bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Comparisons, Conflict, and Risk Acceptability Claims
Authors: Johnson Branden B.
Published: February 2004

Despite many claims for and against the use of risk comparisons in risk communication, few empirical studies have explored their effect. Even fewer have examined the public's relative preferences among different kinds of risk comparisons. Two studies, published in this journal in 1990 and 2003, used seven measures of “acceptability” to examine public reaction to 14 examples of risk comparisons, as used by a hypothetical factory manager to explain risks of his ethylene oxide plant. This study examined the effect on preferences of scenarios involving low or high conflict between the factory manager and residents of the hypothetical town (as had the 2003 study), and inclusion of a claim that the comparison demonstrated the risks' acceptability. It also tested the Finucane et al. (2000) affect hypothesis that information emphasizing low risks—as in these risk comparisons—would raise benefits estimates without changing risk estimates. Using similar but revised scenarios, risk comparison examples (10 instead of 14), and evaluation measures, an opportunity sample of 303 New Jersey residents rated the comparisons, and the risks and benefits of the factory. On average, all comparisons received positive ratings on all evaluation measures in all conditions. Direct and indirect measures showed that the conflict manipulation worked; overall, No‐Conflict and Conflict scenarios evoked scores that were not significantly different. The attachment to each risk comparison of a risk acceptability claim (“So our factory's risks should be acceptable to you.”) did not worsen ratings relative to conditions lacking this claim. Readers who did or did not see this claim were equally likely to infer an attempt to persuade them to accept the risk from the comparison. As in the 2003 article, there was great individual variability in inferred rankings of the risk comparisons. However, exposure to the risk comparisons did not reduce risk estimates significantly (while raising benefit estimates), and Conflict‐Claim respondents found the risk of the hypothetical factory less acceptable than No‐Conflict respondents. Results suggest that neither risk comparisons nor risk acceptability claims are automatically anathema to audiences, but they may have tiny or unintended effects on audience judgments about risky situations.
Ethics and Choosing Appropriate Means to an End: Problems with Coal Mine and Nuclear Workplace Safety
Authors: Shrader‐Frechette Kristin , Cooke Roger
Published: February 2004

A common problem in ethics is that people often desire an end but fail to take the means necessary to achieve it. Employers and employees may desire the safetyendmandated by performance standards for pollution control, but they may fail to employ themeans, specification standards, necessary to achieve this end. This article argues that current (de jure) performance standards, for lowering employee exposures to ionizing radiation, fail to promotede factoworker welfare, in part because employers and employees do not follow the necessary means (practices known as specification standards) to achieve the end (performance standards) of workplace safety. To support this conclusion, the article argues that (1) safety requires attention to specification, as well as performance, standards; (2) coal‐mine specification standards may fail to promote performance standards; (3) nuclear workplace standards may do the same; (4) choosing appropriate means to the end of safety requires attention to the ways uncertainties and variations in exposure may mask violations of standards; and (5) correcting regulatory inattention to differences betweende jureandde factois necessary for achievement of ethical goals for safety.
A Critical Look at Risk Assessments for Global Catastrophes
Authors: Kent Adrian
Published: February 2004

Recent articles by Busza et al. (BJSW) and Dar et al. (DDH) argue that astrophysical data can be used to establish small bounds on the risk of a “killer strangelet” catastrophe scenario in the RHIC and ALICE collider experiments. The case for the safety of the experiments set out by BJSW does not rely solely on these bounds, but on theoretical arguments, which BJSW find sufficiently compelling to firmly exclude any possibility of catastrophe.

Nonetheless, DDH and other commentators (initially including BJSW) suggested that these empirical bounds alone do give sufficient reassurance. This seems unsupportable when the bounds are expressed in terms of expectation value—a good measure, according to standard risk analysis arguments. For example, DDH's main bound, pcatastrophe < 2 × 10−8, implies only that the expectation value of the number of deaths is bounded by 120; BJSW's most conservative bound implies the expectation value of the number of deaths is bounded by 60,000.

This article reappraises the DDH and BJSW risk bounds by comparing risk policy in other areas. For example, it is noted that, even if highly risk‐tolerant assumptions are made and no value is placed on the lives of future generations, a catastrophe risk no higher than ≈10−15 per year would be required for consistency with established policy for radiation hazard risk minimization. Allowing for risk aversion and for future lives, a respectable case can be made for requiring a bound many orders of magnitude smaller.

In summary, the costs of small risks of catastrophe have been significantly underestimated by BJSW (initially), by DDH, and by other commentators. Future policy on catastrophe risks would be more rational, and more deserving of public trust, if acceptable risk bounds were generally agreed upon ahead of time and if serious research on whether those bounds could indeed be guaranteed was carried out well in advance of any hypothetically risky experiment, with the relevant debates involving experts with no stake in the experiments under consideration.
Thinking Aloud about Trust: A Protocol Analysis of Trust in Risk Management
Authors: Earle Timothy C.
Published: February 2004

There are two general theories of trust in risk management. One, derived from normative considerations, claims that trust is based on universally applicable factors such as fairness and objectivity. According to the second, social‐psychological theory, trust is based on agreement or similarity and is context specific. Although the first theory is normative, it also claims, along with the second, to be a descriptive account of how trust judgments are made. The present study was designed to test the adequacy of these two theories by using a think‐aloud procedure to examine the thinking associated with trust judgments in an experimental simulation of a typical risk management context. Contrary to the universalist theory, results supported two hypotheses derived from the social‐psychological theory. First, study participants—who read brief policy statements designed to address global climate change—based their trust judgments on specific forms of agreement, ranging from agreement on the importance of the issue to agreement on values inferred from the policy statement. Second, the extent and depth of participants' conscious information processing was negatively related to the level of trust. Disagreement and distrust generated more conscious consideration than agreement and trust. These results provide a more detailed understanding than previously available of how trust in risk management is based on local forms of agreement that vary across people, contexts, and time.
GM Foods and the Misperception of Risk Perception
Authors: Gaskell George , Allum Nick , Wagner Wolfgang , Kronberger Nicole , Torgersen Helge , Hampel Juergen , Bardes Julie
Published: February 2004

Public opposition to genetically modified (GM) food and crops is widely interpreted as the result of the public's misperception of the risks. With scientific assessment pointing to no unique risks from GM crops and foods, a strategy of accurate risk communication from trusted sources has been advocated. This is based on the assumption that the benefits of GM crops and foods are self‐evident. Informed by the interpretation of some qualitative interviews with lay people, we use data from the Eurobarometer survey on biotechnology to explore the hypothesis that it is not so much the perception of risks as the absence of benefits that is the basis of the widespread rejection of GM foods and crops by the European public. Some respondents perceive both risks and benefits, and may be trading off these attributes along the lines of a rational choice model. However, for others, one attribute—benefit—appears to dominate their judgments: the lexicographic heuristic. For these respondents, their perception of risk is of limited importance in the formation of attitudes toward GM food and crops. The implication is that the absence of perceived benefits from GM foods and crops calls into question the relevance of risk communication strategies for bringing about change in public opinion.
Defining Susceptibility for Microbial Risk Assessment: Results of a Workshop
Authors: Balbus John , Parkin Rebecca , Makri Anna , Ragain Lisa , Embrey Martha , Hauchman Fred
Published: February 2004

An interdisciplinary workshop was convened by the George Washington University in June 2001 to discuss how to incorporate new knowledge about susceptibility to microbial pathogens into risk assessment and management strategies. Experts from government, academic, and private sector organizations discussed definitions, methods, data needs, and issues related to susceptibility in microbial risk assessment. The participants agreed that modeling approaches need to account for the highly specific nature of host‐pathogen relationships, and the wide variability of infectivity, immunity, disease transmission, and outcome rates within microbial species and strains. Concerns were raised about distinguishing between exposure and dose more clearly, interpreting experimental and outbreak data correctly, and using thresholds and possibly linearity at low doses. Recommendations were made to advance microbial risk assessment by defining specific terms and concepts more precisely, designing explicit conceptual frameworks to guide development of more complex models and data collection, addressing susceptibility in all steps of the model, measuring components of immunity to characterize susceptibility, reexamining underlying assumptions, applying default methods appropriately, obtaining more mechanistic data to improve default methods, and developing more biologically relevant and continuous risk estimators. The interrelated impacts of selecting specific subpopulations and health outcomes, and of increasing model complexity and data demands, were considered in the contexts of public policy goals and resources required. The participants stated that zero risk is unattainable, so targeted and effective risk reduction and communication strategies are essential not only to raise pubic awareness about water quality but also to protect the most susceptible members of the population.
Cryptosporidiosis Susceptibility and Risk: A Case Study
Authors: Anna Makri  , Modarres Reza , Parkin Rebecca
Published: February 2004

Regional estimates of cryptosporidiosis risks from drinking water exposure were developed and validated, accounting for AIDS status and age. We constructed a model with probability distributions and point estimates representing Cryptosporidium in tap water, tap water consumed per day (exposure characterization); dose response, illness given infection, prolonged illness given illness; and three conditional probabilities describing the likelihood of case detection by active surveillance (health effects characterization). The model predictions were combined with population data to derive expected case numbers and incidence rates per 100,000 population, by age and AIDS status, borough specific and for New York City overall in 2000 (risk characterization). They were compared with same‐year surveillance data to evaluate predictive ability, assumed to represent true incidence of waterborne cryptosporidiosis. The predicted mean risks, similar to previously published estimates for this region, overpredicted observed incidence—most extensively when accounting for AIDS status. The results suggest that overprediction may be due to conservative parameters applied to both non‐AIDS and AIDS populations, and that biological differences for children need to be incorporated. Interpretations are limited by the unknown accuracy of available surveillance data, in addition to variability and uncertainty of model predictions. The model appears sensitive to geographical differences in AIDS prevalence. The use of surveillance data for validation and model parameters pertinent to susceptibility are discussed.
A Dynamic Model to Assess Microbial Health Risks Associated with Beneficial Uses of Biosolids
Authors: Eisenberg Joseph N. S. , Soller Jeffrey A. , Scott James , Eisenberg Don M. , Colford John M.
Published: February 2004

There is increasing interest in the development of a microbial risk assessment methodology for regulatory and operational decision making. This document presents a methodology for assessing risks to human health from pathogen exposure using a population‐based model that explicitly accounts for properties unique to an infectious disease process, specifically secondary transmission and immunity. To demonstrate the applicability of this risk‐based method, numerical simulations were carried out for a case study example in which the route of exposure was direct consumption of biosolids‐amended soil and the pathogen present in the soil was enterovirus. The output from the case study yielded a decision tree that differentiates between conditions in which the relative risk from biosolids exposure is high and those conditions in which the relative risk from biosolids is low. This decision tree illustrates the interaction among the important factors in quantifying risk. For the case study example, these factors include biosolids treatment processes, the pathogen shedding rate of infectious individuals, secondary transmission, and immunity. Further refinement in methods for determining biosolids exposures under field conditions would certainly increase the utility of these approaches.
Scenario Tree Modeling to Analyze the Probability of Classical Swine Fever Virus Introduction into Member States of the European Union
Authors: De Vos Clazien J. , Saatkamp Helmut W. , Nielen Mirjam , Huirne Ruud B. M.
Published: February 2004

The introduction of classical swine fever virus (CSFV) into a country free of disease without vaccination may have huge consequences in terms of both disease spread and economic losses. More quantitative insight into the main factors determining the probability of CSFV introduction (PCSFV) is needed to optimally use resources for the prevention of CSFV introduction. For this purpose a spreadsheet model was constructed that calculates the annual PCSFV into member states of the European Union (EU). The scenario pathway approach was used as most probabilities in the model are very small. Probability distributions were used to take into account inherent variability of input parameters. The model contained pathways of CSFV introduction including the import of pigs and pork products, returning livestock trucks, and contacts with wild boar. All EU member states were included as possible sources of CSFV. Default results for the Netherlands showed a mean overall annual PCSFV of approximately 0.06, indicating that the Netherlands can expect CSFV introduction on average once every 18 years from the pathways and countries included in the model. Almost 65% of this probability could be attributed to the pathway of returning livestock trucks. The most likely sources of CSFV introduction were Germany, Belgium, and the United Kingdom. Although the calculated probabilities were rather low when compared with expert estimates and recent history, the most likely causes of CSFV introduction indicated by the model were considered to be realistic. It was therefore concluded that the model is a useful tool to structure and analyze information for decision making concerning the prevention of CSFV introduction.
A Bayesian Approach to Quantify the Contribution of Animal‐Food Sources to Human Salmonellosis
Authors: Hald Tine , Vose David , Wegener Henrik C. , Koupeev Timour
Published: February 2004

Based on the data from the integrated DanishSalmonellasurveillance in 1999, we developed a mathematical model for quantifying the contribution of each of the major animal‐food sources to human salmonellosis. The model was set up to calculate the number of domestic and sporadic cases caused by differentSalmonellasero and phage types as a function of the prevalence of theseSalmonellatypes in the animal‐food sources and the amount of food source consumed. A multiparameter prior accounting for the presumed but unknown differences between serotypes and food sources with respect to causing human salmonellosis was also included. The joint posterior distribution was estimated by fitting the model to the reported number of domestic and sporadic cases perSalmonellatype in a Bayesian framework using Markov Chain Monte Carlo simulation. The number of domestic and sporadic cases was obtained by subtracting the estimated number of travel‐ and outbreak‐associated cases from the total number of reported cases, i.e., the observed data. The most important food sources were found to be table eggs and domestically produced pork comprising 47.1% (95% credibility interval, CI: 43.3–50.8%) and 9% (95% CI: 7.8–10.4%) of the cases, respectively. Taken together, imported foods were estimated to account for 11.8% (95% CI: 5.0–19.0%) of the cases. Other food sources considered had only a minor impact, whereas 25% of the cases could not be associated with any source. This approach of quantifying the contribution of the various sources to human salmonellosis has proved to be a valuable tool in risk management in Denmark and provides an example of how to integrate quantitative risk assessment and zoonotic disease surveillance.
Differences in Perception of Risk Between People Who Have and Have Not Experienced Salmonella Food Poisoning
Authors: Parry Sharon M. , Miles Susan , Tridente Ascanio , Palmer Stephen R. ,   South and East Wales Infectious Disease Group
Published: February 2004

It is believed that food hygiene precautions in domestic kitchens are an important strategy in efforts to reduce the incidence of sporadic food poisoning, but recent research has shown that people who have suffered food poisoning handle the same types of foods and adopt similar food hygiene precautions in their kitchens to the rest of the population. This suggests the need to examine other factors. A case‐control study of sporadic Salmonella food poisoning was conducted to investigate several domestic kitchen risk factors. Measures of perception of risk, knowledge, and control associated with food poisoning in case and control respondents are reported here. It was found that perceived personal risk from food poisoning in the home was less than perceived risk to other people. In contrast, ratings of personal knowledge about food poisoning and personal control over food poisoning in the home were seen to be greater than other people's knowledge and control. There were no differences between the cases and the controls in their ratings of knowledge about food poisoning or their control over food poisoning. However, cases perceived their personal risk from food poisoning to be higher than controls. Both case and control samples exhibited optimistic bias but this was reduced in the case sample, suggesting that experience with food poisoning may reduce optimistic bias.
The evolution of echolocation in swiftlets
Authors: Jordan Price J. , P. Johnson Kevin , H. Clayton Dale
Published: February 2004

The abilities of some cave‐nesting swiftlets to echolocate has traditionally been used to separate the genus Aerodramus, which includes echolocating species, from the genus Collocalia, thought to lack echolocation. Here we report the discovery of echolocation in a member of the latter genus, the pygmy swiftlet Collocalia troglodytes. We also present a well‐supported molecular phylogeny for the swiftlets and their relatives based on DNA sequence data from two mitochondrial genes, which we use to reconstruct the evolution of echolocation. Our data provide strong evidence that the swiftlets are a monophyletic group. This monophyly plus the presence of echolocation in C. troglodytes indicate that either (1) echolocation evolved much earlier in the swiftlets than previously thought and has since been lost in most Collocalia taxa, or (2) this ability evolved independently in Aerodramus and Collocalia. Based on our results, echolocation can no longer be considered a useful character for distinguishing these two genera.
Characterization of MCH‐gene‐overprinted‐polypeptide‐immunoreactive material in hypothalamus reveals an inhibitory role of pro‐somatostatin1−64 on somatostatin secretion
Authors: Allaeys Isabelle , Bouyer Karine , Loudes Catherine , Faivre‐Bauman Annie , Petit Florence , Ortola Christine , Cardinaud Bruno , Epelbaum Jacques , Nahon Jean‐Louis
Published: February 2004

The melanin‐concentrating hormone (MCH) gene encodes two proteins, pro‐MCH and MCH‐gene‐overprinted polypeptide (MGOP), produced through alternative splicing of the primary transcript. Our initial purpose was to characterize the MGOP‐immunoreactive material. First, MGOP mRNA was clearly found in rat and mouse hypothalami but Western blot analysis failed to unambiguously identify MGOP in protein extracts. Immunohistochemical experiments with wild‐type and MCH gene‐null mice demonstrated genuine expression of MGOP confined to the MCH‐containing neurons in the lateral hypothalamus area and the presence of an ‘MGOP‐like’ antigen in periventricular nucleus and arcuate nucleus neurons and their area of projection. This suggested a colocalization in somatostatin (SRIF) hypophysiotropic neurons. Further characterization, using SRIF gene‐null mice and Western blot analysis with recombinant proteins, revealed that the MGOP‐like product was pro‐SRIF1−64. The role of pro‐SRIF1−64 on fetal hypothalamic neurons was evaluated and a strong tonic inhibitory effect on SRIF secretion was found. These results (i) indicate that MGOP expression is restricted to the MCH neurons in the lateral hypothalamus and that MGOP‐like immunoreactivity outside this system corresponds to pro‐SRIF1−64, and (ii) provide the first evidence for a negative feedback regulation by pro‐SRIF1−64 on SRIF secretion, suggesting new mechanisms by which the pro‐region of a neuropeptide precursor may control the regulated secretion of a neuropeptide derived from the same precursor.
Enhancement of stimulation‐induced ERK activation in the spinal dorsal horn and gracile nucleus neurons in rats with peripheral nerve injury
Authors: Wang Hu , Dai Yi , Fukuoka Tetsuo , Yamanaka Hiroki , Obata Koichi , Tokunaga Atsushi , Noguchi Koichi
Published: February 2004

It has been suggested that low‐threshold sensory pathways have an important role in the formation and maintenance of sensory abnormalities which are observed after peripheral nerve injury. In the present study, we examined the involvement of these pathways in the development of hyperexcitability after sciatic nerve injury (SNI) by detecting the intracellular signal molecule. The rats that received a transection of the sciatic nerve 7 days before were electrically stimulated at 0.1 mA and 3 mA in the proximal region of the nerve injury site. We found a small number of phosphorylated extracellular signal‐regulated kinase (pERK)‐labelled neurons in laminae I–II and III–IV of the spinal dorsal horn in the control rats after 0.1 mA stimulation. By contrast, there was a marked increased of pERK‐labelled neurons both in the superficial laminae and laminae III–IV after the same stimulation in the SNI rats. Enhancement of ERK activation induced by 3 mA stimulation was also observed. Immunoreactivity of pERK in gracile nucleus neurons was also dramatically increased after 0.1 mA stimulation to the injured nerve. These data suggest that the rats with peripheral nerve injury had an increased responsiveness to the low‐ or high‐threshold peripheral stimuli in I–II, III–IV and gracile nucleus neurons. Furthermore, SNI rats that received neonatal capsaicin treatment showed a decreased number of pERK neurons after 0.1 mA stimulation in the dorsal horn and gracile nucleus neurons compared to the control rats. Thus, C‐fibres may contribute to the enhanced excitability of the low‐threshold sensory neurons after peripheral nerve injury.
Advances in the treatment of the diabetic foot: Is there a role for adjunctive hyperbaric oxygen therapy?
Authors: Cianci Paul
Published: February 2004

There have been many advances in the treatment of wounds made in the last decade. Innovative techniques of wound closure, topical agents, aggressive vascular repair, focused wound care management, and adjunctive hyperbaric oxygen therapy are but a few of these improvements. The vital role of oxygen in wound healing is becoming better understood, in no small part, due to Dr. T. K. Hunt and his colleagues at the Wound Healing Laboratory at the University of California, San Francisco. Elements of that contribution will be examined in this article. How these elements may be applied to improve wound healing will be explained and the possible role of adjunctive hyperbaric oxygen therapy based on sound science in the management of the difficult diabetic foot wound, will be highlighted.
The chemokine receptor CCR1 is strongly up‐regulated after skin injury but dispensable for wound healing
Authors: Kaesler Susanne , Bugnon Philippe , Gao Ji‐Liang , Murphy Philip M. , Goppelt Andreas , Werner Sabine
Published: February 2004

To identify key regulators of cutaneous wound repair, we analyzed a subtractive cDNA library of normal and wounded mouse skin. One of the identified genes encodes the chemokine receptor CCR1, which binds several chemokines present at the wound site. Expression of CCR1 was barely detectable in nonwounded skin, but strong up‐regulation was observed after injury to wild‐type mice. Most important, the healing abnormalities observed in glucocorticoid‐treated mice and activin‐overexpressing transgenic mice correlated with an altered expression of CCR1. CCR1‐positive cells were identified as macrophages and neutrophils within the wounded area. To determine the importance of CCR1 for wound repair, we analyzed this process in CCR1 knockout mice. Surprisingly, no alterations in either wound closure, wound appearance, wound bursting strength, granulation tissue formation, or re‐epithelialization were observed. In addition, the inflammatory response was unaltered in CCR1‐deficient mice and the expression of several chemokines, chemokine receptors, and other important regulators of wound repair were normal in these animals. These results show that CCR1 is dispensable for wound healing, most likely due to redundancy in chemokine/chemokine receptor signaling.
Upside‐down transfer of porcine keratinocytes from a porous, synthetic dressing to experimental full‐thickness wounds
Authors: Van Den Bogaerdt Antoon J. , Ulrich Magda M. W. , Van Galen Mieke J. M. , Reijnen Linda , Verkerk Michelle , Pieper Jeroen , Lamme Evert N. , Middelkoop Esther
Published: February 2004

Currently, the use of cultured epithelial autografts as an alternative to split‐thickness skin autografts for coverage of full‐thickness wounds is limited due to fragility of the sheet and variability in the outcome of healing. This could be circumvented by the transfer of proliferating keratinocytes, instead of differentiated sheets, to the wound bed and the “in vivo” regeneration of epidermis. The aim of this study was to achieve re‐epithelialization on experimental full‐thickness wounds in the pig using a porous, synthetic carrier seeded with proliferating keratinocytes. Porcine keratinocytes were isolated by enzymatic digestion and cultured in Optimem® basal medium with mitogens. In a full‐thickness wound model, carriers with different seeding densities were transplanted upside down onto the wound bed. Keratinocytes were labeled using a fluorescent red membrane marker, PKH‐26 GL. Transfer of keratinocytes and re‐epithelialization were recorded macroscopically and histologically. On day 4 after transplantation, transfer of fluorescently labeled keratinocytes was shown by their presence in the granulation tissue. An immature epidermis, as well as epithelial cords and islands, formed as early as day 8. At day 12 a stratified epidermis and wound closure were established and epithelial cysts were formed by differentiation of epithelial islands. Wounds treated with seeding densities as low as 50,000 cells/cm2 showed wound closure within 12 days, whereas wounds treated with 10,000 cells/cm2 or the nonseeded (acellular) carriers did not show complete re‐epithelialization before day 17 after treatment. This study showed that porcine keratinocytes, transplanted “upside down” in experimental full‐thickness wounds using a synthetic carrier, continued to proliferate and started to differentiate, enabling the formation of a new epidermis in a time frame of 12 days.
008  The Effect of the Gelatin Sheet Containing bFGF on Wound Healing
Authors: Michiyo Goji , Shigehiko Suzuki , Takeshi Kawazoe , Yasumi Saso , Hisayuki Mihara , Yasuhiko Tabata
Published: February 2004

Aim: It is well recognized that bFGF accelerates proliferation of almost all cells concerned with wound healing and there is a report that bFGF was well sorbed with time to the acidic gelatin hydrogel with isoelectric points of 5.0. We investigated the effect of the acidic gelatin sheet containg bFGF.

Methods: Full thickness defects of skin (1.5 × 1.5 cm) were created on the backs of mice.1) The wounds were covered with gelatin sheets (2 × 2 cm)containg bFGF(100 ìg/site), (A), and without bFGF(B). The concentration of bFGF in plasma was estimated by ELISA. 2) The wounds were covered with A, B and hydrogel dressing(control group, C) and wound area was measured with computer planimeter and neoepithelium was observed using the light microscope.

Results: 1) The concentration of bFGF in plasma in (A) was statistically greater than (B) by the 7th day. 2) Statistically smaller wound area was found 2 weeks postoperatively in (A) than in (C) and (D). Neoepithelium from edge of the wound was statistically longer in (A) than in (C).

Conclusions: Controlled release of bFGF from the acidic gelatin sheet was fouhd and acidic gelatin sheet containg bFGF promoted neoepithelization and wound closure. The acidic gelatin sheet containg bFGF was thought to be effective on wound healing.
024  Accelerated Epithelization of STSG Donor Wounds by Cultured Cellular Sheet Composed of Mixture of Keratinocytes and Fibroblasts
Authors: Yoshihiro Takami , Hideharu Tanaka , Takako Wada , Mika Enoki , Ryo Yamaguchi , Hiroshi Miyauchi , Hideaki Goto , Takeo Koizumi , Matsuda Taketo , Shimazaki Syuuji , Ken Ogo
Published: February 2004

Aim: Available donor skin is so limited in extensive burns that wounds are usually closed using STSG harvested repeatedly from unburned skin. In such cases, it is important to accelerate the epithelization process of the donor wounds. We have developed a cultured cellular sheet composed of mixture of keratinocytes (KC) and fibroblasts (FB) seeded on a polyurethane membrane (mixed culture sheet) and investigated its effectiveness for the wound healing of STSG donor wounds.

Methods: Normal human KC and FB were primarily cultured from a surplus human skin in a skin graft surgery. After a few passages of the cultivation, both cells were seeded on a thin polyurethane membrane. Each seeding density of KC and FB were equal. Several days after the co‐cultivation, the mixed culture sheet was transferred to a freshly harvested STSG donor wound in an extensive burn patient. A polyurethane membrane without cells was used for control coverage. Seven patients were treated using the mixed culture sheets. Autologous cells were used in 3 cases, and allogenic cells were used in the other 4 cases. The time for the final epithelization was determined. In vitro production of several growth factors by a cellular sheet was also investigated by ELASA.

Results and Conclusion: TGF‐alpha, EGF, TGF‐beta, VEGF were well produced by the mixed culture sheet. The time for final epithelization of the wounds was reduced by 2.5 days with the mixed culture sheet application as compared to the control sites. It was suggested that the mixed culture sheet may be useful for the treatment of STSG donor wounds.
025  Clinical Application of Autologous Cultured Dermal Substitutes for Giant Congenital Pigmented Nevus
Authors: Shinji Kobayashi , Hitoshi Okumura , Yoshimitsu Kuroyanagi , Kentaro Kubo , Hiromichi Matsui , Katsuyuki Torikai
Published: February 2004

This study was designed to try the application of autologous cultured dermal substitute (CDS) in conjunction with patient's own epidermis. The autologous CDS was prepared by seeding cultured autolougus fibroblasts on the spongy matrix of hyaluronic acid and atelo‐collagen. A 9‐year‐old man with a giant congenital pigmented nevus (intradermal type) was included in this clinical study. A part of nevus (30 cm × 10 cm) was excised superficially at a thickness of 20/1000 inches, and followed by second excision to remove nevus at a level of full‐thickness skin. The autologous CDS was applied to the debrided wound surface. The split‐thickenss skin obtained by first excision was preserved at 4 °C. After 1 week, the epidermis was obtained from the preserved split‐thickness skin using dispase, and followed by grafting on the wound bed, which was prepared by applying autologous CDS. This patient's own epidermis was found to take permanently, achieving an excellent clinical results.
S‐I‐03  Differentiation of Mesenchymal Progenitor Cells Derived from Rat Bone Marrow
Authors: Hiroko Satoh , Kazuo Kishi , Tatsuo Nakajima
Published: February 2004

We showed mesenchymal progenitor cells(MPC) contain various cells, and the differentiational capacities and effects on wound healing were different each other. Bone marrow of the femur of adult F344 rat was suspended into culture medium and plated on a plastic dish.10–15 passaged cells were cloned in 100 types cells. For investigation of the differentiational capacity, the cells were treated by differentiational medium. The capacity of myogenesis was examined immunohistochemically with anti‐skeletal muscle myosin antibody. Osteochondrogenesis were investigated by alcian blue staining and adipogenesis by oil red O staining. The 53% of cells showed myogenesis, 78% osteochondrogenesis and 100% adipogenesis. The one type of cell showed amazing adipogenesis pattern, which we named “O” cell. Next we injected MPC and this “O” cell into the rats’ dorsal skin, and 1 cm full thickness incisional wounds were made immediately after. 2 weeks later, wounds were harvested and examined histologically. The wounds transplanted with high dose of MPC healed with very fine scar and collagen fibers were thick and aligned like normal dermis. But by transplanting the “O” cells, wounds healed with ordinary scar formation. By tansplantating mesenchymal progenitor cells, lesion healed with less scars. And there was a possibility that the MPC responded to the wound healing and regenerated dermal structure nearly normally. But the wounds healed not well by transplanting just “O” cell although it possesses the amazing differentiational capacity. The data demonstrate that plural types cells were necessary for wound healing.
038  Neovascularization in Artificial Dermis after Secondary Skin Grafting‐Scanning Electron Microscopic Observation of Molded Blood Vessels‐
Authors: Junko Yasuda , Shigehiko Kawakami
Published: February 2004

Aim: This study observed neovascularization in an artificial dermis after secondary skin grafting both light microscopically and electron microscopically and examined the optimal time of operation for secondary skin grafting through change in form of the graft.

Method: Using 31 adult rabbits, full‐thickness skin defects were produced inside the ear. Artificial dermis was fixed on one side of the wounds (AD group). On the other side of the wound, artificial dermis was not used (Control group). On the fifth, seventh, and tenth day, thin split‐thickness skin was taken from the back of a rabbit, and grafted.

Result: It mainly observed about the tenth day because more than 60% of grafts exhibited complete take on the tenth day, while on the fifth or seventh day no taking was observed. Electron microscopic findings reveled that, in the AD group before transplant, neovascularization was seen, extending from the bed to artificial dermis vertically, but there was no angiogenesis observed extending from the wound margin centripetally. This centripetal angiogenesis was observed in the control group and seemed to indicated the contraction of the wound and grafted skin.

Conclusion: It was concluded that the most suitable period for secondary skin grafting in the experiment model was 10 days after implantation of artificial dermis.
042  Comparative Evaluation of Duplex‐Derived Parameters in Patients with Chronic Venous Insufficiency: Correlation with Clinical Manifestation
Authors: Takashi Yamaki , Motohiro Nozaki , Osamu Fujiwara
Published: February 2004

Aim: To compare the duplex‐derived parameters between patients with early, and those with advanced chronic venous insufficiency (CVI), and to determine the indicative parameters reflecting the progression of CVI.

Methods: A total of 1132 limbs in 914 patients with of primary valvular incompetence were included. The clinical manifestations were categorized according to the CEAP (clinical, etiologic, anatomic, and pathophysiologic) classification, and the patients were divided into two groups: group I (C1−3EP,AS,D,P,PR) and group (C4−6EP,AS,D,P,PR). The distribution of venous insufficiency was determined, and the parameters assessed were the duration of reflux (s), the peak reflux velocity (cm/s), and the flow at peak reflux (ml/s).

Results: There was no significant difference in overall superficial venous reflux between the groups. And the frequency of isolated deep and perforator incompetence did not differ between the groups. The duration of reflux did not improve the discrimination power between the groups. In contrast, the peak reflux velocity had significant discrimination power at the sapheno‐femoral junction (SFJ, p < 0.0001) and sapheno‐popliteal junction (SPJ, p = 0.0002), and in the greater saphenous vein (GSV, p < 0.0001), in the superficial femoral vein (SFV, p = 0.0041), and popliteal vein (POPV, p = 0.003). The peak reflux flow was significantly higher in group II at the SFJ (p < 0.0001) and SPJ (p = 0.0029), and in the GSV (p < 0.0001), in the common femoral vein (p = 0.006), in the SFV (p = 0.0005), and POPV (p = 0.0003).

Conclusions: Superficial venous insufficiency may play a major role in the disease development of advanced CVI. The peak reflux velocity and peak reflux volume improve discrimination power between early‐stage and advanced CVI.
S‐II‐02  The Effects of IL‐10 and TNFα on Wound Healing of Intestinal Anastomosis
Authors: Akito Moroguchi , Ken Ishimura , Keiichi Okano , Taijiro Miyake , Takashi Maeba , Hajime Maeta
Published: February 2004

Aim: This study aimed to define the participation of local expression of IL‐10 and TNFα around the anastomotic segment and clarify the effects of IL‐10 and TNFα on anastomotic wound healing after digestive surgery under septic condition.

Methods: Experimental animals were divided into LPS and control groups, which had either LPS or normal saline solution injected into the peritoneal cavity 24 h before transection and anastomosis of the colon. Immunohistochemical staining for IL‐10 and TNFα on tissue samples were examined after the operation. Fibroblasts were cultured with IL‐10 and TNFα, then proliferation rates were determined using the MTT assay. Type I collagen protein and MMP‐I were detected by indirect immunofluorescence.

Results: In the LPS group, IL‐10 and TNFα expression were more enhanced than that in the control group 24 h after the operation. IL‐10 reduced fibroblasts proliferation in dose dependent fasion in the presence of TNFα. Indirect immunofluorescence showed that IL‐10 reduced type I collagen protein and increased MMP‐I.

Conclusions: Local expression of IL‐10 and TNFα at the anastomotic site acted as an inhibitory factor in the wound healing process. IL‐10 suppressed the remodeling of the extracellular matrix during wound healing.
S‐IV‐05  Study in Hybridized Tissue Engineered Trachea by Using Acellular Trachea Scaffold
Authors: Inoue H , Tsukada H , Osada H , Oshima H , Kumagai N
Published: February 2004

Aim: A method for preparing acellular trachea scaffold and its effectiveness were investigated by using rabbits and dogs

Methods: The sacrificed dog or rabbit trachea was collected. The spiral stent of stainless steel was inserted in the obtained trachea. To remove all of cellular components in tissues, the trachea was rinsed with sterilized 0.5% Triton X‐100 for 24 to 48 hours at ambient temperature and then for removing the detergents completely using fresh water. The acellular trachea obtained was lyophilized and sterilized by ethylene oxide gas. Before implantation, the lyophilized acellular trachea was soaked in phosphate buffered saline containing 0.5% gelatin and other adhesive molecules for 2 to 18 hours at 37 degree. After 15 mm of rabbit neck trachea was removed surgically under anesthesia, the same length of reengorged acellular rabbit trachea was implanted the removed region. In the case of dog, 50 mm of thoracic trachea was removed under the mechanical ventilation and then the same length of reengorged acellular trachea was implanted by technique of end to end anastomosis. The implanted trachea was rapped by omentum. The effectiveness of acellualr scaffold on implanted‐animals was evaluated by endoscope finding.

Results: 1) The rabbits implanted reengorged‐acellular trachea survived for minimum 10 days and maximum 60 days. It was suggested that the cause of death was the infection of implantation region. 2) The dog implanted reengorged‐acellular trachea survived for over 60 days at least. The cause of death was strangulated hernia. 3) The acellular trachea containing various growth factors or cultured with fibroblasts was not always effective.

Discussion: It is not necessary for the animal implanted acellular trachea to be administered the immunodepressants such as the animal implanted cryopreserved trachea. From these results, the tissue engineered acellular trachea may be more effective than the cryopreserved trachea.
P‐II‐01  Development of allogeneic cultured dermal substitute (CDS)
Authors: Kentaro Kubo , Yoshimitsu Kuroyanagi
Published: February 2004

The authors have developed a CDS by culturing fibroblasts on the two‐layered spongy matrix of hyaluronic acid (HA) and atelo‐collagen (Col). This CDS is designed to promote wound healing by synergistic effect of fibroblasts and matrix. Both HA and Col molecules seem to function biologically in the process of wound healing. HA molecules play a critical role in several cellular functions such as migration and proliferation by promoting adhesion and disadhesion between the cell and the tissue substrate. Besides providing structural support and strength to the new tissue, Col molecules have a profound effect on the cells within and on its matrix. Col and Col‐derived peptides act as chemoattractants for fibroblasts in vitro and may have a similar activity in vivo. Fibroblasts seeded on the Col surface of two‐layered spongy matrix were found to attach, proliferate, and release vascular endothelial growth factor (VEGF) as well as fibronectin. The cryopreserved CDS was found to keep the original potency to release VEGF after thawing followed by re‐culturing. Multi‐center's clinical research using allogeneic CDS has been proceeded as a national millennium project for regenerative medicine. These products are able to be stored in a freezer and transported to other hospitals in a frozen state. The clinical evaluation involving 180 cases has been already conducted using allogeneic cryopreserved CDS at 30 hospitals across Japan since April 2001. The results obtained in our clinical study suggest that this type of allogeneic CDS is able to provide an effective therapy for patients with severe full‐thickness skin defects. These excellent clinical evaluations seem to be closely related to the results obtained in this fundamental study, especially related to the potency of cryopreserved allogeneic CDS to release VEGF and fibronectin.
007  Differences in Expression of Basic Fibroblast Growth Factor during Wound Healing between Oral Mucosa and Skin
Authors: Nukumi K. , Masuda M. , Obata A. , Yumoto E.
Published: February 2004

Introduction: Oral mucosa heals faster with less scar than skin, but its mechanism has not been elucidated enough. We have studied whether there are any differences in the dynamic study of the bFGF expression in vivo during wound healing between oral mucosa and skin.

Methods: Male Wistar rats were anesthetized, and a 3 mm circular exisional wound was made on the dorsum skin and intrabuccal mucosa of each rat. At days 0,1,3,5,7 and 10 post‐wounding,wounds were harvested, and embedded in OCT. From photographs of the wounds, each wound area was measured by means of NIH images. Also, for histological study, sections were stained haematoxylin and eosin, and for immunohistochemical study, sections were stained with anti‐bFGF antibody.

Results: Oral wounds contracted significantly faster than skin. Regenerated skin appeared at day 1 post‐wounding in oral wounds, but at day 3 in skin. Re‐epithelialization was completed on day 5 post‐wounding in oral, but on day 7 in skin. The number of bFGF‐positive cells gradually increased in the granulation tissue, and the peak of positive cells in oral was observed on day 5 post‐wounding, while that in skin on day 7.

Conclusion: Oral mucosa healed faster than skin. The peak of bFGF expression was faster in oral mucosa than skin. It was thougt that bFGF effects the differences during wound healing between oral mucosa and skin.
Natural materno-fetal transfer of antibodies to PspA and to PsaA
Authors: BARIL L , BRILES D E , CROZIER P , KING J D , HOLLINGSHEAD S K , MURPHY T F , MCCORMICK J B
Published: February 2004

PspA and PsaA are Streptococcus pneumoniae surface proteins and potential pneumococcal vaccine antigens. The aim of this study was to characterize the transplacental transfer of antibodies to PspA and to PsaA. Paired mother and cord blood sera were obtained at delivery from 28 women. Concentrations of antibodies against PspA, PsaA, tetanus toxoid (vaccine-induced antibodies) and P6-outer membrane protein (OMP) of nontypeable Haemophilus influenzae were determined by ELISA. Antibodies to PspA of the IgG, IgG1 and IgG2 antibodies were also determined. The geometric mean percentage (GM%) of the paired infant:mother antibody were calculated. Results: The GM% of the infant:mother antibody concentrations against PspA, PsaA and P6-OMP antibodies were 64·7% (3·3 µg/ml in infants vs. 5·1 µg/ml in mothers), 50·4% (6·8 µg/ml vs. 13·5 µg/ml) and 66·7% (5·6 µg/ml vs. 8·4 µg/ml), respectively; the GM% of antibodies against tetanus toxoid was 104·5% (4·6 µg/ml vs. 4·4 µg/ml). Transplacental transfer of IgG1 was more efficient than that of IgG2 (approximately 120%vs. 65%). A transplacental transfer of antibodies to PspA and to PsaA exist. Moreover, these data suggest an active placental transfer of IgG1 antibodies to PspA since the concentration of these antibodies were consistently higher in cord sera than in the mother's sera.