bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding and Managing Indoor Air Exposure Assessments at RCRA Sites
Authors: Brown Michael J. , Phillips William H. , Vondracek James E. , Ogilvie Kenneth G.
Published: February 2007

The 2000 RCRA National Conference was conducted August 15‐17, 2000, in Washington, D.C., to allow state and federal authorities to review regulatory issues associated with the Resource Conservation and Recovery Act (RCRA) program. One of the RCRA reform issues discussed at the conference included the Government Performance and Results Act (GPRA) Environmental Indicators (EI). EIs have been designed to provide clarity in cleanup objectives and spur progress towards meeting the U.S. Environmental Protection Agency's (USEPA's) national RCRA cleanup goals. This article focuses on the human exposure indicator and, more specifically, on indoor air exposures and how to assess whether such exposure is actually occurring. While indoor air exposure can be a critical component of the human exposure scenarios, realistic predictions of the exposures are difficult to produce. This article provides an overview of the regulatory issues related to the indoor air exposure pathway. It also discusses the use of modeling in criteria development and risk evaluation and presents a case study of how the USEPA wants the modeling to occur, and an opinion of where this RCRA reform issue is heading and how to evaluate indoor air exposures.
A quantitative method for dual‐pass electrostatic force microscopy phase measurements
Authors: Yan Minjun , Bernstein Gary H.
Published: February 2007

Electrostatic force microscopy (EFM) has become a powerful tool for investigating charges on surfaces. The use of phase measurement in EFM is a direct and fast way to detect electrostatic force gradients, but only qualitatively. With the dual‐pass scheme, the phase signal at lifted height is often assumed to exclude any influences from the topography, but it does not. We report the collection of both topography and phase data by EFM on charged, micron‐sized metal wires. In order to quantify the electrostatic force, a cone model and finite element analysis are provided to integrate the force gradient from the phase signal. Copyright © 2007 John Wiley & Sons, Ltd.
Multiple imputation: review of theory, implementation and software
Authors: Harel Ofer , Zhou Xiao‐Hua
Published: January 2007

Missing data is a common complication in data analysis. In many medical settings missing data can cause difficulties in estimation, precision and inference. Multiple imputation (MI) (Multiple Imputation for Nonresponse in Surveys. Wiley: New York, 1987) is a simulation‐based approach to deal with incomplete data. Although there are many different methods to deal with incomplete data, MI has become one of the leading methods. Since the late 1980s we observed a constant increase in the use and publication of MI‐related research. This tutorial does not attempt to cover all the material concerning MI, but rather provides an overview and combines together the theory behind MI, the implementation of MI, and discusses increasing possibilities of the use of MI using commercial and free software. We illustrate some of the major points using an example from an Alzheimer disease (AD) study. In this AD study, while clinical data are available for all subjects, postmortem data are only available for the subset of those who died and underwent an autopsy. Analysis of incomplete data requires making unverifiable assumptions. These assumptions are discussed in detail in the text. Relevant S‐Plus code is provided. Copyright © 2007 John Wiley & Sons, Ltd.
Sampling an unknown universe: problems of researching mass casualty incidents (a history of ECRU's field research)
Authors: Scanlon Joseph
Published: January 2007

This paper reviews how the Emergency Communications Research Unit (ECRU) at Carleton University in Ottawa, Canada, developed its field research techniques with emphasis on some of its approaches to sampling. Then based on ECRU's experience, it discusses the problems that would arise if an attempt were made to research an incident involving not only mass casualties, but also chemically contaminated mass casualties. While ECRU's findings have been published in scores of book chapters, monographs and academic and other articles, this is only the second time since 1977 that its methods have been described [The Development of a Standby Research Capacity at Carleton University. Emergency Planning: Ottawa, Canada; Int. J. Mass Emergencies and Disasters 1977; 2(1):35–41; Methods of Disaster Research. Xlibris Corporation, 26–302], and the very first time its approaches to sampling have been discussed. Copyright © 2007 John Wiley & Sons, Ltd.
Customer‐driven environmental information management systems
Authors: FitzGerald Chris
Published: February 2007

The most successful corporate environmental programs regard environmental compliance as an opportunity to improve productivity and profits and seek to integrate environmental information management systems (EIMS) into line information functions. Integrated EIMS should provide timely, accurate data to support all three types of environmental management responsibilities: results and comparison reports for source management; material and waste transaction and emission reports for materials management; and compliance, summary, exception, and trend data for risk managers at every level.
EPA and business: Who is the customer, who is the supplier?
Authors: Morris Alvin R.
Published: February 2007

By focusing on regulated businesses as “customers,” the EPA is bringing a new way of thinking to the negotiating table that is producing creative, workable solutions. The author, who was instrumental in initiating the adoption of TQM in the Environmental Protection Agency, discusses how it can be used in negotiation to resolve impasses between EPA and business and meet the needs of both.
Maintaining quality focus with critical data
Authors: Rubin Michael P.
Published: February 2007

Total Quality Management measurement tools are often the very tools necessary to ensure compliance with the rapidly growing regulatory demand for data. At the same time, interest in the environment by average citizens, environmental groups, and regulatory agencies has put increasing pressure on environmental managers for “zero defects.” Violations and exceedances are actively pursued and are, at a minimum, made public to produce incentive for companies to comply. Even companies in compliance face pressure to further improve their performance. No business can afford the lost legal, operational, and public relations costs of noncompliance. There is no room for error. This article discusses the basic tools used at IBM Rochester to better manage and control some key environmental operations and shows how these basic control steps work in an actual wastewater treatment process at the facility.
A team approach to implementing MACT standards
Authors: Davis Bruce C.
Published: February 2007

The requirements of the MACT Standards for Emissions from Leaking Equipment and the requirements of the amended Clean Air Act will change how environmental control programs are administered within plants. No longer will the programs be the responsibility solely of the separate environmental function. The programs will need to be administered via a team of personnel that involves maintenance, computer systems, environmental, emissions measurement specialists, and planning personnel as well as management. Compliance with the rules will be based on an inspection of paper records and computer databases. The enforcement penalties will not be trivial. The ability of the plant to grow and be modified will need to be balanced against the potential benefits from early reduction programs, which will allow for delayed implementation of some programs.
Questions and Answers. From waste to improved production?
Authors: Johannson Lynn
Published: February 2007

Please send me your comments and questions on TQEM. Address it to me: TQEM Questions & Answers Editor, 22 West 21st Street, New York, NY 10010. I will credit you with the question and send out an extra copy of TQEM. My thanks to James, Jack, and Sheila for sharing in the quality revolution this issue.
Breaking the reactive paradigm: A proactive approach to risk assessment management
Authors: Belluck David A. , Benjamin Sally L. , Kiamos Maria A.
Published: February 2007

Risk assessments are fast becoming an indispensable tool for both government and industry. Unfortunately, organizations required to perform risk assessments often lack the ability to either generate or critically evaluate the quality of risk assessment reports and must rely on contractors to tell them what they need and whether they have received it. The authors advocate a proactive approach to contractual risk assessment management in which a client team directs the production of the report and maintains quality control at each step in the process.
From a culture of fixing to a culture of preventing at arm & hammer brand
Authors: Thomlison Bryan M.
Published: February 2007

Companies with a total quality management program in place are beginning to understand the need for of a fuller integration of environmental and health and safety functions within their overall quality framework. Intense international competition, a flat global economy, and an increasingly stringent environmental and health and safety regulatory climate are forcing management to consolidate whatever gains they have made on the compliance side.

At the same time, a total quality approach demands flattening of hierarchies, increased empowerment in divisions and plant floors, and much greater integration through a team approach of most management functions. Making all of this work puts a heavy premium on communication and individual responsibility. As companies that are going through the process now understand, this calls for major changes in corporate culture and a deep commitment from top management. This article describes the quality improvement process at Church & Dwight, makers of the Arm & Hammer line of products, where the TQEM challenge is orchestrated by a triumvirate representing three management functions: engineering, quality, and marketing/public relations.
Environmental marketing's new relationship with corporate environmental management
Authors: Coddington Walter
Published: February 2007

Issues of environmental marketing track back to issues of environmental management—i.e., to issues of overall corporate environmental commitment and responsibility. It is absolutely essential that a commitment to corporate environmental improvement be in place before an environmental marketing program is launched. Additionally, marketers can and should play a central role in the greening of the corporation. The marketer brings at least two important skills or strengths to the environmental improvement process—strengths of perspective and strengths of skill set.
Supporting environmental quality: Developing an infrastructure for design
Authors: Allenby Braden
Published: February 2007

Ten years ago, environmental problems were easy to define: The Hudson and Potomac were polluted; Los Angeles had lousy air; some waste dumps were highly toxic. Solutions were also relatively straightforward: the Clean Air Act for dirty airsheds; the Clean Water Act for dirty rivers; the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA, better known as Superfund) for hazardous waste sites. Unfortunately, reality is not quite so neat. We now know that we were seeing—and treating—symptoms, not the disease itself.
Environmentally conscious product design through total quality management
Authors: Paton Bruce
Published: February 2007

The actions of governments, customers, and competitors are influencing corporate environmental management in unprecedented ways. Market requirements are affecting both revenues and costs in ways that individual firms cannot control. The uncertainty that these new requirements create underscores the critical importance of planning and implementing a systematic approach to the design of products and the processes used to build, ship, support, and recover them. In this article the author shows how Total Quality Management offers a useful framework for aligning a company'S market focus, its business plans, and its management of critical business processes. This alignment is critical, if companies are to create environmentally conscious products while remaining competitive in a global marketplace.
Quality metrics in design for environment
Authors: Fiksel Joseph
Published: February 2007

There is a growing commitment by manufacturers, both in the United States and abroad, to assure environmental responsibility for all of their operations. This trend is driven partly by market demands for “green” products and partly by changes in international standards and regulations. In response, leading companies are demonstrating that environmental improvement can actually increase profitability, and design for environment (DFE) is emerging as an important business practice.

The ability to evaluate environmental quality in objective, measurable terms is a key component of an effective DFE capability. In particular, environmental quality metrics are essential to support goal setting, monitoring, and continuous improvement in the design of products and processes. This article describes environmental quality measurement tools and procedures, particularly as they relate to DFE. One of the challenges of performance measurement is to incorporate a life‐cycle view of environmental performance into measurement tools that can be easily computed and tracked.
A design for environment methodology for evaluating materials
Authors: Allenby Braden R.
Published: February 2007

Industrial ecology is a new multidisciplinary field of study requiring that economic activity be integrated with, and have minimal impact on, surrounding natural systems. This systems‐based approach is beginning to be implemented in private firms through the development of Design for Environment (DFE) methodologies and tools which support the integration of technological and environmental considerations in all economic activities. As part of this development process, a matrix system is proposed by the author by which the environmental and energy costs embedded in materials as used in generic applications may be identified, facilitating environmentally and economically efficient selection of materials. This Material Environmental Evaluation Matrix is supported by checklists which inform the evaluation process. A set of completed matrices for major materials in common applications forms the basis for an Environmentally Efficient Materials Database (EEMD). Once completed, the EEMD would inform consumers, product and process designers, business planners and managers, regulators and government purchasers, public interest groups, and others in their choice of optimal, environmentally and economically efficient, material options.
The audit orientation tour: Ten steps for improving productivity
Authors: Cahill Lawrence B. , Woltjen Deborah
Published: February 2007

It seems like a simple enough exercise. After the opening meeting, the audit team embarks on an orientation tour to familiarize itself with the layout of the facility. A simple „walk about”︁ as the Australians would say. If the site is bigenough, maybe the team climbs into a vehicle for the tour. Although the orientation tour typically represents only one hour, this hour is as important as any other for the audit team. This article discusses ten steps audit teams can take to maximize the effectiveness of the tour. The ten steps came about as a result of observing audit teams during many training audits and seeing persistent problems arise.
Business‐oriented environmental performance metrics: Building consensus for environmental management systems
Authors: Russell William G. , Sacchi Guido F.
Published: February 2007

Today, environmental managers are learning new ways of adding value to their organizations. Before, the environmental department was an overhead expense—an indirect support group required for complying with burdensome regulations. Now, such departments add insights and value during strategic planning sessions, identify efficiency improvement opportunities, provide a superior return on investment, and—bottom line—improve profits. The primary approach to meeting the challenge is a new environmental management system (EMS) that identifies, measures, and manages a diverse set of internal and external customer needs. These needs include environmental cleanups, regulatory compliance, pollution prevention, and design for the environment—and each represents a potential improvement opportunity. Unfortunately, most organizations have so many such needs that all cannot be addressed at once, given the resource constraints of a competitive business climate. Thus, priority is a key concept of an effective EMS. This article describes an innovative application of consensus‐building tools that quickly identify and set priorities for diverse environmental programs. The article also shows how appropriate performance measures will align these programs with corporate goals and objectives.
Industry's role in air quality improvement: Environmental management opportunities for the 21st century
Authors: Rondinelli Dennis A. , Berry Michael A.
Published: February 2007

More than 200 years ago, Adam Smith, the founder of modern economics, wrote in the Wealth of Nations that “…consumption is the sole end and purpose of all production; and the interest of the producer ought to be attention to…that of the consumer.” In recent years, the rapid growth of the world economy has given Adam Smith's maxim new meaning. The age‐old desire for consumption grows unabated and increasing numbers of consumers around the world are attaching new value to the environmental quality of goods and services and expressing concern over the environmental impacts of industrialization. That concern is growing because more than 70 percent of the world's urban population live in areas where the air is seriously polluted and as many as 750,000 people—the majority in developing countries—die each year of ailments caused by air pollution.1

Over the past 25 years, corporations throughout the world have made dramatic changes in the way they do business as more people come to understand how the ecological system works and how polluted air and water endanger human health. The key to increasing industry's participation in the drive for higher standards of air quality is the growing realization that effective environmental management, technological development, and technology dissemination are cost‐effective and profitable business strategies. Global competition is making firms around the world more customer‐conscious and, to the extent that consumers demand products that minimize environmental degradation and enhance the quality of their lives, businesses in every industry must respond in order to survive.2

This article examines how changes in business practices, driven by a better understanding of how natural environments function, are converging to provide new opportunities for environmental management that go beyond regulatory compliance to reduce air pollution. Although sound and well‐enforced environmental regulations are an essential foundation for improving air quality, command‐and‐control systems alone are unlikely to achieve the lower levels of pollution that will be necessary to achieve sustainable development in the 21st century. In cooperation with government, businesses in every industry can play crucial roles in achieving higher standards of air quality while at the same time maintaining acceptable levels of economic growth. We explore three ways in which corporations can contribute to environmentally sustainable development: (1) by adopting proactive environmental management systems that focus on air pollution prevention; (2) by developing new technologies for air pollution control and reduction; and (3) by transferring air pollution control and prevention technologies through international trade and investment.
Environment drives financial performance: The Jury is in
Authors: Kiernan Matthew J. , Levinson Jonathan
Published: February 2007

In a single day, June 13, 1994, the total stock market capitalization of Exxon dropped by a full 5 percent, with news of the company's exposure to additional legal damages from the Exxon Valdez disaster. Despite what should have been a jarring wake‐up call, however, Wall Street investors and company CEOs continue for the most part to conduct business as usual, unpersuaded that environmental considerations are anything more than a superficial and temporary blip on their Bloomberg screens. There is mounting evidence that they're dead wrong. In this article, the authors contend what they're currently sleeping through is nothing less than the beginnings of a profound, worldwide industrial restructuring.
Systems vs. metasystems: EMIS at the crossroads
Authors: Fitzgerald Chris
Published: February 2007

As environmental management responsibilities expand beyond regulations to address business issues such as design for the environment, total cost accounting, and strategic planning, it is tempting to plan for expanded information systems (EMIS) to handle new responsibilities. The author argues that we should pursue exactly the opposite course: shrink the EMIS to the minimum size possible. It would be impossible to feed the self‐standing EMIS with all the data it needs—replicas of almost any data tracked by the organization. The EMS and EMIS should be “meta‐systems” that store the organization's knowledge about how EH&S relates to various business processes, and what should be measured and reported to assure that EH&S objectives are met. The author provides examples of how companies are creating these EMS “metasystems” by leveraging enterprise systems implemented for accounting, business planning, groupware, maintenance, and process control.
Environmental performance benchmarking for electric utilities
Authors: Miakisz Joseph A. , Miedema Allen K.
Published: February 2007

Electric utility companies in the United States and Canada are participating in a unique environmental benchmarking program (EBP) designed to comparatively assess environmental performance. Each company annually provides data on emissionslwastes, compliance, and other environmental aspects to an independent consultant, Research Triangle Institute (RTI), whose staff compiles the data and computes approximately 80 discrete environmental performance metrics for each company. RTI provides a confidential report for each participant presenting the results of the assessment. In addition, RTI conducts a follow‐up assessment to determine “best‐practices” of each of the top performers for each metric. The EBP provides each participant with useful information on its strengths and weaknesses relative to the other companies in the program as well as ideas on how to improve its environmental performance. Annual participation in the program allows a company to measure improvement in performance on an annual basis. This article summarizes the evolution of the EBP and describes the study methods and reporting approach. Our goal in sharing this information is to demonstrate the usefulness of the program and encourage further participation by all major North American electric utilities.
Expanding the benefits of environmental management systems through DFE
Authors: Eagan Patrick D. , Pferdehirt Wayne
Published: February 2007

Industry's role in environmental protection is changing and growing. Increasing evidence shows that a corporation's understanding and response to environmental issues and concerns can have strategically important consequences for some kinds of businesses.1 Focusing on concepts of prevention, industry has developed and struggled with a number of environmental approaches, all of which attempt to link the environment with common business practice. Industry has followed and in some cases embraced concepts and approaches like sustainable development, eco‐efficiency, green manufacturing, pollution prevention, and extended product responsibility. A particularly timely and promising strategy to reduce the environmental impact of both manufacturing and product use while enhancing business success is the integration of environmental management systems (EMS) with design for the environment (DFE) efforts.

A desirable relationship can and should exist between DFE and EMS. This relationship has not been well understood, but is crucial to fulfill the promise of each.

In application, the institutionalization of DFE in an organization is difficult and tenuous at best. Some authors suggest that management issues block the implementation of DFE.2 Others say that DFE has not been institutionalized to the extent that pollution prevention has.3 This article suggests that through an explicit connection between an EMS and DFE, DFE can extend the promise of EMS to reduce industry's environmental impact and produce business success, and it can do so in an ongoing way. The authors will show the importance of an EMS/DFE linkage, suggest company types that might benefit from investigating these approaches, and then review a series of DFE tool types.
Practical life cycle assessment through streamlining
Authors: Weitz Keith A. , Sharma Aarti
Published: February 2007

Life cycle assessment (LCA) provides a concept, framework, and method to identify and evaluate the environmental burdens of products and processes. An ongoing concern of companies trying to implement LCA is the value of LCA in supporting actual decisions versus the resources and time needed to conduct a “full” LCA. In response to these concerns, there has been a lot of activity surrounding the “streamlining” of LCA to keep it more manageable yet provide useful and acceptably accurate results. This article explores the concept of streamlining, discusses where and how streamlining decisions can be made in an LCA, and presents issues related to conducting more streamlined LCAs. Due to the wide variety of purposes and scenarios in which LCAs are conducted, it is difficult to devise a one‐size‐fits‐all method for streamlining. Instead, we have focused on presenting the streamlining options in the context of major decision points that are common to most LCAs.
Investor attitudes toward the value of corporate environmentalism: New survey findings
Authors: Soyka Peter A. , Feldman Stanley J.
Published: February 2007

During the past several years, an increasing body of evidence and opinion has formed concerning the relationships between advancements in environmental, health, and safety (EH&S) management and the financial performance of the organization. In recent work,1 we have described a new theoretical model linking improvements in environmental management systems and environmental performance to corporate risk, stock volatility, and market value, as well as an empirical evaluation that validated our model. A number of other studies2 have documented changes in the market value of corporate equity as a function of environmental accidents, incidents, and (conversely) accomplishments. These are in addition to the numerous examples presented in the literature and at EH&S conferences and symposia that suggest that concerted efforts to reduce the organization's environmental “footprint” can yield cost savings, increased market share, reduced time to market, and perhaps other financial benefits. Some have gone so far as to proclaim that a new era has begun, in which environment‐friendly corporations will increasingly be recognized and rewarded by financial market participants, and organizations that lag behind will be severely penalized.3 This article documents a new survey undertaken to identify important environmental factors, if any, investors employ in evaluating the quality and worth of equity and debt financing instruments.
ISO 14001 registration: The process, the benefits, and the choice of registrar
Authors: Davies Chris , Webber Phil
Published: February 2007

This article introduces the concept of ISO 14001 registration, outlines related assessment processes, and reviews the drivers behind developing an ISO‐14001‐concordant environmental management system (EMS) and seeking third party registration of that EMS. It focuses on registration strategies for larger organizations and considerations in choosing a registrar, including: auditor qualifications, standards for the conduct of EMS audits, and some issues for audit and registration service providers.

The authors conclude that it is beneficial to pursue an ISO‐14001‐concordant EMS and that the value of the system can be enhanced through registration. However, some thought should be given to choosing the appropriate registrar, in particular to their EMS and audit approaches and to the qualifications of their audit team. Service providers are also cautioned to remember that ISO 14001 is not the same as ISO 9000, and that the registrar's standard of care in the discharge of their work should reflect that. © 1998 John Wiley & Sons, Inc.
Education for sustainability: Are we flunking the future?
Authors: Henn Carl L.
Published: February 2007

When New Jersey's Office of Sustainability was originally established in 1997, it was at first quizzically referred to as the “Office of What?” Now, good people, high purpose, and new name (Sustainable Business Division of the Commerce Commission) have steadily gained respect as skeptics reflected on what the term sustainability can mean to life on earth as we know it in New Jersey and elsewhere. Current rates of growth in population, industrial production, consumerism, and environmental degradation cannot be supported indefinitely by Earth's finite carrying capacity. New ways of thinking, working, and living will be required to change our course of unsustainable human activity both locally and globally. Such a transformation is achievable only through major changes in education. This article contends that the rate, content, and scope of learning required to take a sustainable path in America are not happening. Some ideas for what needs to be done are suggested.© 1999 John Wiley & Sons, Inc.
Selling green: What managers and marketers need to know about consumer environmental attitudes
Authors: Kaufman Lois
Published: February 2007

Research clearly shows that the environment is not going to go away as an issue of public concern. In fact, for many people, the environment is no longer simply an issue—it is a way of life. This is not likely to change. What has changed, however, is today's consumer. Today we are faced with a different type of consumer: one who is more knowledgeable on environmental issues—and more demanding. Environmental messages can be effective in reaching these potential buyers—but only if corporate managers and marketers understand public concerns and learn how to craft their environmental marketing strategies. © 1999 Integrated Marketing Services (IMS) and Environmental Research Associates, a division of IMS, Princeton, New Jersey. Reprinted with permission.
Environmental risk and liability management and its influence on profitability
Authors: Fletcher Charles D. , Paleologos Evan K.
Published: February 2007

Managing environmental risk and liability for corporations and consultants requires a prudent combination of insurance techniques, company risk control plans, pollution prevention, and the proper allocation of retention funds. This article presents a review of current risk management techniques used to shield profits from limited and catastrophic loss scenarios. We recommend that corporations and consulting firms integrate insurance and risk management planning to mitigate environmental liabilities, navigate business risks, and safeguard corporate performance..© 1999 John Wiley & Sons, Inc.
Kinetic studies of human and rat neutrophil lysoPAF acetyltransferase using lysoPAF and dansyllysoPAF as substrates
Authors: Schindler Peter W. , Ninio Ewa
Published: February 2007

Enzyme kinetic studies of lysoPAF acetyltransferase from microsomal preparations of human and rat neutrophils were carried out using lysoPAF or dansyllysoPAF as substrate. With the human enzyme, incomplete conversion of the substrate into the product was observed at 37°C with both substrates. The acetyltransferase was inactivated at 37°C in the absence of substrate with a half‐life of 7.5 min. However, the initial rate of product formation under the assay conditions was linear up to 10 min. Both enzymes were optimally active at 40 μM concentration with either substrate, but enzyme activity was inhibited at higher substrate levels. At a constant substrate concentration (40 μM), the Km (μM) and Vmax (nmol product/min/mg protein) values for the human acetyltransferase, with respect to acetyl‐CoA were 132 and 23.1, respectively, with lysoPAF as substrate, and 105 and 26.7, respectively, when dansyllysoPAF was used. The Km and Vmax values for the rat enzyme were 105 and 6.5, respectively, with lysoPAF as substrate, and 120 and 5.4, respectively, when dansyllysoPAF was used. Under our standard conditions, lysoPAF required 1 mg of BSA per mL in the assay, whereas full activity of both enzymes was seen with dansyllysoPAF even in the absence of BSA. The results show that dansyllysoPAF can replace lysoPAF in the assay without any significant changes in kinetic parameters.
The hormonal regulation of platelet‐activating factor acetylhydrolase activity in plasma
Authors: Miyaura Shuichi , Maki Noriei , Byrd William , Johnston John M.
Published: February 2007

We have previously reported that certain fetal tissues including the lung and kidney have an increased platelet‐activating factor (PAF) content and enzymatic mechanism for its elevated biosynthesis during the latter stages of pregnancy. In contrast, in the maternal plasma compartment of both the rabbit and human, a decreased capacity to inactivate PAF has been demonstrated. The PAF acetylhydrolase in the fetal plasma is also suppressed. The present study was undertaken to determine the mechanism(s) involved in the regulation of PAF acetylhydrolase. The 17α‐ethynylestradiol was administered (intraperitoneal [i.p.] 2.5 mg/kg body wt 5 days) to female and male rats. The plasma PAF acetylhydrolase activity decreased 5‐fold. A decrease was observed when a concentration of the estrogen as low as 50 μg/kg was employed. The injection of dexamethasone (i.p., 1.3 mg/kg body wt, 5 days) to male and female rats resulted in a 3‐fold increase in the plasma PAF acetylhydrolase activity. The activity returned to the values prior to hormone treatment 4 days after cessation of treatment. Testosterone and progesterone were without effect on plasma acetylhydrolase activity. The change in PAF acetylhydrolase activity caused by estrogen and the glucocorticoid was reflected by a change in the activity in the HDL fraction and not due to the presence of an inhibitor or activator in the plasma of the hormone‐treated animals. Human serum obtained from a group of women, in which the 17β‐estradiol concentration was elevated in preparation for anin vitro fertilization procedure, showed an inverse relationship between the plasma estrogen concentration and the PAF acetylhydrolase activity. It is suggested that estrogen is responsible for the regulation of PAF acetylhydrolase and the decrease in the plasma PAF acetylhydrolase during the latter stages of pregnancy in both the maternal and fetal plasma caused by the hyperestrogenic state that occurs during this period. The observed increase in PAF acetylhydrolase by dexamethasone may account for, in part, the known anti‐inflammatory properties of this steroid by decreasing the concentration of this potent autacoid.
Recent advances in our understanding of the biochemical interactions between platelet‐activating factor and arachidonic acid
Authors: Chilton Floyd H. , Cluzel Marc , Triggiani Massimo
Published: February 2007

In the last few years, it has become increasingly apparent that the biochemistry of PAF (platelet‐activating factor) and that of arachidonic acid are interrelated in a number of inflammatory cells. Experiments presented here further point out that arachidonic acid plays a crucial role in the catabolism and biosynthesis of PAF. In addition, they suggest that the same phospholipid molecular species may serve as a source for both arachidonic acid and 1‐alkyl‐2‐lyso‐sn‐glycero‐3‐phosphocholine during cell activation. Finally, they reveal that there may be common regulatory mechanisms for the biosynthesis of PAF and arachidonic acid metabolites. Taken together, studies examining the relationship between PAF and arachidonic acid suggest it may be difficult to consider the biochemistry of PAF without considering arachidonic acid metabolism and vice versa.
Chemical synthesis and physiological activity of sulfonium analogues of platelet activating factor
Authors: Kates Morris , Adams George A. , Blank Merle L. , Snyder Fred
Published: February 2007

Phosphatidylsulfocholine (PSC), the sulfonium analogue of phosphatidylcholine (PC), occurs naturally in some diatoms. The replacement of the −N+(CH3)3 group by a −S+(CH3)2 results in an increase in the polar head group size in PSC relative to that of PC, consistent with the observed increase in permeability of PSC bilayers towards urea. It was of interest to see whether replacement of the −N+(CH3)3 group in platelet activating factor (PAF) by an −S+(CH3)2 group leads to any change in platelet aggregation or other physiological activity. Synthesis of the sulfonium analogue of PAF was carried out by suitable modifications of known procedures. The PAF‐sulfonium analogue was found to have almost the same platelet aggregating activity as PAF itself, in the concentration range 1–20 μM, but a much lower activity in the range 0.01–1 μM. The analogue had little or no effect on the platelet aggregation activity of PAF when added in the concentration range 0.01–1 μM and had about half the hypotensive activity of PAF towards hypertensive CDF male rats. The sulfonium analogue, however, was much more cytotoxic to HL‐60 cells than PAF itself, in the concentration range 0–15 μM; replacement of the acetate group by a benzyl group increased the cytotoxicity to the level of that of the methoxy analogue of PAF. Thus, replacement of the −N+(CH3)3 group by a −S+(CH3)2 group in the polar head group region of PAF results in a relatively small change in its platelet aggregation activity and a decrease in its hypotensive activity, but greatly increases its antitumor activity.
Thieno‐triazolo‐1,4‐diazepines as antagonists of platelet‐activating factor: Present status
Authors: Casals‐Stenzel Jorge
Published: February 2007

The platelet‐activating factor, 1‐O‐alkyl‐2‐acetyl‐sn‐glycero‐3‐phosphocholine, (PAF) antagonistic activity of thienotriazolodiazepines has recently been described. The lead compound in this series was brotizolam, which also exhibits sedative and hypnotic effects. By combination of brotizolam with the benzodiazepine receptor antagonist RO 15‐1788, PAF antagonistic and central nervous system (CNS) activities could be segregated. Systematic structure variation has led to potent and selective PAF antagonists without CNS effects. WEB 2086 and its analogues WEB 2170 and STY 2108 are representative examples of this structural type and have shown a high potency and selectivity in PAF‐induced and PAF‐dependentin vitro tests and in experimental models. Studies in healthy volunteers have demonstrated potent pharmacological activity and good safety and tolerance of oral, intravenous or inhaled WEB 2086 in man. These agents should therefore prove useful for the further elucidation of the pathophysiological role of PAF and provide an opportunity for therapeutic applications in diseases in which the involvement of PAF has been implicated.
PAF receptor structure: A hypothesis
Authors: Godfroid J. J. , Dive G. , Lamotte‐Brasseur J. , Batt J. P. , Heymans F.
Published: February 2007

Different hypotheses of the structure of platelet‐activating factor (PAF) receptor based on structure‐activity relationships of agonists and antagonists are reviewed. For an agonistic effect, strong hydrophobic interactions and an ether function are required in position‐1 of the glycerol backbone; chain length limitations and steric hindrance demand a small group in position‐2. The unusual structural properties of non‐PAF‐like antagonists required 3‐D electrostatic potential calculations. This method applied to seven potent antagonists suggests a strong “Cache‐oreilles” (ear‐muff) effect,i.e., two strong electronegative wells (isocontour at −10 Kcal/mole) are located at 180° to each other and at a relatively constant distance. Initial consideration of the “Cache‐oreilles” effect implied the structure of a bipolarized cylinder of 10–12 Å diameter for the receptor. However, very recent results on studies with agonists and antagonists structurally similar to PAF suggest that the receptor may in fact be a multi‐polarized cylinder.
Intracellular Ca2+ concentration and H2O2 production in mouse peritoneal macrophages are stimulated by platelet activating factor
Authors: Sasaki Masayuki , Maeyama Kazutaka , Watanabe Takehiko
Published: February 2007

The intracellular calcium concentration ([Ca2+]i) in mouse peritoneal macrophages cultured on a coverglass was measured in the superfusion system using fura‐2 as a fluorescent calcium probe and platelet activating factor (PAF) as a stimulant. In the presence of extracellular Ca2+, 10−7M PAF sharply increased [Ca2+]i from a basal level of 90 nM to 340 nM. Thereafter, the [Ca2+]i level gradually decreased in two phases, in an initial rapid phase and a subsequent slow phase of decrease. The calcium response was dependent on the PAF concentration. In the absence of extracellular Ca2+, a single sharp peak was observed, suggesting two different modes of Ca2+ movement, one from intracellular stores and the other from the extracellular medium. A simple, sensitive fluorometric assay system was developed for measuring H2O2 in the superfusate of macrophages after stimulation by use of immobilized peroxidase and 3‐(p‐hydroxyphenyl)propionic acid as a fluorogenic substrate. With this system, as little as 2 pmol of H2O2 could be measured. PAF (1 μM) increased H2O2 production in peritoneal macrophages in the presence of extracellular Ca2+, but H2O2 production was not observed in the absence of extracellular Ca2+.
Platelet‐activating factor stimulates receptor‐mediated fromation of reactive oxygen intermediates in human monocytes
Authors: Pustynnikov M. G. , Porodenko N. V. , Makarova O. V. , Kozyukov A. V. , Moskaleva E. Yu. , Sokolovsky A. A. , Severin E. S.
Published: February 2007

Stimulation of production of reactive oxygen intermediates (ROI) was examined in human peripheral blood monocytes by luminol‐dependent chemiluminescence. The dose‐response cureve characterizing the dependence of ROI production on the concentration of platelet‐activating factor (PAF) showed that stimulation occurred within a concentration range of 2×10−9M to 5×10−6M. Transformation of the dose‐response curve to an Eadie‐Hofstee plot indicated that the process is characterized by two Km values. The Km value corresponding to the high‐affinity branch of the curve is 1.3±0.14 nM. In the same cells, the dissociation constant for the [3H]PAF/receptor complex was determined. The Kd value was 0.8±0.1 nM, which agreed quite well with the high‐affinity Km value obtained in the Eadie‐Hofstee plot. The data indicate that stimulation of ROI generation is mediated through PAF binding at specific receptor sites at nanomolar PAF concentrations. Along with the specific receptor‐mediated ROI generation, a nonspecific effect of PAF at a high concentration was demonstrated.
Role of platelet‐activating factor (PAF) in superoxide production by human polymorphonuclear leukocytes
Authors: Takahashi Shuji , Yoshikawa Toshikazu , Naito Yuji , Tanigawa Toru , Yoshida Norimasa , Kondo Motoharu
Published: February 2007

The effect of platelet‐activating factor (PAF) in superoxide production by human polymorphonuclear leukocytes (PMN) was studied. Cypridina luciferin analog (CLA) dependent chemiluminescence was used to detect superoxide anion radicals. PAF induced superoxide generation in human PMN in a dose‐dependent manner. Preincubation with a small amount of PAF (5 x 10−9 M) enhanced PMN superoxide release induced by various stimuli, such as phorbol myristate acetate (PMA), opsonized zymosan (OZ), calcium ionophore (A23187) andN‐formyl‐methionyl‐leucyl‐phenylalanine (FMLP). The PAF antagonist, CV‐6209, inhibited superoxide production induced by PAF, but not that induced by other stimuli. These findings would indicate that PAF may play an important role at inflammatory reaction sites and that CV‐6209 may inhibit excessive inflammatory reaction.
Platelet activating factor‐induced pulmonary accumulation of111indium‐oxine labelled neutrophils in anesthetized guinea pigs
Authors: Hultkvist‐Bengtsson Ursula , Anderson Gary P. , Kings Madeleine , Morley John
Published: February 2007

The thoracic accumulation of neutrophils labelled with111Indium‐oxine in response to infusion of platelet activating factor (PAF, 18 ng/kg/min × 5 min, i.v.) was studied using an automated isotope monitoring system (AIMSplus) in anesthetized guinea‐pigs. Loss of cell associated radioactivityin vitro was less than 1% over 4 hr. Labelled neutrophils maintained their functional capacity (oxidative response to the cell stimulants N‐formyl‐L‐methionine‐L‐leucine‐L‐phenylalanine and phorbol myristate acetate) and >95% viability (ethidium bromide/acridine orange stain)in vitro. Total thoracic radioactivity increased significantly from baseline in response to PAF with a slight tachyphylaxia in the neutrophil‐accumulation after a repeat PAF infusion. The highest ratios of radiolabel (tissue/blood) were found in the spleen >>liver>lung.
Platelet activating factor induced respiratory mucosal damage
Authors: Hisamatsu Ken‐ichi , Ganbo Tetsuya , Nakazawa Tsutomu , Murakami Yoshihiko
Published: February 2007

Human sinus mucosal specimens from eight normal individuals were exposed to platelet activating factor (PAF) at concentrations ranging from 10−6 M to 10−11 M in a humidified CO2 chamber at 37°C. The mucosal surface of the specimens was recorded on video tapes and magnified 2,500 times on a 19‐inch television (TV) monitor. Ciliary activity of each ciliated cell was photoelectrically measured on the TV monitor in real time. PAF induced mucosal damage which resulted in a coarse profile including ciliostasis and exfoliation of epithelial cells. The length of the incubation period in which the initial coarse profile occurred on the mucosal surface inversely correlated with the concentration of exposed PAF ranging from 10−6 M to 10−10 M with r=−0.712 (p<2×10−4). Both the control medium and 10−8 M lysoPAF showed no effect on ciliary activity or mucosal surface alteration even after 24 hr of exposure. Significant ciliary inhibition was noted after 6 hr of exposure to PAF at concentrations of 10−8 M and 10−10 M (p<0.05). After 10 hr of exposure, significant ciliary inhibition (p<0.01) was noted at all concentrations. Inhibition occurred in a time‐ and dose‐dependent manner. The length of the incubation period in which initial ciliostatis occurred and the level of PAF concentration showed an inverse correlation with r=−0.918 (p<10−6). These results indicate that PAF is cytotoxic to human respiratory mucosa.