bluuebunny/crossref_metadata_2025 huggingface dataset:
Different mechanisms of steatosis in hepatitis C virus genotypes 1 and 3 infections
Authors: Hézode C. , Roudot‐Thoraval F. , Zafrani E.‐S. , Dhumeaux D. , Pawlotsky J.‐M.
Published: September 2004

Summary.  This study reports evidence that hepatocellular steatosis, a frequent histological feature of chronic hepatitis C, is principally metabolic in hepatitis C virus (HCV) genotype 1‐infected patients, whereas it is principally virus‐induced in HCV genotype 3‐infected patients. Multivariate analysis of data on 176 patients with chronic hepatitis C revealed that the severity of steatosis was independently related to HCV RNA load alone in patients infected by HCV genotype 3, whereas it was independently related to the body mass index, daily alcohol intake and histological activity grade (but not viral load) in patients infected by HCV genotype 1. These findings suggest that steatosis is a cytopathic lesion induced by HCV genotype 3, whereas HCV genotype 1 is not steatogenic per se or at the usual in vivo expression levels.
Interferon‐γ‐associated responses to woodchuck hepatitis virus infection in neonatal woodchucks and virus‐infected hepatocytes
Authors: Wang Y. , Jacob J. R. , Menne S. , Bellezza C. A. , Tennant B. C. , Gerin J. L. , Cote P. J.
Published: September 2004

Summary.  Acute hepatitis and recovery from woodchuck hepatitis virus (WHV) infection involves increased intrahepatic expression of interferon‐gamma (IFN‐γ) and tumour necrosis factor‐alpha (TNF‐α) mRNAs. In the present study, recovery correlated with increased intrahepatic expression of mRNAs for major histocompatibility complex class 1 (MHC1), β2‐microglobulin, 2′5′‐oligoadenylate synthetase (2′5′‐OAS), and indoleamine dioxygenase (IDO). By comparison, acute WHV infection progressing to chronicity was associated with diminished expression of these IFN‐γ‐associated mRNAs in liver. Transfection of WHV‐infected primary hepatocytes (WPH) from WHV carriers with an IFN‐γ‐expressing plasmid (pIFN‐γ) resulted in dose‐dependent accumulations of MHC1, TNF‐α, 2′5′‐OAS, and IDO mRNAs within 96 h. Markers of T cells and immune‐mediated cytotoxicity that accumulate in recovering liver were not apparent in WPH based on the relative lack of CD3, CD4, Fas ligand, perforin, and granzyme B mRNAs. Expression of pIFN‐γ, and TNF‐α‐expressing plasmid (pTNF‐α), did not affect total WHV RNA, or fully double‐stranded WHV DNA in WPH, but each reduced some of the replicative intermediate (RI) species of WHV DNA synthesis. WPH treated with recombinant IFN‐α protein had a higher fold induction of 2′5′‐OAS mRNA associated with partial reductions in WHV RNAs and the major RI species. Thus, IFN‐γ expression in carrier WPH induced several host responses often observed in liver of recovering woodchucks, and impaired a stage of WHV DNA synthesis by a non‐cytolytic mechanism mediated by TNF‐α. Local enhancement of IFN‐γ‐associated responses in chronic WHV‐infected hepatocytes may promote therapeutic antiviral effects, but additional effector mechanisms evident during recovery appear necessary for more complete clearance of WHV infection.
Antinuclear antibodies (ANA) in chronic hepatitis C virus infection: correlates of positivity and clinical relevance
Authors: Yee L. J. , Kelleher P. , Goldin R. D. , Marshall S. , Thomas H. C. , Alberti A. , Chiaramonte M. , Braconier J.‐H. , Hall A. J. , Thursz M. R.
Published: September 2004

Summary.  We examined correlates of antinuclear antibody (ANA) positivity (ANA+) in individuals with chronic hepatitis C virus (HCV) infection and the effect of positivity on clinical outcome of HCV. Pretreatment sera from 645 patients from three centres in Sweden (n = 225), the UK (n = 207) and Italy (n = 213) were evaluated by indirect immunofluorescence on Hep‐2 cells for ANA pattern and titre by a single laboratory. Liver biopsies were all scored by one pathologist. A total of 258 patients were subsequently treated with interferon monotherapy. There was a significant difference in the prevalence of ANA (1:40) by geographic location: Lund 4.4%, London 8.7%, Padova 10.3% [odds ratio (OR) = 0.66; 95% CI: 0.46–0.94; P = 0.023]. Duration of HCV infection, age at infection, current age, route of infection, viral genotype, alcohol consumption, fibrosis stage and inflammatory score were not correlated with ANA+ or ANA pattern. Female gender was correlated with ANA+ and this association persisted in multivariable analyses (OR = 3.0; P = 0.002). Increased plasma cells were observed in the liver biopsies of ANA‐positive individuals compared with ANA‐negative individuals, while a trend towards decreased lymphoid aggregates was observed [hazard ratio (HR) = 9.0, P = 0.037; HR = 0.291, P = 0.118, respectively]. No correlations were observed between ANA positivity and nonresponse to therapy (OR = 1.4; P = 0.513), although ANA+ was correlated with faster rates of liver fibrosis, this was not statistically significant (OR = 1.8; P = 0.1452). Low titre ANA+ should not be a contraindication for interferon treatment. Our observation of increased plasma cells in ANA+ biopsies might suggest B‐cell polyclonal activity with a secondary clinical manifestation of increased serum immunoglobulins.
HCV infection and oral lichen planus: a weak association when HCV is endemic
Authors: Campisi G. , Fedele S. , Lo Russo L. , Di Fede O. , Aricò P. , Craxì A. , Mignogna M. D.
Published: September 2004

Abstract  Oral lichen planus (OLP), an immune‐mediated disorder, has been reported as an extra‐hepatic manifestation of Hepatitis C virus (HCV) infection, especially in HCV hyperendemic areas such as southern Europe and Japan. The aim of this study was to investigate from an epidemiological standpoint whether HCV infection is an important factor affecting the relative risk of OLP in a Mediterranean population or whether this relates to the degree of HCV endemicity. Two cohorts of OLP patients resident in two different regions of southern Italy (Campania and Sicily; n = 859) were evaluated for HCV infection status and categorized into five age classes to respective region‐matched controls. No significant difference was found between OLP patients and the general population in this area, when data were corrected by the age‐stratified prevalence of HCV. Therefore, the age‐specific prevalence of HCV infection in OLP patients shows a close trend of direct association with increasing age, without significant differences with the general population of each geographical area. An aetiological link between OLP and HCV cannot be inferred solely by epidemiological data.
Hepatitis C virus infection in Egyptian children: single centre experience
Authors: El‐Raziky M. S. , El‐Hawary M. , El‐Koofy N. , Okasha S. , Kotb M. , Salama K. , Esmat G. , El‐Raziky M. , Abouzied A. M. , El‐Karaksy H.
Published: September 2004

Summary.  The outcome of hepatitis C virus (HCV) infection acquired in childhood is uncertain because of the diversity of the epidemiological and clinical features of infection and disease. The aim of this study was to determine the outcome of HCV infection in 105 Egyptian children who tested positive for HCV antibody (anti‐HCV). The data of 105 anti‐HCV‐positive children presenting to the Pediatric Hepatology Unit, Cairo University Children's Hospital, between 1995 and 2002, were retrospectively analysed for risk factors. Seventy‐four children with available polymerase chain reaction results were further analysed clinically, serologically and histologically. The age range was 1.3–22 years, with a mean of 11.2 ± 4.9 years. History of blood transfusion was found in 81 children (77%). HCV RNA was detected in 58.1% of 74 children. Persistently elevated alanine aminotransferase (ALT) levels were present in 40 patients (54.1%). Hepatitis B virus markers (HBsAg and/or anti‐HBc) were detected in 18 patients (24.3%). Twenty‐six of the 43 HCV RNA‐positive children underwent a diagnostic liver biopsy that showed chronic hepatitis in 19 patients (73.1%), cirrhosis in one case only (3.8%), and normal biopsy findings in seven children (26.9%). Blood transfusion remains a major risk of HCV transmission among Egyptian children. HCV infection is not always benign in the childhood period. ALT levels remain elevated in half of the children and histological abnormalities are detected in three quarters of HCV RNA‐positive cases.
Immune thrombocytopenic purpura in a patient treated with interferon alfacon‐1
Authors: Dimitroulopoulos D. , Dourakis S. P. , Xinopoulos D. , Tsamakidis K. , Paraskevas E.
Published: September 2004

Summary.  Immune thrombocytopenic purpura is an acquired disorder characterized by severe thrombocytopenia and caused by one or more antiplatelet autoantibodies. We present a case of a 20‐year‐old woman referred to our Unit for chronic hepatitis  C virus (HCV) infection. At week 28 of treatment with interferon (alfacon‐1), undetectable HCV RNA and transaminase levels within normal limits, the patient presented with immune thrombocytopenic purpura, which was successfully treated with immunoglobulin and methylprednisolone. Despite the high doses and long life of corticosteroid treatment HCV RNA remained undetectable.
Sustained response after a 2‐year course of lamivudine treatment of hepatitis B e antigen‐negative chronic hepatitis B
Authors: Fung S. K. , Wong F. , Hussain M. , Lok A. S. F.
Published: September 2004

Summary.  Lamivudine has demonstrated efficacy for the treatment of hepatitis B e antigen‐negative chronic hepatitis B (e‐CHB). However, treatment withdrawal after 1 year has been associated with a high rate of relapse while long‐term treatment is associated with increasing risks of drug resistance. We report our treatment experience of 50 Chinese‐Canadian patients with e‐CHB. All patients received lamivudine for 2 years. Treatment was withdrawn at month 24 in patients who had undetectable hepatitis B virus (HBV) DNA by PCR and normal aminotransferases during the second year of therapy. All patients had HBV genotype B or C. Biochemical response at months 6, 12 and 24 was 74%, 71% and 66%, respectively. HBV DNA was undetectable at months 6, 12 and 24 by hybrid capture and PCR assays in 100%, 92% and 86%; and 94%, 88% and 74% patients, respectively. The cumulative rates of genotypic resistance (GR) after 1 and 2 years were 15% and 25%, respectively. Four (44%) patients with GR experienced a hepatitis flare. The probability of clinical and virological relapse 6, 12, and 18 months after treatment withdrawal were 12% and 30%, 18% and 50%, and 30% and 50%, respectively. Reinstitution of lamivudine resulted in prompt virological and biochemical responses. Our study demonstrates that a sustained response can be achieved after a 2‐year course of lamivudine in a subset of patients with e‐CHB.
High risk of hepatocellular carcinoma in anti‐HBe positive liver cirrhosis patients developing lamivudine resistance
Authors: Andreone P. , Gramenzi A. , Cursaro C. , Biselli M. , Cammà C. , Trevisani F. , Bernardi M.
Published: September 2004

Summary.  The emergence of drug‐resistant virus in hepatitis B virus patients treated with lamivudine is well documented. However, its clinical impact in the long‐term treatment of anti‐HBe positive compensated cirrhotic patients is not well known. In this study, we treated 22 consecutive patients with anti‐HBe compensated cirrhosis with lamivudine for a median period of 42 months. All patients responded to lamivudine, but viral breakthrough occurred in 13 patients (59%) between 9 and 42 months of therapy due to the emergence of a mutant strain. During the follow‐up, 11 developed hepatocellular carcinoma. Of these, 10 occurred soon after the emergence of viral resistance, generally showing aggressive behaviour, and one in the nine long‐term responder patients (P = 0.013). Lamivudine resistance was the only independent predictor of hepatocellular carcinoma development (risk ratio: 10.4; 95% CI: 1.3–84.9). Our study suggests that the occurrence of lamivudine resistance increases the risk of hepatocellular carcinoma in anti‐HBe positive cirrhosis and warrants further research.
What is the nature of the problem?
Authors: Delahooke T. E. S.
Published: September 2004

This review concentrates on the natural history of the infection. The virology and epidemiology of the disease are covered elsewhere. There are a number of inherent difficulties in studying the outcome of HCV infection: the onset is often not recognized, it can be asymptomatic, the progression is slow and patients may have had treatment. However some insights in recent years have been made.
Hepatitis C: who is at risk and how do we identify them?
Authors: Goldberg D. , Anderson E.
Published: September 2004

Summary.  The transmission of, and screening for, HCV infection varies considerably throughout the world; differences between resource‐poor and resource‐rich countries are particularly pronounced. The perspective of this review, principally, is that of resource‐rich countries. The UK, particularly Scotland, experience is drawn on.
How should we manage the patient?
Authors: Main J. , Thomas H.
Published: September 2004

Summary.  The patient with HCV infection may present with a variety of problems and range from the asymptomatic patient with mild liver damage to a patient presenting with complications of cirrhosis or hepatocellular carcinoma. The diagnosis of hepatitis C may be a complete surprise to the patient or be an expected diagnosis in someone with known risk factors. Similarly the physician may be faced with a patient who knows very little about hepatitis C or someone who has read extensively on the subject. The initial consultation is useful for gaining information on the patient's background, physical examination may give useful clinical clues on the stage of the liver disease. The consultation gives the physician a chance to educate the patient on the current thinking on hepatitis C and to organize confirmatory and other investigations that will help decide on the next line of management, i.e. whether the patient is a candidate for combination therapy of interferon and ribavirin.
What lies ahead and can we afford it?
Authors: Howie H. , Hutchinson S. J.
Published: September 2004

Summary.  Hepatitis C is a chronic disease with a slow and variable progression over 20–50 years and it is an important public health problem for the 21st century. This paper describes the information required to estimate what lies ahead in terms of morbidity, mortality and the implications for the health service in Scotland and summarises work undertaken in other countries. There will be an increasing number of people with severe liver disease in the next 10–20 years and we need to invest now in primary prevention and effective treatment strategies to reduce the burden of disease in the future.
What is the best treatment?
Authors: Dillon J. F.
Published: September 2004

Summary.  The treatment of hepatitis C is expensive, difficult and arduous from the patient's perspective. It is similarly difficult for the clinician to decide who and when to treat. If hepatitis C is viewed from the liver's perspective we need only treat those patients who will develop the complications of chronic liver disease within their lifetimes. If we take a more holistic approach, then we have to consider the implications of being a carrier of a potentially transmissible blood borne virus on the patient themselves, their relationships, their families and their sense of wellbeing. There is now evidence of the large impact HCV has on quality of life and we have to consider extra hepatic manifestations of hepatitis C infection, possibly including the syndrome of ‘brain fog’ recently described. An additional factor that has to be considered in the decision to treat is whether patients perceive hepatitis C as a significant problem for themselves. For some patients, who have chaotic live styles, it is extremely difficult to get them to access healthcare. To then undergo the rigors and tribulations of hepatitis C therapy that is posing no current problem is unlikely to succeed. However, failure to engage these patients with therapy will lead to a significant proportion of them presenting with serious complications of chronic liver disease, with its attendant mortality, morbidity and cost. Underlying all these considerations is the tension between the costs of therapy and the benefits of therapy. Good arguments can be made in terms of cost‐effectiveness for treating patients with a high likelihood of progressing to chronic liver disease and its complications. These arguments become much less persuasive when all patients are concerned.
Large‐scale screening of Arabidopsis circadian clock mutants by a high‐throughput real‐time bioluminescence monitoring system
Authors: Onai Kiyoshi , Okamoto Kazuhisa , Nishimoto Harumi , Morioka Chisato , Hirano Minako , Kami‐ike Nobunori , Ishiura Masahiro
Published: September 2004

Using a high‐throughput real‐time bioluminescence monitoring system, we screened large numbers of Arabidopsis thaliana mutants for extensively altered circadian rhythms. We constructed reporter genes by fusing a promoter of an Arabidopsis flowering‐time gene – either GIGANTEA (GI) or FLOWERING LOCUS T (FT) – to a modified firefly luciferase gene (LUC+), and we transferred the fusion gene (PGI::LUC+ or PFT::LUC+) into the Arabidopsis genome. After mutagenesis with ethyl methanesulfonate, 50 000 M2 seedlings carrying the PGI::LUC+ and 50 000 carrying PFT::LUC+ were screened their bioluminescence rhythms. We isolated six arrhythmic (AR) mutants and 29 other mutants that showed more than 3 h difference in the period length or phase of rhythms compared with the wild‐type strains. The shortest period length was 16 h, the longest 27 h. Five of the six AR mutants carrying PGI::LUC+ showed arrhythmia in bioluminescence rhythms in both constant light and constant dark. These five AR mutants also showed arrhythmia in leaf movement rhythms in constant light. Genetic analysis revealed that each of the five AR mutants carried a recessive mutation in a nuclear gene and the mutations belonged to three complementation groups, and at least one of which was mapped on a novel locus. Our results suggest that the three loci identified here may contain central clock or clock‐related genes, at least one of which may be a novel.
AtSUC8 and AtSUC9 encode functional sucrose transporters, but the closely related AtSUC6 and AtSUC7 genes encode aberrant proteins in different Arabidopsis ecotypes
Authors: Sauer Norbert , Ludwig Andreas , Knoblauch Alexander , Rothe Petra , Gahrtz Manfred , Klebl Franz
Published: September 2004

Three members of the Arabidopsis sucrose transporter gene family, AtSUC6–AtSUC8 (At5g43610; At1g66570; At2g14670), share a high degree of sequence homology in their coding regions and even in their introns and in their 5′‐ and 3′‐flanking regions. A fourth sucrose transporter gene, AtSUC9 (At5g06170), which is on the same branch of the AtSUC‐phylogenetic tree, shows only slightly less sequence homology. Here we present data demonstrating that two genes from this subgroup, AtSUC6 and AtSUC7, encode aberrant proteins and seem to represent sucrose transporter pseudogenes, whereas AtSUC8 and AtSUC9 encode functional sucrose transporters. These results are based on analyses of splice patterns and polymorphic sites between these genes in different Arabidopsis ecotypes, as well as on functional analyses by cDNA expression in baker's yeast. For one of these genes, AtSUC7 (At1g66570), different, ecotype‐specific splice patterns were observed in Wassilewskija (Ws), C24, Columbia wild type (Col‐0) and Landsberg erecta (Ler). No incorrect splicing and no sequence polymorphism were detected in the cDNAs of AtSUC8 and AtSUC9, which encode functional sucrose transporters and are expressed in floral tissue. Finally, promoter‐reporter gene plants and T‐DNA insertion lines were analyzed for AtSUC8 and AtSUC9.
The Effect of Intravaginal Applied GnRH‐agonist on the Time of Ovulation and Subsequent Reproductive Performance of Weaned Multiparous Sows
Authors: Baer C , Bilkei G
Published: September 2004

Retraction: The following article fromReproduction in Domestic Animals, “The Effect of Intravaginal Applied GnRH‐agonist on the Time of Ovulation and Subsequent Reproductive Performance of Weaned Multiparous Sows” by C. Baer and G. Bilkei, published online on 13 September 2004 in Wiley InterScience (http://www.interscience.wiley.com), has been retracted by agreement between the authors, the journal Editor‐in‐Chief, Heriberto Rodriguez‐Martinez and Blackwell Publishing Ltd.

The retraction has been agreed due to concern about the reliability of the data and overlap with the article “Intravaginal GnRH agonist‐gel advances time of ovulation and facilitates timed AI in weaned sows” by R.V. Knox, K.L. Willenburg, S.L. Rodriguez‐Zas, D.L. Greger, M.E. Swanson and H.D. Hafs published in the proceedings of the American Association of Swine Veterinarians in 2003.
Prostaglandin F2α Treatment Associated with Timed Artificial Insemination in Ewes
Authors: Menchaca A , Miller V , Gil J , Pinczak A , Laca M , Rubianes E
Published: September 2004

Contents

Traditional treatments of two prostaglandin F2 alpha (PGF2α) doses at 10‐day intervals or more did not result in acceptable pregnancy rates in timed artificial insemination (TAI) programmes in ewes. An explanation might be the undefined time‐period of the onset of oestrus and ovulation after the treatment. Recently a consistent interval to oestrus and ovulation was obtained by giving PGF2α at day 3 post‐ovulation, i.e. when the largest follicle of the first follicular wave of the cycle was still growing. This can be achieved when a second dose of PGF2α is given 7 days after a first dose. In this work, we evaluated the synchronization of oestrus and determined which of three different moments of TAI was the most successful using a PGF2α (PG‐7d) protocol in a large flock. A total of 436 nulliparous and multiparous ewes were treated with two doses of a PGF2α analogue (delprostenate 160 μg, i.m.) separated by 7 days. Onset of oestrus was recorded twice a day and a single cervical TAI with fresh undiluted semen was performed either at 42 h (n = 152), 48 h (n = 120), or 54 h (n = 164), after the second PGF2α dose without taking into account the oestrous response. Pregnancy rate was determined by transrectal ultrasonography 30 days after insemination. Onset of oestrus was detected in 308 of 328 and 89 of 108 multiparous and nulliparous ewes, respectively (p < 0.001), within 72 h after treatment. The distribution of the onset of oestrus did not differ between multiparous and nulliparous ewes and the highest proportion of ewes in oestrus was detected between 25 to 48 h (313/397) from the second PGF2α dose. The pregnancy rate in ewes inseminated at 42 h tended to be higher than those inseminated at 48 h (p = 0.09) and was higher than those inseminated at 54 h (p < 0.05) (56/152, 31/120, 37/164; respectively). Therefore, the use of the PG‐7d protocol resulted in a very high synchronization of oestrus with the highest concentration (around 80%) between 25 to 48 h from the end of treatment. The best pregnancy rate (37%) was obtained after a single cervical TAI with fresh semen at 42 h.
Mating system and pollination biology of the spring‐flowering shrub,Dirca palustris
Authors: WILLIAMS CHARLES E.
Published: September 2004

Dirca palustrisL., eastern leatherwood or wicopy (Thymelaeaceae), a widely distributed shrub of eastern North America, flowers in early spring and so may face some of the same constraints faced by ephemeral vernal herbs of the eastern deciduous forest, most notably the influence of low temperature on pollinator activity. I studied the mating system ofD. palustrisand the influence of temperature on pollinator visitation of flowers, during three field seasons in a small stream valley in north‐western Pennsylvania, USA. Specifically, I was interested in how a species with apparently specialized floral morphology, likeD. palustris,may ensure reproductive success in a thermally unpredictable vernal environment. Pollinator visitation of flowers ofD.palustriswas strongly regulated by temperature, with no visits occurring below 14.9°C. Lack of treatment effects in mating system studies, especially the lack of significant differences in fruit set between the bagged, self‐pollination treatment and various cross‐pollination treatments accessible to pollinators, suggests thatD. palustrisis self‐compatible or perhaps apomictic. Thus, like other spring‐flowering species faced with pollinator unpredictability,D. palustrismay rely on a mixed mating system to ensure reproductive success during cool temperate springs.
Clinical medicine and successful aging
Authors: Orimo Hajime
Published: September 2004

The aging of society is increasing very rapidly in most of the Asian countries. In Japan, the population of elderly aged 65 years and over is estimated to increase to 17.0% in 2000 – and to 25.0% of the entire population by 2020. The primary aim of geriatric medicine is to promote the health and quality‐of‐life of the elderly, leading them towards successful and active aging. In this plenary lecture, I would like to cover the following issues. (1) major diseases that cause disability in the elderly; (2) prevention of lifestyle and age‐related disease; (3) medical care of the elderly in 21st century; and (4) future perspectives.
The social sciences and successful aging: Issues for Asia–Oceania
Authors: Kendig Hal
Published: September 2004

Aim: This paper presents social science understandings of successful aging for a broad audience in multidisciplinary gerontology in Asia–Oceania.

Methods: The international literature on social science aspects of successful aging is reviewed with a focus on Asia and social improvement.

Results: New positive approaches to aging research are identifying opportunities for maintaining capacities and well‐being over the life course. Successful aging, productive aging, and active aging are key concepts. Increasing life expectancy and fertility control are major social achievements that underpin population aging as the mainstream social transformation facing the world. Asia will be at the forefront of this change and the consequences will vary greatly between cultures, nations, and subgroups within them. Older people generally maintain good quality of life and the capacity to ‘age well’ is influenced by life‐long maturation and emotional, social, and economic resources. Good health can be enhanced through positive actions such as physical activity, good nutrition, and not smoking. Mental capacities can also be improved and maintained throughout old age. In advanced old age, the ‘fourth age’, the focus turns to ameliorating the effects of loss and to maintaining dignity.

Conclusions: The social sciences contribute knowledge useful for improving life experiences for older people and aging societies. Population aging is central to national economic development. Public policy and individual action concerning aging can benefit all age groups. To better inform these developments it is important to address the serious shortfall of social science research on aging in the Asia–Oceania region.
Phenotypic adjustment of senescent cells: Replace or restore
Authors: Park Sang Chul
Published: September 2004

The historical concept of aging as an irreversible, inevitable, and inefficient biologic status led to the deterministic view of aging, which resulted in the replacement principle of aging control. For this purpose, the replacements of genes, cells, tissues, or organs have been proposed, but without satisfactory results. The novel concept of aging as a responsive and adaptive response to survival has resulted in the development of a new hypothesis of aging; namely, the Gate Theory. The prerequisites of the new hypothesis are gatekeeper molecules and a responsive aging field. Based on this concept, the modulation of gatekeeper molecules affects the cellular aging field, and result in the adjustment of the senescent phenotype. As a candidate for such molecules, caveolin has been examined with respect to its association with the aging phenotype. This new concept proposes the possibility of a restoration principle, which changes our view of aging in the community from simple longevity to a functional longevity. Functional longevity engenders the notions of active participation, positive thinking, and responsible behavior by the elderly. Therefore, it can be suggested that now is the time to accept the restoration principle as a key approach to individual aging control as well as the long live community in substitution with replace principle.
Asian value and aged care
Authors: Chow Nelson
Published: September 2004

Based on the findings of research studies on the practice of filial piety in East and South‐east Asian societies, this paper maps out a new basis for the formulation of aged care policies. Evidence shows that filial piety, while diminishing in influence, remains to be the most important value in regulating the behavior of children towards their elderly parents and relatives. Hence, neither a complete rejection nor a total acceptance of the value is appropriate. It is argued that a policy on care, especially long‐term care, for elderly people in East and South‐east East Asian societies must recognize the changes that have taken place in the practice of filial piety. The adoption of a community care approach that combines formal and informal support is suggested to be the most effective strategy in enhancing the welfare of the elderly.
Molecular basis of Alzheimer's disease: From amyloid hypothesis to treatment in the foreseeable future
Authors: Tabira Takeshi
Published: September 2004

Alzheimer's disease (AD) is the most common dementing disorder in the elderly. It is clinically characterized by insidious onset of memory disturbance followed by slowly progressive global dementia. The patient's brain at autopsy shows diffuse cerebral atrophy, and microscopic findings are characterized by the presence of intraneuronal neurofibrillary tangle (NFT), senile plaques with extraneuronal β amyloid deposits, and dystrophic changes of neuronal processes with synaptic and neuronal loss. The pathological mechanism of these hallmarks are now well understood on the molecular basis, and new strategies to prevent and reverse these pathological changes are now being developed. Here I review some personal interest of the mechanism, and describe future strategies for prevention and treatment of AD.
Population aging in the Asia–Oceania region
Authors: Sagaza Haruo
Published: September 2004

Recently the term ‘global aging’, which refers to the universal trend of aging of the world population, is being widely used. First of all, I will shed some light on this trend of world population aging from the viewpoint of regional populations and their future projections.

Second, I will discuss about the determinants of population aging in the Asia and Oceania region. So far as the region is concerned, it will be divided into three groups of countries according to the level of population aging. The first group is the most advanced aged countries such as Japan, Australia, and New Zealand whose percentage of the elderly aged 65 and over is more than 10% in the year of 2000. The second group is the aging countries such as Korea, Taiwan, Singapore, and China whose percentage of the elderly is between 5 and 10%. and the third group is the remaining countries in this region whose percentage is less than 5%. The demographic aspects of each group are analyzed and the relationships between the fertility reduction and aging are also discussed in the perspectives of the demographic transition.

Third, I will discuss about the consequences of population aging in this region with special reference to Asian developing countries. In this section, I will mention the problems of dependency burden, the so‐called population bonus, health expectancy, and social security systems. Fourth, some prominent characteristics concerning the living conditions and norms or attitudes of the elderly will be indicated, and I will also raise such points like family systems, living arrangements, social participation, and Ikigai (the worth of life) peculiar to Asian countries. Fifth and finally, I will touch on the topics of the issues and policies of the aging society. At present the social status of the elderly is improving in Asian countries and it is in the hope that the myth of aging will disappear in the near future.
Mental health of elderly in the Asia–Oceania region
Authors: Chiu Edmond
Published: September 2004

The mental health of the elderly can be conceptualized through universal values that facilitate, promote, and maintain it. The provision of care for the mentally disordered elderly is discussed with reference to a WHO/WPA Consensus statement.

Examples of services available in China, Indonesia, Hong Kong, and Singapore are given in line with the expectations contained in the Consensus statement.

Conclusions of a positive view that the region has the potential to provide quality service for the mental health of the elderly.
Public policy on aging in Korea
Authors: Cha Heung Bong
Published: September 2004

Korea has undergone the most dynamic social changes in the world during its modernization in the latter half of the 20th century. During the dynamic modernization period, the traditional rural society has been disorganized, and industrialization and urbanization has rapidly proceeded.

In this trend the traditional family system has changed, and the problem of the elderly has emerged as a social issue. However, public policy on aging has been laggedly developed, compared to the social change during the modernization.

In order to explain the public policy on aging in Korea, this paper examines the social changes and population aging, the family changes and the problem of the elderly, and then the development of the public policy on aging social care programs by stages. and this paper examines the reason why the development of the public policy on aging in Korea has been delayed.
Chinese Longitudinal Healthy Longevity Survey and some research findings
Authors: Zeng Yi
Published: September 2004

We first present a brief introduction to the Chinese Longitudinal Healthy Longevity Survey (CLHLS) conducted in 1998, 2000, and 2002, including the age‐sex distribution of the uniquely largest sample size of the oldest‐old interviewees, coverage, contents of the extensive questionnaire data collected for both survival and deceased interviewees, etc. We then summarize some examples of research findings based on the unique CLHLS data sets. This includes: (1) Oldest‐old Chinese women are seriously disadvantaged in both socioeconomic and health status and extent of morbidity before death; (2) analysis has shown that the rural oldest‐old have higher active life expectancy than do their urban counterparts; (3) the conventional approach without active/disable data before death caused statistically significant biases of underestimating the disabled life expectancy, and we extended the multi‐state life table method for computing active/disabled life expectancies with consideration of active/disable status before death and applied it to the CLHLS data to improve the estimates; (4) positive association of late childbearing and healthy longevity at oldest‐old ages was found, and the association is stronger in oldest‐old women than in men; (5) evidences have demonstrated that optimism is one of the contributing factors of longevity.
Assessment of family caregiver burden in the context of the LTC insurance system: J‐ZBI
Authors: Arai Yumiko , Kumamoto Keigo , Washio Masakazu
Published: September 2004

This paper covers our recent work regarding cross‐sectional studies on caregiver burden, changes in caregiver burden, appropriateness of the LTC insurance assessment scheme, attitude towards caregiving among caregivers, and the development of the short version of the Japanese version of the Zarit Caregiver Burden Interview (J‐ZBI_8).
The rural elderly support in China and Thailand
Authors: Ding Shijun
Published: September 2004

Aims:  This paper aims to investigate support mechanisms for the elderly in rural China and rural Thailand, and to take lessons from each other on its rural elderly support and the policy interventions.

Methods:  Using data from secondary sources, the situation of the rural elderly was investigated from different aspects. Policies and programs designed for the rural elderly were then summarized in the following section.

Results:  China and Thailand are both under tremendous social changes and economic development processes, with Thailand more economically developed. Family remains the main source of support for the rural elderly in both countries, however, it has been suffering increasing difficulties and problems such as industrialization, modernization, and rural‐to‐urban migration have been taking place. This calls for attention and the development of social security services to support the elderly in rural areas.

Both countries have set up a number of policies, plans, and programs toward supporting the elderly, the coverage, however, is relatively low.

Conclusions:  Governments should introduce policies for integrating the rural elderly into national development strategies. Family should be empowered to become strong sociocultural units, as well as an economic resource and a focal point for the preservation of social and moral values in providing support for the elderly. Health care should be given freely to the rural elderly. Programs providing support to the rural elderly should be gender‐specific with more focus on female elderly.
Japanese rural aging in transition: Evaluation of the model plan of habitation for older persons
Authors: Ogawa Takeo
Published: September 2004

In Japan, there are many depopulating municipalities with population aging in rural areas. They are making efforts not only to establish public long‐term care insurance systems, but also to promote productiveness of senior survivors at place. Their efforts were evaluated by professional animators. Suo‐Oshima island in Yamaguchi‐prefecture was selected as one of highest‐level aging areas in Japan. Professional animators evaluated these programs. Professional animators evaluated moderately the introduction of public long‐term care insurance system, the promotion of active aging society, and ‘The Model Plan of Habitation for Older Persons.’ Professional animators are expected to mediate between older residents and policy makers. They will be empowered for dealing with new programs developed for older persons in active.
Societal filial piety has made traditional individual filial piety much less important in contemporary Japan
Authors: Maeda Daisaku
Published: September 2004

In contemporary Japan, the phrase ‘oya‐koh‐koh’–‘filial piety’ is seldom used by young and middle‐aged persons. This is because before and during World War II, the then ultra‐nationalistic Japanese government placed extreme emphasis on the importance of filial piety in parallel with loyalty to the Emperor and to the nation. Therefore, after the war, Japanese people had a strong tendency to regard filial piety as a phrase having a negative connotation that recalls the memory of the terrible and merciless pre‐war rule by the then ultra‐nationalistic government. However, as far as the value is concerned it can rightfully be said that the virtue that the phrase ‘oya‐koh‐koh’–‘filial piety’ did stand for is still maintained and even upheld in contemporary Japan. Another important reason why filial piety receives little attention in contemporary Japan can be found in the highly developed social security and social service programs for the elderly. Owing to these programs Japanese adult children are now only required to care for their parents within the limits of their physical and financial ability.
Filial piety revisited in the context of modernizing Asian societies
Authors: Mehta Kalyani K , Ko Helen
Published: September 2004

This paper discusses the concept of filial piety in the context of social changes in Asia, in particular Singapore. The changing meaning and expression of this concept, which is also a cultural value, has to be researched by Asian gerontologists. The empirical research in Singapore shows that while this concept is still considered important its definition is shifting.
Hormesis and intervention of aging
Authors: Yu Byung Pal
Published: September 2004

The concept of hormesis has recently been introduced into the gerontological field. The tenet of this concept embraces the notion that the aging process has been evolved through the organism's physiologic adaptation to the ever‐changing stressful environmental conditions for survival. The hormetic phenomenon is exhibited by a biphasic bell‐shape curve response that is the characteristic biological reaction, rather than a linear response. The beneficial effect of hormesis is due to a mild and low stress inductive to stimulated response, while high stress resulting in inhibitory or harmful results.

The adaptive response to a mild stress induces the organism's ability to maximize the metabolic efficiency to cope with a new challenging environment. Evidence strongly suggests that most of stresses under sub‐lethal levels can in fact to be beneficial for the survival of the organism, as exhibited by a growth stimulation of bacteria treated by sub‐lethal pesticides or the life‐span extension of mice by a low dose of irradiation. The anti‐aging action of calorie restriction stimulated by the mild nutritional deprivation considered being another good example of this hormetic phenomenon. For the future intervention of the aging and age‐related diseases based on hormesis concept, one could conceive experimental models in which the endogenous defense systems and certain immune components may be strengthened by selective stimulatory measures. In this review, discussion is presented for further development of this hormetic concept on the premise as the potential anti‐aging strategies.
Radiation hormesis: Stimulatory effects of low doses ionizing radiation
Authors: Ohyama Harumi , Wang Bing , Yukawa Osami
Published: September 2004

Low to small doses of ionizing radiation conditionally show stimulatory effects in various cells and organisms, contrasting with detrimental effects induced at high doses. Radiation hormesis is defined as biopositive health effects, such as augmentation of growth and survival, enhancement of immune response, suppression of mutagenesis, and increase in resistance to damages induced by subsequent high dose exposure. Accumulating data on molecular, cellular, and organism levels demonstrate a variety of hormetic phenomena produced by low dose radiation. Living organisms have been exposed to low doses radiation since the early period of evolution, therefore, radiation hormesis may be established at least in part as a defense mechanism, and thus has important implications for health and diseases. In this review, data of radiation hormesis were presented with special emphasis on the responses of organisms. Recent studies also show potential application of low dose radiation for intervention of diseases. Research on radiation hormesis will indisputably contribute to elucidate aging processes.
Implementation of the Madrid International Plan of Action on Aging: Research dimension
Authors: Sidorenko Alexandre
Published: September 2004

This article identifies the role of research in follow‐up of the Second World Assembly on Aging (Madrid, Spain, 2002). It briefly describes the Research Agenda on Aging for the 21st century, which has been developed to support the major policy document adopted by the Second World Assembly – the Madrid International Plan of Action on Aging.
Treatments of geriatric syndrome
Authors: Sasaki Hidetada
Published: September 2004

Aging is often seen as disadvantageous in human history. However, longevity reduces medical costs of the whole life compared with that of short life. Therefore, in order to reduce medical costs, we have to take care of the elderly in order to promote health and longevity. Health problems in the elderly should be solved by both medical and elderly care facilities. However, few studies have analyzed the health problems of the elderly. In this presentation, based on the pathophysiology of the health problems of the elderly we describe the recent advances for treatments for the geriatric syndrome.
Interventions to prevent pneumonia in older adults
Authors: Ohrui Takashi
Published: September 2004

Aspiration of oropharyngeal bacterial pathogens to the lower respiratory tract is one of the most common risk factors for pneumonia. Impairments in swallowing and cough reflexes among older adults, for example related to cerebrovascular disease, increase the risk of pneumonia. Thus, strategies to reduce the volumes and pathogenicity of aspirated material should be pursued. Since both swallowing and cough reflexes are mediated by endogenous substance P, pharmacologic therapy using angiotensin‐converting enzyme inhibitors, which decrease substance P catabolism, may improve both reflexes and result in the lowering of the risk of pneumonia. Similarly, since the production of substance P is regulated by dopaminergic neurons in the cerebral basal ganglia, treatment with dopamine analogs or potentiating drugs such as amantadine, may affect the incidence of pneumonia. Furthermore, since mortality from infections correlates with cutaneous anergy, interventions that reverse these age‐associated changes in the immune system are also effective.
Families in North‐East Asia
Authors: Sodei Takako
Published: September 2004

The purpose of this paper is to clarify similarities and differences in the family of older people in North‐East Asia where there is a common tradition of filial piety based on Confucianism and also now the experience of rapid population aging. Compared with Western countries, in this region many older people are still living with their children. However, the ratio of cohabitation has been declining. Changes in living arrangements affect family relations and family functions. Though older people are still maintaining close relationships with their children, it is getting difficult to rely on children when they become frail. In North‐East Asia, the core family caregiver is still a daughter‐in‐law but the increase in employment and the changing attitudes of women make it difficult to secure family caregivers, and so social services outside the home became inevitable. Now facing population aging and financial difficulties, each country is trying to find an optimum balance between social services and family care in order to maintain a sustainable social security system.
Non‐shivering thermogenesis in brown adipose tissue and aging
Authors: Yahata Takehiro
Published: September 2004

The aging‐induced decrease in non‐shivering thermogenic capacity was prevented in the genetically CCK‐A receptor deficient, diabetic obese OLETF rats, provably by an increase in the responsiveness of BAT to glucagon. The potential metabolic capacities can be sustained until aged period.