bluuebunny/crossref_metadata_2025 huggingface dataset:
Lymphoid cell infiltration during breast cancer growth: A syngeneic rat model
Authors: Zhang Xu Dong , Schiller Grant David , Gill Peter Grantly , Coventry Brendon John
Published: March 2003

The systematic study of potential alterations in lymphoid infiltrates during tumour growth is extremely limited in humans. Therefore, development of a model utilizing a spontaneously arising mammary adenocarcinoma in Dark Agouti rats was adopted for the study of the dynamics of lymphoid cell infiltration during tumour development. Syngeneic rats were inoculated with tumour cell suspensions and the tumours were resected from 5 to 15 days. Serial sections were immunohistochemically stained using a panel of monoclonal antibodies. Irrespective of tumour age, ED2 (macrophages) and W3/25 (CD4)‐positive cells were the most prominent cell infiltrates in tumours. There were no significant differences in cell counts for any marker between 8‐day and 15‐day tumours. However, in 5‐day tumours there were significantly fewer macrophages, OX19+ T cells, W3/25+ cells, OX8+ (CD8) cells and OX62+ dendritic cells. Interleukin‐2 receptor α chain expression was low at all examined stages of tumour growth, indicating a lack of tumour infiltrating lymphocyte (TIL) activation and/or possible TIL anergy. B cell staining was absent in all tumours, negating the possibility of these cells mediating coregulatory signals for TIL activation in the micro‐environment of established tumours. The results parallel previous immunohistochemical findings in humans, suggesting that a dysfunctional local immune response in breast cancer may be determined very early during tumour development.
Basic pathogenic mechanisms operating in experimental models of acute anterior uveitis
Authors: Smith Justine R , Hart Prue H , Williams Keryn A
Published: March 2003

Acute anterior uveitis is a recurrent inflammatory disease of the eye that occurs commonly, is distressing for the patient, and may have potentially blinding sequelae. The pathogenesis of the disease is poorly understood, and anti‐inflammatory treatment is consequently non‐specific and may be associated with significant complications. Animal models are a possible key to a better understanding of this disease. In one model, rats and mice develop a relatively short‐lived anterior uveal inflammation almost immediately after systemic injection of bacterial endotoxin. Accumulating evidence suggests that cytokine production by resident uveal macrophages initiates endotoxin‐induced uveitis which is characterized by an infiltration of neutrophils and mononuclear cells. A second model displays features in keeping with a delayed‐type hypersensitivity immune response. Experimental melanin‐induced uveitis is an acute recurrent uveitis with delayed onset but extended duration, observed when rats are immunized with bovine ocular melanin. Both animal models have clinical features in common with acute anterior uveitis, although experimental melanin‐induced uveitis appears to mimic the human disease more closely. Novel treatment options to target implicated inflammatory cells and molecules are currently under consideration.
Long‐term stroma‐dependent cultures are a consistent source of immunostimulatory dendritic cells
Authors: O’Neill Helen C , Ni Keping , Wilson Heather
Published: March 2003

A long‐term culture (LTC) system has been established that supports the continuous production of dendritic cells (DC) from haemopoietic cells present in the culture. The production of cells depends on the presence of an intact stromal cell layer containing a mixture of fibroblasts and endothelial cells. Cells are shed from foci of dividing cells in contact with the stromal cell matrix. They resemble DC in terms of morphology and cell surface marker expression. The LTC can be derived from different lymphoid tissues, but most success has been achieved with murine spleen. Different LTC vary in capacity to produce immunostimulatory DC. Some LTC produce DC that are very effective APC and can stimulate both mixed lymphocyte and antigen‐specific T cell responses. The DC produced in others are weak APC. Different LTC appear to produce DC reflecting different stages of maturation or development, reflected by different phenotypic and functional characteristics. The production of cells within LTC occurs independently of added cytokines and is dependent on maintenance of the stromal cell layer and the presence of a subset of smaller progenitor cells. Long‐term cultures remain a valuable source of cells for study of DC development and function.
Dendritic cells at the end of the Millennium
Authors: Rescigno M , Granucci F , Ricciardi‐Castagnoli P
Published: March 2003

We have recently proposed a dual role for dendritic cells (DC) in the amplification of innate immune responses and in the activation of adaptive immune responses. The DC are localized along the major routes of entry of micro‐organisms, where they perform a sentinel function for incoming pathogens. Soon after interaction with appropriate stimuli, DC undergo a coordinated process of maturation and respond to danger signals by re‐ programming their functions. The DC first regulate leucocyte recruitment at the site of inflammation, through the production of chemokines, inflammatory cytokines and interferons, and then they acquire migratory properties and undergo a rapid switch in chemokine receptor expression. This allows them to leave the inflamed tissue and to reach the lymph node T cell area. During this migration, DC complete their maturation process and acquire the ability to prime T cell responses. Thus, DC bridge innate and adaptive immunity.
Dendritic cells: The driving force behind autoimmunity in rheumatoid arthritis?
Authors: Pettit Allison R , Thomas Ranjeny
Published: March 2003

Dendritic cells (DC) are likely to play a significant role in immune‐mediated diseases such as autoimmunity and allergy. To date there are few treatments capable of inducing permanent remission in rheumatoid arthritis (RA) and elucidation of the role of DC may provide specific strategies for disease intervention. Dendritic cells have proven to be powerful tools for immunotherapy and investigations are under way to determine their clinical efficacy in transplantation and viral and tumour immunotherapy. The present review will focus on the current view of DC and their role in autoimmunity, in particular RA. Two possible roles for DC in the pathogenesis of RA will be proposed, based on recent advances in the field.
Immune response to orally consumed antigens and probiotic bacteria
Authors: Chin James , Turner Bernadette , Barchia Idris , Mullbacher Arno
Published: March 2003

The gut mucosal system must fulfil conflicting roles in suppressing immune responses against orally fed antigens (tolerance) while still retaining the ability to respond to potential enteric pathogens. It must also, to a large degree, not mount an immune response against commensal enteric bacteria and the administration of large numbers of probiotic bacteria formulated as dietary supplements in food products. Contrary to this dogma, it has been found that feeding ovalbumin as a marker antigen, in association with selected probiotic bacteria, appears to prime for an intestinal immune response that is further augmented by skin vaccination. Skin immunization is known to stimulate a strong innate, humoral and cellular immune response. Such dominant immunogenic signals appear to override tolerogenic signals engendered by oral feeding of antigen. High‐dose antigen feeding stimulated a strong Th2‐dependent antibody response to skin vaccination but completely suppressed cytotoxic T cell responses. This was true even when ovalbumin was administered in conjunction with various selected probiotic bacteria. However, while yeast appeared to be better at priming for an enhanced humoral response, Lactobacillus fermentum and Staphylococcus carnosus were more effective in enhancing the postvaccinal lymphoproliferative response against ovalbumin.
Regulation of T cell cytokine production by dendritic cells
Authors: Kronin Vadim , Hochrein Hubertus , Shortman Ken , Kelso Anne
Published: March 2003

Previous work has established that the dendritic cells (DC) of mouse spleen regulate the IL‐2 production, and hence the extent of proliferation, of the CD8 T cells they activate. It is now reported here that interaction of primary CD8 T cells with splenic CD8α DC induced much higher production of IL‐3, IFN‐γ and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), as well as IL‐2, than did interaction with CD8α+ splenic DC. Furthermore, the CD8α DC also induced higher levels of IL‐2, IL‐3 and IL‐10 production in primary CD4 T cells, compared with that induced by CD8α+ DC. These quantitative differences did not involve qualitative shifts in the type of cytokine produced. Interleukin‐4 production remained low in all the primary T cell cultures and restimulation experiments in secondary cultures did not reveal any bias in the cytokine production profile. When exogenous IL‐2 was added to the primary cultures to ensure equal proliferation in response to CD8α or CD8α+ DC, the higher level of production of IL‐3, IFN‐γ and GM‐CSF induced by CD8α DC was maintained. Thus, this general control of T cell cytokine production by splenic DC involves factors additional to those that govern activation of T cells into cell cycle.
Dexamethasone‐induced apoptosis of mouse thymocytes: Prevention by native 7α‐hydroxysteroids
Authors: Chmielewski V , Drupt F , Morfin R
Published: March 2003

Dehydroepiandrosterone (DHEA) has been shown to decrease the dexamethasone (DEX)‐induced apoptosis of thymocytes and to be one of the native 3β‐hydroxysteroids extensively 7α‐hydroxylated in thymus. This led us to question whether DHEA or 7α‐hydroxy‐DHEA is responsible for the decrease in DEX‐induced apoptosis of thymocytes and whether this property is shared with other native 3β‐hydroxysteroids and their 7α‐hydroxylated metabolites. Treatment of mice with DHEA or 7α‐hydroxy‐DHEA prior to DEX led to a smaller decrease in thymus weight than with DEX alone and to a disappearance of the DEX‐induced changes in thymocyte phenotypes. Thymocyte apoptosis induced by DEX treatment was significantly lowered in DHEA‐ and 7α‐hydroxy‐DHEA‐treated thymi, even after 18 h culture with additional 10−6 mol/L DEX. Extensive apoptosis of thymocytes cultured with 10−7 mol/L DEX was brought back to control levels when 10−5 mol/L 7α‐hydroxy‐DHEA or 10−5 mol/L 7α‐hydroxy‐epiandrosterone was added. After use of DHEA and epiandrosterone or pregnenolone, less significant and no significant changes were obtained, respectively. These findings imply that the 7α‐hydroxylation of 3β‐hydroxysteroids may be a prerequisite for an exquisite regulation of the thymocyte‐positive selection driven by the glucocorticoids produced in thymic epithelial cells.
Transcription factor‐mediated molecular mechanisms involved in the functional cross‐talk between cytokines and glucocorticoids
Authors: Refojo D , Liberman AC , Holsboer F , Arzt E
Published: March 2003

After antigenic stimulation the increase in cytokine levels constitutes a fundamental event in the host defense and mediates many processes such as inflammation, B‐ and T‐cell growth and differentiation and activation of effector cells. Most of these processes depend on the cytokine‐induced activation of transcription factors that modulate the expression of target genes. Cytokines induce a rise in glucocorticoid levels, which are instrumental in controlling immune–cytokine overreactions. Because of their anti‐inflammatory and immunosuppressive actions, glucocorticoids are highly useful as therapeutic drugs in a range of diseases. The cross‐talk between cytokine‐induced transcription factors such as nuclear factor‐κB, activating protein‐1, cAMP responsive element binding protein and nuclear factor of activated T cells, and glucocorticoid receptors involves both genomic and non‐genomic actions, and constitutes the mechanism by which glucocorticoid repressive effects on cytokine synthesis and action take place. These molecular interactions represent the key for the study of physiological compensatory actions of corticosteroids, the interactions of cytokines and glucocorticoids at their target cells, as well as the therapeutic benefits and side‐effects of synthetic steroids. For this reason, we will focus on the molecular aspects of cytokine–glucocorticoid interactions, represented by the cross‐coupling between cytokine‐mediated transcription factors and glucocorticoid receptors.
Induction of multiple chemokine and colony‐stimulating factor genes in experimental Burkholderia pseudomallei infection
Authors: Barnes Jodie L , Ulett Glen C , Ketheesan Natkunam , Clair Timothy , Summers Phillip M , Hirst Robert G
Published: March 2003

Melioidosis is a disease of the tropics caused by the facultative intracellular bacterium Burkholderia pseudomallei. In human infection, increased levels of IFN‐γ in addition to the chemokines interferon‐γ‐inducible protein 10 (IP‐10) and monocyte interferon‐γ‐inducible protein (Mig) have been demonstrated. However, the role of these and other chemokines in the pathogenesis of melioidosis remains unknown. Using BALB/c and C57BL/6 mice as models of the acute and chronic forms of human melioidosis, the induction of mRNA was assessed for various chemokines and CSF (G‐CSF, M‐CSF, GM‐CSF, IP‐10, Mig, RANTES, MCP‐1, KC and MIP‐2) in spleen and liver following B. pseudomallei infection. Patterns of chemokine and CSF induction were similar in liver and spleen; however, responses were typically greater in spleen, which reflected higher tissue bacterial loads. In BALB/c mice, high‐level expression of mRNA for all chemokines and CSF investigated was demonstrated at day 3 postinfection, correlating with peak bacterial load and extensive infiltration of leucocytes. In contrast, increased mRNA expression and bacterial numbers in C57BL/6 mice were greatest between 4 and 14 days following infection. This paralleled increases in the size and number of abscesses in liver and spleen of C57BL/6 mice at days 3 and 14 postinfection. Earlier induction of cytokine‐induced neutrophil chemoattractant (KC), macrophage inflammatory protein‐2 (MIP‐2), monocyte chemoattractant protein‐1 (MCP‐1), granulocyte‐macrophage CSF (GM‐CSF) and macrophage CSF (M‐CSF) mRNA was demonstrated in spleen, while MIP‐2, MCP‐1, IP‐10 and Mig were demonstrated in liver of BALB/c mice when compared to spleen and liver of C57BL/6. The magnitude of cellular responses observed in the tissue correlated with increased levels of the chemokines and CSF investigated, as well as bacterial load. Compared with C57BL/6 mice, greater infiltration of neutrophils was observed in liver and spleen of BALB/c mice at day 3. In contrast, early lesions in C57BL/6 mice predominantly comprised macrophages. These results suggest that the inability of BALB/c mice to contain the infection at sites of inflammation may underlie the susceptible phenotype of this mouse strain towards B. pseudomallei infection.
Interleukin‐dependent modulation of HLA‐DR expression on CD4 and CD8 activated T cells
Authors: Salgado Francisco J , Lojo Juan , Fernández‐Alonso Carmen M , Viñuela Juan E , Cordero Oscar J , Nogueira Montserrat
Published: March 2003

Interleukins (IL) regulate differentT‐cell surface Ag known as activation markers that have distinct functional roles. In this paper, while studying the influence of some cytokines(IL‐12, IL‐2 and IL‐4) on the expression of several markers [CD69,CD25, CD26, CD3, human leukocyte antigen (HLA‐DR), CD45R0] in in vitro activated human T lymphocytes, we observed two groups of donors responding to phytohaemagglutinin (PHA) activation with high or low HLA‐DRAg expression. We also found that CD4 and CD8 populations had different HLA‐DR densities under PHA activation (particularly the high HLA‐DR‐expressing group). Interleukins, in a dose‐dependent manner (IL‐2 partially), upregulated these HLA‐DR levels. In 5 day cultures, IL‐12and IL‐2 enhanced the CD8/CD4 ratio of activated T cells, which was responsible, in part, for the IL‐dependent HLA‐DR upregulation. IL‐12 and IL‐2 also upregulated the HLA‐DR expression at the molecular level on CD8, and IL‐12 downregulated it on CD4 cells. It seems that IL‐4 upregulated HLA‐DR by shortening the mitogen‐dependent regulation kinetics. We hypothesize that the different effect of each IL on HLA‐DR expression might be related to the regulation of the dose of antigenic peptide presentation and, thus, also influence TH1/TH2 dominance.
Control or persistence of hepatitis B virus: The critical role of initial host–virus interactions
Authors: Webster George JM , Bertoletti Antonio
Published: March 2003

Following infection with hepatitis B virus (HBV), the period before symptomatic disease is now recognized as a time of dynamic interaction between virus and host. Recent work has shown that this period is the phase of infection during which maximal changes in virus replication and the activation of critical components of the immune system occurs. This suggests that the different outcomes following exposure might be determined during the early phase of infection, before the onset of clinical disease. The hypothesis that small differences in the dynamic relationship between host and virus, such as in the kinetics of HBV replication, may influence the final outcome of infection, will be discussed.
Rac2‐deficient mice display perturbed T‐cell distribution and chemotaxis, but only minor abnormalities in TH1 responses
Authors: Croker Ben A , Handman Emanuela , Hayball John D , Baldwin Tracey M , Voigt Valentina , Cluse Leonie A , Yang Feng‐Chun , Williams David A , Roberts Andrew W
Published: March 2003

The haematopoietic‐specific RhoGTPase, Rac2, has been indirectly implicated in T‐lymphocyte development and function, and as a pivotal regulator of T Helper 1 (TH1) responses. In other haematopoietic cells it regulates cytoskeletal rearrangement downstream of extracellular signals. Here we demonstrate that Rac2 deficiency results in an abnormal distribution of T lymphocytes in vivo and defects in T‐lymphocyte migration and filamentous actin generation in response to chemoattractants in vitro. To investigate the requirement for Rac2 in IFN‐γ production and TH1 responses in vivo, Rac2‐deficient mice were challenged with Leishmania major and immunized with ovalbumin‐expressing cytomegalovirus. Despite a minor skewing towards a TH2 phenotype, Rac2‐deficient mice displayed no increased susceptibility to L. major infection. Cytotoxic T‐lymphocyte responses to cytomegalovirus and ovalbumin were also normal. Although Rac2 is required for normal T‐lymphocyte migration, its role in the generation of TH1 responses to infection in vivo is largely redundant.
Selection of escape mutants from immune recognition during HIV infection
Authors: Bernaschi M , Castiglione F
Published: March 2003

We present computer simulations of the HIV infection based on a sophisticated cellular automata model of the immune response. The infection progresses following the well‐known three‐phase dynamics observed in patients, that is, acute, silent and acquired immunodeficiency. Antigenic shift and selection of escape viral mutants with low transcription rate explain the long term course of the asymptomatic phase, while the immunodeficiency status appears to be the consequence of a drastic reduction in T helper cell repertoire.
Induction of immune tolerance by dendritic cells: Implications for preventative and therapeutic immunotherapy of autoimmune disease
Authors: Thompson Angus G , Thomas Ranjeny
Published: March 2003

Dendritic cells (DC) have a key role in controlling the immune response, by determining the outcome of antigen presentation to T cells. Through costimulatory molecules and other factors, DC are involved in the maintenance of peripheral tolerance through modulation of the immune response. This modulation occurs both constitutively, and in inflammation, in order to prevent autoimmunity and to control established immune responses. Dendritic cell control of immune responses may be mediated through cytokine or cell‐contact dependent mechanisms. The molecular and cellular basis of these controls is being understood at an increasingly more complex level. This understanding is reaching a level at which DC‐based therapies for the induction of immune regulation in autoimmunity can be tested in vivo. This review outlines the current state of knowledge of DC in immune tolerance, and proposes how DC might control both T cell responses, and themselves, to prevent autoimmunity and maintain peripheral tolerance.
Immune responses to hepatitis B surface antigen following epidermal powder immunization
Authors: Osorio Jorge E , Zuleger Cindy L , Burger Melissa , Chu Qili , Payne Lendon G , Chen Dexiang
Published: March 2003

Langerhans cells in the epidermis of skin are potent antigen‐presenting cells that trigger the immune system to respond to invading microorganisms. We have previously shown that epidermal powder immunization with a powdered inactivated influenza virus vaccine, by targeting the Langerhans cell‐rich epidermis, was more efficacious than deeper tissue injection using a needle and syringe. We now report enhanced humoral and cellular immune responses to recombinant hepatitis B surface antigen following epidermal powder immunization. We observed that epidermal powder immunization with unadjuvanted hepatitis B surface antigen elicited an antibody titre equivalent to that induced by the alum‐adjuvanted vaccine delivered by intramuscular injection, suggesting that epidermal powder immunization can overcome the need for adjuvantation. We demonstrated that synthetic CpG oligonucleotides (CpG DNA) could be coformulated with hepatitis B surface antigen and delivered by epidermal powder immunization to further augment the antibody response and modulate T helper cell activities. Epidermal powder immunization of hepatitis B surface antigen formulated with CpG DNA formulations resulted in 1.5–2.0 logs higher IgG antibody titres than alum‐adjuvanted commercial vaccines administered by intramuscular injection. Formulation of hepatitis B surface antigen with CpG DNA elicited an augmented IgG2a antibody response and increased frequency of IFN‐γ secreting cells. In addition, CpG DNA was found to activate epidermal Langerhans cells and stimulate the production of TNF‐α and IL‐12 cytokines by epidermal cells, explaining its strong adjuvant activity following epidermal powder immunization. These results show that epidermal powder immunization is a safe and effective method to deliver hepatitis B surface antigen and the addition of new adjuvants, such as CpG DNA, may further enhance the efficacy of this vaccine.
Facilitating positive changes in community dementia management through participatory action research
Authors: Chenoweth Lynn , Kilstoff Kathleen
Published: March 2003

Chenoweth L and Kilstoff K. International Journal of Nursing Practice 1998; 4: 175–188

Facilitating positive changes in community dementia management through participatory action research

This paper reports on a participatory action research study which arose out of the initiatives of people caring for clients attending a multicultural dementia day‐care program. Through a democratic decision making process, the day‐care staff and family carers consulted with clients to design, implement and evaluate a new therapy program. The researchers acted as facilitators in this process, with a view to empowering participants at each stage in the action research cycles. What started out as a negative situation for the majority of study participants, evolved to become a satisfying group process and positive outcomes resulted from the therapy program itself. For clients there was the renewal of close personal relationships with family carers, increased alertness and a reduction in some of their distressing symptoms. For the family carers, there arose an awareness of new purposes in the caring role and therefore less distress in their daily lives, for day‐care staff there emerged a re‐conceptualisation of purpose of dementia care programs and the benefits to be gained from community collaboration in program design. The focus of this paper is to describe the action research process, which resulted in positive outcomes for the study participants.
Evaluation of a constipation risk assessment scale
Authors: Zernike Wendy , Henderson Amanda
Published: March 2003

This project was undertaken in order to evaluate the utility of a constipation risk assessment scale and the accompanying bowel management protocol. The risk assessment scale was primarily introduced to teach and guide staff in managing constipation when caring for patients. The intention of the project was to reduce the incidence of constipation in patients during their admission to hospital.
Smoking: Rates and attitudes among nursing staff in central Sydney
Authors: Hughes Ann‐Maree , Rissel Chris
Published: March 2003

The objectives of this study were to determine the prevalence and predictors of smoking and attitudes to smoking‐related issues among nurses employed by the Central Sydney Area Health Service in Sydney, Australia. A self‐administered questionnaire, was distributed via the internal mail system of the Central Sydney Area Health Service in November 1997 to 610 randomly selected nursing staff. Twenty‐one per cent (n= 127) of respondents smoked. Smokers were significantly younger than non‐smokers and were more likely to speak mainly English at home. There were clear differences between smokers and non‐smokers in response to all attitude statements. Interventions specifically directed at nurses who smoke to assist them to stop and maintain cessation are indicated. Future health service workplace tobacco control programmes should address deficits in knowledge about the health effects of passive smoking, should raise awareness among nurses who smoke about their potential to affect the behaviours of others through modelling, and should provide all nurses with the skills required to be smoking educators and advocates for tobacco control.
The effect on staff of essential oil burners in extended care settings
Authors: Tysoe Pat
Published: March 2003

Because hospital wards may be associated with smells, such as chemicals, food, and people and their produce, essential oils in burners were considered a way of improving the ward atmosphere for staff. A study was conducted in three parts. A questionnaire covering a period of 1 month; lavender oil in burners for a 3‐month period; and a second questionnaire. A significant number of respondents (88%) indicated in the first questionnaire their belief that the use of essential oil would have a positive effect on the workplace. Eighty‐five per cent of respondents to the second questionnaire believed that there had been an improvement in the work environment following the use of the lavender oil burners.
Development of northwest Pacific guyots: General results from Ocean Drilling Program legs 143 and 144
Authors: Flood Peter
Published: March 2003

Results of the Ocean Drilling Program legs 143 and 144, which investigated the nature and origin of seven guyots in the northwest Pacific Ocean, document a history of prolonged volcanism (128–84 Ma), followed by subsidence, accumulation of shallow‐water carbonates, emersion following a sea‐level fall, then continued subsidence, and drowning. Generally, the life span of a guyot is of the order of 5–20 million years. The stratigraphic sequence in each guyot consists of 3–10 m‐thick, shoaling‐upward cycles, which display a 100‐Ka periodicity perhaps related to sea‐level fluctuations. The drilling results indicate that the demise of the shallow‐water carbonate platforms is related to either a temporal (110–100 Ma) event or paleolatitude location (0–10°S) involving nutrient‐rich water not conducive to production of calcium carbonate by shallow‐water organisms. Following emergence and erosion, re‐submergence occurred during a rise of sea‐level. However, the rate of sediment accumulation was unable to keep pace with the rate of sea‐level rise and the guyots drowned. Subsidence continued as the lithospheric plate cooled. The majority of guyots are now at ~ 1500 m below sea‐level. Plate movements over the past 100 million years have carried the guyots from ~ 14°S to their current location in the northwest Pacific. Guyots are flat‐topped submerged volcanic islands capped by thick sequences of shallow‐water carbonates. The flat‐top morphology is constructional, not related to wave planation as originally thought and reported in most textbooks.
Metamorphic evolution of garnet–clinopyroxene–amphibole rocks from the Proterozoic Songshugou mafic–ultramafic complex, Qinling Mountains, central China
Authors: Zhang Z. J.
Published: March 2003

Garnet–clinopyroxene–amphibole rocks from the Songshugou mafic–ultramafic complex (ca 1029 Ma) in the Qinling Mountains, central China, occur in a metabasite unit that is situated structurally beneath the peridotite body. These rocks have many records testifying to a multistage metamorphic history for the metabasites. Through petrographic and mineralogic investigations, at least three metamorphic stages were recognized: (i) a pre‐eclogite stage of the amphibolite‐facies condition as inferred from inclusions in garnet; (ii) an eclogite‐facies stage as inferred from Pl‐Cpx symplectites and from their reconstructed omphacite compositions (Jd17–35); and (iii) a post‐eclogite stage characterized by various reaction textures such as coronas and reaction zones around garnets, clinopyroxenes and fine‐grained mineral aggregates after garnets and clinopyroxenes. A textural relationship observed in the field and thin‐section scales indicates that a breakdown of the Grt–Cpx–Amp assemblage led to the Grt‐free and the Cpx‐free assemblages, that is, Amp + Pl assemblage at the end. The eclogite‐facies metamorphism of the metabasites, discussed in the present report, was related to subduction at the age intervening between ca 983 and ca 1029 Ma. Regional geologic data indicate that the eclogite‐related subduction took place during the opening of the Kuanping marginal basin in the southern margin of the North China craton, and slightly before the formation of the Danfeng magmatic arc (ca 984 Ma). The exhumation and emplacement of the eclogite‐facies domain probably resulted from a collision between the Danfeng magmatic arc terrain and a fragment of the North China craton (i.e. the Qinling Complex) during 790–890 Ma.
Sr–Nd isotopic systematics and geochemistry of intermediate plutonic rocks from Ikoma Mountains, Southwest Japan: evidence for a sequence of Mesozoic magmatic activity in the Ryoke Belt
Authors: Fujii Hiroaki , Tainosho Yoshiaki , Kagami Hiroo , Kakiuchi Takashi
Published: March 2003

Abstract The Ryoke Belt in the Ikoma Mountains, Nara Prefecture, Japan, is composed mainly of various granitic, intermediate and gabbroic rocks. Igneous activity in this area is divided into two periods, early–middle Jurassic and late Cretaceous, based on isotopic dating. The intermediate plutonic rocks in the Fukihata area are composed of two rock types: Kyuanji quartz diorite and Fukihata tonalite. Rb–Sr whole‐rock isochron ages have been determined for both plutonic rocks. Their ages and initial 87Sr/86Sr ratios are as follows: the Kyuanji quartz diorite has an age of 161.0 ± 17.9 Ma with an initial 87Sr/86Sr ratio of 0.70727 ± 0.00007, while the Fukihata tonalite has an age of 121.4 ± 24.6 Ma with an initial 87Sr/86Sr ratio of 0.70753 ± 0.00020. Our chronological results indicate that the Kyuanji quartz diorite belongs to the Jurassic mafic rocks, such as the Ikoma gabbroic mass, while the Fukihata tonalite belongs to the early Cretaceous granitic rocks. Both these intermediate plutonic rocks have different chemical characteristics and were derived from different magmas.
Isotopic equilibration ages for the Miyanohara tonalite from the Higo metamorphic belt in central Kyushu, Southwest Japan: Implications for the tectonic setting during the Triassic
Authors: Kamei Atsushi , Owada Masaaki , Hamamoto Takuji , Osanai Yasuhito , Yuhara Masaki , Kagami Hiroo
Published: March 2003

Abstract Miyanohara tonalite occurs in the middle part of the Higo metamorphic belt in the central Kyushu, Southwest Japan. This tonalite intrudes into early Permian Ryuhozan metamorphic rocks in the south and is intruded by Cretaceous Shiraishino granodiorite in the north. The Miyanohara tonalite yielded three mineral ages: (i) 110–100 Ma for Sm–Nd and Rb–Sr internal isochrons and for K–Ar hornblende; (ii) 183 Ma for Sm–Nd internal isochron; and (iii) 211 Ma for Sm–Nd internal isochron. The ages of 110–100 Ma may indicate cooling age due to the thermal effect of the Shiraishino granodiorite intrusion. The ages of 183 Ma and 211 Ma are consistent with timing of intrusion of the Miyanohara tonalite based on geologic constraints. The hornblende in the sample which gave 183 Ma shows discontinuous zoning under microscope, whereas the one which gave 211 Ma does not show zonal structure. These mineralogical features suggest that the 183 Ma sample has suffered severely from later tectonothermal effect compared with the 211 Ma sample. Therefore, the age of 211 Ma is regarded as near crystallization age for the Miyanohara tonalite. The magmatic process, geochronology and initial Sr and Nd isotope ratios for the Miyanohara tonalite are similar to those of early Jurassic granites from the Outer Plutonic Zone of the Hida belt that constitutes a marginal part of east Asia before the opening of the Japan Sea. Intrusion of the Miyanohara tonalite is considered to have taken place in the active continental margin during the late Triassic.
Three‐dimensional finite strain analysis in the high‐grade part of the Sanbagawa Belt using deformed meta‐conglomerate
Authors: Moriyama Yoshinori , Wallis Simon
Published: March 2003

Abstract  Regional ductile deformation of the Sanbagawa belt is generally thought to be characterized by constrictional strain, based on strain analysis using deformed radiolarians in the low‐grade regions. Similar strain analysis could not be carried out in the medium‐ to high‐grade zones, because it is very difficult to identify individual radiolarians after strong recrystallization. However, discovery of the first known meta‐conglomerate in the high‐grade region of the Sanbagawa Belt allows quantitative 3‐D strain to be estimated in this region. Using a development of the Rf‐φ method, an evaluation of appropriate errors for this estimate can be determined. The principal strain ratios and estimated errors are X/Y = 5.4–6.6 and Y/Z = 3.8–3.9 implying deformation in the flattening field and refuting the idea of uniform constrictional strain. Semi‐quantitative markers of the shape of the strain ellipse throughout the high‐grade regions suggest that the deformation of the Sanbagawa Belt is dominantly in the flattening field. The difference with the earlier results may be due to late‐stage overprinting by upright folding of the main ductile fabric in the low‐grade region of western Shikoku.
Rat gastrointestinal motor responses mediated via activation of neurokinin receptors
Authors: Chang Full‐Young , Lee Shou‐Dong , Yeh Guey‐Hwa , Wang Paulaus
Published: March 2003

Natural neurokinins (NK) and their specific receptor agonists, including substance P (SP), neurokinin A (NKA), neurokinin B (NKB), septide, [NIe10]‐NKA4–10 and senktide, were used to assess whether they could activate established NK receptors in rat gastrointestinal tract and central nervous system to alter gastric emptying or intestinal transit. Fasting rats were intubated with an orogastric catheter to feed them liquid radiochromium. Neurokinins and analogues (at 10−10, 10−9, 10−8 and 10−7 mol/kg) and vehicle (saline +0.1% bovine serum albumin) were injected via an intraperitoneal route. Rats were killed 15 min later and the whole gut was removed. The radioactivity of the stomach and 10 equally divided small intestinal segments was counted to determine gastric emptying and the geometric centre of intestinal transit. Septide treatment at 10−8 and 10−7 mol/kg markedly delayed gastric emptying. All doses of NKA inhibited gastric emptying. However, other peptides did not influence gastric emptying. Both septide and NKB treatment at 10−8 and 10−7 mol/kg enhanced intestinal transit. Substance P or senktide treatment (10−7 mol/kg) also enhanced intestinal transit. Stasis of remaining radioactivity in the proximal intestine was found following SP, septide, NKA and NKB treatment, whereas accelerated transit in the distal intestine was induced following NKA, NKB and senktide treatment. In conclusion, the in vivo study of NK and their specific agonists manifests a selective influence of these compounds on rat gastrointestinal tract. This selective activation of stomach NK1 and NK2 receptors delays gastric emptying, whereas activation of intestinal NK1 and NK3 receptors enhances intestinal transit.
Mucosal macrophage inflammatory protein‐1α activity in Helicobacter pylori infection
Authors: Kusugami Kazuo , Ando Takafumi , Imada Akira , Ina Kenji , Ohsuga Masahiro , Shimizu Tatsuji , Sakai Tetsu , Konagaya Toshihiro , Kaneko Hiroshi
Published: March 2003

Mucosal chemokines are considered to be important in the pathogenesis of Helicobacter pylori‐associated gastritis. The aims of this study are to examine the levels of macrophage inflammatory protein‐1α (MIP‐1α) in organ cultures, the expression of MIP‐1α mRNA and the cellular source of MIP‐1α, using the antral mucosal specimens obtained from H. pylori‐positive and ‐negative patients. Enzyme‐linked immunosorbent assay was used to measure the levels of MIP‐1α in organ cultures of mucosal tissues and cell cultures of fractionated mucosal cells. The expression of MIP‐1α mRNA and protein was analysed in fresh biopsy tissues with reverse transcriptase–polymerase chain reaction (RT‐PCR) and double immunofluorescence microscopy, respectively. The mucosal specimens obtained from H. pylori‐positive patients exhibited significantly higher values of MIP‐1α activity in organ cultures with increased numbers of CD68+ macrophages, myeloperoxidase+ neutrophils and mononuclear cells in the lamina propria compared with those from H. pylori‐negative patients. The RT‐PCR analysis detected MIP‐1α mRNA in more than 50% of the specimens with H. pylori infection, but not in those without infection. In cell cultures, the macrophage fraction contained substantially higher amounts of MIP‐1α on a per cell basis than the lymphocyte fraction and MIP‐1α activity was not detected in cultures of gastric epithelial cells. This observation was also confirmed by a double immunofluorescence microscopic study in which most (> 90%) MIP‐1α‐positive infiltrating cells were CD68+ macrophages. This study indicates that synthesis and secretion of MIP‐1α are increased in H. pylori‐infected antral mucosa and that mucosal macrophages are the main cell type responsible for this phenomenon.
Anorectal physiology and transit in patients with disorders of thyroid metabolism
Authors: Deen Kemal , Seneviratne Suranjith , Silva H
Published: March 2003

Background: Data on anorectal physiology in patients with disordered thyroid metabolism are lacking. This prospective study was performed to evaluate anorectal physiology in patients with either hyperthyroidism and diarrhoea, or hypothyroidism and constipation in order to assess slow transit in hypothyroid patients.

Methods: Thirty patients with hypothyroidism and constipation (24 females, median age 59 years, range 23–80) and 20 patients with hyperthyroidism and diarrhoea (12 females, median age 46 years, range 36–62) were evaluated by anal manometry, rectal balloon sensation and whole‐gut transit markers. Data were compared with anorectal physiology and whole‐gut transit in 22 healthy controls (13 females, median age 51 years, range 24–65).

Results: In the hypothyroid patients, maximum resting pressure (MRP) and maximum squeeze pressure (MSP) were similar to controls (patients, median MRP 55 mmHg (18–98); controls, median MRP 41 mmHg (20–105) and patients, median MSP 83 mmHg (39–400); controls, median MSP 88 mmHg (30–230); P > 0.05 for both resting and squeeze pressures). In hyperthyroid patients, median MRP and MSP were significantly lower than controls (patients, MRP 33 mmHg (8–69); controls MRP 41 mmHg (20–105) P = 0.04 and patients, MSP 60 mmHg (26–104); controls, MSP 88 mmHg (30–230); P = 0.03). Threshold sensation for impending evacuation in hypothyroid patients was significantly higher than controls, while in hyperthyroid patients, threshold sensation was significantly lower compared with controls. Maximum tolerable rectal volumes in hypothyroid patients was significantly lower compared with controls, while no significant difference was found between maximum tolerable rectal volumes in hyperthyroid patients and controls. Prevalence of delayed whole‐gut transit in both hypothyroid and hyperthyroid patients was similar to controls. Furthermore, 33% of hypothyroid patients and 40% of hyperthyroid patients experienced symptoms of bowel dysfunction prior to the onset of their thyroid disorder.

Conclusions: Patients with altered thyroid function and bowel dysfunction demonstrated abnormalities of anal manometry and rectal sensation.
Helicobacter pylori: Evidence for spouse‐to‐spouse transmission
Authors: Singh V , Trikha B , Vaiphei K , Nain CK , Thennarasu K , Singh K
Published: March 2003

Background
: Spouse‐to‐spouse transmission of Helicobacter pylori infection still remains controversial.

Methods
: We studied the prevalence of H. pylori infection among spouses of H. pylori‐positive or ‐negative individuals and looked for intraspousal transmission. Twenty‐five couples were studied. Initially, one individual per couple was selected as the index subject. Spouses of these H. pylori‐positive or ‐negative index individuals underwent screening for H. pylori by serology, the rapid urease test and histology. Those couples in whom only one spouse was positive were followed up and H. pylori status was re‐evaluated using the above tests after approximately 1 year in the H. pylori‐negative spouse.

Results
: Of 25 randomly selected index subjects, 18 were H. pylori positive and seven were negative. There was no significant difference in age, sex, socioeconomic status, presence of dyspeptic symptoms, duration of marriage and number of children in these index subjects. Spouses of H. pylori‐infected index subjects had a significantly higher prevalence of H. pylori infection than the spouses of H. pylori‐negative index subjects (83.3 vs 28.5%; P < 0.01). Age, sex, socioeconomic status, dyspeptic symptoms, duration of marriage and number of children were not different in H. pylori‐positive or ‐negative spouses of H. pylori‐positive index subjects. There were five such couples in whom only one spouse was H. pylori positive initially. At follow up, three of these H. pylori‐negative spouses became positive. These findings suggest person‐to‐person transmission or common source exposure within couples.
Metaplastic polyp of the colon develops in response to inflammation
Authors: Higaki Shingo , Akazawa Akiko , Nakamura Hiroki , Yanai Hideo , Yoshida Tomoharu , Okita Kiwamu
Published: March 2003

Background: The metaplastic polyp of the colon is a non‐neoplastic lesion that is generally identified as white, flat and having a smooth surface. In general, this polyp is small, is less than 5 mm in diameter but is occasionally larger than 5 mm in diameter, and forms a swelling. The aims of the present study were to clarify the factors that determine the morphology of protruding metaplastic polyps. More specifically, we investigated whether the metaplastic polyp forms as a result of an abnormality in cell proliferation or inflammation of the region.

Methods: We examined 15 endoscopically resected metaplastic polyps of the colon having a longitudinal diameter of more than 5 mm. To study aspects of cell proliferation, we used proliferating‐cell nuclear antigen (PCNA) staining. For examination of histological changes caused by inflammation, we used α‐smooth muscle actin (αSMA) staining, in which myofibroblasts are specifically stained.

Results: Metaplastic polyps showed significantly higher expression of PCNA, not only in the deep layer, but also in the intermediate and superficial layers, compared with the normal mucosa of the colon. In the protruding metaplastic polyps, anti‐αSMA staining revealed bundle‐like myofibroblasts in the interstitium.

Conclusions: The factors responsible for the formation of non‐neoplastic metaplastic polyps larger than 5 mm with a protruding morphology are: an increased number of epithelial cells due to the movement of these cells toward the ductal epithelium in the proliferating zone; and expansion of interstitial tissues due to infiltration of myofibroblasts and other inflammatory cells in response to inflammation.
Efficacy of an implanted drug delivery system for advanced hepatocellular carcinoma using 5‐fluorouracil, epirubicin and mitomycin C
Authors: Seno Hiroshi , Ito Kazuki , Kojima Koichi , Nakajima Nobuaki , Chiba Tsutomu
Published: March 2003

Background
: In order to assess the efficacy of repeated hepatic arterial infusion (HAI) therapy for advanced hepatocellular carcinoma, we administered HAI therapy using 5‐fluorouracil, epirubicin and mitomycin C, with an implanted drug delivery system.

Methods and Results
: Thirty‐seven patients received HAI therapy with a response rate of 21.6%. The 6‐month and 1‐year survival rates were 67.6 and 29.7%, respectively. Responders to HAI therapy showed significantly longer survival than non‐responders, while patients with mild liver dysfunction tended to survive longer than those with severe dysfunction. Neither tumour thrombosis of the main trunk of the portal vein nor extrahepatic metastases were considered to constitute contraindications for HAI therapy. Catheter‐related trouble occurred in eight patients and biloma in one patient, but other side effects were transient and tolerable. These patients received HAI therapy as outpatients for an average of 79.6% of the entire course of therapy.

Conclusions
: Hepatic arterial infusion therapy proved effective for patients with advanced hepatocellular carcinoma in terms of improving survival and outpatient rates.
Effective hepatic artery chemoembolization for advanced hepatocellular carcinoma with extensive tumour thrombus through the hepatic vein
Authors: Kashima Yasushige , Miyazaki Masaru , Ito Hiroshi , Kaiho Takashi , Nakagawa Koji , Ambiru Satoshi , Shimizu Hiroaki , Furuya Seiji , Nakajima Nobuyuki
Published: March 2003

Background and Aims
: Advanced hepatocellular carcinoma (HCC) with extensive tumour growth through the hepatic vein still has an extremely poor prognosis, even after cancer chemotherapy and/or transarterial embolization. Although aggressive surgical treatments using extracorporeal circulation and liver transplantation have been performed by some authors, the reported results were still unsatisfactory. In this study, we report the favourable result of hepatic artery chemoembolization and subsequent surgical resection in three patients with advanced HCC with extensive tumour thrombus through the hepatic vein.

Methods and Results
: Three irresectable patients with HCC with extensive tumour thrombus through the hepatic vein underwent hepatic artery chemoembolization with aclarubicin, mitomycin C, lipiodol and/or Gelfoam. After the reduction of tumour extent with hepatic artery chemoembolization, two of the three patients underwent surgical resection. These two patients are still alive at 59 and 21 postoperative months, respectively. In the other case, the extent of the tumour and functional reserve of the liver prevented us from performing surgical resection, but the patient is doing well 62 months after the initial treatment.

Conclusions
: Hepatic artery chemoembolization with aclarubicin, mitomycin C, lipiodol and/or Gelfoam might be an effective treatment for irresectable advanced HCC with extensive tumour thrombus into the inferior vena cava or the right atrium through the hepatic vein. Radical surgical resection might be applicable for selected patients without high surgical risk after reducing tumour extent by hepatic artery chemoembolization.