bluuebunny/crossref_metadata_2025 huggingface dataset:
PERCS, DECS, AND OTHER MANDATORY CONVERTIBLES
Authors: Arzac Enrique R.
Published: April 2005

From their beginnings in 1988, mandatory convertibles such as PERCS and DECS have grown to account for as much as 25% of a convertible market that experienced new issuance of $20 billion in 1996. Mandatory convertibles usually pay a higher dividend than the company's common stock (generally for a three‐year period) and then require the holders to convert into common stock under terms that provide limited appreciation until conversion.

This article examines the rationale for mandatory convertibles from the point of view of issuers as well as investors. Like conventional convertibles securities, mandatory convertibles reduce the costs of the information asymmetry problem that confronts equity issuers. But, to a greater degree than ordinary convertibles, mandatory convertibles provide a solution to the financial restructuring problem faced by highly leveraged (and, in some cases, troubled) companies. They also enable growth companies to signal confidence about their future, particularly by including features such as guaranteed appreciation.

The last section of the article discusses the valuation of three varieties of mandatory convertibles: PERCS, DECS, and mandatory convertibles with a value guarantee. The valuation method builds on the insight that each of these securities can be decomposed into three basic components: (1) the underlying common stock; (2) the fixed‐income cash flow promised investors; and (3) the option on the company's stock embedded in the security.
SECURITIZATION: A LOW‐COST SWEETENER FOR LEMONS
Authors: Hill Claire A.
Published: April 2005

Since the launching of the mortgage backed market in the early 1970s, securitization has experienced extraordinary growth and spread to a remarkable variety of receivables. But financial economists in the tradition of Miller and Modigliani have been hard pressed to explain such growth. When viewed within the context of an M & M world of “perfect markets,” securitization appears to be simply another way—and a highly complex and costly one, at that—for a company to carve up its operating cash flows and repackage them for investors.

This article seeks to explain the growth of securitization by identifying reductions in costs that M & M assume out of existence. For some types of companies, the largest sources of the cost savings are fairly obvious. Most mortgage securitizations are effectively subsidized by the U.S. government, which contributed greatly to the launching of the securitization movement. And commercial banks forced to meet regulatory capital requirements have found securitization of loans to be a low‐cost compliance strategy.

But securitization appears to offer more than regulatory benefits. For example, higher rated companies with a variety of financing options appear to use securitization to diversify their funding sources and arbitrage small price differences in financial markets. But if such arbitrage profits can be significant, the non‐regulatory benefits appear to be largest for companies with few financing alternatives—those firms that face what economists refer to as a “lemons problem.” Available information about such companies is often limited (as in the case of smaller companies), unfavorable (companies in financial distress), or particularly difficult to appraise (companies in volatile industries, or facing unstable political environments or potentially large liabilities). Especially in the case of such “lemons” companies, securitization may reduce overall financing costs by carving up the evaluation of a company's securities into tasks amenable to greater specialization. In so doing, it may reduce aggregate information costs for all its securities and thus increase total value.
THE NEW LEVERAGED LOAN SYNDICATION MARKET
Authors: Barnish Keith , Miller Steve , Rushmore Michael
Published: April 2005

Over the past ten years, commercial lending has been transformed from a one‐off, bilateral “market” in which issuers maintained one or more separate banking relationships into a capital market in which one or more underwriters structure and price loans for syndication to groups of investors. This market‐driven evolution has been most dramatic in the leveraged lending segment (defined as loans priced at LIBOR plus 150 basis points or more), where wide margins have attracted a large and growing field of underwriters, intermediaries, and investors.

Liquidity is the overriding theme in today's syndicated loan market, making the market a more user‐friendly one for corporate borrowers and deal sponsors. As a result, a record number of corporate issuers are taking advantage of the syndicated loan market to finance strategic transactions or simply to reduce their borrowing costs. Deal sponsors, too, are tapping the market to finance leveraged buyouts, recapitalizations, and acquisitions at a pace not seen since the late 1980s. But, although acquisition pricing has reached cash flow multiples that recall those of the late '80s, equity contributions by sponsors are larger and credit structures are more conservative.

For banks and other investors, reduced loan pricing and more flexible credit structures have been balanced by much greater access to a large volume of diversified assets, as well as the ability to manage asset‐specific and portfolio risk more effectively. As a result of more effective portfolio management strategies, lenders today are less vulnerable to credit problems with individual issuers or a given industry segment, and the bank market as a whole should be much less subject to disruption than it proved to be in the early 1990s.
INITIAL PUBLIC OFFERINGS: GOING BY THE BOOK
Authors: Benveniste Lawrence M. , Wilhelm William J.
Published: April 2005

In the U.S., and increasingly in other countries as well, IPO securities are marketed to investors in a process known as “book‐building”—one that amounts to polling institutional investors to establish a demand schedule for the issue and then allotting stock to individual investors according to the strength of their professed interest. Although book‐building methods require use of discriminatory tactics that have attracted strong criticism from investors and regulators, this article defends such practices by demonstrating that book‐building is more efficient than alternative methods. It effectively allows issuers to increase the net proceeds of their offerings by making better use of information about market demand conditions.

In the process of explaining the efficiency of the book‐building method, this article also offers a plausible explanation for a phenomenon that has long puzzled economists: the systematic underpricing of IPOs. The key to the success of a book‐building effort lies in the use of a strategic pricing and allocation policy designed to offset the investor's incentive to understate his or her interest in an IPO. By committing to favor investors who provide strong indications of interest with relatively large allocations of underpriced shares, the investment bank can limit the distortion of investor's incentives in bidding and so increase the level of proceeds the issuing firm can expect to generate from its IPO.
EVA AND TOTAL QUALITY MANAGEMENT
Authors: Bacidore Jeffrey M. , Boquist John A. , Milbourn Todd T. , Thakor Anjan V.
Published: April 2005

Both TQM and EVA can be viewed as organizational innovations designed to reduce “agency costs”—that is, reductions in firm value that stem from conflicts of interest between various corporate constituencies. This article views TQM programs as corporate investments designed to increase value by reducing potential conflicts among non‐investor stakeholders such as managers, employees, customers, and suppliers. EVA, by contrast, focuses on reducing conflicts between managers and shareholders by aligning the incentives of the two groups. Besides encouraging managers to make the most efficient possible use of investor capital, EVA reinforces the goal of shareholder value maximization in two other ways: (1) by eliminating the incentive for corporate overinvestment provided by more conventional accounting measures such as EPS and earnings growth; and (2) by reducing the incentive for corporate underinvestment provided by ROE and other rate‐of‐return measures.

At a superficial level, EVA and TQM seem to be in direct conflict with each other. Because of its focus on multiple, non‐investor stakeholders, TQM does not address the issue of how to make value‐maximizing trade‐offs among different stakeholder groups. It fails to provide answers to questions such as: What is the value to shareholders of the increase in employees' human capital created by corporate investments in quality‐training programs? And, given that a higherquality product generally costs more to produce, what is the value‐maximizing quality‐cost combination for the company? The failure of TQM to address such questions may be one of the main reasons why the adoption of TQM does not necessarily lead to improvements in EVA.

Because a financial management tool like EVA has the ability to guide managers in making trade‐offs among different corporate stakeholders, it can be used to complement and reinforce a TQM program. By subjecting TQM to the discipline of EVA, management is in a better position to ensure that its investment in TQM is translating into increased shareholder value. At the same time, a TQM program tempered by EVA can help managers ensure that they are not under investing in their non‐shareholder stakeholders.
EVA AND DIVISIONAL PERFORMANCE MEASUREMENT: CAPTURING SYNERGIES AND OTHER ISSUES
Authors: Zimmerman Jerold L.
Published: April 2005

This article makes three basic points about divisional performance measurement that managers should keep in mind when attempting to choose between EVA and more conventional, accounting‐based measures.

First, no divisional performance measure, whether it be EVA, divisional net income, or ROA, is capable of capturing synergies among divisions—those shared benefits or costs that make the sum of the parts worth more than the whole. And EVA is neither more nor less effective than more conventional financial measures in deterring divisional managers from taking actions that increase divisional profits at the expense of corporate value.

Thus, there is a fundamental contradiction in the very attempt to evaluate the divisions of a multi—divisional firm as if they were independent companies. If there are synergies, divisional performance measures—even those employing transfer prices—are likely to prove inadequate in some respects (and this article recommends some methods for encouraging synergies that might be used to supplement if not replace divisional measures). But if there are no synergies, then top managers should re‐examine their business strategy and consider selling or spinning off divisions.

Second, a given performance measure's degree of correlation with stock returns should not be management's sole, or even its most important, criterion in choosing to adopt a given performance measure. A better method for evaluating performance measures is to weigh the behavioral or incentive benefits of a given measure against all direct and indirect costs associated with its implementation. In making such a costbenefit analysis, the incentive benefits from the tighter linkage of rewards to share prices provided by more market‐based measures should be traded off against the greater market risk and exposure to other uncontrollables imposed by such measures as well as the costs involved in changing the firm's internal accounting and reporting systems.

Third, the EVA practice of “decoupling” performance measures from GAAP accounting, while having have potentially significant incentive benefits, also has potential costs in the form of increased auditing requirements and the possibility of litigation.
CONTRACTING FOR VALUE: EVA AND THE ECONOMICS OF ORGANIZATIONS
Authors: Glassman David M.
Published: April 2005

EVA becomes more difficult to apply the farther down in the company you go, especially in organizations with more traditional “functional” designs. Because centralized functions are not independent self‐contained entities with direct control over their own revenues, costs, and capital, the performance measures used to evaluate them are necessarily incomplete; they reveal only part of the picture. For example, Marketing may increase sales and operating income—the measures on which it is evaluated—but at the same time drive excessive use of capital in the Manufacturing plants. Manufacturing may reduce unit cost through long production runs, thereby minimizing changeovers and setups, but create excess inventory in the process. Costreducing measures could also lead to declining quality and customer satisfaction, ultimately eroding the company's reputation. In short, each critical function influences results in other parts of the company, and focusing only on activities under a manager's direct control can result in myopic and misleading measures of performance.

In organizing key processes as internal EVA Centers, joint costs and benefits shared by different corporate functions or business units can be built into financial measures in a way that encourages collaboration.

As one example, a firm can attempt to replicate market forces internally by requiring each marketing region to contract for capacity with the internal manufacturing group. In a traditional management system, Marketing reserves (and relinquishes) manufacturing capacity at no cost; the consequence is excessive demand for resources. An internal pricing mechanism that requires Marketing to pay a fee for capacity will force its managers to assess trade‐offs as if it were contracting with an outside party.

Such a system effectively requires that functional managers take a more company‐wide view of their responsibilities. By including the cost of capital, it forces managers to define costs more carefully. By including the impacts on other functions, it also forces a broader definition of costs. And by using multi‐year contracts among different divisions, the framework extends the time horizon over which costs and benefits matter.
Insurance Derivatives: A New Asset Class for the Capital Markets and a New Hedging Tool for the Insurance Industry
Authors: Canter Michael S. , Cole Joseph B. , Sandor Richard L.
Published: April 2005

The number and severity of natural catastrophes has increased dramatically over the last decade. As a result, there is now a shortage of capacity in the property catastrophe insurance industry in the U.S. This article discusses how insurance derivatives, particularly the Chicago Board of Trade's catastrophe options contracts, represent a possible solution to this problem. These new financial instruments enable the capital markets to provide the insurance industry with the reinsurance capacity it needs. The capital markets are willing to perform this role because of the new asset class characteristics of securitized insurance risk: positive excess returns and diversification benefits.

The article also demonstrates how insurance companies can use insurance derivatives such as catastrophe options and catastrophe‐linked bonds as effective, low‐cost risk management tools. In reviewing the performance of the catastrophe contracts to date, the authors report promising signs of growth and liquidity in these markets.
INTERNATIONAL PRODUCTION LOCATION AND “PRO FORMA” FINANCIAL HEDGING OF EXCHANGE RATE RISK
Authors: O'Brien Thomas J.
Published: April 2005

There are many considerations in a firm's choice of where to locate a production facility. One of the least understood is the implication of foreign exchange risk. The issue is complex because, in addition to the concept of operational hedging, managers must also consider economic exposure and, in cases with foreign competitors, competitive exposure. As shown in this article, a firm's competitive exposure to exchange rate changes depends upon the location of its competitors' plants as well as its own.

The currency exposures of various international production strategies are demonstrated using hypothetical scenarios. The scenarios can also be used to perform a “pro forma” financial hedging analysis of currency exposure in simple “three‐outcome” cases. By implicitly accounting for the market's pricing of exchange rate risk, the financial hedging analysis provides a straightforward way for managers to evaluate various international production possibilities.
Best Practices in Corporate Governance: What Two Decades of Research Reveals
Authors: Shivdasani Anil , Zenner Marc
Published: April 2005

This report addresses two key questions for today's top executives: Do acquisitions create value for acquirers? And under what circumstances have acquisitions created the most value for acquiring shareholders?

The authors' analysis of over 1,500 completed deals by non‐financial companies in the United States over the past 12 years shows that, at announcement, acquirers' shareholders suffer small losses, on average, in the short term around the initial deal announcement. Over longer intervals, such as one or two years following the announcement of the transaction, acquirers tend to slightly outperform industry peers.

The average or median market response hides tremendous variability in how the market has reacted to individual deals, however. This article provides evidence that the “right” M&A transaction can create substantial value for acquirers. One‐quarter of the transactions lead to market‐adjusted gains in excess of 5% for the acquirer and oneeighth of the transactions lead to gains in excess of 10% in the short term. However, some deals have also destroyed substantial shareholder value.

Financing structure is a key driver of the stock market reaction. Stock‐financed transactions, on average, have a negative stock market reaction, while cash‐financed transactions have benefited acquirers in both the short term as well as the long term.

Acquisitions of private companies or assets and units of public companies have consistently generated higher returns for acquirers than purchases of public companies.

Moreover, EPS dilution is not a major driver of how the stock market reacts to a deal. Although “accretive” deals perform slightly better than “dilutive” ones in the short and long run, the difference is small and not statistically significant. Over the long run, acquiring shareholders have benefited the most from deals within the same industry and that avoid targets with relatively optimistic earnings growth projections.
ALIGNMENT EXPOSED: HOW CEOS ARE PAID, AND WHAT THEIR SHAREHOLDERS GET FOR IT
Authors: Hodak Marc
Published: April 2005

This article begins by arguing that, for many companies, there is a significant “disconnect” between how managers are paid and what is actually achieved for shareholders. This paper answers two questions of prime importance to investors: Is there a way to know beforehand whether managers' incentives are well aligned with those of its shareholders? And does such alignment actually make a difference in the returns one is likely to see?

In answering the first question, the author argues that cash bonuses and performance‐based equity grants (i.e., grants based on managers' meeting accounting‐based operating targets) are likely to provide stronger, more cost‐effective incentives than grants of stock or options because the former are generally based on measures over which managers have significantly more control than the stock price. Using this insight, the author develops a method for evaluating compensation structures based on the variability of compensation, the number and type of compensation metrics purportedly driving that variability (including the award of performance shares or options), the stability of those metrics over time, and the apparent level of discretion in the use of those metrics to either fund or distribute bonuses (including equity). All these elements are disclosed to varying degrees in the proxy statements or annual reports of companies.

Using his compensation scores for 140 companies and their return history over the last eight years, the author concludes that “high alignment” companies outperform their “low alignment” peers by more than 5% per year in total shareholder returns. Furthermore, increases in alignment scores by individual companies over time tend to lead to higher total shareholder returns, and degradation of scores lead to lower returns. In short, observable improvements in compensation structure appear to pay off in the form of significant abnormal returns.
Product Costing and Inventory Accounting: A New Approach to an Old Problem
Authors: Rosson Richard D.
Published: April 2005

Traditional methods of accounting—including full‐absorption accounting, labor and cost standards, overhead allocations, and variance analysis–can stand in the way of attempts by managers and others to improve their company's overall performance and the ability to compete globally. Many companies have recognized the need to shift the role of accounting toward higher‐value, more strategic tasks, such as financial and operational analysis, tactical decision support, and even process improvement and reengineering. But the accounting tools at their disposal often prove inadequate. In fact, there is a core conflict between the need to provide accurate and consistent financial reports for external consumption–reports that comply in all respects with GAAP, Sarbanes‐Oxley, SEC requirements, and the like–and the need for value‐relevant and informative reports for internal management purposes.

The author proposes using multiple sets of financial reports, all deriving from a single, common database, to meet external reporting requirements while addressing the distortions and limitations of GAAP for internal purposes. In particular, he has developed a new approach called Value Added Accounting that eliminates the distortions of full‐absorption accounting but that uses GAAP financial statements as its starting point. The article describes the key adjustments, presents a case study, and discusses how VAA aligns with Lean Manufacturing, Quick Response Manufacturing, Just‐In‐Time, and other common process improvement initiatives.
Morgan Stanley Panel Discussion on Seeking Growth in Emerging Markets: Spotlight on China
Authors:   Financial Decision Makers' Conference
Published: April 2005

The treasurer of McDonald's discusses investment opportunities in China with Morgan Stanley's chief economist and its head of investment banking in China. The consensus is that the economic outlook for the country is strong, subject to some concerns about the currency, and that ongoing reforms are expected to bring about greater stability and productivity. Progress in raising Chinese banks to international capital adequacy standards, and imposing transparency and accounting requirements, has been particularly impressive.

McDonald's first went to mainland China in the early 1990s. Thanks to its success in attracting suppliers and local financing and partners, it now has 600 restaurants and an ambitious expansion plan. For other U.S. and overseas companies, China's position as a global manufacturing center, its R&D capabilities, and its potential consumer market will lead to acquisitions of local companies, joint ventures, and other forms of direct investment. China's accession into the World Trade Organization has also opened a number of sectors that were previously restricted to foreign investors, including financial services.
Incorporating Competition into the APV Technique for Valuing Leveraged Transactions
Authors: Ehrhardt Michael C.
Published: April 2005

According to a recent survey, the discounted cash flow approach is the valuation technique most widely used by companies evaluating acquisition targets. But because the DCF approach is inappropriate when the capital structure is changing during the forecast period, many analysts turn to the adjusted present value (APV) approach, which can easily accommodate a changing capital structure. Still, the finance literature has not shown how to incorporate assumptions about the effect of competition in the post‐forecast period into an APV analysis.

This paper provides two new tools for calculating horizon values with changing leverage and competition. First, it provides a new model, based on more realistic assumptions, for valuing a growing annuity of free cash flows when ROIC is expected to decline due to competition. Second, it provides a model for valuing tax shields that correctly incorporates the impact of competition in the post‐forecast period. When used together with the APV approach, these two new tools allow an analyst to estimate the value of a company with a changing capital structure that faces competition in the post‐forecast period.
A Framework for Corporate Treasury Performance Measurement
Authors: Kalotay Andrew
Published: April 2005

Corporations generally do not have a formal process for evaluating the effectiveness of their treasury departments in managing debt. To the extent that corporate borrowing decisions are predicated on “market timing” rather than matching the interest rate sensitivity of the firm's liabilities to that of its assets, the firm is effectively making bets on interest rates that should be monitored and evaluated.

The author has developed an approach that allows for periodic reporting of treasury's performance to investors and that also provides a framework for treasury to compare and choose among alternatives in the capital markets. The basic idea is to calculate a company's liability return and then establish a benchmark portfolio that allows measurement of relative performance. For a nonfinancial corporation, a useful benchmark can be constructed using the collective debt obligations of the company's industry peers. The assumption underlying this benchmark is that the financing of the industry as a whole is designed to produce an “optimal” asset‐liability configuration and net exposure to interest rates.
Leverage
Authors: Miller Merton H.
Published: April 2005

In his 1990 Nobel Prize address, the “father of modern finance” begins by discussing the benefits of debt financing and hen goes on to discuss potential costs. Although certainly capable of excesses, private capital markets have self‐correcting mechanisms that limit corporate “overleveraging.” Contrary to popular perception, corporate leveraging does not increase risk for the economy as a whole, and the financial difficulties of highly leveraged companies involve “mainly private, not social costs.” (And provided the Chapter 11 process doesn't get in the way, debt often plays the socially constructive role of eliminating excess capacity.) Finally, regulations designed to reinforce capital markets' built‐in controls against overleveraging are generally not only unnecessary but positively harmful to the economy.
Assessing Growth Estimates in IPO Valuations—A Case Study
Authors: Mills Roger W.
Published: April 2005

A common practice in discounted cash flow (DCF) valuations of growth businesses is to forecast cash flows over some initial period (say, five years) and then use a “perpetuity‐with‐growth” calculation to estimate the “terminal” value beyond that period. The assumed growth rate generally has a very large effect on the overall valuation, and there is no universally accepted method for challenging the assumptions underlying the selected growth rate. This article presents a framework based on the concept of Market Implied Competitive Advantage Period (MICAP) analysis that can be used to evaluate such growth assumptions and then demonstrates the use of that framework in the IPO valuation of Jordan Telecom.
Granulocyte Transfusions in Children With Chronic Granulomatous Disease and Invasive Aspergillosis
Authors: İkincioğulları Aydan , Doḡu Figen , Solaz Nuri , Reisli İsmail , Kemahlı Sabri , Cin Şükrü , Babacan Emel
Published: April 2005

Abstract:  The transfusion of granulocytes to restore host defenses in severely granulocytopenic patients or in patients with defective granulocyte functions has been studied for more than 60 years. However, inadequate dosage of cells and inconsistent efficacy has limited the usage of these transfusions. Recently, the use of mobilizing agents such as granulocyte colony stimulating factors and dexamethasone has renewed interest in these treatment modalities. The present study is conducted to determine an appropriate method of enriched granulocyte collection with Fresenius AS.TEC.204 cell separator (Fresenius, Bad Homburg, Germany) and to evaluate the preliminary clinical results of granulocyte transfusion therapy in patients with chronic granulomatous disease and invasive Aspergillosis in parallel with in vitro granulocyte function. Three patients who have been treated for chronic granulomatous disease and invasive Aspergillosis received a total of 20 granulocyte transfusions. To mobilize granulocytes, healthy donors were given 450 µg of granulocyte colony‐stimulating factor (G‐CSF) subcutaneously and 8 mg of dexamethasone orally approximately 12 h before collection. Five µg/kg/day of G‐CSF was also subcutaneously administered prior to granulocyte transfusions. The first patient received 4; the second, 14 and the third, 2 transfusions. The granulocyte count given to these patients ranged between 0.4 and 3.0 × 109/kg. Most transfusions were well tolerated. The nitroblue tetrazolium (NBT) tests that were done 16–24 h after the transfusion showed 14–46% dye reduction. Two of the three patients survived the infection. Granulocyte transfusions from G‐CSF and dexamethasone stimulated donors could be a choice of treatment in chronic granulomatous disease patients, especially with disseminated invasive Aspergillosis.
Synergistic Cytotoxicity of Acidity and 3,4‐Dideoxyglucosone‐3‐ene Under the Existence of Lactate in Peritoneal Dialysis Fluid
Authors: Tomo Tadashi , Okabe Eiji , Yamamoto Takashi , Namoto Shinji , Iwashita Tomohiko , Matsuyama Kazuhiro , Kadota Jyunichi , Nasu Masaru
Published: April 2005

Abstract:  Of the non‐physiological compounds in glucose‐rich peritoneal dialysis fluid, we investigated the synergistic cytotoxicity of acidity and 3,4‐Dideoxyglucosone‐3‐ene(3,4‐DGE) under the existence of lactate using human peritoneal mesothelial cells (HPMC). The effect of pH on cell viability at various levels of pH (5.5, 6.7, 7.15), with or without lactate was examined by adding 1N‐HCl to phosphate buffer solution. We also examined the cytotoxic effects of 3,4‐DGE and pH (5.5, 6.7 or 7.15). Additionally, we compared the cytotoxic effects of 3,4‐DGE and pH (5.5, 6.7 or 7.15) under existence of lactate (40meq/L) or absence of lactate. The cells were exposed to these solutions for 2 or 4 h. Cell viability was determined by MTT (3‐[4, 5‐dimethylthiazol‐2‐yl]‐2, 5‐diphenylterazolium bromide) assay. 3,4‐DGE or acidic solution alone had no significant effects on MTT viability under the absence of lactate. However, acidic solutions containing 3,4‐DGE significantly decreased MTT viability under the existence of lactate. The MTT viability of HPMC was not decreased by 3,4‐DGE or acidity alone under the absence of lactate. However, the combination of acidity and 3,4‐DGE markedly decreased MTT viability under the existence of lactate, strongly suggesting the synergistic cytotoxicity of 3,4‐DGE and acidity under the existence of lactate.
Suppression of Inflammatory Cytokine Secretion by Granulocyte/Monocyte Adsorptive Apheresis in Active Ulcerative Colitis
Authors: Andoh Akira , Tsujikawa Tomoyuki , Inatomi Osamu , Deguchi Yasuyuki , Hata Kazunori , Kitoh Katsuyuki , Sasaki Masaya , Mitsuyama Keiichi , Fujiyama Yoshihide
Published: April 2005

Abstract:  To elucidate the molecular mechanisms involved in the therapeutic effects of granulocyte/monocyte adsorption apheresis, changes were investigated in the cytokine responses of peripheral blood mononuclear cells (PBMC) before and after granulocyte/monocyte adsorptive apheresis in ulcerative colitis (UC) patients. Four patients with active UC were enrolled. All patients responded to granulocyte/monocyte adsorptive apheresis. A total of 20 sessions of four patients were analyzed. Peripheral blood mononuclear cells were isolated from peripheral venous blood within 5 min before and after each session of granulocyte/monocyte adsorptive apheresis. The cells were stimulated with interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α for 24 h, and the secreted IL‐8 and IL‐6 levels were determined by enzyme‐linked immunosorbent assay (ELISA). IL‐1β‐induced IL‐8 and IL‐6 secretion was significantly decreased after granulocyte/monocyte adsorptive apheresis. TNF‐α‐induced IL‐8 secretion was also significantly decreased after apheresis, but there was no significant difference in TNF‐α‐induced IL‐6 secretion (P = 0.052). In conclusion, granulocyte/monocyte adsorptive apheresis down‐regulates the IL‐1β‐ and TNF‐α‐induced inflammatory responses in PBMC. The induction of hyporesponsiveness to pro‐inflammatory cytokines may be an important factor mediating the clinical effects of granulocyte/macrophage adsorptive apheresis in UC patients.
Non‐invasive Monitoring of Hemodynamic Changes During Hemodialysis by the Use of a Newly Developed Admittance Cardiograph
Authors: Yoshii Masayoshi , Minami Junichi , Ishimitsu Toshihiko , Yamakoshi Ken‐ichi , Matsuoka Hiroaki
Published: April 2005

Abstract:  Only a little information is available for the evaluation of the complex hemodynamic changes that occur during hemodialysis. Recently, we developed the transthoracic electrical admittance cardiograph for repeated measurements of cardiac output, and monitored hemodynamic changes during hemodialysis by the use of this device. We measured cardiovascular hemodynamic and autonomic parameters non‐invasively during 210 min of hemodialysis in 19 chronic hemodialysis patients who for more than 2 months had no history of cardiovascular collapses during hemodialysis. Blood pressure was monitored every 10 min using a cuff‐oscillometric device (TM‐2425; A & D, Tokyo, Japan). Cardiac output was monitored on a beat‐by‐beat basis by a newly developed electrical admittance cardiograph (NICOVIEW PA1100; NEC, Tokyo, Japan). Electrocardiogram R‐R intervals were also monitored by the TM‐2425. Power spectral analysis of R‐R intervals was performed to obtain the low‐frequency (LF; 0.05–0.15 Hz) and the high‐frequency (HF; 0.15–0.40 Hz) components based on an autoregressive model. Change in circulatory blood volume was also monitored by a CRIT‐LINE (In‐Line Diagnostics, Riverdale, UT, USA). Although blood volume declined significantly by 16.3 ± 1.4% (mean ± SE) during hemodialysis (P < 0.0001), mean blood pressure did not change significantly. Heart rate increased significantly from the initial values of 76.3 ± 3.4–86.4 ± 4.9 beats/min (P = 0.03). Cardiac output and stroke volume decreased significantly from 4.47 ± 0.30 to 2.91 ± 0.32 L/min (P < 0.0001), and from 57.0 ± 3.7 to 33.9 ± 3.1 mL (P < 0.0001), respectively. Total peripheral vascular resistance increased significantly from 1940 ± 146 to 3117 ± 280 dyne × s × cm5 (P < 0.0001). The LF component did not show significant change, while the HF component decreased significantly (P = 0.007), and the LF/HF ratio increased significantly (P = 0.03). These results suggest that a reduction in parasympathetic nerve activity and sympathetic nerve activation and a marked increase in total peripheral vascular resistance are responsible for the maintenance of blood pressure during hemodialysis in chronic hemodialysis patients. The admittance cardiograph seems to be one of the best options for serial measurements of cardiac output.
Is Lipoprotein (a)—Apheresis Useful?
Authors: Bambauer Rolf
Published: April 2005

Abstract:  Numerous epidemiological investigations have shown the importance of cholesterol, and in particular low density lipoprotein (LDL), and of the lipoproteins in the development of coronary sclerosis. A continuing relationship between cholesterol levels and coronary morbidity has been established. The LDL concentration in the blood is, in particular, to be made responsible for the development of arteriosclerosis and especially of coronary heart disease (CHD). Lipoprotein (a) [Lp(a)], as a risk factor for premature cardiovascular and cerebrovascular diseases, can be lowered by LDL‐apheresis. Especially in isolated high levels of Lp(a) with CHD or polygenic hypercholesterolemia with elevated Lp(a) levels, LDL‐apheresis can be indicated and can be useful to improve endothelium regulation and induce changes in coronary tone by an increase in endothelial derived relaxing factor. Lipoprotein (a) can be dramatically lowered by LDL‐apheresis, but clinical improvement especially by low LDL is not still not clarified. Studies with weekly apheresis with statins versus drug therapy alone are necessary. To clarify the controversial discussions of whether lowering Lp(a) may be unnecessary or necessary to arrest progression of CHD, more clinical and randomized studies are needed. Lipoprotein (a) can be also  lowered  by current  LDL‐apheresis methods.
Incidence of Peripheral Arteriosclerotic Complications of the Lower Extremities in Diabetic Patients With Chronic Renal Failure
Authors: Hosokawa Kazuhiro , Kuriyama Satoru , Astumi Yosihito , Kaneda Satoshi , Mastuoka Kempei
Published: April 2005

Abstract:  Patients with diabetes mellitus are at high risk of arteriosclerotic complications. The same is true for those with chronic renal failure (CRF). The present study evaluated clinical factors on the occurrence of peripheral arterial diseases. The severity of peripheral arterial disease was defined as mild (plaque, calcifications) or severe (70% stenosis, obstructions) based upon ultrasonographical examination. Overall in diabetic patients, mild ultrasonographical findings such as plaque and calcification were observed in 25% (17/69) of predialysis patients and in 18% (7/38) of those on hemodialysis (HD). Severe arteriosclerotic findings such as stenosis and obstruction were seen in 42% (29/69) of predialysis patients and in 50% (19/38) of those on HD. The incidence is identical between predialysis patients and patients on HD, regardless of the severity of peripheral arterial diseases. In an attempt to compare diabetics with non‐diabetics, the incidence of mild abnormal findings was found in 22% (24/107) of diabetics and in 30% (11/37) of non‐diabetics. Similarly, the percentage of patients with severe arteriosclerotic findings was found in 45% (48/107) in diabetics and 11% (4/37) in non‐diabetics. The incidence of the severe type findings in the diabetics is significantly more frequent than that in the non‐diabetics (P < 0.01, by the χ2 test). In non‐diabetic predialysis patients, the incidence of mild arteriosclerotic findings was observed in 30% (7/23), and 29% (4/14) of non‐diabetic patients on HD. Similarly, the percentage of severe type was 9% (2/23) in non‐diabetic predialysis patients, and 14% (2/14) in non‐diabetic patients on HD. These data are not only supportive of previous data that diabetes is a risk factor for arteriosclerosis, but also suggestive that, even before the initiation of dialysis, patients with CRF are already susceptible to arteriosclerotic assault of peripheral arterial complications.
Functional differentiation and organization of feline midlumbar commissural interneurones
Authors: Jankowska E. , Edgley S. A. , Krutki P. , Hammar I.
Published: April 2005

Interneurones interconnecting the two sides of the spinal cord (commissural interneurones) are critically important for interlimb coordination, but little is known about their organization. We have examined the inputs to commissural interneurones located in the midlumbar segments with projections to contralateral motor nuclei, aiming to determine whether they form distinct subpopulations. Based on intracellular records from 78 interneurones, two major non‐overlapping subpopulations were identified: one monosynaptically excited by group II muscle afferents (n= 10), the other monosynaptically excited by reticulospinal neurones (n= 52). Monosynaptic input from group I muscle afferents and/or from vestibulospinal tract neurones was found in those with monosynaptic reticulospinal, but not group II input, and in a few other neurones (n= 6). Only disynaptic input from these sources was found in the remaining 10 interneurones. Disynaptic excitatory input from ipsilateral and contralateral muscle afferents and from descending tracts was distributed less selectively and might mediate coexcitation of interneurones with monosynaptic afferent or descending input. The dominant disynaptic and polysynaptic input was, however, inhibitory. IPSPs were evoked from the descending tracts in a high proportion of the commissural interneurones that were monosynaptically excited by group II afferents (55%) and from group II afferents in a high proportion of the commissural interneurones that were monosynaptically excited by reticulospinal fibres (78%). This distribution suggests that the two subpopulations are activated differentially, rather than being coactivated, in either centrally initiated movements or reflex adjustments. This would be consistent with the previous demonstration that noradrenaline differentially affects commissural neurones of the two subpopulations.
Opposing muscarinic and nicotinic modulation of hypoglossal motor output to genioglossus muscle in rats in vivo
Authors: Liu Xia , Sood Sandeep , Liu Hattie , Horner Richard L.
Published: April 2005

The genioglossus (GG) muscle of the tongue, innervated by the hypoglossal motor nucleus (HMN), helps maintain an open airway for effective breathing. In vitro studies in neonatal rodents have separately characterized muscarinic and nicotinic receptor influences at the HMN but the net effects of combined nicotinic and muscarinic receptor activation and increased endogenous acetylcholine have not been determined in adult animals in vivo. Urethane‐anaesthetized, tracheotomized and vagotomised rats were studied. Microdialysis perfusion of acetylcholine into the HMN significantly decreased respiratory‐related GG activity (28.5 ± 11.0% at a threshold dose of 0.1 mm). Application of the cholinergic agonists carbachol and muscarine have similar suppression effects (GG activity was decreased 11.8 ± 4.3 and 20.5 ± 5.8%, respectively, at 0.01 μm). Eserine, an acetylcholinesterase inhibitor, also decreased the amplitude of respiratory‐related GG activity (36.4 ± 11.3% at 1.0 μm) indicating that endogenous acetylcholine modulates GG activity. Although these results showed that suppression of GG activity predominates during cholinergic stimulation at the HMN, application of the nicotinic receptor agonist dimethyl‐4‐phenylpiperazinium iodide significantly increased tonic and respiratory‐related GG activity (156 ± 33% for respiratory activity at 1.0 mm) showing that excitatory responses are also present. Consistent with this, 100 μm carbachol decreased GG activity by 44.2 ± 7.5% of control, with atropine (10 μm) reducing this suppression to 13.8 ± 4.0% (P < 0.001). However, the nicotinic receptor antagonist dihydro‐β‐erythroidine (100 μm) increased the carbachol‐mediated suppression to 69.5 ± 5.9% (P= 0.011), consistent with a role for nicotinic receptors in limiting the overall suppression of GG activity during cholinergic stimulation. Application of eserine to increase endogenous acetylcholine also showed that inhibitory muscarinic and excitatory nicotinic receptors together determine the net level of GG activity during cholinergic stimulation at the HMN. The results suggest that acetylcholine has mixed effects at the HMN with muscarinic‐mediated GG suppression masking nicotinic excitation.
Critical amino acid residues involved in the electrogenic sodium–bicarbonate cotransporter kNBC1‐mediated transport
Authors: Abuladze Natalia , Azimov Rustam , Newman Debra , Sassani Pakan , Liu Weixin , Tatishchev Sergei , Pushkin Alexander , Kurtz Ira
Published: April 2005

We have previously reported a topological model of the electrogenic Na+–HCO3− cotransporter (NBC1) in which the cotransporter spans the plasma membrane 10 times with N‐ and C‐termini localized intracellularly. An analysis of conserved amino acid residues among members of the SLC4 superfamily in both the transmembrane segments (TMs) and intracellular/extracellular loops (ILs/ELs) provided the basis for the mutagenesis approach taken in the present study to determine amino acids involved in NBC1‐mediated ion transport. Using large‐scale mutagenesis, acidic and basic amino acids putatively involved in ion transport mediated by the predominant variant of NBC1 expressed in the kidney (kNBC1) were mutated to neutral and/or oppositely charged amino acids. All mutant kNBC1 cotransporters were expressed in HEK‐293T cells and the Na+‐dependent base flux of the mutants was determined using intracellular pH measurements with 2′,7′‐bis‐(carboxyethyl)‐5(6)‐carboxyfluorescein (BCECF). Critical glutamate, aspartate, lysine, arginine and histidine residues in ILs/ELs and TMs were detected that were essential for kNBC1‐mediated Na+‐dependent base transport. In addition, critical phenylalanine, serine, tyrosine, threonine and alanine residues in TMs and ILs/ELs were detected. Furthermore, several amino acid residues in ILs/ELs and TMs were shown to be essential for membrane targeting. The data demonstrate asymmetry of distribution of kNBC1 charged amino acids involved in ion recognition in putative outward‐facing and inward‐facing conformations. A model summarizing key amino acid residues involved in kNBC1‐mediated ion transport is presented.
Vasopressin and Oxytocin Excite Distinct Neuronal Populations in the Central Amygdala
Authors: Huber Daniel , Veinante Pierre , Stoop Ron
Published: April 2005

Vasopressin and oxytocin strongly modulate autonomic fear responses, through mechanisms that are still unclear. We describe how these neuropeptides excite distinct neuronal populations in the central amygdala, which provides the major output of the amygdaloid complex to the autonomic nervous system. We identified these two neuronal populations as part of an inhibitory network, through which vasopressin and oxytocin modulate the integration of excitatory information from the basolateral amygdala and cerebral cortex in opposite manners. Through this network, the expression and endogenous activation of vasopressin and oxytocin receptors may regulate the autonomic expression of fear.
Structure of a γδ T Cell Receptor in Complex with the Nonclassical MHC T22
Authors: Adams Erin J. , Chien Yueh-Hsiu , Garcia K. Christopher
Published: April 2005

γδ T cell receptors (TCRs), αβ TCRs, and antibodies are the three lineages of somatically recombined antigen receptors. The structural basis for ligand recognition is well defined for αβ TCR and antibodies but is lacking for γδ TCRs. We present the 3.4 Å structure of the murine γδ TCR G8 bound to its major histocompatibility complex (MHC) class Ib ligand, T22. G8 predominantly uses germline-encoded residues of its δ chain complementarity-determining region 3 (CDR3) loop to bind T22 in an orientation substantially different from that seen in αβ TCR/peptide-MHC. That junctionally encoded G8 residues play an ancillary role in binding suggests a fusion of innate and adaptive recognition strategies.
In Search of Time
Authors: Gerstel Naomi
Published: April 2005

The Time Divide
Work, Family, and Gender Inequality.
By Jerry A. Jacobs and Kathleen Gerson
. Harvard University Press, New York, 2004. 259 pp. $45, £29.95, €41.50. ISBN 0-674-01153-8.

Working in a 24/7 Economy:
Challenges for American Families.
By Harriet B. Presser
. Russell Sage Foundation, New York, 2003. 281 pp. $39.95. ISBN 0-87154-670-1.

Jacobs and Gerson examine the origins of time pressures and possible means of alleviating them. Presser considers the effects of non-standard work hours on families, especially those raising young children.