bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allicin inhibits SDF‐1α‐induced T cell interactions with fibronectin and endothelial cells by down‐regulating cytoskeleton rearrangement, Pyk‐2 phosphorylation and VLA‐4 expression
Authors: Sela Uri , Ganor Sharon , Hecht Iris , Brill Alexander , Miron Talia , Rabinkov Aharon , Wilchek Meir , Mirelman David , Lider Ofer , Hershkoviz Rami 
Published: March 2004

SummaryAllicin, a major ingredient of fresh garlic extract that is produced during the crushing of garlic cloves, exerts various beneficial biological effects, including a broad spectrum of antimicrobial activity, antihyperlipidaemic and antihypertensive effects. However, how allicin affects the immune system is less well known, and its effect on human T cells has never been studied. Here, we examined the in‐vitro effects of allicin on the functioning of T cells related to their entry to inflamed extravascular sites. We found that allicin (20–100 µm) inhibits the SDF‐1α (CXCL12)‐induced T cell migration through fibronectin (FN), and that this inhibition is mediated by the down‐regulation of (i) the reorganization of cortical actin and the subsequent T cell polarization, and (ii) T cell adhesion to FN. Moreover, allicin also inhibited T cell adhesion to endothelial cells and transendothelial migration. The mechanisms underlying these inhibitory effects of allicin are associated with its ability to down‐regulate the phosphorylation of Pyk2, an intracellular member of the focal adhesion kinases, and to reduce the expression of the VCAM‐1‐ and FN‐specific α4β1‐integrin (VLA‐4). The ability of allicin to down‐regulate these chemokine‐induced and VLA‐4‐mediated T cell functions explains its beneficial biological effects in processes where T cells play an important role and suggests that allicin may be used therapeutically with chronic inflammatory diseases.
Methylenedioxymethamphetamine (MDMA, ‘Ecstasy’): a stressor on the immune system
Authors: Connor Thomas J. 
Published: March 2004

SummaryDrug abuse is a global problem of considerable concern to health. One such health concern stems from the fact that many drugs of abuse have immunosuppressive actions and consequently have the potential to increase susceptibility to infectious disease. This article is focused on the impact of the amphetamine derivative, methylenedioxymethamphetamine (MDMA; ‘Ecstasy’) on immunity. Research conducted over the last 5 years, in both laboratory animals and humans, has demonstrated that MDMA has immunosuppressive actions. Specifically, MDMA suppresses neutrophil phagocytosis, suppresses production of the pro‐inflammatory cytokines tumour necrosis factor‐α (TNF‐α) and interleukin (IL)‐1β, and increases production of the endogenous immunosuppressive cytokine (IL‐10), thereby promoting an immunosuppressive cytokine phenotype. MDMA also suppresses circulating lymphocyte numbers, with CD4+ T cells being particularly affected, and alters T‐cell function as indicated by reduced mitogen‐stimulated T‐cell proliferation, and a skewing of T‐cell cytokine production in a T helper 2 (Th2) direction. For the most part, the aforementioned effects of MDMA are not the result of a direct action of the drug on immune cells, but rather caused by the release of endogenous immunomodulatory substances. Consequently, the physiological mechanisms that are thought to underlie the immunosuppressive effects of MDMA will be discussed. As many of the physiological changes elicited by MDMA closely resemble those induced by acute stress, it is suggested that exposure to MDMA could be regarded as a ‘chemical stressor’ on the immune system. Finally, the potential of MDMA‐induced immunosuppression to translate into significant health risks for abusers of the drug will be discussed.
The myoepithelial cell differentiation of mucoepidermoid carcinoma in a collagen gel‐based coculture model
Authors: Yook Jong In , Lee Seoung Ae , Chun Yong Chan , Huh Jung , Cha In Ho , Kim Jin 
Published: March 2004

Background:  Mucoepidermoid carcinomas (MECs) are the most common malignant tumor of the salivary glands; however, the histogenesis of MECs has been still controversial. This study was undertaken to investigate the histogenesis of MECs by the examination of their collagen gel‐based coculture tissue and transplanted tumors.Methods:  Two cell lines from a primary and a metastatic MECs were established and characterized by the mutational analysis of the p53 gene and in vivo tumorigenicity in athymic nude mice. Collagen gel‐based organotypic cocultures were performed, and the ultrastructural and immunohistochemical findings were examined.Results:  Two cell lines demonstrated p53 point mutation at the same codon. A metastatic cell line of MEC showed in vivo tumorigenicity. Transplanted tumors and the collagen gel‐based culture tissues showed poorly differentiated squamous cell carcinomas devoid of mucous cell differentiation; however, they disclosed the differentiation of myoepithelial cells.Conclusions:  MECs appear to be centered on the squamous cell differentiation, and the specific differentiation of myoepithelial or mucous cells seems to be modulated by the property of microenvironment.
Expression of hepatocyte growth factor and c‐met protein is significantly associated with the progression of oral squamous cell carcinoma in Taiwan
Authors: Chen Yu‐Shan , Wang Jeng‐Tzung , Chang Yu‐Fong , Liu Bu‐Yuan , Wang Yi‐Ping , Sun Andy , Chiang Chun‐Pin 
Published: March 2004

Background:  Hepatocyte growth factor (HGF) is a pleotropic growth factor that regulates cell proliferation, migration, survival, tumor angiogenesis, and tumor cell invasion and metastasis. Its diverse biological effects are mediated through its interaction with its receptor, c‐met protein.Methods:  In this study, we examined the expression of HGF and c‐met protein in 93 specimens of oral squamous cell carcinoma (OSCC), 10 specimens of oral epithelial dysplasia (OED), 14 specimens of oral epithelial hyperkeratosis (OEH), and 16 specimens of normal oral mucosa (NOM) by immunohistochemistry. The HGF and c‐met labeling indices (LIs) in OSCC, OED, OEH, and NOM groups were calculated and compared between groups. The correlation between the expression of HGF or c‐met in OSCCs and clinicopathological parameters, or survival of OSCC patients was analyzed statistically to investigate the possible influence of HGF or c‐met on the progression and prognosis of OSCCs in Taiwan.Results:  Positive HGF or c‐met staining was mainly cytoplasmic. The mean HGF LI increased significantly from NOM (3.1 ± 5.1%) through OEH (32.5 ± 19.8%) and OED (52.0 ± 19.3%) to OSCC (71.9 ± 28.6%; P = 0.000). The mean c‐met LI also increased significantly from NOM (25.8 ± 30.8%) and OEH (34.4 ± 19.3%) through OED (53.0 ± 20.0%) to OSCC (73.0 ± 29.4%; P = 0.000). Statistical analysis showed that the c‐met LI in either the tumor center or invasion front was significantly associated with T status, N status, and clinical staging of OSCC. However, only the HGF LI in the tumor invasion front was significantly correlated with N status and clinical staging of OSCC.Conclusion:  Our results suggest that the expression of HGF and c‐met protein is an early event in oral carcinogenesis in Taiwan. The HGF LI in the tumor invasion front and the c‐met LI in either the tumor center or invasion front can predict the progression of OSCCs in Taiwan.
The relationship of proliferating cell density at the invasive tumour front with prognostic and risk factors in human oral squamous cell carcinoma
Authors: Tumuluri Vijay , Thomas Graham A. , Fraser Ian S. 
Published: March 2004

BACKGROUND:  We hypothesise that the density of proliferating cells at the invasive tumour front (ITF) has a positive relationship with prognostic and risk factors in human oral squamous cell carcinoma (SCC).METHODS:  Tissues from 47 human oral SCC specimens were collected and stained with a monoclonal antibody directed against the Ki‐67 antigen using a horseradish peroxidase based two‐step immunostaining method. Counting was performed on two parallel sections at the ITF using an image analyser. The Ki‐67 labelling index (LI) was determined by measuring the number of nuclei/mm2 of epithelium.RESULTS:  Our results show that the density of proliferating cells is related to clinical staging, with advanced stage of disease having a significantly higher Ki‐67 LI compared with early stage of disease (2111 ± 905 vs. 1908 ± 913; P = 0.03). Importantly, this study shows that tumours that have metastasised have a significantly higher Ki‐67 LI than tumours where distant metastasis was not detected (3257 ± 650 vs. 1966 ± 881; P < 0.0001).CONCLUSIONS:  Cell proliferation, as measured by the Ki‐67 LI at the ITF, has a positive relationship with clinical staging, tumour thickness, smoking status of the patient and alcohol consumption. Further, we suggest that a multicenter study with a large cohort of patients is indicated to fully elucidate whether cell proliferation at the ITF is directly related to patient survival.
HLA typing in Taiwanese patients with oral submucous fibrosis
Authors: Chen Hsin‐Ming , Hsieh Rhong‐Phong , Yang Hsiang , Kuo Ying‐Shiung , Kuo Mark Yen‐Ping , Chiang Chun‐Pin 
Published: March 2004

Background:  A significant association of certain human leukocyte antigens (HLA) and haplotypic pairs with oral submucous fibrosis (OSF) has been reported. However, controversial result of no HLA association with OSF has also been reported. In this study, the phenotype and haplotype frequencies of HLA‐A, ‐B, ‐C, ‐DRB1, and ‐DQB1 in 135 Taiwanese OSF patients were calculated and compared with those in 540 healthy control Taiwanese.Methods:  The analysis of HLA‐A, ‐B, and ‐C antigens, and of HLA‐DRB1 and ‐DQB1 alleles in OSF patients and healthy control subjects, was performed by serologic typing and DNA typing using polymerase chain reaction with sequence‐specific primers (PCR‐SSP), respectively.Results:  We found that the phenotype frequency of HLA‐B76 (3.0%) in OSF patients was significantly greater than that (0%) in healthy control subjects (corrected P (Pc) = 0.000). In addition, the haplotype frequencies of HLA‐B48/Cw7 (3.0%), ‐B51/Cw7 (6.7%), and ‐B62/Cw7 (8.2%) in OSF patients were significantly greater than the corresponding haplotype frequencies (0, 0.7, and 1.9%, respectively) in healthy control subjects (Pc = 0.000). The relative risk (RR) values of haplotypes B51/Cw7 (9.57) and B62/Cw7 (4.7) were greater than the RR values of phenotypes B51 (1.81), B62 (2.31), and Cw7 (1.91) in OSF patients. In addition, the etiologic fraction (EF) value of haplotype B51/Cw7 (0.63) was higher than the EF values of phenotypes B51 (0.2) and Cw7 (0.59).Conclusions:  We conclude that some Taiwanese areca quid (AQ) chewers with particular HLA phenotypes and haplotypes are prone to have OSF. In addition, some particular HLA haplotypes may play more important roles than the individual HLA phenotypes for the genetic susceptibility to OSF. However, the significantly increased HLA phenotype B76 and three of the common HLA haplotypes detected are present in only about 20% of incident cases of OSF.
Reassessing the role of defensin in the innate immune response of the mosquito, Aedes aegypti
Authors: Bartholomay L. C. , Fuchs J. F. , Cheng L.‐L. , Beck E. T. , Vizioli J. , Lowenberger C. , Christensen B. M. 
Published: March 2004

AbstractDefensin is the predominant inducible immune peptide in Aedes aegypti. In spite of its activity against Gram‐positive bacteria in vitro, defensin expression is detected in mosquitoes inoculated with Gram‐positive or negative bacteria, or with filarial worms. Defensin transcription and expression are dependent upon bacterial dose; however, translation is inconsistent with transcription because peptide is detectable only in mosquitoes inoculated with large doses. In vitro translation assays provide further evidence for post‐transcriptional regulation of defensin. Clearance assays show that a majority of bacteria are cleared before defensin is detected. In gene silencing experiments, no significant difference in mortality was observed between defensin‐deficient and control mosquitoes after bacteria inoculation. These studies suggest that defensin may have an alternative function in mosquito immunity.
DNA methylation in insects
Authors: Field L. M. , Lyko F. , Mandrioli M. , Prantera G. 
Published: March 2004

AbstractCytosine DNA methylation has been demonstrated in numerous eukaryotic organisms and has been shown to play an important role in human disease. The function of DNA methylation has been studied extensively in vertebrates, but establishing its primary role has proved difficult and controversial. Analysing methylation in insects has indicated an apparent functional diversity that seems to argue against a strict functional conservation. To investigate this hypothesis, we here assess the data reported in four different insect species in which DNA methylation has been analysed more thoroughly: the fruit fly Drosophila melanogaster, the cabbage moth Mamestra brassicae, the peach‐potato aphid Myzus persicae and the mealybug Planococcus citri.
Synchronization of Plodia interpunctella lepidopteran cells and effects of 20‐hydroxyecdysone
Authors: Siaussat D. , Mottier V. , Bozzolan F. , Porcheron P. , Debernard S. 
Published: March 2004

AbstractWe have investigated the molecular and cellular mechanisms involved in the control of insect cell cycle by 20‐hydroxyecdysone (20E) using the IAL‐PID2 cell line established from imaginal wing discs of Plodia interpunctella. We first defined conditions for use of hydroxyurea, a reversible inhibitor of DNA synthesis, in order to synchronize the IAL‐PID2 cells in their division cycle. A high degree of synchrony was reached when cells were exposed to two consecutive hydroxyurea treatments at 1 mm for 36 h spaced 16 h apart. Under these conditions, flow cytometry analysis demonstrated that 20E at 10−6 m induced an inhibition of cell growth by an arrest of 90% of the cells in G2/M phase. Using cDNA probes specifically designed from E75 and HR3 nuclear receptors of Plodia interpunctella, we showed that PiE75 and PHR3 were highly induced by 20E through S and G2 phases with maximal enhancement just before the G2/M arrest of cells. These findings suggest that PiE75 and PHR3 could be involved in a 20E‐induced genetic cascade leading to G2/M arrest.
Work of Female Rural Doctors
Authors: Wainer Jo 
Published: March 2004

ABSTRACTObjective:  To identify the impact of family life on the ways women practice rural medicine and the changes needed to attract women to rural practice. Design:  Census of women rural doctors in Victoria in 2000, using a self‐completed postal survey. Setting: General and specialist practice. Subjects: Two hundred and seventy‐one female general practitioners and 31 female specialists practising in Rural, Remote and Metropolitan Area Classifications 3–7. General practitioners are those doctors with a primary medical degree and without additional specialist qualifications. Main outcome measure: Interaction of hours and type of work with family responsibilities. Results: Generalist and specialist women rural doctors carry the main responsibility for family care. This is reflected in the number of hours they work in clinical and non‐clinical professional practice, availability for on‐call and hospital work, and preference for the responsibilities of practice partnership or the flexibility of salaried positions. Most of the doctors had established a satisfactory balance between work and family responsibilities, although a substantial number were overworked in order to provide an income for their families or meet the needs of their communities. Thirty‐six percent of female rural general practitioners and 56% of female rural specialists preferred to work fewer hours. Female general practitioners with responsibility for children were more than twice as likely as female general practitioners without children to be in a salaried position and less likely to be a practice partner. The changes needed to attract and retain women in rural practice include a place for everyone in the doctor's family, flexible practice structures, mentoring by women doctors and financial and personal recognition. What this paper adds:   Women make up less than a quarter of the rural general practice workforce and an even smaller percentage of the specialist rural medical workforce. As a result their experiences are not well articulated in research on rural medical practice and their needs are not well represented in policies and programs for rural doctors. The incoming cohort of rural general practitioners has a majority of women and it is essential that the practice styles and needs of women doctors are understood in order to attract and retain women in rural medicine. This survey identifies some of the effects of family responsibilities on the work practices of female rural doctors and the changes needed to the structure of rural practice to include the way women work.
Rural Doctors’ Satisfaction in Japan: A Nationwide Survey
Authors: Matsumoto Masatoshi , Okayama Masanobu , Kajii Eiji 
Published: March 2004

ABSTRACTObjectives:  The purpose of this paper was to discover to what degree Japanese rural doctors are satisfied with various aspects of their jobs and lives, and to find out whether they intend to continue their rural careers. Design:  Nationwide postal survey Setting:  Public clinics or hospitals in municipalities that are authorised as ‘rural’ by the national government. Subjects:  A total of 4896 doctors working for public clinics or hospitals. Interventions:  Self‐evaluation questionnaires were mailed. The rural doctors were asked to evaluate their satisfaction with 19 items related to their job conditions and 10 items concerning life conditions, using a four‐point scale. They also were asked to evaluate their intent to stay in rural practice until retirement. Results:  The response rate was 64%. Overall, rural doctors were satisfied with both their work and life conditions. However, only 27% of respondents hoped to continue rural practice beyond the usual age of retirement. Among job‐related items, continuing medical education and interactions with municipal governments were rated as least satisfactory. Among lifestyle‐related items, duration of holidays and workload were unsatisfactory. Subgroup analysis revealed male doctors showed greater intent to stay in rural practice. Doctors aged > 50 years were more satisfied with most aspects of their job and lifestyle than younger doctors. A strong correlation was found between the degree of intent to stay and several items such as interactions with municipal government, human interactions salary and job fulfilment. Conclusions:  Strategies, based on the results of this survey, should be implemented. Particularly in Japan, positive interaction between doctors and municipal governments is crucial. What this paper adds:   Though rural doctors in Japan in general were satisfied with their lifestyle and work conditions, they have low intentions to stay in rural areas. Among the various factors that can cause this dissociation between satisfaction and intention to stay, doctors’ interactions with municipal governments play a pivotal role.
Psychosocial Investigation of Individual and Community Responses to the Experience of Ovine Johne's Disease in Rural Victoria
Authors: Hood Bernadette , Seedsman Terence 
Published: March 2004

ABSTRACTObjective:  This paper explores the psychosocial outcomes for individuals and communities in rural Victoria who experienced the outbreak of Ovine Johne's Disease (OJD). Design:  The study uses a qualitative methodology to analyse the minutes of evidence provided by the inquiry into the control of OJD to identify the psychosocial events, experiences and outcomes associated with the control of this outbreak. The inquiry was undertaken by the Environment and Natural Resources Committee of the Victorian State Government. Setting:  Public hearings were undertaken by the committee across several rural Victorian communities and the state capital, Melbourne. Subjects:  The transcripts detail 136 submissions from 98 individuals and 23 organisations. Outcome measures:  The analysis aimed to provide insight into the impact of the disease on individuals and communities and also to explore the factors individuals perceived as associated with these outcomes. Results:  While the paper identifies that aspects of stock loss associated with the outbreak caused substantial emotional and economic distress, for farmers the most significant finding was the impact of the government control program on individuals, families and rural communities. The control program was perceived as having very limited scientific credibility and its implementation was described as heartless, inflexible and authoritarian. Involvement with the program resulted in farmers reporting emotions, such as, trauma, shame, guilt and stigma. Families became discordant and the sense of community within rural townships fragmented. Psychological outcomes of grief, depression and anxiety emerged as prevalent themes within families and communities. Conclusions:  These data highlight the need for significant attention to the management of rural disasters, such as, the OJD program. What this paper adds:  There is an acknowledgement in the literature that rural disasters have a significant impact on the well‐being of individuals, families and communities. The major focus of the previous research has, however, been on the impact of economic losses with less recognition of the other psychosocial loss experiences that accompany the experience of rural disaster. This paper achieves a clear description of the experiences for individuals (trauma, stigma, sense of personal failure, loss of identity, diminished self esteem and family disruption) and communities (destroyed social cohesion, economic disharmony) caught up in the OJD disaster and explores the factors that individuals perceive as responsible for these outcomes. The mental health outcomes for individuals, such as, loss, grief and depression are also explored within this paper. This paper highlights the psychosocial complexity of the experience of rural disaster for individuals and communities significantly extending the current knowledge base in this area.
Activation of human macrophages by allogeneic islets preparations: inhibition by AOP‐RANTES and heparinoids
Authors: Sigrist Séverine , Oberholzer José , Bohbot Alain , Esposito Guy , Mandes Karim , Lamartine Roger , Toso Christian , Bucher Pascal , Pinget Michel , Kessler Laurence 
Published: March 2004

SummaryDuring transplantation, pancreatic islets release chemokines which promote macrophage attraction, hampering engraftment of islets. The aim of this study was to modulate chemotaxis and the immune response of human macrophages induced by islets. Human monocyte‐derived macrophages of healthy subjects were exposed to supernatants of human islets. Chemotaxis, tumour necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) release were evaluated. To modulate migration, human macrophages were incubated in the presence of aminooxypentane‐regulated on activation, normal, T‐cell expressed, and secreted (AOP‐RANTES), a potent antagonist of CCR5. Chemotactic activity of islets supernatant was modulated by the addition of heparin or heparinoids [pentosan and calix[8S]arene (C8S)]. AOP‐RANTES significantly reduced, in a dose‐dependent manner, macrophage chemotaxis and cytokine release induced by islets supernatant. The chemotactic index was reduced from 3·05 ± 0·27 to 0·71 ± 12, TNF‐α from 1205 ± 52 to 202 ± 12 pg/ml, and IL‐1β from 234 ± 12 to 10 ± 6 pg/ml. The trapping of chemokines by heparinoids reduced the chemotactic activity of islets supernatant from 3·05 ± 0·27 to 1·2 ± 0·1 with heparin or pentosan and to 1·72 ± 0·22 with C8S, and also decreased the TNF‐α release by human macrophages from 1205 ± 35 to 1000 ± 26 (C8S), 250 ± 21 (heparin) and 320 ± 19 (pentosan) pg/ml, and IL‐1β from 234 ± 13 to 151 ± 5 (C8S), 50 ± 3 (heparin) and 57 ± 4 (pentosan) pg/ml. In conclusion, AOP‐RANTES and heparinoids inhibit human macrophage activation and migration induced by islets supernatant.