bluuebunny/crossref_metadata_2025 huggingface dataset:
Dysregulated expression of CD69 and IL‐2 receptor α and β chains on CD8+ T lymphocytes in flaky skin mice
Authors: Abernethy Nevin J , Hagan Colin , Tan Paul LJ , Watson James D
Published: March 2003

T‐cell activation is considered to be an important element in the pathogenesis of psoriasis, a human skin disease characterized by keratinocyte hyperproliferation, altered keratinocyte differentiation and inflammation of the dermis and epidermis. Mice homozygous for the flaky skin (fsn) mutation develop a skin disorder that has histopathological and biochemical features resembling some forms of psoriasis. It has been reported recently that peripheral lymph nodes (PLN) in fsn/fsn mice exhibit various abnormalities in T‐cell development suggestive of dysregulated T‐ and B‐cell activation. In the present study, the expression of the inducible T‐cell activation antigens CD69 and IL‐2 receptor α chain (CD25) on PLN cells from fsn/fsn mice and their phenotypically normal littermates is examined. Expression of CD69 was significantly increased on PLN cells in fsn/fsn mice (mean ± SD, 49.9 ± 14.7% of cells) compared with control mice (14.6 ± 4.2 %). Analysis of CD4+ and CD8+ T cell subsets revealed that expression of CD69 in fsn/fsn PLN was significantly biased toward CD8+ cells. Although expression of CD25 was preferentially associated with CD4+ rather than CD8+ cells in both fsn/fsn and control PLN, with most CD4+CD25+ cells being CD25hi, the proportion of CD4+ cells expressing CD25 was higher in fsn/fsn than control PLN. In contrast, CD25 was expressed by 2–3 % of CD8+ PLN cells in both fsn/fsn and control mice and CD25hi cells accounted for < 1 % of CD8+ cells in fsn/fsn PLN. The paucity of CD25 on CD8+ cells in fsn/fsn PLN did not appear to be due to a defect in the ability of these cells to upregulate CD25, because T cell receptor stimulation in vitro induced high expression of CD25 on both CD4+ and CD8+ cells. A striking and consistent finding was that most CD8+ cells in fsn/fsn PLN expressed high levels of IL‐2R β chain (CD122). In contrast, CD122 was expressed at low levels on CD8+ cells in control mice. Analysis of PLN cells from newborn fsn/fsn mice revealed that the high expression of CD122 on CD8+ cells was established by 2 weeks of age, prior to the appearance of clinical skin disease. These data indicate that large numbers of T cells in fsn/fsn mice are activated and reinforce the view that fsn is an important regulator of lymphocyte development and function. The relationship between T‐cell activation and flaky skin disease in these mice remains to be established.
Human peripheral blood lymphocyte severe combined immunodeficiency (hu‐PBL SCID) models of toxoplasmosis
Authors: Beaman Miles H , Remington Jack S , Meyer Desiree J
Published: March 2003

Toxoplasmosis is a potentially fatal opportunistic infection of immunocompromised hosts. Improved animal models of toxoplasmosis are needed to more nearly approximate conditions that occur in immunocompromised humans. The development of models of toxoplasmosis using human peripheral blood lymphocytes (hu‐PBL) transplanted into severe combined immunodeficiency (SCID) mice is described here. Transplantation of hu‐PBL into SCID mice without prior conditioning of the mice resulted in detectable differences in quantitative histological scores of brain inflammation due to Toxoplasma gondii infection, but did not alter mortality when compared to SCID mouse controls. The lack of detectable differences in survival were due to inadequate engraftment of hu‐PBL, as assessed by flow cytometry. Unconditioned hu‐PBL SCID mice had low titre T. gondii‐ specific antibody detectable after infection. When pretransplantation conditioning with irradiation and antiasialo GM 1 (n‐glucolyl neuraminic acid) antibody was used, prolonged hu‐PBL engraftment was observed in SCID mice, which was associated with worsened histopathology and usually impaired survival when compared with SCID mouse controls. When pretransplantation conditioning with irradiation, antiasialo GM antibody and polyethylene glycol‐conjugated IL‐2 was used, prolonged hu‐PBL engraftment was also documented, but this did not affect survival from T. gondii infection when compared with similarly conditioned SCID mouse controls. The latter conditioning protocol resulted in hu‐PBL SCID mice producing high titre T. gondii‐specific antibody after infection. Conditioned hu‐PBL SCID mice had evidence of increased T. gondii‐induced inflammatory scores when compared with conditioned SCID mice. These models show promise for the study of the pathogenesis of toxoplasmosis and conditioned hu‐PBL SCID mice may have applications for the evaluation of novel therapies for toxoplasmosis in immunocompromised humans.
Effect of localized cytokine dysregulation: Accelerated rejection of IL‐2‐expressing skin grafts
Authors: Blackburn CC , Grogan JL , Augustine CL , Miller JFAP , Varigos G , Morahan G
Published: March 2003

Transgenic mice were created in which a sheep keratin promoter directed the expression of IL‐2 into the dermis. These KIL‐2 transgenic mice were used to investigate the effects of localized IL‐2 dysregulation on immune responses. Peripheral tolerance to skin antigens was not broken by in situ IL‐2 expression because syngeneic KIL‐2 skin grafts were not rejected. However, MHC Class I‐disparate skin grafts from KIL‐2 donors were rejected faster (median survival time (MST) 12 days) than grafts of non‐transgenic littermate skin (MST 18 days). In contrast, the kinetics of KIL‐2 H‐Y‐disparate skin graft rejection (MST 14 days) did not differ significantly from controls (MST 16 days), suggesting that upregulation of IL‐2 at the effector site could affect CD4+ T cell‐ independent, but not CD4+ T cell‐dependent, responses. No effect on rejection kinetics was observed when wild type allogeneic skin was grafted onto transgenic mice that expressed bcl2 constitutively in their lymphocytes (MST of 14 days, both sets), indicating that this was not simply due to increased longevity of T cells within the IL‐2 expressing graft. We therefore suggest that aberrant expression of IL‐2 can accelerate helper‐independent CD8+ T cell responses by increasing proliferation and/or differentiation of cytolytic T cells at the effector site.
Overcoming the poor immunogenicity of a protein by DNA immunization as a fusion construct
Authors: Sutherland Robyn M , McKenzie Brent S , Corbett Alexandra J , Brady Jamie L , Lew Andrew M
Published: March 2003

The production of antibodies against poorly immunogenic proteins is problematic. Often there is a failure to generate such antibodies. Furthermore, antibodies against other specificities are frequently induced. We describe a simple approach, analogous to conjugation to a protein carrier, whereby immunization with naked DNA was used to raise antibody to a highly homologous and poorly immunogenic allotypic protein. Deoxyribonucleic acid encoding the protein of interest was fused to DNA encoding the Fc region of a foreign Ig, resulting in increased immunogenicity. The potential applications of this approach include the production of antisera and mAb to allotypic variants, mutant proteins, and proteins that are highly conserved between species.
Distinct spatial requirement for eosinophil‐induced airways hyperreactivity
Authors: Webb DC , McKenzie ANJ , Matthaei KI , Rothenberg ME , Foster PS
Published: March 2003

T helper (Th)‐2‐derived cytokines and their involvement in the recruitment and activation of inflammatory cells crucially orchestrate asthma pathogenesis. A notable cellular component of this allergy‐induced inflammation is the eosinophil. However, whether the eosinophil is an obligatory mediator for enhancing airways hyperreactivity (AHR) to cholinergic stimuli, a watershed of the asthmatic lung, is somewhat controversial. In this investigation we have endeavoured to define the spatial requirements for IL‐4 and IL‐13, and the downstream effector molecules, IL‐5 and the CC chemokine eotaxin, for the recruitment of eosinophils and the development of AHR in a murine model of allergic pulmonary disease. These studies are of particular importance considering clinical trials, with either the soluble IL‐4Rα subunit or a humanized anti‐IL‐5 antibody, are being conducted. Interestingly, our studies show that depletion of both IL‐4 and IL‐13 is necessary to ablate pulmonary eosinophilia and AHR, and that this may be attributed to the role these cytokines play in regulating the expression of the eosinophil‐ activating molecules, IL‐5 and eotaxin. While it is clear that depletion of IL‐5 diminishes pulmonary eosinophilia, we demonstrate in BALB/c mice that a deficiency in both IL‐5 and eotaxin is necessary to abolish both the trafficking of eosinophils to the lung and AHR. However, in contrast to the neutrophil‐rich inflammation observed in mice deficient in both IL‐4 and IL‐13, inflammation per se in mice deficient in both IL‐5 and eotaxin is significantly attenuated. This suggests that asthma immunotherapy may be better directed towards the eosinophil‐ activating molecules IL‐5 and eotaxin, rather than towards pleiotrophic molecules such IL‐4 and IL‐13, which are additionally important in modulating alternative inflammatory responses.
Binding of Griffonia simplicifolia 1 isolectin B4 (GS1 B4) to α‐galactose antigens
Authors: Kirkeby Svend , Moe Dennis
Published: March 2003

Glycoconjugates with terminal Galα1–3Galβ1–4GlcNAc sequences (α‐galactosyl epitopes, natural xenoreactive antigens) are present on various tissues in pigs and are recognized by human anti‐αgalactosyl (αGal) antibodies1. Hence xenotransplantation (pig‐to‐human) would trigger immune reactions involving complement activation and lead to the hyperactute rejection of the graft. Xenoreactive antigens are often studied by using the lectin Griffonia simplicifolia 1 isolectin B4 (GS1 B4), which shows high affinity to galactose. We here estimate the specificity of GS1 B4 for detecting various galactosyl epitopes by measuring lectin binding to neoglycoproteins, thyroglobulin and pig skeletal muscle. Enzyme linked lectin assays confirmed that GS1 B4 was highly specific to α‐galactosylated neoglycoproteins while the lectin did not detect a β‐galactosylated ligand. The length of the sugar chains influenced the lectin–carbohydrate interaction. A monosaccharide linked to serum albumin showed higher lectin affinity than did neoglycoproteins with di‐ and tri‐α‐galactosyl epitopes. When the carbohydrate was extended, as in the xenoreactive pentasaccharide (Galα1‐3Galβ1‐4GlcNAcβ1‐3Galβ1‐4Glc), the carbohydrate– lectin interaction was meagre. Not only the terminal, but also the subterminal sugar affected the lectin binding because the GS1 B4 affinity to Galα1‐3Gal was much stronger than to Galα1‐3GalNAc. In bovine and porcine thyroglobulin most αGal epitopes appear to be cryptic, but are unmasked by a heat denaturation. In pig skeletal muscle there was lectin reaction not only in the muscle capillaries, but also in the connective tissue and intracellularly in muscle fibres. In Western blots of isolated proteins from pig muscle at least three bands were strongly stained after incubation with lectin.
Identification of soluble transforming growth factor‐β receptor III (sTβIII) in rat milk
Authors: Zhang MF , Zola H , Read LC , Penttila IA
Published: March 2003

Transforming growth factor‐β (TGF‐β) is present at high concentrations in maternal milk. In milk TGF‐β2 is the predominant isoform. For function TGF‐β2 requires TβRIII to facilitate efficient binding to the TGF‐β receptor types I and II signalling complex. We have shown that TGF‐β receptor types I (TβRI), II (TβRII) and III (TβRIII) are coexpressed in the suckling rat intestine. Immunostaining for TβRIII was also observed in the intestinal lumen prior to weaning. TβRIII (or betaglycan) has been reported in serum, cell culture medium and extracellular matrix. To determine whether a soluble form of TβRIII is present in milk, the rat milk aqueous phase was analysed by slot‐blot and Western blot. Soluble TβRIII was detected in milk throughout lactation. Western blot analysis of rat milk revealed a high molecular weight band of glycosylated protein of >200 kDa, with a core protein of approximately 110–120 kDa that comigrated with recombinant TβRIII. Immunoabsorption of soluble TβRIII (sTβRIII) from milk resulted in partial depletion of active TGF‐β from milk, suggesting that the receptor may interact with ligand in milk. In addition rat pups suckled on mother's milk demonstrated an enhanced labelling of TβRIII in the gut, as compared with pups fed on a rat milk substitute (RMS). These findings suggest that milk sTβRIII is functional, and may modulate milk‐derived TGF‐β function in the developing intestine.
Trends in mucosal immunity in Antarctica during six Australian winter expeditions
Authors: Francis J Lynn , Gleeson Maree , Lugg Desmond J , Clancy Robert L , Ayton Jeff M , Donovan Kevin , McConnell Christine A , Tingate Trevor R , Thorpe Bruce , Watson Anne
Published: March 2003

The mucosal immune status of Australian Antarctic personnel was monitored during six wintering expeditions at two Australian Antarctic Research Stations, Casey in 1992, 1993, 1994, and Mawson in 1992, 1995, 1996. Salivary immunoglobulin and albumin levels were examined for differences between stations and expeditions, and for monthly changes over the expedition year. Salivary IgA and IgM concentrations were on average higher for the 1993 Casey expeditioners, and all salivary protein levels were lower for 1996 Mawson expeditioners compared to levels of the other expeditions. The change in salivary IgA and IgM concentrations over the 1‐year period revealed a consistent pattern between expeditions. Salivary IgA levels were lower in March, April and May compared to other months of the year (P = 0.0002). Salivary IgM levels were lowest in the first 4 months of the year, with peak levels in June and July (P < 0.0001). There were no changes in salivary IgG and albumin concentrations over the expedition year. Though the cause of the changes in salivary IgA and IgM levels over the year is unknown, the changes could reflect alterations in mucosal immunity in response to stressors associated with isolation.
15‐Deoxy‐Δ12,14‐prostaglandin J2 inhibitsCX3CL1/fractalkine expression in human endothelial cells
Authors: Imaizumi Tadaatsu , Matsumiya Tomoh , Tamo Wakako , Shibata Takeo , Fujimoto Koji , Kumagai Mika , Yoshida Hidemi , Cui Xue‐Fan , Tanji Kunikazu , Hatakeyama Masaharu , Wakabayashi Koichi , Satoh Kei
Published: March 2003

Peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) is a member of nuclear hormone receptor superfamily, and is known to play a role in various biological processes including inflammatory responses and adipocyte differentiation. CX3CL1/fractalkine is a potent agonist for chemotaxis and adhesion of monocytes and lymphocytes. Endothelial cells produce fractalkine when stimulated with cytokines such as interleukin‐1 (IL‐1), tumour necrosis factor‐α and interferon‐γ (IFN‐γ). We herein report that 15‐deoxy‐n12,14 ‐prostaglandinJ2 (15d‐PGJ2), a PPAR‐γ agonist, inhibits the expression of fractalkine induced by IFN‐γ or IL‐1β in human endothelial cells. Agonist for PPAR‐α (WY14643) or PPAR‐γ (ciglitazone) did not inhibit the cytokine‐inducedfractalkine expression, and the effect of 15d‐PGJ2 maybe independent of PPAR. 15‐Deoxy‐D12,14 prostaglandin J2 also inhibited the adhesion of blood mononuclear cells to endothelial monolayers treated with IFN‐γ or IL‐1β. The data suggest that 15d‐PGJ2 regulates inflammatory reactions, at least in part, through the inhibition of fractalkine expression and leucocyte traffic through the endothelium.
Experimental models linking dendritic cell lineage, phenotype and function
Authors: Fazekas De St Groth Barbara , Smith Adrian L , Bosco Julian , Sze Daniel M‐Y , Power Carl A , Austen Felicity I
Published: March 2003

One of the important issues in dendritic cell (DC) biology today is how DC control the fate of T cells. Our data suggest that an important branch point in determining T cell fate is the decision between deletion and memory. We have previously hypothesized that this binary decision is determined by contact with DC derived from lymphoid‐ versus myeloid‐restricted progenitors. However, the false attribution of CD8α expression as a reliable marker of lymphoid origin has underpinned a number of studies in which DC expressing CD8α did not induce deletion, thereby clouding the issue of whether deletion is indeed a function of lymphoid DC. By returning to basics, that is, functional testing of the progeny of lymphoid‐ and myeloid‐restricted progenitors in vivo, we hope to provide clear evidence of the in vivo roles of lymphoid and myeloid DC subsets, independent of assumptions about the surface phenotypes they can assume.
Truth‐telling versus hope: A dilemma in practice
Authors: Begley Ann , Blackwood Bronagh
Published: March 2003

This paper presents a brief outline of the attributes and therapeutic nature of hope in the context of truth‐telling. It is suggested that, in some circumstances, withholding the truth to protect hope can be considered a morally acceptable option when truth‐telling has the potential to destroy hope’s therapeutic effects. A clinical vignette that highlights how the practitioner can be confronted with a clash of principles is presented. The possible consequences of both truth‐telling and the withholding of truth are discussed and the moral positions of the health‐care professionals involved are examined. This article is intended to provide a framework for discussion/group work, particularly at undergraduate level.
Clinical development units (nursing): Issues surrounding their establishment and survival
Authors: Greenwood Jennifer
Published: March 2003

Clinical development units (nursing) are clinical units in which nurses systematically and strategically develop client‐focused care and reflective and research‐based practice. In addition, they are units typified by permissive and participatory governance and the recognition of the rights of all staff, irrespective of qualifications or experience, to continuing professional development. Clinical development units (nursing) (CDU(N)s), therefore, should be ‘learning’ units which provide rich opportunities to develop the transformational leadership skills of all nurses who work in them. As such, they provide important potential resources in terms of nursing's disciplinary and professional development. Western Sydney Area Health Service (WSAHS), in recognition of the important potential of CDU(N)s, sponsored the establishment of a network of nine CDU(N)s in 1997–1998. This will increase by a further five CDU(N)s in 1999–2000. Issues surrounding the establishment of this network, particularly in terms of unit preparation, the acquisition of adequate ‘expert’ and financial resources and leadership training will be discussed in this paper. In addition, threats to the survival of WSAHS's CDU(N)s will be identified and the strategies implemented by the Area in response to these threats will be outlined.
Breaking the silence: Women living with multiple sclerosis and urinary incontinence
Authors: Koch Tina , Kralik Debbie , Eastwood Sue , Schofield Ann
Published: March 2003

This study examined women's understandings of living with multiple sclerosis (MS) and urinary incontinence and the challenges they have encountered in their day‐to‐day lives. As health‐care professionals, we aimed to understand how people living with MS manage urinary incontinence. This paper reports the findings from a Participatory Action Research (PAR) group with four women, the researcher and two Continence Nurse Advisors (CNAs). The group met on five occasions between March and June 1999. The women's stories held personal and gendered meanings about living with MS and urinary incontinence. Four themes were derived from the transcripts: maintaining control; seeking understanding; avoiding shame; and good and bad days. The women and the CNAs benefited from an exchange of knowledge about living with MS and incontinence. The CNAs became sensitive to the women's experience and have been able to incorporate these understandings into their practice. By sharing our research we hope the findings may be more widely incorporated into sensitive health practice.
Mental health literacy survey of psychiatrically and generally trained nurses employed in a Singapore psychiatric hospital
Authors: Yeo Soo Gim , Parker Gordon , Mahendran Rathi , Jorm Anthony F , Yap Hwa Ling , Lee Cheng , Loh Min Ing
Published: March 2003

Mental health literacy studies consider the capacity of respondents to recognize certain psychiatric disorders, judge the comparative utility of a range of interventions, and make estimates about outcome and prognostic issues. We report such a study involving a sample of nursing staff employed at a large psychiatric institution in Singapore, and who were provided with separate brief vignettes of mania, schizophrenia and depression. Subjects were highly accurate in ‘diagnosing’ schizophrenia, less accurate for depression and even less accurate in diagnosing mania. Depression was alternately diagnosed as stress, mania was most commonly misdiagnosed as schizophrenia, and for both psychotic conditions, a percentage returned non‐psychotic diagnoses. In terms of treatment options, staff distinctly favoured a ‘medical model’ and viewed traditional and alternative healing options as distinctly harmful. Analyses contrasted psychiatrically trained and generally trained nurses, but identified few significant differences. Such information has the potential to shape the education and training of mental health professional staff, as well as provide important insights about how nurses may diagnose, view and favour alternative treatments and strategies to assist those with common psychiatric disorders.
Children’s needs during hospitalization: An observational study of hospitalized boys
Authors: Runeson Ingrid , Hallström Inger , Elander Gunnel , Hermerén Göran
Published: March 2003

Twenty‐one boys (age range 5 months to 16 years) were followed during their stay at hospital. Total observation time was 120 h. Field notes were made immediately after each observation. These were then transcribed into a narrative text, which was analysed by content analysis. Six categories of needs were identified during non‐threatening situations at the hospital: the need for activity, the need for new experiences, the need for information, the need for participation, the need for praise and recognition, and needs related to physical resources. Four categories of needs were found during episodes of threat, discomfort and pain: the need for control, the need for having their parents nearby, the need for what is familiar, and the need for integrity. These results indicate that those involved in the care of children should be alert to the fact that as circumstances change, different needs have to be met. During non‐threatening situations efforts should be made to inform children and to allow them to continue with their everyday lives. During threatening situations the children should be assisted and supported in keeping the situation under control.
Congruence or conflict? Challenges in implementing problem‐based learning across nursing cultures
Authors: Conway Jane , Little Penny , McMillan Margaret
Published: March 2003

Using the ‘real‐life’ situation of delivering an Australian nursing curriculum in the Maldives, this paper argues that successful offshore delivery requires far more than simply implementing an existing programme on a different site. In health education, cultural and contextual circumstances necessitate a critical appraisal of the needs of the community and the corresponding attributes of those who provide health‐care services. This means designing programmes that are process oriented and easily adapted to different circumstances, and a commitment to maintaining effective communication systems. Although it would seem that problem‐based learning (PBL) provides the framework for a process‐oriented, learner‐centred curriculum, the paper raises questions about how universally relevant the processes embedded in PBL are and describes concerns about the intent and purpose of nominating PBL as the preferred instructional strategy for cross‐cultural projects.
Defining the cultural milieu for implementing faculty practice in Pakistan
Authors: Upvall Michele J , Kanji Zeenatkhanu , Jaffer Salma , Khowaja Khurshid , Barolia Rubina , Amarsi Yasmin
Published: March 2003

Faculty practice can promote a collaborative partnership mutually beneficial to both nursing education and service. However, little is known about its implementation in developing countries. The purpose of this study was to explore the potential for introducing faculty practice within the cultural milieu of Karachi, Pakistan. Focus groups of nursing faculty, staff and students were conducted in various settings: government, semigovernment and private institutions to elicit the data. Data analysis revealed that a more comprehensive definition of faculty practice is needed that will provide the foundation for a culturally acceptable model of faculty practice in Pakistan. Hierarchy dominates the current cultural milieu and must be addressed before faculty practice can be implemented.
Lithostratigraphy of Permian marine sequences, Khao Pun Area, central Thailand: Paleoenvironments and tectonic history
Authors: Chutakositkanon Vichai , Charusiri Punya , Sashida Katsuo
Published: March 2003

Geologic mapping and subsurface lithostratigraphic investigations were carried out in the Khao Pun area (4 km2), central Thailand. More than 250 hand specimens, 70 rock slabs, and 70 thin sections were studied in conjunction with geochemical data in order to elucidate paleoenvironments and tectonic setting of the Permian marine sedimentary sequences. This sedimentary succession (2485 m thick) was re‐accessed and re‐grouped into three lithostratigraphic units, namely, in ascending order, the Phu Phe, Khao Sung and Khao Pun Formations. The Lower to lower Upper Permian sedimentary facies indicated the transgressive/regressive succession of shelf sea/platform environment to pelagic or abyssal environment below the carbonate compensation depth. The sedimentological and paleontological aspects, together with petrochemical and lithological points of view, reveal that the oldest unit might indicate an Early Permian sheltered shallow or lagoonal environment. Then the depositional basin became deeper, as suggested by the prolonged occurrence of bedded chert‐limestone intercalation with the local exposure of shallower carbonate build‐up. Following this, the depositional environment changed to pelagic deposition, as indicated by laminated radiolarian (e.g. Follicucullus sp.) cherts. This cryptic evidence might indicate the abyssal environment during middle Middle to early Late Permian; whereas, previous studies advocated shelf‐facies environments. Following this, the depositional condition might be a major regression on the microcontinent close to Indochina, from the minor transgressive/regressive cycles that developed within a skeletal barrier, and through the lagoon with limited circulational and anaerobic conditions, on to the tidal flat to the sheltered lagoon without effective land‐derived sediments.
Geology of the Kokchetav UHP‐HP metamorphic belt, Northern Kazakhstan
Authors: Kaneko Y. , Maruyama S. , Terabayashi M. , Yamamoto H. , Ishikawa M. , Anma R. , Parkinson C. D. , Ota T. , Nakajima Y. , Katayama I. , Yamamoto J. , Yamauchi K.
Published: March 2003

Abstract Ultrahigh‐pressure metamorphic (UHPM) rocks of the Kokchetav Massif of Kazakhstan contain metamorphic microdiamond and coesite inclusions inside rigid capsules such as garnet and zircon. Precambrian protoliths of the UHPM rocks were metamorphosed at around 530 Ma, at pressures of about 7 GPa, which suggests that crustal protoliths were subducted to depths of over 200 km. Primary UHPM minerals are poorly preserved due to partial obliteration by subsequent Barrovian overprint during exhumation and later collision events in Caledonian times. We report the results of detailed mapping of the Kokchetav Massif and use structural data to propose intrusion and exhumation mechanisms for the UHPM rocks. Detailed mapping revealed that many subvertical structures in the ultrahigh‐pressure–high‐pressure (UHP–HP) units were formed due to later folding. The primary structure appears to be subhorizontal and the total thickness of the UHP rocks is estimated at around 2 km. The first order structure is sandwich‐like; that is, the UHP–HP units are separated from underlying low‐P metamorphic rocks of the Daulet Series and from feebly metamorphosed to unmetamorphosed sedimentary strata on the top by subhorizontal faults. Kinematic indicators show top‐to‐the‐south sense of shear along the top, and top‐to‐the‐north displacement along the bottom boundaries. These shear senses, together with the observed metamorphic gradients, suggest that the thin UHPM sheet was extruded toward the north. We consider wedge extrusion to have been the most effective mechanism for the exhumation of the UHPM rocks.
Diamond‐bearing and diamond‐free metacarbonate rocks from Kumdy–Kol in the Kokchetav Massif, northern Kazakhstan
Authors: Ogasawara Yoshihide , Ohta Masahito , Fukasawa Kyoka , Katayama Ikuo , Maruyama Shigenori
Published: March 2003

Abstract Dolomite marble from the Kumdy–Kol area of the Kokchetav Massif contains abundant microdiamond, mainly in garnet and a few in diopside. The mineral assemblage at peak metamorphic condition consists of dolomite + diopside + garnet (+ aragonite) ± diamond. Inclusions of very low MgCO3 calcite and almost pure calcite occur in diopside and are interpreted as aragonite and/or aragonite + dolomite. Single‐phase Mg–calcite in diopside with a very high MgCO3 component (up to 21.7 mol%) was also found in diamond‐free dolomitic marble, and is interpreted as a retrograde product from aragonite + dolomite to Mg–calcite. The dolomite stability constrains the maximum pressure (P) at < 7 GPa using previous experimental data, whereas the occurrence of diamond yields the minimum peak pressure–temperature (P–T) condition at 4.2 GPa and 980 °C at X
co2 = 0.1. The highest MgCO3 in Mg–calcite constrains the minimum P–T condition higher than 2.5 GPa and 800 °C for the exhumation stage. As these marbles were subjected to nearly identical P–T metamorphic conditions, the appearance of diamond in some carbonate rocks was explained by high X
co2. A low X
co2 condition refers to high oxidized conditions and diamond (and/or graphite) becomes unstable. Difference in X
co2 for marble from the same area suggests local heterogeneity of fluid compositions during ultrahigh‐pressure metamorphism.
Geochemical and Sm–Nd isotopic characteristics of metabasites from central Hainan Island, South China and their tectonic significance
Authors: Li Xian‐Hua , Zhou Hanwen , Chung Sun‐Lin , Ding Shijiang , Liu Ying , Lee Chi‐Yu , Ge Wenchun , Zhang Yeming , Zhang Renjie
Published: March 2003

Abstract  Major and trace elements and Sm–Nd isotopic data are presented for metabasites that are present as lenses within Paleozoic metasediments in the Chenxing and Bangxi regions, central Hainan Island, Southeast (SE) China. Most metabasites are metamorphosed cumulated gabbroic rocks tholeiitic in nature, and characterized by varying degrees of depletion in Th, Nb, Ta and light rare earth elements (LREE). Moreover, they show high positive ∈Nd(T) values of approximately +7, similar to those of mid‐ocean ridge basalts (MORB). A Sm–Nd isochron age of 333 ± 12 Ma obtained for the metabasites is interpreted as their crystallization age. The combined geochemical and Sm–Nd isotopic data suggest that the metabasites were generated by dynamic partial melting from a MORB‐like mantle source in an oceanic regime. These rocks probably represent remnants of fragmented oceanic crust of the eastern part of Paleo‐Tethys. They were obducted onto the continental crust as part of the ‘Shilu Mélange’ in earliest Mesozoic time when southern Hainan (part of the Indochina block) collided with northern Hainan (part of South China). Alternatively, they could be formed in a volcanic rifted passive margin at the sea‐floor spreading stage as part of MORB‐like seaward‐dipping reflector break‐up packages.
Quaternary reactivation of Tertiary faults in the southeastern Korean Peninsula: Age constraint by optically stimulated luminescence dating
Authors: Ree Jin‐Han , Lee Young‐Joon , Rhodes Ed J. , Park Youngdo , Kwon Sung‐Tack , Chwae Ueechan , Jeon Jeong‐Soo , Lee Bongjoo
Published: March 2003

Abstract  Two groups of Quaternary faults occur in the southeastern Korean Peninsula. The first group is north‐northeast‐striking, high‐angle dextral strike–slip faults. The second group is north‐northeast‐striking, low‐angle reverse faults that represent the reactivation of the pre‐existing normal faults. Optically stimulated luminescence dating of Quaternary sediments cut by one of the reverse faults constrains the faulting age to post‐32 Ka. These faults seem to be capable of further slip under the current tectonic stress regime, as determined by recent earthquake events in northeast Asia. Therefore, the traditional concept that the southeastern Korean Peninsula is seismically stable should be reappraised.
Absence of Archean basement in the South Kunlun Block: Nd‐Sr‐O isotopic evidence from granitoids
Authors: Yuan Chao , Sun Min , Zhou Mei‐Fu , Zhou Hui , Xiao Wenjiao , Li Jiliang
Published: March 2003

Abstract  The West Kunlun mountain range along the northwestern margin of the Tibetan Plateau is crucial in understanding the early tectonic history of the region. It can be divided into the North and South Kunlun Blocks, of which the former is considered to be part of the Tarim Craton, whereas consensus was not reached on the nature and origin of the South Kunlun Block. Samples were collected from the 471 Ma Yirba Pluton, the 405 Ma North Kudi Pluton and the 214 Ma Arkarz Shan Intrusive Complex. These granitoids cover approximately 60% of the Kudi area in the South Kunlun Block. Sr, Nd, and O isotope compositions preclude significant involvement of mantle‐derived magma in the genesis of these granitoids; therefore, they can be used to decipher the nature of lower–mid crust in the area. All samples give Mesoproterozoic Nd model ages (1.1–1.5 Ga) similar to those of the exposed metamorphic complex of this block but significantly different from those of the basement of the North Kunlun Block (2.8 Ga). This indicates that the South Kunlun Block does not have an Archean basement, and, thus, does not support the microcontinent model that suggests the South Kunlun Block was a microcontinent once separated from and later collided back with the North Kunlun Block.
Health‐related quality of life and gastrointestinal disease
Authors: GLISE HANS , WIKLUND INGELA
Published: March 2003

Society is changing rapidly, and new aspects need to be considered when evaluating treatment of disease. Health‐related quality of life (HRQL) is a relatively new addition to the tools clinicians use to gain a better understanding of the impact of disease and its treatment. The questions ‘What is it?’, ‘How it is measured?’ and ‘How can the information be used?’ are now better understood than a few years ago. Generic instruments to capture HRQL enable a broad assessment of a range of aspects and can be used to make comparisons between different patient populations. Irrespective of the choice of instrument, they can classify the influence of different factors, such as gender, age, general health status and disease severity. Health‐related quality of life assessments have been made in many areas of gastroenterology, such as reflux disease, inflammatory bowel disease and irritable bowel syndrome, to describe the burden of illness and the impact of treatment. Health‐related quality of life as a prediction of treatment response is another interesting option. Its ability in the context of surgical intervention and outcomes is also emerging even though more work must be done in this area. Health‐related quality of life evaluations, as an additional tool in the management of patients, are here to stay.
DNA vaccination against hepatitis E virus infection in cynomolgus macaques
Authors: KAMILI SALEEM , SPELBRING JOHN , KRAWCZYNSKI KRZYSZTOF
Published: March 2003

Background
:
The feasibility of DNA vaccination against hepatitis E in non‐human primates has not been evaluated. In the present study a full‐length hepatitis E virus (HEV) open reading frame (ORF)2 (Burmese strain) was assembled, cloned, and used for genetic immunization of cynomolgus macaques (cynos), which were subsequently challenged with a heterologous HEV strain (Mexico).

Methods
:
Four cynos were vaccinated intramuscularly with the HEV ORF2 DNA cassette and one animal was vaccinated with a mock DNA construct.

Results
:
Following vaccination anti‐HEV antibodies were detected in the four HEV‐DNA‐vaccinated cynos, but not in the control animal. When challenged, two of the four HEV‐DNA‐vaccinated cynos were protected against HEV infection and had no elevated alanine aminotransferase activity, viremia, or fecal shedding. The two other DNA‐vaccinated animals developed HEV infection and disease.

Conclusion
:
These findings demonstrate the feasibility of DNA vaccination for the protection of HEV infection and warrant further studies to explore routes other than intramuscular for induction of a stronger and efficacious immune response.

© 2002 Blackwell Publishing Asia Pty Ltd
The effects of a high dose, short course of interferon on hepatitis C
Authors: Nomura Hideyuki , Tsuchiya Yoshihiro , Maruyama Toshihiro , Miki Kouichiro , Yokota Tsutomu , Okubo Hideo
Published: March 2003

To shorten the period of interferon (IFN) treatment for chronic hepatitis C, we investigated the clinical efficacy of a regimen using a higher dose and a shorter treatment period. Fifty chronic hepatitis C patients who were hepatitis C virus (HCV)‐RNA positive and who were histologically diagnosed as having chronic hepatitis, took part in the study. Virus levels were measured before and 2 weeks after starting the treatment. We administered natural IFNα, 10 MU, i.m. daily for 2 consecutive weeks and then three times per week for the subsequent 14 weeks (total dose 560 MU). Patients who were HCV‐RNA negative at the completion of the therapy and 6 months later, were evaluated as sustained responders (SR; 32%). Those who were not HCV‐RNA negative at the two time points were evaluated as non‐responders. Nucleotide and clone differences in the hypervariable region (HVR) and predictive factors for prognosis were also analysed. Low virus level and HCV‐RNA genotype 2a/2b were the predictors for good prognosis, whereas the numbers of nucleotide differences and clone differences in HVR were not. Sustained responder patients became HCV‐RNA negative 2 weeks after starting the treatment at a significantly higher rate, whereas no non‐responder patients were HCV‐RNA negative at that time. The SR rate (32%) was equivalent to those reported in previous 24 week treatment studies. This IFN therapy using a higher dose and a shorter period was useful.
Prevalence of TT virus before and after blood transfusion in patients with chronic liver disease treated surgically for hepatocellular carcinoma
Authors: Kobayashi Masahiro , Chayama Kazuaki , Arase Yasuji , Kobayashi Mizuho , Tsubota Akihito , Suzuki Yoshiyuki , Koida Isao , Saitoh Satoshi , Murashima Naoya , Ikeda Kenji , Koike Hiromi , Hashimoto Michie , Kobayashi Mariko
Published: March 2003

Background: To examine the prevalence of TT virus (TTV) before and after blood transfusion, we retrospectively examined serum samples obtained from 55 patients who received blood transfusions before, during and after resection of hepatocellular carcinoma.

Methods: TT virus DNA was extracted from serum samples and detected by nested polymerase chain reaction. Before transfusion, seven (12.7%) were positive for TTV. Patients were transfused whole blood or separated blood components (fresh frozen plasma, platelet and/or red blood cells), the total amount of transfused fresh frozen plasma ranging from 12 to 271 (median 38) units.

Results: Seven (14.6%) of the 48 TTV‐negative patients became positive for TTV‐DNA 1 month after transfusion. Only one of the seven patients, who was already positive for HCV‐RNA, exhibited elevation of alanine aminotransferase. Five of the newly infected seven patients become negative for TTV during a 2 year follow up.

Conclusions: Our findings suggest that the proportion of patients with TTV was relatively high in this sample, and that the prevalence of TTV transmission by blood components was also relatively high (14.6%). Although TTV persisted for more than 6 months in some patients, infection was not noticeable during the course of chronic liver disease.
Detection of telomerase activity in biopsy samples of colorectal cancer
Authors: Fang Dian‐Chun , Young Joanne , Luo Yuan‐Hui , Lu Rong , Jass Jeremy
Published: March 2003

Background: Telomerase is a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends. The expression of telomerase is thought to be required for cellular immortality and oncogenesis.

Methods: To investigate the role of telomerase in the pathogenesis of colorectal cancer, we analysed telomerase activity in biopsy samples of colorectal cancer and colonic adenomas. Using a polymerase chain reaction‐based assay, we examined telomerase activity in 52 samples of colorectal cancer, 12 colonic adenomas and 30 normal colonic mucosa samples obtained by endoscopic biopsy.

Results: Telomerase activity was detectable in 88.5% (46/52) of colorectal carcinomas, in 50% (6/12) of colonic adenomas but not in normal colorectal mucosa. There was no correlation between telomerase activity and tumour location, type, size and differentiation (P > 0.05).

Conclusions: It was concluded that telomerase activation plays a role in the evolution of colorectal cancer, and that measurement of telomerase activity in biopsied colorectal mucosa samples may provide information both as a diagnostic marker to detect small numbers of cancer cells, and as a screening method for patients at high risk for colorectal carcinoma.
Relationship of hydrolase activities to epithelial cell turnover in distal colonic mucosa of normal rats
Authors: Gibson Peter R , Nov Rien , Fielding Marisa , Mcintyre Ann , Finch Caroline F , Rosella Ourania , Mariadason John M , Barkla David H , Young Graeme P
Published: March 2003

Background
: The relationships between changes induced by diet in colonic epithelial kinetics and in the activities of brush border hydrolases are poorly defined. The aims of this study are to define these relationships, as changes in kinetics would be expected to influence differentiation, and to determine whether the type of ingested dietary indigestible carbohydrates influences hydrolase activities.

Methods
: Groups of eight rats were fed a low fibre diet ± supplements of different types of indigestible carbohydrates for 4 weeks. Alkaline phosphatase (ALP) and dipeptidyl peptidase IV (DPPIV) activities and epithelial kinetics were measured in distal colonic mucosa.

Results
: Median ALP activities correlated positively and DPPIV activity negatively with the median proportion of cells entering metaphase (r = 0.58 and – 0.58, respectively; P < 0.05) and number of metaphase arrests per crypt column across the diets (r = 0.59 and –0.58, respectively; P < 0.05). Stepwise regression analysis showed that both hydrolases independently predicted these kinetic indices (R2 > 63% for each). Mucosal ALP activities were markedly elevated during consumption of raw potato starch, guar gum and methylcellulose, while only potato starch caused a significant elevation of DPPIV activities.

Conclusions
: The type of indigestible carbohydrate in the diet influences colonic mucosal hydrolase activities. The opposite relationship between kinetics and each of the two hydrolases indicates that these hydrolases do not reflect the same event; dipeptidyl peptidase IV might relate to differentiation status while ALP could also be influenced by epithelial irritation due to changes in luminal conditions.
Expression of heparin‐binding epidermal growth factor‐like growth factor in the hepatocytes of fibrotic rat liver during hepatocarcinogenesis
Authors: Kiso Shinichi , Kawata Sumio , Tamura Shinji , Miyagawa Jun‐Ichiro , Ito Nobuyuki , Tsushima Hirofumi , Yamada Akira , Umeki Shinobu , Higashiyama Shigeki , Taniguchi Naoyuki , Matsuzawa Yuji
Published: March 2003

Background
: Heparin‐binding epidermal growth factor‐like growth factor is an hepatotrophic factor expressed in non‐parenchymal liver cells but not in hepatocytes in regenerating rat liver after partial hepatectomy. Human hepatocellular carcinoma cells also produce this growth factor. In this study, the expression of the growth factor in the hepatocytes of fibrotic liver during hepatocarcinogenesis was investigated.

Methods
: Hepatic fibrosis was induced in rats by oral administration of 0.05% thioacetamide. Hepatocytes were isolated by in situ perfusion methods. Growth factor gene and protein expression were investigated by northern hybridization and immunohistochemistry, respectively. Expression of glutathione
S‐transferase P, which is expressed when hepatocytes undergo neoplastic transformation, was also investigated.

Results
: Some hepatocytes in fibrotic liver, but not in normal liver, stained positively by immunohistochemistry for heparin‐binding epidermal growth factor‐like growth factor. The growth factor and glutathione
S‐transferase P gene transcript were present in hepatocytes isolated from fibrotic liver, but not in those isolated from normal liver. Immunohistochemical localization of both proteins in fibrotic liver revealed similar patterns.

Conclusions
: In essence, hepatocytes in fibrotic rat liver produce heparin‐binding epidermal growth factor‐like growth factor. Expression of this growth factor may occur as hepatocytes are transformed to a neoplastic phenotype.

© 1999 Blackwell Science Asia Pty Ltd
Prevalence of non‐ulcer dyspepsia in the Japanese population
Authors: Hirakawa Kazuya , Adachi Kyoichi , Amano Kazutoshi , Katsube Tomoko , Ishihara Shunji , Fukuda Ryo , Yamashita Yukimasa , Shiozawa Shunichi , Watanabe Makoto , Kinoshita Yoshikazu
Published: March 2003

Background
: Non‐ulcer dyspepsia (NUD) is one of the most frequently encountered disorders in general practice in Western countries. The prevalence of this disorder in the Japanese, however, has not been fully investigated. This study is designed to clarify the characteristics and prevalence of dyspepsia in the Japanese.

Methods
: The subjects were 1139 people who visited our institutes for their annual medical check up for gastric cancers. After routine medical examination, all subjects were asked standardized questions in order to check for the presence of any symptoms suggesting dyspepsia.

Results
: The results of the study showed that dysmotility‐like dyspepsia, characterized by the presence of nausea, fullness and early satiety, is the most frequently observed dyspepsia in Japanese and that this type of dyspepsia decreases with age. Ulcer‐like dyspepsia, which is the major type of dyspepsia in Western countries, is the least frequently experienced dyspepsia in the Japanese.

Conclusions
: This study clarified that NUD is also one of the most prevalent disorders in the Japanese, although its characteristics may be somewhat different from those in Western countries.

© 1999 Blackwell Science Asia Pty Ltd