bluuebunny/crossref_metadata_2025 huggingface dataset:
Designing effective community relations programs
Authors: Forrest Carol J. , Mays Renee Hix
Published: February 2007

Cleanup of a contaminated site is halted as community residents launch a legal challenge against the method that those responsible for the site have selected for remediation.

Parents and teachers at a public school call for an investigation to determine if substances in the building are making students and staff sick. Midway into the investigation, they also become concerned as to whether the right tests are being performed to detect contamination that may be present, and how they will know what the test results mean.

Industrial neighbors of a facility oppose its air permit application out of concern for the effects the facility's emissions might have on their own workers.

Virtually no business enterprise or government entity is immune from the potential for public interest in or concern about environmental issues. Within the public arena, environmental issues are rarely viewed only in terms of their scientific, technical, or regulatory merits. Instead, they are invariably intertwined with other issues and perceptions regarding health and safety, property values, social justice, and overall quality of life. As such, environmental issues have the potential to create significant controversy, concern, and opposition among community residents.

Fortunately, in many cases, much, if not all, of the anger and fear that community residents feel can be relieved through a substantive dialogue that either corrects misinformation or provides a platform for discussing actions that could, should, or are taking place to remedy a situation. Promoting and sustaining such dialogues is the goal of community relations. This article covers the process of designing and implementing a community relations program plan to address serious or long‐term environmental issues surrounding facilities, sites, or projects.
A strategy for integrating NEPA with EMS and ISO 14000
Authors: Eccleston Charles H.
Published: February 2007

It is vital that federal managers consider new approaches for enhancing environmental protection while reducing redundancies and cost. Faced with increasing environmental issues, compliance requirements, competing resources, and tightened budget constraints, agencies must seek innovative approaches for doing more with less. The diverse array of confusing and sometimes inappropriate or conflicting regulatory requirements compounds compliance complexities and increases the need to seek resourceful solutions.

At a time when NEPA is coming under closer congressional scrutiny, an integrated NEPA/EMS paradigm provides a key for increasing the effectiveness and uniformity of implementing NEPA at the early planning stage, while reducing cost, delays, and redundancies. Effectively integrated, NEPA satisfies one of the five, and perhaps most important, principles of an EMS‐environmental planning. NEPA's regulatory requirements not only are consistent with the objective of an EMS, but actually enhance the effectiveness of an EMS. An integrated approach provides the added benefit of increased environmental coordination and heightened communications that translates into further cost reduction and fewer delays. The strategy described in this article is designed to balance the rigors of an international standard with the need to efficiently implement an integrated NEPA/EMS system, given a diverse set of challenging circumstances and constraints.
EcoMetrics: Integrating direct and indirect environmental costs and benefits into management information systems
Authors: Friend Gil
Published: February 2007

This article suggests a set of metrics that may impact both profitability and environmental quality, capture and quantify eco‐efficiency costs and benefits, and help managers understand and focus on tangible, yet difficult‐to‐quantify benefits (such as improved morale, innovation, etc.). In order to do this, it will frame the issues pertinent to developing eco‐efficiency metrics; identify criteria for effective metrics to enable companies/consultants/etc. to discuss, evaluate, and select program metrics; outline the universe of possible metrics; suggest key metrics for a typical company; identify data quality, availability and other constraints; and suggest a methodology for incorporating environmental metrics into operating metrics.

[Note: This article is not intended to provide a definitive overview of environmental metrics; rather, it proposes an operational framework for considering, selecting, and implementing metrics that are meaningful in both environmental and business terms. For an overview, see for example, Environmental Policy Performance Indicators;1 Company Environmental Reporting;2 The Greening of Industrial Ecosystems;3 Measuring Corporate Environmental Performance4].

The flow and embodiment of materials and energy in production and consumption activities of the economy underlie both economic growth and environmental perturbations… [Yet] existing accounting systems can prevent modern firms from internalizing environmental costs and considerations, and can compound difficulties encountered in effecting environmentally preferable changes5.
Implementing ecological opportunity assessments: NJTAP's ECŌ·PA program for process safety and risk management
Authors: Wolgast Eileen M. , Roesler Arthur C. , Healey Marcus J.
Published: February 2007

Chemical mishaps, in some cases leading to fires and explosions, may pose a threat to workers in the manufacturing industry, the general public, and to the environment in general. In response to this concern, the New Jersey Technical Assistance Program (NJTAP) for Industrial Pollution Prevention, in conjunction with the Chemical Industry Council and the Responsible Care® Initiative, has launched a new program called ECO¯·PA, an Ecological Opportunity Assessment for Process Safety and Risk Management. Environmental and safety regulations have become more complex, and since small businesses typically have fewer resources available to interpret these regulations, they may have trouble complying despite their good faith efforts. ECO¯·PA addresses this need for compliance. Now that the program is available, how does one contact and provide this assistance to appropriate clients? NJTAP has created an algorithm for targeting clients which may be useful for other nonprofit organizations.
Using envirodaemon to search the internet for environmental information and building custom search engines
Authors: Healey Marcus J. , Lewis Jeffrey T. , Samtani Gunjan
Published: February 2007

The Internet holds vast stores of information pertaining to pollution prevention and environmental issues, and with each day more is added. Yet, as this storehouse grows, the difficulty of finding specific information increases. This article details how EnviroDaemon was built to ease the task of finding this information and knowledge base. It automatically builds and updates a catalog of objects at pre‐selected Internet sites that are related to pollution prevention. Users search for information by submitting keywords. Searches can be restricted to small subsets of the indexed sites by choosing one of five search criteria, or the entire catalog can be searched. The results are returned rapidly and are embedded in several lines of text to provide context. If the text looks promising, the user can click on a hyperlink to access the full article.

Since its release in March, EnviroDaemon has seen increasing use, especially following its demonstration at the National Pollution Prevention Roundtable Conference. The authors also discuss the process of building this search engine to show interested readers how to create other environmental custom search engines.
Case study: Building an ISO 14001‐compatible EMS at Mead Coated Board, Mahrt Mill
Authors: Weisse Carrie , Edgley Gerald , Cooper Laura
Published: February 2007

Many companies are using ISO 14001 as a guide in formalizing their environmental management system (EMS). This article presents Mead Coated Board, Mahrt Mill's experiences in this process, which involved undertaking a gap analysis and developing the key elements and specific procedures that comprise the EMS. Specific issues addressed include the various techniques and approaches used for developing procedures based on the type and level of procedure required; the interaction between the consultants and the mill personnel; the methods for capitalizing on the experience and expertise of the consultant and the internal personnel to achieve the desired results and lessons learned in the process.
Integrating total cost assessment with new management practices and mandates
Authors: Kennedy Mitchell L.
Published: February 2007

Today's environmental manager cannot afford to operate in a vaccum, but continually adjusts to the latest management initiatives, whether it is Activity Based Costing, ISO 14000, or Total Quality Management. These paradigms offer an excellent structure to view process improvements and implement changes, however, they all tend to miss the mark in one critical area—quantifying and tracking the true cost of environmental management. The recent upsurge of interest in Total Cost Assessment (TCA) is proof positive that, although many excellent management programs exist, something is still missing. In this article, the author shows how using TCA in conjunction with these practices enhances their effectiveness and shows the total picture of environmental management costs.
Ecometrics' stakeholder subjectivity: Values, issues, and effects
Authors: Allenby Braden , Yasui Itaru , Lehni Markus , Züst Ranier , Hunkeler David
Published: February 2007

Stakeholder groups, defined according to their transcendent values, have different concepts of sustainability. Their prioritizations of individual, family, collective, and local and global environmental issues also differs. Given this, the metrics required for a given sustainable development path are subjective. Therefore, the questions of who should define ecometrics, their transparency, number, state of aggregation, standardization, and benchmarking are questions that require an enfranchised multi‐stakeholder debate. At present, corporations have been asked to bear the burden of environmental reporting and eco‐indicators have been established to account for material intensity, energy consumption and waste or toxic releases, among other factors. However, the links among these local‐, product‐, or service‐based microecometrics and global states such as temperatures or atmospheric concentrations have yet to be established. The relationship of macroecometrics to individual definitions of sustainable development also has not been addressed. This article summarizes four plenary lectures given at ECOMETRICS '98 in Lausanne, Switzerland. The workshop involved forty participants from industry, academic and government organizations representing seven countries and three continents.
Highlights from a new petroleum industry report benchmarking performance, policies, and expenditures
Authors: Levinson Jonathan
Published: February 2007

Environmental Information Services, Inc. (EIS) publishes detailed reports and offers custom research related to the full spectrum of environmental issues facing corporations. This article highlights several key sections from EIS's new 1998 Petroleum Industry Report. It details the environmental performance, policies, and expenditures of the largest companies in the petroleum industry. EIS industry reports contain data on five key performance criteria—toxic waste management, hazardous waste generation, penalties, spills, and Superfund sites. Here we examine one of those—penalties—and the policies of the three largest companies. In the full report, which can be obtained from EIS, 15 corporations are analyzed based on all the performance criteria.
The electric utility business case for investigating EMS: ISO 14000 and beyond
Authors: Balikov Henry R.
Published: February 2007

This article will focus on how a systems approach can be used as a strategic tool for environmental improvement that makes sense from a perspective of bottom‐line financial performance. The author will discuss some real‐world experience concerning how electric utilities are attempting to align environmental management more closely with business management theory and practice. The ISO 14000 standards have been proposed and, in many instances, finalized as global voluntary standards. How important will they be to the U.S. electric utility sector? ISO 14001, the EMS standard, has been promoted as a necessary “certificate” for those who sell products and/or services overseas. In fact, to be of value to most organizations, the standard must show that it can make a positive financial contribution, whether the service or product is marketed globally, nationally, or locally. © 1998 John Wiley & Sons, Inc.
Highlights from a new aerospace industry report
Authors: Levinson Jonathan
Published: February 2007

Environmental Information Services, Inc. (EIS) publishes detailed reports and offers custom research related to the full spectrum of environmental issues facing corporations. This article highlights several key sections from EIS's new 1998 Aerospace Industry Report. It details the environmental performance, policies, and expenditures of the largest companies in the aerospace industry. EIS industry reports contain data on five key performance criteria—toxic waste management, hazardous waste generation, penalties and enforcement actions, spills, and Superfund sites. Here we examine one of those—penalties and enforcement actions—and the policies of the three largest companies. © 1998 John Wiley & Sons, Inc.
New field report shows ISO 14001 gaining momentum: Acceptance of environmental management system standard parallels ISO 9000
Authors: Jackson Suzan L.
Published: February 2007

Many believe that someday ISO 14001 will be as common as ISO 9001. Whatever the case, companies are finding that ISO 14001 offers a very beneficial way to run an environmentally friendly, profitable business. In this new field report, the author shows how companies are focusing on opportunities to improve their EMSs and achieving financial and business goals with ISO 14001. © 1998 John Wiley & Sons, Inc.
Sustainability metrics for the business enterprise
Authors: Richards Deanna J. , Gladwin Thomas N.
Published: February 2007

Sustainable development poses challenges and opportunities to the development and management of business and technological systems. Most significantly, sustainability moves beyond meeting an economic and environmental bottom line to a triple bottom line of integrated economic, environmental, and social factors. Over 30 years there has been a paradigm shift that has led to the greening of industrial practices with regards to the environment. As evidence continues to demonstrate linkages between environmental causes and effects, problem‐solving techniques have been developed to meet both economic and environmental goals along with metrics to measure environmental performance. Today, sustainable development presents another paradigm shift and adds social considerations as a third element to the bottom line. This article describes the evolution from greening to sustaining and outlines the implication of developing metrics in the sustainable development context.© 1999 John Wiley & Sons, Inc.
Sustainability, eco‐efficiency, life‐cycle management, and business strategy
Authors: Brady Kevin , Henson Patrice , Fava James A.
Published: February 2007

This article outlines some of the rationale for integrating environment and sustainablility issues into core business practises and provides some guidance on how companies can begin to take a strategic view when selecting environmental management tools. Two of these tools, life cycle management and eco‐efficiency, are outlined in brief.© 1999 Five Wind International. Reprinted with permission by John Wiley & Sons, Inc.
Integrating a life‐cycle assessment with NEPA: Does it make sense?
Authors: Eccleston Charles H.
Published: February 2007

The National Environmental Policy Act (NEPA) of 1969 provides the basic national charter for protection of the environment in the United States. Today NEPA provides an environmental policy model, emulated by nations around the world. Recently, questions have been raised regarding the appropriateness and under what conditions it makes sense to combine the preparation of a NEPA analysis with the International Organization for Standardization (ISO) ISO 14000 standards for Life‐Cycle Assessment (LCA). This article advances a decision‐making tool consisting of six discrete factors for use in determining when it is appropriate to perform an integrated NEPA/LCA analysis. Properly applied, this tool should reduce the risk that an LCA may be inappropriately prepared and integrated with a NEPA analysis.© 1999 John Wiley & Sons, Inc.
Off‐site consequences: Life after risk management plans, Part I—public response
Authors: Forrest Carol J.
Published: February 2007

Many environmental and facility managers view the submittal and public availability of their facilities' risk management plans (RMPs) as discrete events and give little thought about how RMP information may influence their future relations with plant communities and other stakeholders. In fact, the public availability of RMPs will have some significant and lasting consequences that have the potential to alter RMP sources' relations with a wide variety of stakeholders.

This article is the first of two installments that will explore some of the likely outcomes of the risk management program, with a particular emphasis on those consequences tied to the public availability of the RMPs themselves. This installment considers likely responses at the community level and from both national and local environmental advocacy groups. The second installment will look at likely responses to RMP information in land use planning, by the financial services sector, by regulatory agencies, and by the senior management of RMP sources' owners and operators.

Although the responses of individual communities to RMPs will be governed by a number of variables, including the nature of existing relations with individual RMP sources, proximity (or perceived proximity) of residences or other public and environmental receptors to RMP sources, and stakeholders' attitudes toward chemicals and chemical use, there are certain potential responses that managers should look for in their communities. These RMP‐driven responses and expectations are discussed in the first installment of this article.© 1999 John Wiley & Sons, Inc.
Alternative energy: Environmental and economic factors associated with renewable energy and creating new integrated energy management systems
Authors: Kolar James L.
Published: February 2007

At best, the future of alternative and renewable energy remains uncertain. Our dependency on fossil fuels is already depleting world supplies of coal and petroleum while increasing greenhouse gas emissions. Most assuredly, the ability of alternative energy, described in this article as biomass, hydrogen, wind, solar, and geothermal power, to compete and even integrate with fossil fuels will depend on several important variables: First, developing, as well as developed, countries must be willing to direct long‐term public and private funding towards innovative energy technologies by increasing research and promoting public education. Secondly, the “bottom line” economics associated with alternative energy technology must clearly show a positive cost/benefit ratio. Revenues and not deficits are paramount to the sustainability of alternative energy. Lastly, many experts argue for the environmental benefits of alternative energy by way of carbon reductions. The 1997 Kyoto Global Warming Treaty requires the United States in particular to reduce carbon dioxide emissions from fossil fuel burning by 7 percent below 1990 levels. While many experts argue that reactions to global warming and the alternative energy benefits anticipated because of them are fiscally irresponsible and not worth the billions of tax dollars intended, we can be assured that a business‐as‐usual attitude will continue without increased government and public support.© 1999 John Wiley & Sons, Inc.
ISO 14001 and total cost assessment: The perfect match?
Authors: Kennedy Mitchell
Published: February 2007

ISO 14001 offers an excellent framework for improving your environmental management system. But making it live up to its potential will depend on using the proper data‐gathering and decision‐making tools. And one of the best tools around is total cost assessment.© 1999 John Wiley & Sons, Inc.
U.S. Postal service northeast area master plans: Cutting edge environmental management for the real world
Authors: Vidich Charles , Robbins Ronald
Published: February 2007

The U.S. Postal Service faces a range of environmental challenges as broad as those encountered by many large industries. The Postal Service's Northeast Area has responded with a carefully crafted, far‐reaching approach to environmental management that relies on several key components—chief among which is a comprehensive Environmental Compliance Master Plan.© 1999 John Wiley & Sons, Inc.
Regulation of the biosynthesis of platelet‐activating factor in alveolar macrophages
Authors: Sugiura Takayuki , Ojima‐Uchiyama Ayako , Masuzawa Yasuo , Fujita Masamichi , Nakagawa Yasuhito , Waku Keizo
Published: February 2007

Activities of enzymes which metabolize lysoplatelet‐activating factor (lysoPAF) and platelet‐activating factor (PAF) were studied in rabbit alveolar macrophage lysates. Substantial acetyltransferase activity was noted in the presence of 100 μM acetyl‐coenzyme A (CoA), and this activity was increased in A23187‐stimulated cell lysate. On the other hand, in the absence of exogenous acetyl‐CoA, lysoPAF was mainly acylated through a transacylation pathway rather than by acetyltransferase in both control and A23187‐stimulated cell lysates. We confirmed that the intracellular concentration of acetyl‐CoA is relatively low. The observations suggest that the transacylation system may play an equally important role in the regulation of the availability of lysoPAF in intact cells. Intracellular lysoPAF was also maintained at relatively low levels. Interestingly, large amounts of PAF were produced even in unstimulated cells upon addition of an excess of exogenous lysoPAF, suggesting that generation of an adequate amount of lysoPAF within cells may be sufficient to trigger PAF synthesis in this type of cells.
Properties of PAF‐synthesizing phosphocholinetransferase and evidence for lysoPAF acetyltransferase activity in rat brain
Authors: Goracci Gianfrancesco , Francescangeli Ermelinda
Published: February 2007

Several reports have indicated that platelet‐activating factor (PAF) may play a role in the physiopathology of nervous tissue. We previously have demonstrated the presence, in the microsomal fractions of rat brain, of a phosphocholinetransferase which is able to synthesize PAF by thede novo pathway. The presence of dithiothreitol in the medium increases the rate of PAF biosynthesis, whereas it inhibits the synthesis of long‐chain alkylacyl‐ and diacyl‐glycerophosphocholines (GPC), including dioctanoyl‐GPC. This and other properties, such as pH dependence and thermal stability, indicate that rat brain may have two distinct enzymes for the synthesis of PAF and other choline phospholipids. The affinity of these enzymes for CDPcholine is similar to that reported for other tissues, the Km being 42 μm and 55 μm with alkylacetylglycerol and dioctanoylglycerol as lipid substrates, respectively. The Vmax values were 3.0 and 2.2 nmol/mg prot/min for PAF and dioctanoyl‐GPC, respectively. In addition, it was shown that the microsomal fraction of rat brain contains an acetyltransferase which can convert lysoPAF to PAF. Since it has been reported previously that brain tissue possesses phospholipase A2 activity that can hydrolyze alkylacyl‐GPC to lysoPAF, we conclude that brain tissue has all enzymic activities for the synthesis of PAF by the “remodeling pathway”. The role of the two routes of PAF biosynthesis in nervous tissue remains to be established.
The metabolism of 1‐acyl‐PAF in rabbit platelets and its possible interaction with PAF
Authors: Touqui Lhousseine , Soares Silva Clystenes , Boris Vargaffig Bernardo
Published: February 2007

The metabolism of 1‐acyl‐2‐acetyl‐sn‐glycero‐3‐phosphocholine (1‐acyl‐PAF), a naturally occurring analogue of platelet activating factor (PAF), was investigated in rabbit platelets. Our studies showed that 1‐acyl‐[3H]PAF (1‐palmitoyl‐2‐acetyl‐sn‐glycero‐3‐phospho[N‐methyl‐3H]‐choline) was converted by platelets into phosphatidyl‐[3H]choline ([3H]PC) in a time‐dependent fashion. The formation of [3H]PC occurred at a rate similar to that observed when lyso‐[3H]PC (palmitoyl‐sn‐glycero‐3‐phospho[N‐methyl‐3H]choline) was used as substrate. In addition, a time‐dependent increase in the level of water‐soluble radioactivity was observed during the incubation of platelets with either 1‐acyl‐[3H]PAF or lyso‐[3H]PC. This increase was parallel to the formation of [3H]PC and was not observed in the presence of [14C]PAF (1‐octadecyl‐2‐acetyl‐sn‐glycerol‐3‐phospho[N methyl‐14C]choline). Analysis by thin‐layer chromatography showed that the soluble radioactivity was mainly associated with glycerophosphocholine (GPC). On the other hand, the preincubation of platelets with phenylmethylsulfonyl fluoride, an inhibitor of the acetylhydrolase, reduced the hydrolysis of 1‐acyl‐[3H]PAF to [3H]GPC with a concomitant accumulation of radioactivity in 1‐acyl‐PAF. These findings suggest that 1‐acyl‐PAF is converted into PC through deacetylation‐reacylation with lysoPC as an obligatory intermediate. The findings also indicate that the lysoPC resulting from 1‐acyl‐PAF is either reacylated to phosphatidylcholine (PC) or hydrolyzed to GPC by lysophospholipase. Finally, we showed that the stimulation of platelets with PAF led to a time‐ and concentration‐dependent increase in the conversion of 1‐acyl‐[3H]PAF to [3H]PC. The stimulatory effect of PAF was not observed when platelets were lysed before incubation, suggesting that PAF enhances the metabolism of 1‐acyl‐PAF, probably by accelerating its translocation through the plasma membrane.
Inositol phospholipid turnover in PAF transmembrane signalling
Authors: Shukla Shivendra D.
Published: February 2007

In a variety of cells and tissues, platelet activating factor (PAF) stimulates phospholipase C catalyzed breakdown of phosphoinositides. This results in the generation of the second messengers, inositol trisphosphate and diglyceride. This process occurs independently of extracellular Ca2+. A number of PAF structural analogues, receptor antagonists and drugs have been utilized to pharmacologically probe the activation of phospholipase C. PAF stimulation of the phosphoinositide turnover was shown to be sensitive to pertussis toxin in some systems, but not in others. The involvement of guanine nucleotide binding protein(s) and tyrosine kinase(s) in this process have also been postulated. These developments give new insights into PAF‐receptor function at the molecular level, and also provide leads towards a better understanding of the cellular responses to PAF.
Inhibition by the PAF antagonist WEB 2086 of PAF induced inositol‐1,4,5‐trisphosphate production in human platelets
Authors: Birke F. W. , Ensinger H. A.
Published: February 2007

Platelet‐activating factor (PAF) activates human platelets by binding to a putative PAF receptor which evokes the rapid formation of inositol‐1,4,5‐trisphosphate (IP3) by phospholipase C mediated phosphatidylinositol‐4,5‐bisphosphate (PIP2) hydrolysis. Stimulation of [3H]inositol‐labeled human platelets by PAF (1 nM‐1μM) resulted in a concentration‐dependent increase of intracellular IP3, IP2 and inositolmonophosphate (IP1). IP1 levels increased up to three‐fold upon maximum stimulation by 100 nM PAF. The EC50 concentration for PAF was 1.2±0.3 nM. Addition of the hetrazepinoic PAF antagonist, WEB 2086, inhibited PAF stimulated hydrolysis of PIP2 in a dose‐dependent manner. WEB 2086 (100 μM) blocked inositol‐1,4,5‐trisphosphate formation down to baseline levels (IC50=33±12 μM WEB 2086). In thrombin and ADP stimulated platelets, inositol phosphate (IP) generation was not influenced by WEB 2086. It is concluded that WEB 2086 selectively antagonizes PAF‐induced increases in IP and does not interfere directly with intracellular signal transduction. Instead, WEB 2086, which has been shown to bind specifically and with high affinity (Ki 15 nM) to human platelets, acts as a competitive antagonist at the PAF receptor level.
Tumor necrosis factor release by human monocytes stimulated with platelet‐activating factor
Authors: Ruis N. M. , Rose J. K. , Valone F. H.
Published: February 2007

Platelet‐activating factor (PAF) is a low molecular weight phospholipid which enhances human monocyte cytotoxicity for tumor cells. In the current studies, the capacity of PAF to stimulate release of tumor necrosis factor α (TNFα) by human monocytes was assessed. PAF induced maximal TNFα synthesis 2–3 hr after monocyte stimulation as assessed by dot blotting of cell‐associated TNFα using polyclonal anti‐TNF antibody. Maximal net release of TNFα occurred 5–16 hr after monocyte stimulation, as assessed by a specific ELISA. Dose‐response studies revealed that a maximal two‐ to three‐fold increase in release of TNFα occurs at 10–100 pM PAF. LysoPAF and the optical isomer of PAF did not stimulate release of TNFα, suggesting that stimulation is mediated by specific PAF receptors. Scatchard analysis of [3H]PAF binding to monocyte membranes revealed 651±495 binding sites/monocyte with a Kd of 4.7±4.2×10−10M. PAF is a structurally unique activator of monocytes whose interactions with TNFα and other cytokines may be critical to host defense against tumors.
Guinea pig bone marrow cells treated with platelet‐activating factor generate factor(s) which affects their DNA synthesis and microbicidal activity
Authors: Kudo Ichiro , Kato Toshiyuki , Hayashi Hidetoshi , Yanoshita Ryohei , Ikizawa Koichi , Uda Hiroko , Inoue Keizo
Published: February 2007

We have previously reported that platelet‐activating factor (PAF) induces proliferation and microbicidal activity of guinea pig bone marrow cells. In the present study, we have found that the conditioned medium of PAF‐ or nonmetabolizable PAF agonist‐treated guinea pig bone marrow cells augmented DNA synthesis and induced microbicial activity of bone marrow cells. A PAF specific antagonist, CV‐6209, inhibited generation of the active conditioned medium by PAF. Addition of the PAF antagonist only partially suppressed the augmentative effect of the active conditioned medium on DNA synthesis; this is consistent with the fact that, because of the rapid breakdown, no appreciable amount of PAF remained in the conditioned medium of PAF‐treated cells. Although mouse bone marrow cells did not respond to PAF unlike guinea pig cells, their DNA synthesis was significantly enhanced by the conditioned medium of PAF‐treated guinea pig bone marrow cells. Thus, some newly generated factor(s) distinct from the originally inoculated PAF seemed to modulate the bioactions of PAF on bone marrow cells. An appreciable amount of PAF was produced by calcium ionophore‐treated guinea pig bone marrow cells. These findings indicate that PAF synthesized in guinea pig bone marrow cells induces generation in the cells of some factor(s) which affects proliferation or microbicidal activity.
Effect of platelet‐activating factor on tumor necrosis factor‐induced superoxide generation from human neutrophils. Possible involvement of G proteins
Authors: Braquet Pierre , Hosford David , Koltz Philipe , Guilbaud Jean , Paubert‐Braquet Monique
Published: February 2007

The effect of platelet‐activating factor (PAF) and of two specific PAF antagonists on tumor necrosis factor (TNF) induced superoxide production by human polymorphonuclear neutrophils (PMN) was examined. PAF alone (0.1 pM to 0.1 nM) failed to evoke superoxide production; however, when PAF was added for 10 min to cells upon prior incubation with 10 ng/mL TNF for 50 min, superoxide production was significantly enhanced as compared to that induced by TNF alone. Maximum amplification (+30%) was obtained with 10 pM PAF; however, the effect was completely abolished by two structurally unrelated PAF antagonists, BN 52021 and BN 52111. The antagonists also decreased by 25% the superoxide production elicited solely by TNF, implicating the involvement of endogenous PAF in this process. Pretreatment of the PMN with either pertussis or cholera toxin attenuated the PAF amplified superoxide production in TNF stimulated cells, suggesting that G proteins sensitive to these toxins may be involved in the mechanisms controlling amplification.
Determination of platelet‐activating factor by a chemiluminescence method and its application to stimulated guinea pig neutrophils
Authors: Hasegawa Yukio , Kunow Eiko , Shindou Junko , Yuki Hidetaka
Published: February 2007

A simple, rapid and sensitive chemiluminescence method has been developed to measure platelet‐activating factor (PAF). Hydrogen peroxide generated from PAF, upon phospholipase D cleavage, by choline oxidase is determined as chemiluminescence by a luminol‐microperoxidase system. The detection limit of PAF by this method is 5 pmol/tube. The method is reproducible with a 5.5% coefficient of variation at 10 pmol of PAF (n=5). Lipids were extracted from guinea pig neutrophils after stimulation with cytochalasin B andN‐formyl‐methionyl‐leucylphenylalanine, and PAF was isolated by high‐performance liquid chromatography and determined by chemiluminescence measurements. The amount of PAF detected was 96.1±39.7 (mean ± SD, n=7) pmol/108 cells. This highly sensitive method could be useful for the determination of PAF generated under pathophysiological conditions.
Specific binding of antibodies to platelet‐activating factor (PAF) as demonstrated by thin‐layer chromatography/Immunostaining
Authors: Karasawa Ken , Satoh Noriko , Hongo Toshio , Nakagawa Yasuhito , Setaka Morio , Nojima Shoshichi
Published: February 2007

The specificity of rabbit antibodies produced by injection of 1‐O‐(15'‐carboxypentadecyl)‐2‐N,N‐dimethylcar‐bamoyl‐sn‐glycero‐3‐phosphocholine bovine serum albumin (BSA) conjugates was examined by a thin‐layer chromatography (TLC)/immunostaining method. Phosphatidylcholine (PC), lysophosphatidylcholine (lysoPC), lyso platelet‐activating factor (lysoPAF), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylserine (PS), sphingomyelin (SM), phosphatidylinositol (PI), phosphatidic acid (PA) and cardiolipin (CL) were not immunostained. Among several synthetic PAF‐related compounds, the antibodies only bound to PAF agonists which have the activity to induce washed rabbit platelet aggregation. The results suggest that the binding sites of the antibodies on the PAF molecule are the acetyl group at thesn‐2 position and the choline moiety at thesn‐3 position of glycerol, both of which are essential for exerting the biological function of PAF and for binding to the PAF receptors located on cellular membranes.
Quantitation by radioimmunoassay of PAF in human saliva
Authors: Cooney Sue J. , Smal Mary A. , Baldo Brian A.
Published: February 2007

Approximately 75% of the PAF present in saliva is recovered on extraction of whole saliva (0.8 vol) with chloroform/methanol/water (2∶2∶1 v/v/v). PAF levels, determined by our recently developed radioimmunoassay, in saliva extracts ranged from 0.5–21 ng/mL with 59% between 2–6 ng/mL. These figures, for apparently healthy subjects, are higher than previously reported levels obtained by platelet assays. The validity of our radioimmunoassay results was checked by isolating and quantitating the PAF fraction from whole saliva. In addition, when we examined our saliva samples by platelet aggregation, low levels of PAF, comparable with the values found in the literature, were detected. Investigations revealed the presence of a substance(s) which inhibited PAF‐induced platelet aggregation but which did not affect the radioimmunoassay.
Discovery and preliminary pharmacology of Sch 37370, a dual antagonist of PAF and histamine
Authors: Motasim Billah M. , Egan Robert W. , Ganguly Ashit K. , Green Michael J. , Kreutner William , Piwinski John J. , Siegel Marvin I. , Villani Frank J. , Wong Jesse K.
Published: February 2007

From a series of amide analogs of the histamine H1 antagonist, azatadine, a potent, orally active, dual platelet‐activating factor (PAF) and histamine antagonist, Sch 37370, namely 1‐acetyl‐4‐(8‐chloro‐5,6‐dihydro‐11H‐benzo‐[5,6]cyclohepta[1,2‐b]pyridin‐11‐ylidine)piperidine, was discovered. Sch 37370 selectively inhibits PAF‐induced aggregation of human plateletsin vitro (IC50=0.6 μM), andin vivo inhibits PAF‐ and histamine‐induced bronchospasm in guinea pigs with ED50 values of 6.0 and 2.4 mg/kg p.o., respectively. Sch 37370 is expected to be more efficacious than single mediator antagonists in allergic diseases, such as asthma.
Pharmacological properties of YM461, a new orally active platelet‐activating factor antagonist
Authors: Yamada Toshimitsu , Saito Munetoshi , Mase Toshiyasu , Hara Hiromu , Nagaoka Hitoshi , Murase Kiyoshi , Tomioka Kenichi
Published: February 2007

The antagonistic effect of YM461 [1‐(3‐phenylpropyl)‐4‐[2‐(3‐pyridyl)thiazolidin‐4‐ylcarbonyl]piperazine fumarate] against platelet‐activating factor (PAF) was examined in severalin vitro andin vivo systems. We found that YM461 inhibited [3H]PAF binding to rabbit platelet membranes with a pKi value of 8.90. YM461 inhibited PAF induced rabbit and human platelet aggregation with pA2 values of 7.52 and 7.29, respectively; the slopes of the Schild plots were 1.07 and 1.01, respectively. However, YM461 at 10−4M did not affect rabbit and human platelet aggregation induced by ADP, collagen, arachidonic acid or epinephrine. YM461 inhibited PAF induced death in mice with an ED50 (50% effective dose) value of 0.35 mg/kgp.o. YM461 at doses above 0.3 mg/kgi.v. inhibited PAF induced hypotension in rats. YM461 showed a dose‐dependent inhibition of PAF induced hemoconcentration in rats with ED50 values of 0.15 and 0.21 mg/kgp.o., respectively, at 0.5 and 1 hr after oral administration. The anti‐PAF effect of YM461 persisted more than 6 hr after 3 mg/kgp.o. in rats. YM461 inhibited the bronchoconstriction induced by PAF with an ED50 value of 1.2 mg/kgp.o. in anesthetized guinea pigs. Furthermore, the compound at doses above 3 mg/kgp.o. significantly inhibited antigen‐induced anaphylactic asthma in conscious guinea pigs pretreated with mepyramine and propranolol. These results indicate that YM461 is a selective, potent and orally active PAF antagonist.
Bioactions of 5‐hydroxyicosatetraenoate and its interaction with platelet‐activating factor
Authors: Rossi Adriano G. , O'Flaherty Joseph T.
Published: February 2007

In a variety of stimulated cells, platelet‐activating factor (PAF) and numerous arachidonate derivatives are coproducts that form as a consequence of receptor‐mediated phospholipid mobilization. These lipid co‐products produce a plethora of biological effects in a wide variety of cell systems. Furthermore, they often have a fascinating, although less widely appreciated, interaction. 5‐HETE, at submicromolar concentrations, exerts relatively few direct bioactions. It does, however, potently (16–160 nM) raise cytosolic free calcium [Ca2+]i and augment PAF‐induced responses in human polymorphonuclear neutrophils (PMN) by as much as 100‐ to 1000‐fold. 5‐HETE acts on PMN by a structurally specific, stereospecific and pertussis toxin‐inhibitable mechanism. In addition, PMN exposed to 5‐HETE exhibit homologous but not heterologous desensitization. These findings suggest that 5‐HETE, like PAF, may bind to its own specific plasmalemmal receptors to exert its unique set of bioactions. However, further investigation is required to demonstrate any putative 5‐HETE receptors. Other potential mechanisms of 5‐HETE‐induced bioactions together with the possible effects of 5‐HETE on PAF transduction mechanisms are also discussed.
Platelet‐activating factor and polyunsaturated fatty acids in cerebral ischemia or convulsions: Intracellular PAF‐binding sites and activation of a fos/jun/AP‐1 transcriptional signaling system
Authors: Bazan Nicolas G. , Squinto Stephen P. , Braquet Pierre , Panetta Thomas , Marcheselli Victor L.
Published: February 2007

Platelet‐activating factor (PAF) is a lipid mediator formed in the early response of the central nervous system to ischemia or convulsions. Free polyunsaturated fatty acids and arachidonic and docosahexaenoic acids are accumulated along with PAF. Antagonists of PAF have been found to improve cerebral blood flow and partially block the rise in free fatty acids, an effect that may arise by way of inhibition of PAF receptors or stimulation of the reacylation of free fatty acids released upon insult. Three intracellular PAF‐binding sites have been identified in rat cerebral cortex. These very high‐affinity binding sites are inhibited by PAF antagonists, with certain antagonists exhibiting specificity for a particular binding site. This specificity indicates heterogeneity in these binding sites. Ischemia or stimulation also leads to protooncogene transcriptional activation. Here, we discuss studies with cells in culture showing that PAF promotes transcriptional activation of immediate‐early genes. PAF activates the transcription of the immediate‐early genesfos andjun, whose gene products are regulators of the transcription of other genes. Transcription offos is also activated by convulsion or ischemia in the central nervous system. The activation of these genes by PAF can be inhibited by PAF antagonists, and is apparently accomplished by way of an AP‐1 transcription regulatory sequence in the promoter region of the target genes. Studies with deletion mutants show that PAF can also exert its activating properties by way of cyclic adenosine‐3′,5′‐monophosphate‐(cAMP) and Ca2+‐responsive elements, and suggest that PAF is involved in an interconnected network of cell signaling that may coordinate short‐term and long‐term responses of cells to stimulus and injury.
Cardiovascular effects of platelet‐activating factor
Authors: Goldstein Robert E. , Feuerstein Giora Z. , Bradley Linda M. , Stambouly Joseph J. , Laurindo Francisco R. M. , Davenport Nancy J.
Published: February 2007

Sudden release of platelet‐activating factor (PAF) into the circulation can cause hypotension, tachycardia, and circulatory collapse. To further examine this response, we performed detailed studies of cardiovascular function after PAF administration to young domestic pigs and newborn piglets. Our results indicate that circulatory dysfunction after PAF reflects severe constriction of pulmonary resistance vessels and consequent acute right ventricular failure. Although PAF‐induced coronary artery constriction and contractile depression may be complicating problems, left ventricular underperfusion and dysfunction after PAF are mainly the result of systemic arterial hypotension and diminished left ventricular filling. The adverse hemodynamic effects of PAF are accompanied by substantial release of thromboxane A2 (TxA2). These effects are mimicked by the TxA2 agonist U‐46619 and partially blocked by specific and nonspecific inhibitors of TxA2 synthesis (OKY‐046 and indomethacin). Even more potent blockade of PAF action is exerted by the TxA2 receptor blocker, SQ 29,548. Taken together, these findings indicate that severe pulmonary vascular constriction and hemodynamic collapse soon after intravenous PAF are at least partially mediated by PAF‐induced TxA2 release.

Tachyphylaxis to PAF influence has been observed in studies of leukocyte and platelet function. We hypothesized that tachyphylaxis to PAF might also occur in our studies of constrictor responses in pulmonary vessels. Recently, we have examined the capacity of PAF to produce sustained pulmonary vasoconstriction in openchested, anesthetized newborn piglets. Infusions sufficient to produce 100% increase in mean pulmonary artery pressure after 3 min showed no loss of efficacy when sustained for 30 min. The same was true for infusions of U‐46619. Thus, the pulmonary vasoconstrictor influence of PAF or U‐46619 is not readily diminished by tachyphylaxis. These findings favor the viewpoint that PAF or TxA2 release during inflammatory processes could have prolonged adverse actions on pulmonary and systemic circulations.
Role for platelet‐activating factor in asthma
Authors: Chung K. F. , Barnes P. J.
Published: February 2007

Recent studies of the effects of platelet‐activating factor (PAF) on huan and animal airways would support a putative role for this lipid mediator in asthma. PAF can induce many aspects of the clinical and pathological features seen in asthmatic airways such as airway oedema, eosinophil accumulation in the airway wall, and bronchial hyperresponsiveness. PAF has potent activity as a chemotactic agent and as an activator of eosinophils, which are prominent cells in asthmatic airways, through the activation of specific surface receptors. The interaction between PAF and eosinophils may be crucial in the pathogenesis of bronchial hyperresponsiveness in asthma. A role for PAF in asthma can now be studied using the recently developed antagonists of the PAF receptor.
Platelet‐activating factor detected in bronchoalveolar lavage fluids from an asthmatic patient
Authors: Horii Tsugio , Okazaki Hitoshi , Kino Minoru , Kobayashi Yohnosuke , Satouchi Kiyoshi , Saito Kunihiko
Published: February 2007

It recently has been recognized that platelet‐activating factor (PAF) may be a mediator of asthma exacerbation. We had the opportunity to analyze bronchoalveolar lavage fluids from an asthmatic infant, which were characterized by neutrophil infiltration. The patient's lungs were washed on three occasions with saline during asthmatic attacks. PAF was found in each case on the basis of its ability to cause the immediate aggregation of washed rabbit platelets. The PAF detected was equivalent to 1–1.4 pmol of 1‐O‐hexadecyl‐2‐acetyl‐sn‐glycero‐3‐phosphocholine, three quarters of which were recovered in cell‐associated form. By contrast, we did not detect PAF in bronchoalveolar exudates from patients with larungeal stenosis or with respiratory distress syndrome. LysoPAF, the direct precursor as well as initial metabolite of PAF, was also analyzed after being converted to PAF by acetylation. There was a wide variation in the amount of lysoPAF present in individual patients, suggesting that lysoPAF levels cannot be taken as an indicator for the presence of PAF.
Platelet‐activating factor (PAF) in allergic diseases: Inhibitory effects of anti‐allergic drugs, ketotifen and three Kampo medicines on PAF production
Authors: Nakamura Tsuneyoshi , Kuriyama Motoaki , Ishihara Keiko , Matsumura Yukio , Miyamoto Terumasa
Published: February 2007

Platelet‐activating factor (PAF) is considered an important mediator in allergic and inflammatory reactions. To further investigate the role of PAF in allergic diseases, we examined thein vitro andex vivo effect of anti‐allergic drugs on PAF production by human neutrophils. Ketotifen and three Kampo medicines, which are widely used in the treatment of allergic diseases in Japan, inhibited PAF production by normal human neutrophils dose‐dependently, whereas disodium chromoglycate (DSCG) and tranilast did not have any inhibitory effect. Ketotifen also suppressedex vivo PAF production by neutrophils from healthy subjects. PAF production decreased from 40.5±5.0 units to 21.6±4.7 units after oral administration of 2 mg of ketotifen per day for one week. We also measured the concentration of lysoPAF in serum from patients with Japanese cedar pollinosis during the pollen season and followed the effect of ketotifen on lysoPAF levels in the serum from these patients. We found that the concentration of lysoPAF, a precursor and degradation product of PAF, in patients with cedar pollinosis (87.8±8.7 units) was significantly higher than in healthy subjects (54.7±7.7 units). After two weeks, lysoPAF levels decreased significantly (82.6 units to 41.3 units) only in the group treated with nasal aerosol and ketotifen. These results suggest that PAF may play a role in allergic diseases and that the clinical effects of anti‐allergic drugs may at least partially be due to their anti‐PAF action.