuclease, catalyzes the first step in intron homing by making a double-strand break in the intronless allele within a sequence designated the homing site. The 28 kDa enzyme, which interacts with the homing site over a span of 37 bp, binds as a monomer, contacting two domains of the substrate. In this study, limited proteolysis experiments indicate that I-TevI consists of two domains that behave as discrete physical entities as judged by a number of functional and structural criteria. Overexpression clones for each domain were constructed and the proteins were purified. The carboxy-terminal domain has DNA-binding activity coincident with the primary binding region of the homing site and binds with the same affinity as the full-length enzyme. The isolated amino-terminal domain, contains the conserved GIY-YIG motif, consistent with its being the catalytic domain. Furthermore, site-directed mutagenesis of a conserved arginine residue within the extended motif rendered the full-length protein catalytically inactive, although DNA-binding was maintained. This is the first evidence that the GIY-YIG motif is important for catalytic activity. An enzyme with an N-terminal catalytic domain and a C-terminal DNA-binding domain connected by a flexible linker is in accord with the bipartite structure of the homing site.

Inhibition of renal brush border phosphate transport and stimulation of renal gluconeogenesis by cyclic amp and parathyroid hormone.

The aims of the study were to determine whether 8-bromo-cyclic AMP (8BcAMP) in vivo mimics the inhibitory action of parathyroid hormone (PTH) on phosphate transport across the brush border membrane (BBM) of the renal proximal tubule, and to examine whether changes in BBM transport are accompanied by changes in the rate of renal gluconeogenesis. Thyroparathyroidectomized dogs were anesthetized and equilibrated, and control urine collections were obtained prior to removing the left kidney. Subsequent intravenous infusion of 8BcAMP at 50 mg/hr for 2 hr increased fractional excretion of phosphate from 4 +/- 1 (controls) to 29 +/- 4% (P less than 0.001) without changing glomerular filtration. In BBM vesicles isolated from the renal cortex, the initial Na+-dependent transport of phosphate was decreased from 747 +/- 135 (controls) to 564 +/- 126 pmoles per mg per 0.25 min after 8BcAMP (P less than 0.025), but Na+-independent phosphate uptake and Na+-dependent L-proline uptake were not changed significantly. Renal gluconeogenesis in the same animals was increased from 2.5 +/- 0.3 (controls) to 5.3 +/- 0.5 mumoles glucose per g tissue per hr after infusion of 8BcAMP (P less than 0.001). Infusion of PTH, like 8BcAMP, inhibited BBM phosphate transport and stimulated renal gluconeogenesis. We conclude that the inhibitory action of cyclic AMP and PTH on BBM phosphate transport is accompanied by stimulation of gluconeogenesis which suggests, indirectly, that changes in gluconeogenesis may be part of the intracellular mechanism for regulating BBM phosphate uptake in response to certain stimuli.

Repeated infections of Brugia pahangi in the jird, Meriones unguiculatus.

Male jirds, Meriones unguiculatus, were subcutaneously inoculated in the groin with 1 to 5 doses of infective-stage larvae of Brugia pahangi at weekly or monthly intervals. When a dose of either 25 or 75 larvae or 4 weekly doses of 25 larvae were given, 15-16% of the larvae were recovered as adults approximately 4 to 7 months post inoculation. Only 8-10% of the larvae were recovered if 4 weekly or 5 monthly doses of 75 larvae each were given. After an inoculation of 75 larvae, 25% of the worms were recovered at 30 days. The 30 day-old population consisted of an average of 10 female and 8.8 male worms. Jirds previously inoculated with 4 weekly or 5 monthly doses were challenged with an additional 75 larvae 30 days prior to necropsy. An average of only 4.5 thirty day-old female worms were recovered in these cases, presenting a 55% decrease as compared to the single inoculation situation. There was some decrease in the mean length of female worms in multiply-inoculated jirds, but no difference in the mean lengths of the male worm population from singly or multiply-inoculated jirds was observed. No differences in prepatent periods or in patterns of microfilaraemia were observed in singly or multiply-inoculated jirds.

Materials management crucial to overall efficiency.

Because supplies are important to many departments, improved materials management may be an integral part of a hospital's productivity assessment. A successful program should encompass technical as well as managerial aspects of materials management. While looking at national performance statistics may provide a basis, each hospital should set its own standards in line with its strategic plan.

Inventory to go: can stockless deliver efficiency?

Influenced by the Japanese management concept of "just-in-time," healthcare organizations are looking to their departmental inventories for possible cost reductions. Some organizations have developed a materials management technique known as stockless inventory, in which much of the management of an organization's supplies is switched to an outside vendor. By eliminating its storeroom and many of the staffing needs that go along with it, a hospital with a stockless inventory program can realize significant cost savings. Whether these savings offset potentially large service fees is a question each hospital must decide on its own.

CEO/CFO responses to materials management survey.

A national survey of chief executive officers (CEOs) and chief financial officers (CFOs) reveals that while CEOs and CFOs are satisfied overall with materials management at their hospitals, a number of individual facets of materials management need improvement. The survey also shows that reducing supply expenses and better managing operating room (OR) inventories are two of the best ways that materials managers can help reduce hospitals' total annual operating expenses.

CEOs and CFOs express concern about materials management.

In a recent survey, CEOs and CFOs expressed concern regarding the effectiveness of their materials management departments. Both groups of executives would like to see more improvement in their materials managers' supply expense reduction efforts and leadership skills. More than a third of CFOs are even considering outsourcing the materials management function. Both CEOs and CFOs did admit, however, they needed to learn more about materials management, and both groups of executives could lend their authority to materials management programs to ensure their success. CEOs and CFOs need to reach consensus regard materials management priorities, performance levels, and professional characteristics and desired skills. They also should hold materials managers accountable for operations they can and should be managing by using performance-based compensation.

Controlling supply expenses through capitated supply contracting.

Some providers dealing with the financial challenges of managed care are attempting to control supply expenses through capitated supply contracting and similar risk/reward sharing arrangements. Under such arrangements, a supplier sells products and services to a provider for a fixed, prospective price in exchange for the provider's exclusive business. If expenses exceed the prospectively established amount, the supplier and provider share the loss. Conversely, if expenses are less than the fixed amount, they share the savings. For a capitated supply arrangement to be successful, providers must be able to identify and track supply expense drivers, such as clinical pathways, technology utilization, and product selection and utilization. Sophisticated information systems are needed to capture data, such as total and per-transaction product usage/volume; unit price per item; average and cost per item; average and total cost per transaction; and total cost per outcome. Providers also will need to establish mutually cooperative relationships with the suppliers with whom they contract.

Just-in-time for hospitals--so what's new?

In response to increasing competition, many hospital administrators and managers are giving a close look and, in many cases, a quick trial to management methods, techniques, and concepts used by other industries. One of those concepts is Just-in-Time (JIT) production and inventory management. JIT may not be applicable to the unique characteristics of the hospital/health industry; however, upon closer inspection, it will become evident to the reader that JIT has been used to some extent and in various applications, for many years. It has just not been called such.