bluuebunny/crossref_metadata_2025_split huggingface dataset:
15‐deoxy‐Δ12,14‐prostaglandin J2, a ligand for peroxisome proliferators‐activated receptor‐γ, induces apoptosis in human hepatoma cells
Authors: Date Masataka , Fukuchi Kazuhide , Morita Shosuke , Takahashi Hiroshi , Ohura Kiyoshi 
Published: November 2003

Abstract:Background/Aims: 15‐deoxy‐Δ12,14‐prostaglandin J2 (15‐d‐PGJ2) induces apoptosis in several carcinoma cell lines and is a potent activator of peroxisome proliferators‐activated receptor‐γ (PPAR‐γ). In the present study, we examined the effect of 15‐d‐PGJ2 on human hepatoma cells.Methods: HuH‐7 and HepG2 cell lines were used in all the experiments. The mRNA expression of PPAR‐γ was studied by reverse transcriptase‐polymerase chain reaction. The cell viability was determined by a modified MTT assay. Two methods were used for the determination of apoptosis in hepatoma cells: the TUNEL assay, and detection of fragmented mono‐ and oligo‐nucleosomes by ELISA.Results: The expression of PPAR‐γ mRNA and protein was detected in HuH‐7 and HepG2. Treatment with 15‐d‐PGJ2 decreased cell viability in a time‐ and dose‐dependent manner. 15‐d‐PGJ2 induced apoptosis and this effect was time‐dependent. Exposure of cells to 15‐d‐PGJ2 induced caspase‐3 and ‐9 activation. Furthermore, co‐treatment with the pan‐caspase inhibitor Z‐VAD‐FMK or the caspase‐3 inhibitor Z‐DEVD‐FMK blocked apoptosis of human hepatoma cells that had been treated with 15‐d‐PGJ2.Conclusions: Our study demonstrates that PPAR‐γ is expressed in human hepatoma cell lines and that treatment with 15‐d‐PGJ2 inhibits the growth of these cells by inducing apoptosis through caspase activation.
Hepatic dysfunction in patients with extrahepatic portal venous obstruction
Authors: Rangari M. , Gupta R. , Jain M. , Malhotra V. , Sarin S.K. 
Published: November 2003

Abstract:Background: Extrahepatic portal venous obstruction (EHPVO) developing due to thrombotic occlusion of the portal vein in children is generally considered a benign disease. Whether hepatic dysfunction develops in these patients in the absence of a gastrointestinal bleed has not been well studied.Materials and methods: Forty‐three patients with EHPVO who had not bled in the last 3 months were studied. Patients were divided into those with (group I) or without ascites (group II). Matched cirrhotic patients with ascites (group III) served as controls. Clinical, biochemical, ultrasonographic, and histopathological evaluation was carried out. Portal biliopathy was assessed in five patients in group I and in 12 patients in group II by cholangiography.Results: Of 43 EHPVO patients, ascites was seen in nine (21%) patients (group I). Thirty‐four patients had no ascites (group II). Serum ALT (54±24 vs. 34±10 IU/l, P<0.01), albumin (3.2±0.3 vs. 3.7±0.4 g/dl, P<0.01), and prothrombin time difference (9.0±4.5 vs. 2.4±1.9 s, P<0.05) were deranged in patients in group I compared with group II. Patients in group I were 4 years older, and the duration of portal hypertension was longer than in group II (11.5 vs. 5.6 year, P<0.05). Portal biliopathy changes were significantly more severe in group I than in group II patients. Ascites was high gradient in all the patients in group I and the serum‐ascitic albumin gradient was comparable between groups I and III. None of the EHPVO patients, but four cirrhotic patients, developed spontaneous bacterial peritonitis during a follow‐up of 11±4 months.Conclusions: Hepatic dysfunction in the form of ascites and deranged liver functions is not uncommon in patients with EHPVO, more so in patients with prolonged portal hypertension. Based on our data it would be worthwhile to study whether prolonged portal vein thrombosis in EHPVO patients could lead to progressive liver disease.
Vascular endothelial growth factor increases fenestral permeability in hepatic sinusoidal endothelial cells
Authors: Yokomori Hiroaki , Oda Masaya , Yoshimura Kazunori , Nagai Toshihiro , Ogi Mariko , Nomura Masahiko , Ishii Hiromasa 
Published: November 2003

Abstract:
Vascular endothelial growth factor (VEGF) is an important regulator of vasculogenesis and vascular permeability. Hepatic sinusoidal endothelial cells (SECs) possess sieve‐like pores that form an anastomosing labyrinth structure by the deeply invaginated plasma membrane. Caveolin is the principal structural protein in caveolae. In this study, we examined the role of VEGF on the fenestration and permeability of SECs and the relation with caveolin‐1. SECs isolated from rat livers by collagenase infusion method were cultured for 24 h with (10 or 100 ng/ml) or without VEGF. The cells were then examined by transmission and scanning electron microscopy (EM). The expression of caveolin was investigated by confocal immunofluorescence, immunogold EM, and Western blot. Endocytosis and intracellular traffic was studied using horseradish peroxidase (HRP) reaction as a marker of fluid phase transport in SECs.Both transmission and scanning EM showed an increased number of sinusoidal endothelial fenestrae (SEF) in SECs cultured with VEGF. By confocal immunofluorescence, SECs cultured with VEGF displayed prominent caveolin‐1‐positive aggregates in the cytoplasm, especially surrounding the nucleus region. Immunogold EM depicted increased caveolin‐1 reactivity on vesicles and vacuoles of VEGF‐treated SECs compared with VEGF‐nontreated cells. However, there was no change in the level of caveolin‐1 protein expression on Western blot. After HRP injection, an increase of electron‐dense tracer filled the SEF in cells treated with VEGF. Our results suggested that VEGF induced fenestration in SECs, accompanied by an increased number of caveolae‐like vesicles. Increased caveolin‐1 might be associated with vesicle formation but not with fenestration. Increased fenestration may augment hepatic sinusoidal permeability and trans‐endothelial transport.
“Conclusions about exposure to ETS and health that will be unhelpful to us”: How the tobacco industry attempted to delay and discredit the 1997 Australian National Health and Medical Research Council report on passive smoking: Table 1
Authors: Trotter L , Chapman S 
Published: November 2003

Background:Major reviews of the health effects of passive smoking have been subjected to tobacco industry campaigns to refute the scientific evidence. Following the 1992 US Environmental Protection Agency review, the Australian National Health and Medical Research Council (NHMRC) initiated a review of the health effects of passive smoking. At the time of this review, evidence that environmental tobacco smoke causes disease was being increasingly accepted in courts of law and voluntary adoption of smoking restrictions was rapidly growing.Objective:To demonstrate how the tobacco industry attempted to delay and discredit the publication of a report on passive smoking that the tobacco industry anticipated to contain recommendations that would be unfavourable to their business.Methods:A search of tobacco industry documents on the Master Settlement Agreement websites was conducted using the terms and acronyms representative of the NHMRC review.Results:The tobacco industry sought to impede the progress of the NHMRC Working Party by launching an intensive campaign to delay and discredit the report. The main strategies used were attempts to criticise the science, extensive use of Freedom of Information provisions to monitor all activity of the group, legal challenges, ad hominem attacks on the credibility of the Working Party members, rallying support from industry allies, and influencing public opinion through the media.Conclusions:The Australian tobacco industry deliberately impeded the NHMRC Working Party’s progress and successfully prevented the publication of the report’s recommendations. The tobacco industry’s motivation and capacity to disrupt the advancement of scientific knowledge and policy in tobacco control should be recognised and anticipated.
“Can’t stop the boy”: Philip Morris’ use of Healthy Buildings International to prevent workplace smoking bans in Australia
Authors: Chapman S , Penman A 
Published: November 2003

Objective:To document the relationship of the indoor air consultancy company Healthy Buildings International (HBI) with the Australian tobacco industry.Design:Systematic keyword and opportunistic website searches of tobacco industry internal documents made available through the Master Settlement Agreement.Results:Since 1987 HBI has played a high profile role in advancing the Australian tobacco industry’s concerns to prevent building owners introducing smoke-free workplaces by advocating for ventilation solutions. HBI invoiced Philip Morris’ US lawyers Covington and Burling for work undertaken in Australia and sought to publicly deny its association with the industry. HBI breached Standards Australia protocols in providing PM with confidential public submissions made to a review of the Australian standard on ventilation and acted as an undeclared cipher into the review for Philip Morris’s concerns, leading to the eventual dismissal of the HBI representative from the standards subcommittee.Conclusions:HBI in Australia exemplifies the tobacco industry’s use of third party strategy in publicly advancing a case against smoke-free indoor air.
“Avoid health warnings on all tobacco products for just as long as we can”: a history of Australian tobacco industry efforts to avoid, delay and dilute health warnings on cigarettes
Authors: Chapman S , Carter S M 
Published: November 2003

Objective:To review critically the history of Australian tobacco industry efforts to avoid, delay, and dilute pack warnings on cigarettes.Design:Systematic keyword and opportunistic website searches of tobacco industry internal documents made available through the Master Settlement Agreement.Results:Four industry strategies and six recurrent arguments used by the industry are described, which were used to thwart the passage of three generations of health warnings (implemented in 1973, 1987, and 1995). These strategies are shown to have been associated with major delays in the implementation of the warnings and in keeping them inconspicuous, unattributed to the industry and non-specific, and particularly in delaying the use of warnings about addiction. The industry today continues to oppose warnings, which might “repel” smokers from tobacco use.Conclusions:Efforts by governments to introduce potent health warnings will be resisted by the tobacco industry. Tobacco control advocates should anticipate and counter the strategies and arguments used by the industry, which are described in this paper if they wish to maximise the use of the pack as a vehicle for raising awareness about the harms of smoking.
Smoking, disease, and obdurate denial: the Australian tobacco industry in the 1980s
Authors: Carter S M , Chapman S 
Published: November 2003

Objective:To contrast the Australian tobacco industry’s awareness of the diseases caused by smoking with their aggressive public denial on the relation between smoking and disease in the 1980s.Design:Analysis of 325 industry documents from the world wide web.Results:In the 1980s Australian cigarette manufacturers were informed constantly by the international industry of the medical consensus that smoking caused disease. In addition Philip Morris (Australia) Limited received reports of Philip Morris’ international biological research programme and visited its Richmond research facility; and WD&HO Wills part funded, co-managed, and contributed research to the British American Tobacco groups’ biological research programme. Despite this knowledge, the Australian manufacturers had a policy of arguing to their employees, decision makers, and the general public that questions of smoking and disease were unresolved. The industry catalogued the literature, developed arguments against the main claims made by health groups, and attacked public health advocates who made statements linking smoking to death and disease. Industry studies suggested that a 20–30% minority of the Australian public agreed with the industry on smoking and disease, diminishing across the decade.Conclusion:Australian manufacturers were clearly negligent in the 1980s, deliberately working to undermine Australians’ understandings of the diseases caused by smoking despite their own private knowledge. Continuing scepticism about smoking and disease, corresponding with the industry’s deceptions, exists in Australian smokers today, suggesting that their actions may have slowed the rate of decline in smoking prevalence. These revelations provide important evidence for Australian litigation and advocacy.
“We are anxious to remain anonymous”: the use of third party scientific and medical consultants by the Australian tobacco industry, 1969 to 1979
Authors: Chapman S 
Published: November 2003

Objective:To document the history of visits to Australia by tobacco industry sponsored scientists and news media reports about smoking and health matters generated by their visits.Design:Systematic keyword and opportunistic website searches of tobacco industry internal documents made available through the Master Settlement Agreement.Results:At least nine sponsored scientists visited Australia from 1969 until 1979. The industry sought to promote the scientists as independent from the industry and on occasion, scientists publicly lied about their industry connections. The industry was sometimes delighted with the extensive and favourable media coverage given to the visits.Conclusions:These media reports are likely to have influenced many who were exposed to them to believe that the evidence against smoking remained equivocal.
“A deep fragrance of academia”: the Australian Tobacco Research Foundation
Authors: Chapman S , Carter S M , Peters M 
Published: November 2003

Objectives:(1) To review the history of the tobacco industry supported Australian Tobacco Research Foundation (ATRF)(1970–1994) for evidence of the industry’s use of the Foundation to further its objectives that “more research was needed” on smoking and health and to promulgate the view that nicotine was not addictive. (2) To review efforts by public health advocates to discredit the ATRF as a public relations tool used by the Australian industry.Methods:Systematic search of previously internal industry documents released through the US Master Settlement Agreement.Results:The ATRF was headed by prestigious Australian medical scientists, with at least one considered by the industry to be “industry positive”. An international ATRF symposium on nicotine was vetted by the industry and heavily attended by industry approved scientists. Following sustained criticism from the health and medical community about the industry’s creation of the ATRF to further its objectives, the ATRF’s scientific committee was provoked to publicly declare in 1988 that smoking was a causative agent in disease. This criticism led to growing ATRF boycotts by scientists and substandard applications, causing the industry to see the ATRF as being poor value-for-money and eventually abandoning it.Conclusions:The raison d’etre for the ATRF’s establishment was to allow the Australian industry to point to its continuing commitment to independent medical research, with the implied corollary that tobacco control measures were premature in the face of insufficient evidence about tobacco’s harms. Sustained criticism of tobacco industry funded research schemes can undermine their credibility among the scientific community.
“Keep a low profile”: pesticide residue, additives, and freon use in Australian tobacco manufacturing
Authors: Chapman S 
Published: November 2003

Objectives:To review the Australian tobacco industry’s knowledge of pesticide residue on Australian tobacco and its policies and practices on resisting calls by tobacco control advocates that consumers should be informed about pesticide residue as well as additives.Methods:Review of previously internal industry documents relevant to pesticides and additives in Australian tobacco located from the Master Settlement Agreement websites.Results:Between 1972 and 1994 Philip Morris Australia was aware that its leaf samples were often contaminated with pesticide residue, sometimes including organochlorine levels described by PM’s European laboratories as being “extremely high”. Consumers were not advised of the contamination nor products withdrawn. From 1981, the industry also resisted calls to declare fully the extent of use and long term safety data on all additives used in their products. They developed standard public responses that were evasive and misleading and, in 2000, implemented voluntary additive disclosure which allowed the companies to continue to avoid disclosure of any ingredient they deemed to be a trade secret. There was extensive use of ozone depleting freon in Australian tobacco manufacturing. Again, the industry kept this information away from consumers.Conclusions:Australian smokers are unable to make informed decisions about smoking because pesticide and additive disclosure remains voluntary. The Australian government should regulate tobacco to require full disclosure including information on the likely health consequences of inhaling pesticide and additive pyrolysis products.
The Australian tar derby: the origins and fate of a low tar harm reduction programme
Authors: King W , Carter S M , Borland R , Chapman S , Gray N 
Published: November 2003

Objective:To document the development of the low tar harm reduction programme in Australia, including tobacco industry responses.Data sources:Tobacco industry documents, retail tobacco journals, newspapers, medical journals, and Anti-Cancer Council of Victoria (ACCV) newsletters and archival records.Study selection:Documents on the strategies and knowledge bases of the ACCV, other Australian health authorities, and the tobacco industry.Results:The ACCV built a durable system for measuring and publicising the tar and nicotine yields of Australian cigarettes and influencing their development. The tobacco industry initially sought to block the development of this system but later appeared to cooperate with it, as is evidenced by the current market dominance of low tar brands. However, behind the scenes, the industry used its substantial knowledge advantage regarding compensatory smoking and its ability to re-engineer cigarettes to gain effective control of the system and subvert the ACCV’s objectives.Conclusions:Replacement of the low tar programme with new means of minimising the harms from cigarette smoking should be a policy priority for the Australian government. This will require regulation, rather than further voluntary agreements, and stringent monitoring of successor programmes will be necessary.
“Some convincing arguments to pass back to nervous customers”: the role of the tobacco retailer in the Australian tobacco industry’s smoker reassurance campaign 1950–1978: Figure 1
Authors: Tofler A , Chapman S 
Published: November 2003

Background:Epidemiological studies and reports on smoking and health published in the 1950s and 1960s threatened the tobacco industry worldwide, which acted to reassure smokers and counteract mounting evidence that smoking posed a serious risk to smokers’ health.Objective:To document the use of tobacco retailers (1) as a conduit to pass messages of reassurance onto smokers, and (2) to recruit youth and women into smoking.Methods:Review of an extensive collection of Australian tobacco retail trade journals (1950–1978) for articles consistent with the industry’s efforts to counter messages about smoking and health, and how to attract non-smokers, particularly youth and women.Results:The main arguments advanced in the journals included the notion that air pollution and other substances cause cancer, that “statistics” did not constitute proof in the tobacco health scare, and that the industry was committed to research into the causes of cancer and into developing a “safer” cigarette.Conclusions:Numerous articles designed to be reiterated to customers were published, arguing against the link between tobacco and ill health. Tobacco retailers, salesmen and retail trade organisations played a significant role in dissembling the tobacco health nexus. Tobacco retail journals may be an important component in tobacco industry misinformation strategies.
From legitimate consumers to public relations pawns: the tobacco industry and young Australians
Authors: Carter S M 
Published: November 2003

Objective:To document the Australian tobacco industry’s activities regarding youth smoking to support tobacco control.Method:492 industry documents from primary and secondary websites were abstracted and analysed.Results:Australian legislation and rhetoric on youth and tobacco has changed dramatically over the last 50 years, from an unproblematic association of teenagers and smoking in the 1960s, through the industry’s aggressive attacks and denials in the 1980s, to the 1990s, when industry became newly compliant with “societal expectations” and youth became a dominant bargaining issue in the industry’s public relations strategy. The industry’s current policy is to simultaneously blame others for underage smoking, frame the industry as socially responsible via voluntary marketing codes, youth access programmes, and school education, and market actively to young adults.Conclusions:The arbitrary distinction between 17 and 18 year olds is, particularly in Australia’s dark market, a liability for tobacco control and an opportunity for the industry, which is attempting to claim the high moral ground traditionally occupied by tobacco control on the youth issue. The current review of Australia’s Tobacco Advertising Prohibition Act of 1992 should prohibit all forms of industry communication targeting young people, including retail access and schools programmes and below-the-line marketing. Tobacco control advocacy should highlight the industry’s attempts to use the youth issue in its own favour while laying the blame elsewhere.
Going below the line: creating transportable brands for Australia’s dark market
Authors: Carter S M 
Published: November 2003

Objective:To investigate non-point-of-sale cigarette marketing in Australia, one of the “darkest” markets in the world.Design:Analysis of 172 tobacco industry documents.Results:The tobacco industry has continued to market their products despite severe restrictions on legal marketing activity. They made careful plans to circumvent regulation well in advance. In preparation for bans, they chose and strengthened existing brands to enable their continued success in a dark market and prepared the consumer for bans by increasing their spending on below the line activities. Bans reduced the industry’s effectiveness and efficiency. After bans new brand launches stopped: instead key existing brands were strengthened via alterations to the product, line extensions, and stretching loopholes in the legislation as far as possible. In line with the general trend towards integrated marketing, a range of activities have been used in combination, including guerrilla marketing, advertising in imported international magazines, altering the pack, sponsorships, brand stretching, event promotions, lifestyle premiums, and the development of corporate websites.Conclusions:The tobacco industry acknowledges that marketing restrictions have an impact, validating their continued use in tobacco control. The industry is extremely creative in circumventing these marketing restrictions, requiring tobacco marketing regulations to be informed by marketing expertise, regularly updated, and to adopt the broadest possible scope. Tobacco control advocates, particularly those communicating with young people, could learn from the creativity of the tobacco industry.