bluuebunny/crossref_metadata_2025 huggingface dataset:
Valency or wählency: Is the epitope diversity of the B‐cell response regulated or chemically determined?
Authors: Mitchell Andrew J , Edwards Michael R , Collins Andrew M
Published: March 2003

For almost a century, the humoral immune response has been monitored principally by the measurement of antibody concentrations, although antibody affinity and isotype have also long been acknowledged as critical to their biological activity. In this report, it is argued that these measures alone may provide a poor measure of the activity of serum antibodies. A B‐cell response that is directed against multiple epitopes on a protein can form immune complexes bearing multiple antibody molecules. This is essential for the efficient initiation of processes such as the complement cascade and the activation of leucocytes via Fc receptors. These processes can be dramatically enhanced when B cells target a greater number of epitopes on any antigen. Evidence that the epitope diversity of an immune response may vary between individuals, and that it may vary in an individual over time, is reviewed. This variability is likely to be influenced by a number of host‐specific factors in addition to antigen chemistry. The appropriateness of the chemically deterministic term ‘antigen valency’ to describe the number of epitopes recognized by an individual's B‐cell response is discussed, and the term ‘wählency’ to emphasize the situational nature of B‐cell epitopes is introduced.
Nuclear RelB+ cells are found in normal lymphoid organs and in peripheral tissue in the context of inflammation, but not under normal resting conditions
Authors: Thompson Angus G , Pettit Allison R , Padmanabha Jagdish , Mansfield Helen , Frazer Ian H , Strutton Geoff M , Thomas Ranjeny
Published: March 2003

Differentiated dendritic cells (DC) have been identified by the presence of nuclear RelB (nRelB) and HLA‐DR, and the absence of CD20 or high levels of CD68, in lymph nodes and active rheumatoid arthritis synovial tissue. The current studies aimed to identify conditions in which nRelB is expressed in human tissues, by single and double immunohistochemistry of formalin‐fixed peripheral and lymphoid tissue. Normal peripheral tissue did not contain nRelB+ cells. nRelB+ DC were located only in T‐ or B‐cell areas of lymphoid tissue associated with normal organs or peripheral tissues, including tonsil, colon, spleen and thymus, or in association with T cells in inflamed peripheral tissue. Inflamed sites included skin delayed‐type hypersensitivity reaction, and a wide range of tissues affected by autoimmune disease. Nuclear RelB+–HLA‐DR− follicular DC were located in B‐cell follicles in lymphoid organs and in lymphoid‐like follicles of some tissues affected by autoimmune disease. Lymphoid tissue T‐cell areas also contained nRelB−–HLA‐DR+ cells, some of which expressed CD123 and/or CD68. Nuclear RelB+ cells are found in normal lymphoid organs and in peripheral tissue in the context of inflammation, but not under normal resting conditions.
Characterization of two TCR transgenic mouse lines specific for herpes simplex virus
Authors: Mueller Scott N , Heath William R , McLain Julie D , Carbone Francis R , Jones Claerwen M
Published: March 2003

To better understand the T cell‐mediated processes involved in the immune response to herpes simplex virus type 1 (HSV‐1) infection, two HSV‐specific T cell receptor (TCR) transgenic mouse lines were produced. These mice (gBT‐I.1 and gBT‐I.3) are MHC class I‐restricted and specific for the immunodominant peptide from HSV glycoprotein B (gB), gB498–505. Although derived from the same clone, the mice differ in the chromosomal location of the TCR transgenes and show marked differences in TCR α/β expression on both CD4+ and CD8+ cells in the thymus. Despite this, peripheral CD8+ T cells from both mice express equally high levels of the transgenic TCR and bind the KbgB498–505 tetramer to the same degree. In concordance with this, both were shown to respond equally well in vitro upon stimulation with the gB498–505 peptide or HSV‐infected cells. These data show that selection of broadly equivalent peripheral T‐cell subsets can occur in the presence of distinctly different thymic T‐cell subsets.
Computational immunology: The coming of age
Authors: Petrovsky Nikolai , Brusic Vladimir
Published: March 2003

The explosive growth in biotechnology combined with major advances in information technology has the potential to radically transform immunology in the postgenomics era. Not only do we now have ready access to vast quantities of existing data, but new data with relevance to immunology are being accumulated at an exponential rate. Resources for computational immunology include biological databases and methods for data extraction, comparison, analysis and interpretation. Publicly accessible biological databases of relevance to immunologists number in the hundreds and are growing daily. The ability to efficiently extract and analyse information from these databases is vital for efficient immunology research. Most importantly, a new generation of computational immunology tools enables modelling of peptide transport by the transporter associated with antigen processing (TAP), modelling of antibody binding sites, identification of allergenic motifs and modelling of T‐cell receptor serial triggering.
Macrophage inflammatory protein‐2 and vascular endothelial growth factor regulate corneal neovascularization induced by infection with Pseudomonas aeruginosa in mice
Authors: Xue Mei‐lang , Thakur Archana , Willcox Mark
Published: March 2003

Pseudomonas aeruginosa ocular infection causes extensive corneal neovascularization. The purpose of the present study was to investigate the role of the angiogenic factors macrophage inflammatory protein‐2 (MIP‐2) and vascular endothelial growth factor (VEGF) in the regulation of corneal neovascularization during P. aeruginosa ocular infection. After administering anti‐MIP‐2 antibody or control antibody, mouse corneas were challenged with P. aeruginosa. The expression of MIP‐2 and VEGF was detected using an ELISA from ocular homogenates. Corneal neovascularization was examined by histology. The cellular sources of MIP‐2 and VEGF were identified by immunohistochemistry. In addition, protein expression of MIP‐2 and VEGF in isolated corneas was measured to determine the ability of the cornea to produce these two mediators. Results showed that the expression of MIP‐2 and VEGF was significantly (P < 0.05) elevated after bacterial infection, and high levels of these two mediators paralleled the extensive corneal neovascularization seen at later stages of the infection. Anti‐MIP‐2 antibody treatment resulted in a significant (P < 0.05) reduction in VEGF expression and in corneal neovascularization. Both corneal resident cells and infiltrating neutrophils had the ability to produce MIP‐2 and VEGF after stimulation. The present study demonstrates that both MIP‐2 and VEGF are important mediators in the regulation of corneal neovascularization caused by P. aeruginosa infection, and that MIP‐2 regulates the production of VEGF.
Interferon‐gamma enhances cytotoxic T lymphocyte recognition of endogenous peptide in keratinocytes without lowering the requirement for surface peptide
Authors: Leggatt Graham R , Dunn Linda A , De kluyver Rachel L , Stewart Trina , Frazer Ian H
Published: March 2003

Keratinocytes expressing the human papillomavirus (HPV) type 16 E7 protein, as a transgene driven by the K14 promoter, form a murine model of HPV‐mediated epithelial cancers in humans. Our previous studies have shown that K14E7 transgenic skin grafts onto syngeneic mice are not susceptible to immune destruction despite the demonstrated presence of a strong, systemic CTL response directed against the E7 protein. Consistent with this finding, we now show that cultured, E7 transgenic keratinocytes (KC) express comparable endogenous levels of E7 protein to a range of CTL‐sensitive E7‐expressing cell lines but are not susceptible to CTL‐mediated lysis in vitro. E7 transgenic and non‐transgenic KC are susceptible to conventional mechanisms of CTL‐mediated lysis, including perforin and Fas/FasL interaction when an excess of exogenous peptide is provided. The concentration of exogenous peptide required to render a cell susceptible to lysis was similar between KC and other conventional CTL targets (e.g. EL‐4), despite large differences in H‐2Db expression at the cell surface. Furthermore, exposure of KC to IFN‐γ increased H‐2Db expression, but did not substantially alter the exogenous peptide concentration required to sensitize cells for half maximal lysis. In contrast, the lytic sensitivity of transgenic KC expressing endogenous E7 is modestly improved by exposure to IFN‐γ. Thus, failure of CTL to eliminate KC expressing endogenous E7, and by inference squamous tumours expressing E7, may reflect the need for a sustained, local inflammatory environment during the immune effector phase.
TNF contributes to the immunopathology of perforin/Fas ligand double deficiency
Authors: Cretney Erika , Street Shayna EA , Smyth Mark J
Published: March 2003

Perforin (pfp)/Fas ligand (FasL) double‐deficient mice have previously been shown to be infertile, lose weight and die prematurely due to tissue destruction caused by a significant inflammatory infiltrate of monocytes/macrophages and T cells. Herein we have compared disease progression in mice additionally deficient in the inflammatory mediator TNF. Unlike pfp/FasL double‐deficient mice (TNF+/+ pfp−/− gld), mice lacking functional TNF, FasL and pfp (TNF−/− pfp−/− gld) were comparatively fertile, with the majority of mice not suffering severe pancreatitis or hysterosalphingitis in the first 5 months of life. The mean lifespan of TNF−/− pfp−/− gld mice was 217 ± 79 days compared with 69 ± 10 days for TNF+/+ pfp−/− gld mice and the majority of moribund TNF−/− pfp−/− gld mice appeared to die as a result of severe pancreatitis, suggesting that loss of TNF was not completely protective. At 8 weeks of age, characteristics associated with the gld phenotype, such as expansion of B220+ CD4− CD8− T cells, lymphadenopathy and hypergammaglobulinemia were comparable between TNF+/+ pfp−/− gld and TNF−/− pfp−/− gld mice, although the lymphoid organs of TNF+/+ pfp−/− gld mice contained greater numbers of B220+ CD4− CD8− T cells, macrophages and T cells. We conclude that TNF is necessary for the full manifestation of immune dysregulation caused by pfp/FasL‐deficiency, in particular in the early and overwhelming tissue infiltration and destruction caused by inflammatory cells.
The role of dendritic cell subsets in selection between tolerance and immunity
Authors: Belz Gabrielle T , Heath William R , Carbone Francis R
Published: March 2003

Dendritic cells (DC) are considered nature's adjuvants. They are potent stimulators of naive T cells and key inducers of primary immune responses. In recent times it has become clear that they can also play a central role in the development of T cell tolerance. Further complicating our understanding of DC function is the realization that DC can no longer be viewed as a homogeneous cell type. Rather, they exist as a complex mixture of strikingly different cell populations. The mechanisms that drive the conflicting immunological outcomes of tolerance and immunity have been the subject of intense scrutiny in recent years, most recently in terms of how the various DC subsets are involved in these events. Here we review recent experiments that provide insights into how DC subsets control the outcome of T cell activation and in so doing select between immunity and tolerance induction.
Up‐regulation of production of TGF‐β and IL‐4 and down‐regulation of IL‐6 by apoptotic human bronchial epithelial cells
Authors: Hodge Sandra , Hodge Greg , Flower Robert , Reynolds Paul N , Scicchitano Raffaele , Holmes Mark
Published: March 2003

Human bronchial epithelial cells secrete cytokines that play a role in immune responses in the lung. However, the roles of these cytokines in regulating epithelial repair following acute lung injury are largely unknown. Responses to injury include hyperplasia of epithelial cells and squamous metaplasia. The resolution stage is characterized by discontinuation of hyperplasia. Apoptosis is considered to be the most efficient mechanism of removal of unwanted cells without causing inflammation. The presence of TGF‐β1 increases apoptosis, induces squamous metaplasia and inhibits proliferation of airway epithelial cells. Interleukin‐4 increases the ability of macrophages to phagocytose epithelial cells and produce inflammatory cytokines. The purpose of this study was to investigate the hypothesis that apoptotic lung epithelial cells produce cytokines, which could act in an autocrine manner to control hyperplasia and induce squamous differentiation following acute lung injury. A bronchial epithelial cell line (16 HBE) was used as an in vitro model, to study the production of TGF‐β, IL‐4 and IL‐6 by lung epithelial cells undergoing apoptosis. Apoptotic and live cells were sorted on the basis of bright and negative staining with FITC‐conjugated Annexin V, respectively. Intracellular IL‐6, TGF‐β and IL‐4 was measured using flow cytometric techniques. Electron microscopy, immunohistochemistry and ELISA were used as supportive techniques. Apoptotic cells produced significantly more TGF‐β and IL‐4 (but less IL‐6) than viable cells. Increased production of TGF‐β and IL‐4 by epithelial cells undergoing apoptosis may contribute to the inhibition of proliferation, squamous metaplasia, and reduction of the inflammatory response in acute lung injury.
Reviews of units of care: Combining practice, research and quality assurance
Authors: FitzGerald Mary , Hill Anne , Mann Rosemary , Turrell Susan
Published: March 2003

Fitzgerald M, Hill A, Mann R, Turrell S. International Journal of Nursing Practice 1998; 4: 134–141

Reviews of units of care: Combining practice, research and quality assurance

That nurses should base their practice on the best available knowledge is generally accepted by the profession. However, the operationalisation of this ideal is difficult for hard pressed clinicians. We believe that responsibility for assimilating current knowledge in a practical format belongs to all nurses working in an organisation. This paper describes a project where clinicians, administrators and academics have collaborated to rewrite standards of practice in a format that includes up to date evidence and practical measures for appraising outcomes. This work is a practical example of quality assurance activities serving to create opportunities for collaboration between nurses who have chosen to practice, teach, manage and/or research nursing.
Chinese husbands’ presence during labour: A preliminary study in Hong Kong
Authors: Ip Wan Yim
Published: March 2003

This study compares the childbirth outcomes of women whose husbands were present during labour with those whose husbands were absent. A retrospective comparative design was used. Sixty‐three Hong Kong Chinese primigravid mothers recruited from childbirth education classes were allocated to one of two groups: those whose husband attended labour (n = 45) and those whose husband was not in attendance (n = 18). Details of demographic characteristics, maternal history and antenatal attendance were obtained along with obstetric measures of maternal anxiety, pain perception, dosage of analgesia used, and length of labour. The results indicated that women whose husbands were present during labour used significantly higher dosage of analgesia than those whose husbands were absent. No significant differences were found between groups in other outcome measures. The researcher concluded that nurse‐midwives in Hong Kong need to find ways to help husbands provide the type of support that may help their partners during labour.
Documenting and communicating patient care: Are nursing care plans redundant?
Authors: Rn Bev O'connell , Rn Helen Myers , Rn Di Twigg , Rn Fiona Entriken
Published: March 2003

In Australia, nursing care plans have been the predominant means of documenting and communicating patient care. After 30 years of use, there is growing criticism from nurse clinicians and academics about the clinical utility of nursing care plans. A group of expert nurses at a major teaching hospital initiated a structured evaluation project that evaluated the clinical utility of nursing care plans and clinical protocols. The care plans and protocols were evaluated using a questionnaire that asked nurses to rate the care plans and clinical protocols on 10 measures, using a four‐point Likert scale. The responses from the questionnaire indicated ongoing problems with the use of the care plans and a strong acceptance of the use of clinical protocols. Within this context, one could ask the question, are nursing care plans redundant?
From bedside nursing to managerial roles: Changing occupational perceptions of nursing students
Authors: Yagil Dana , Spitzer Ada , Ben‐Zur Hasida
Published: March 2003

This longitudinal study examined changes in the occupational perceptions of nursing students studying in a non‐traditional undergraduate nursing program. The respondents, 210 first‐ and second‐year nursing students, completed a questionnaire measuring the perceived importance of traditional and non‐traditional nursing interventions and values. Questionnaires were administered at the beginning and at the end of the academic year. Students studying in a more traditional program comprised the control group. The results show that certain traditional nursing activities and values are perceived as more important by first‐year students compared with second‐year students in both programs, whereas the perceived importance of non‐traditional activities is higher among second‐year students. The preference for non‐traditional interventions is stronger among students in the non‐traditional nursing program. The results are discussed with regard to the gradual effect of nursing education on students' occupational perceptions.
Service to the poor: The foundations of community nursing in England, Ireland and New South Wales
Authors: Francis Karen
Published: March 2003

This paper describes the foundations of community nursing in England, Ireland and New South Wales. It is guided by Foucault’s work on power, discourse and knowledge, and argues that the common discourse of poverty coupled with the influence of socially advantaged women in the nineteenth century was the impetus for the development of community nursing in England, Ireland and New South Wales. Throughout the nineteenth century in Great Britain, economic and industrial development, coupled with an unprecedented growth in the population (particularly among the poor) inspired socially advantaged women to extend traditional gender‐specific roles to address the needs of the poor. Protestant women in England advanced professional nursing as a career for women and in Ireland and New South Wales; Catholic women pioneered professional nursing, targeting the poor as the focus of their practice. These women used prevailing social conditions to enhance their life options within the limits prescribed by social norms.
Elderly residents’ participation and autonomy within a geriatric ward in a public institution
Authors: Barkay Aliza , Tabak Nili
Published: March 2003

In this study the importance of the concept of autonomy among residents in geriatric institutions was investigated. By granting the residents more autonomy, their satisfaction increased, their daily routine changed, and their participation in social activity increased. Correlation was found between the degree of autonomy and the degree of the participation in different activities within the ward. The conclusion reached is that the residents’ quality of life improves with more autonomy within the institution's framework.
Phase relations and P–T conditions of the Ryoke pelitic and psammitic metamorphic rocks in the Ina district, Central Japan
Authors: Tokada Tomokazu
Published: March 2003

The Ina district of the Ryoke Belt is divided into two mineral zones, based on the mineral parageneses of the pelitic and psammitic rocks at the peak metamorphism. A biotite–muscovite zone (quartz + plagioclase + biotite + muscovite with or without K‐feldspar) constitutes the northwestern part, and a biotite–cordierite–K‐feldspar zone (quartz + plagioclase + biotite + cordierite + K‐feldspar) comprises the central to southern and eastern parts. The isograd reaction between two mineral zones is defined by a divariant reaction: Mg‐rich biotite + muscovite + quartz = Fe‐rich biotite + cordierite + K‐feldspar + H2O (1), which, in the K2O–FeO–MgO–Al2O3–SiO2–H2O (KFMASH) system, occurs at ∼ 590 °C at 0.2 GPa and 660 °C at 0.4 GPa. Fibrolite accompanied by andalusite porphyroblasts in aluminous pelitic rocks of the biotite–muscovite zone and the low‐grade part of the biotite–cordierite–K‐feldspar zone, suggests that sillimanite was the stable aluminosilicate at the peak metamorphic condition throughout the area. In the high‐grade part of the biotite–cordierite–K‐feldspar zone, fibrolite mostly occurs as inclusions in cordierite or in plagioclase. The phase relations and the compositional zoning of plagioclase in relation to fibrolite inclusions suggest that fibrolite was formed under relatively high‐pressure conditions, and that partial melting took place.
Prograde P–T path of kyanite eclogites from Junan in the Sulu ultrahigh‐pressure province, eastern China
Authors: Ebanu M , Nagasaki A
Published: March 2003

Kyanite‐bearing ultrahigh‐pressure (UHP) eclogites occur as blocks in orthogneisses at Yangzhuang, in the Junan area of the southwestern Sulu province, eastern China. Eclogites have variable bulk rock compositions, with Al2O3 = 16–27 wt%, FeO* + MgO = 6–22 wt% and CaO = 9–13 wt%. Major minerals are garnet, omphacite, phengitic white mica, zoisite, kyanite, rutile and an SiO2 phase. Fe‐rich staurolite (Mg ⇒ Mg# = 0.24 ± 0.01) and paragonite–margarite aggregates are rarely included in the cores of prograde zoned garnet. Metamorphic conditions ranged from 520 to 650°C and <1.4 GPa at an early prograde stage, and mostly reached 660–830°C and 2.7–3.5 GPa at the peak UHP stage. The estimated dP/dT of the prograde P–T path is less than 0.25 GPa/100°C at earlier stages and increases to 0.7–1.4 GPa/100°C just before the UHP stage. The kink of the prograde P–T path closely resembles the steady‐state P–T paths proposed, assuming a two‐parameter brittle‐plastic shear stress model. The estimated P–T path adequately explains the absence of prograde lawsonite and sodic amphibole and the common occurrence of coexisting zoisite, kyanite and sodic‐calcic amphibole in the UHP eclogites throughout the Sulu province. Simple clockwise prograde P–T paths for Sulu UHP eclogites proposed in earlier studies should be carefully re‐examined.
Recycling in the Puerto Rican mantle wedge, Greater Antilles Island Arc
Authors: Jolly Wayne T. , Lidiak Edward G. , Dickin Alan P. , Wu Tsai‐Way
Published: March 2003

Abstract The initial volcanic phase of Cretaceous island arc strata in central Puerto Rico, at the eastern end of the extinct Greater Antilles Arc, comprises a 6‐km thick pile of lava and volcanic breccia (Río Majada Group). Preserved within the sequence is a conspicuous shift in absolute abundances of the more incompatible elements, including Th, Nb, and the light rare earth elements (LREE: La, Ce, Pr and Nd). The compositional shift is marked by a decrease in La/Sm from averages of 2.11 in the lowest third of the pile (Formation A) to 1.48 at the top (Formation C), and by a distinctive flattening of LREE segments of chondrite‐normalized REE patterns. i87Sr/86Sr and ɛNd average about 0.7035 and 8.2, respectively, in early Formation A basalts. These ranges normally overlap samples from later Formations B and C. Isotope compositions of the latter group are more variable, however, and several samples are considerably more radiogenic than Formation A basalts, such that i87Sr/86Sr averages almost 0.7042 while ɛNd‐values decrease to 7.5 in Formation B and C basalts. Theoretical models of non‐modal melting processes in both amphibole peridotite and spinel lherzolite sources provide insight into the origin of depleted Th, Nb, and LREE abundances in Puerto Rican basalts. Low Nb concentrations less than normal mid‐oceanic ridge basalts in Formation A basalts indicate the wedge was slightly depleted by low‐volume decompression fusion due to induced convection in the back‐arc region prior to entry of the source into the arc melting zone. However, depleted patterns in Formation C basalts cannot be generated by relatively greater degrees of decompression fusion in the back‐arc, because addition of the La‐enriched slab‐derived component to more depleted source material invariably produces elevated rather than decreased La/Sm. Refluxing of Formation A harzburgitic residua is similarly precluded. In contrast, the observed patterns are readily reproduced by multistage melting models involving hybridized sources containing normal Formation A lherzolite source material blended with recycled, unrefluxed harzburgite residua. Successful models require hybrid sources containing large volumes of recycled harzburgite (up to 50%) during generation of Formation C basalts. Slightly elevated radiometric Sr and Nd isotopes in a few flows from Formation C are attributed to partial refluxing of the hybrid sources within the wedge.
Tyatya Volcano, southwestern Kuril arc: Recent eruptive activity inferred from widespread tephra
Authors: NAKAGAWA MITSUHIRO , ISHIZUKA YOSHIHIRO , KUDO TAKASHI , YOSHIMOTO MITSUHIRO , HIROSE WATARU , ISHIZAKI YOSHIO , GOUCHI NOBUO , KATSUI YOSHIO , SOLOVYOW ALEXANDER W. , STEINBERG GENRIKH S. , ABDURAKHMANOV ARSLAN I.
Published: March 2003

Abstract  Tyatya Volcano, situated in Kunashir Island at the southwestern end of Kuril Islands, is a large composite stratovolcano and one of the most active volcanoes in the Kuril arc. The volcanic edifice can be divided into the old and the young ones, which are composed of rocks of distinct magma types, low‐ and medium‐K series, respectively. The young volcano has a summit caldera with a central cone. Recent eruptions have occurred at the central cone and at the flank vents of the young volcano. We found several distal ash layers at the volcano and identified their ages and sources, that is, tephras of ad 1856, ad 1739, ad 1694 and ca 1 Ka derived from three volcanoes of Hokkaido, Japan, and caad 969 from Baitoushan Volcano of China/North Korea. These could provide good time markers to reveal the eruptive history of the central cone, which had continued intermittently with Strombolian eruptions and lava flow effusions since before 1 Ka. Relatively explosive eruptions have occurred three times at the cone during the past 1000 years. We revealed that, topographically, the youngest lava flows from the cone are covered not by the tephra of ad 1739 but by that of ad 1856. This evidence, together with a report of dense smoke rising from the summit in ad 1812, suggests that the latest major eruption with lava effusion from the central cone occurred in this year. In 1973, after a long period of dormancy, short‐lived phreatomagmatic eruptions began to occur from fissure vents at the northern flank of the young volcano. This was followed by large eruptions of Strombolian to sub‐Plinian types occurring from several craters at the southern flank. The 1973 activity is evaluated as Volcanic Explosivity Index = 4 (approximately 0.2 km3), the largest eruption during the 20th century in the southwestern Kuril arc. The rocks of the central cone are strongly porphyritic basalt and basaltic andesite, whereas the 1973 scoria is aphyric basalt, suggesting that magma feeding systems are definitely different between the summit and flank eruptions.
BRIEF COMMUNICATION: Efficacy of ribavirin plus interferon α on viraemia of GB virus‐C/hepatitis G virus: Comparison with interferon α alone
Authors: KAO JIA‐HORNG , LAI MING‐YANG , CHEN WENDY , CHEN PEI‐JER , CHEN DING‐SHINN
Published: March 2003

We investigated the efficacy of ribavirin plus interferon (IFN) α on GB virus‐C (GBV‐C)/hepatitis G virus (HGV) viraemia and compared it with that of interferon α alone in patients coinfected with hepatitis C virus (HCV) and GBV‐C/HGV. Serum HCV and GBV‐C/HGV‐RNA were studied in eight patients with HCV and GBV‐C/HGV coinfection, five received IFNα and three received oral ribavirin plus IFNα. Mean serum GBV‐C/HGV titre at the end of therapy was significantly lower than the titre just before therapy and patients with lower pretreatment titre had a better sustained response rate. Sustained virological response of GBV‐C/HGV to IFNα alone and ribavirin plus IFNα at the end of follow up was observed in one each, respectively. Thus, GBV‐C/HGV in patients with HCV and GBV‐C/HGV coinfection does respond to IFNα and ribavirin plus IFNα may not induce a higher sustained response.
Does steatohepatitis impair liver regeneration? A study in a dietary model of non‐alcoholic steatohepatitis in rats
Authors: Zhang Bao‐Hong , Weltman Martin , Farrell Geoffrey
Published: March 2003

Background: Impaired liver regeneration is a feature of alcoholic hepatitis, but the relative importance of alcohol, nutritional imbalance and inflammatory mediators in causing this effect is unclear. Non‐alcoholic steatohepatitis (NASH) is a form of liver disease with similar morphology to alcoholic hepatitis, but the effect of this disorder on liver regeneration is unclear. We, therefore, examined the status of liver regeneration in a rat nutritional model of hepatic steatosis with inflammation, which is morphologically identical to NASH in humans.

Methods: Male Wistar rats received a methionine–choline‐deficient diet (MCDD) for 4 weeks before experiments and both isocaloric pair‐fed and ad libitum‐fed rats were used as controls. Following partial hepatectomy (68%), the extent of hepatic regeneration was determined 24 h later using [3H]‐thymidine incorporation and restitution of liver mass.

Results: There was no significant difference of [3H]‐thymidine incorporation in MCDD‐fed, pair‐fed and ad libitum‐fed rats (80 ± 27, 78 ± 11 and 80 ± 6.3 d.p.m./μg DNA, respectively). Similarly, restituted liver masses in three groups of rats were not significantly different (17 ± 3.8, 18 ± 1.8 and 17 ± 3.1% initial liver weight, respectively).

Conclusions: The similarities in hepatic histology and cytochrome P450 2E1 induction between this nutritional model of hepatic steatohepatitis and alcoholic steatohepatitis imply that these two disorders share pathogenetic mechanisms. However, liver regeneration is not altered by NASH in rats, indicating that the nutritional and inflammatory changes that appear similar to those of alcoholic liver disease do not cause impairment of liver regeneration.
Carcinoma of the gall‐bladder
Authors: Kyriacou E
Published: March 2003

Carcinoma of the gall‐bladder remains the fifth commonest gastrointestinal malignancy. Its associations, predisposing factors and epidemiology worldwide are reviewed in this article. The clinical presentation of carcinoma of the gall‐bladder is frequently late, which accounts for the poor prognosis: this is also discussed. The use of relevant imaging techniques and aggressive management offer an improved outlook. These important aspects and others, such as the use of frozen section histology, the risks of trocar seeding and inadequate resection are mentioned.
Primary sclerosing cholangitis in children
Authors: Roberts Eve
Published: March 2003

Abstract Primary sclerosing cholangitis (PSC), a chronic inflammatory process affecting the extrahepatic and/or medium to large bile ducts, is not rare in children. It has features suggesting an autoimmune pathogenesis, although the mechanism of tissue damage remains unknown. The clinical presentation of childhood primary sclerosing cholangitis is highly variable and frequently without obvious features of cholestasis. Clinical similarity to autoimmune hepatitis is common. Association with chronic colitis is less common than in adults. Cholangiography is essential for the diagnosis and examination of the medium to large intrahepatic ducts is mandatory, as 40% of children lack extrahepatic duct involvement. Histological findings may help to distinguish childhood PSC from autoimmune hepatitis. In children, sclerosing cholangitis may also develop secondary to other disease processes, notably Langerhans histiocytosis, congenital immunodeficiencies and cystic fibrosis. Neonatal sclerosing cholangitis is chronic inflammatory disease of bile ducts which presents initially with neonatal cholestasis; its pathogenesis remains uncertain and may not be the same as for primary sclerosing cholangitis. Effective treatment modalities for childhood PSC remain undetermined. Liver transplantation is required for children who progress to biliary cirrhosis and hepatic decompensation.

© 1999 Blackwell Science Asia Pty Ltd
CASE REPORT: Inappropriate use of percutaneous drainage in the management of pancreatic necrosis
Authors: Kam Anthony , Young Noel , Markson Gregory , Wong Kai Ping , Brancatisano Roy
Published: March 2003

We describe three cases of severe necrotizing pancreatitis, with Apache II scores of 11, 17 and 22, respectively. There was no significant pancreatic parenchymal perfusion in any of the three patients on contrast‐enhanced computed tomography. All three patients were primarily treated with percutaneous drains and all three subsequently required open laparotomies. We do not recommend percutaneous drainage as a definitive therapy for severe necrotizing pancreatitis.
Effect of rotavirus infection on small gut pathophysiology in a mouse model
Authors: Katyal Ranjan , Rana Satyawati V , Vaiphei Kim , Ohja Sudarshan , Singh Kartar , Singh Virendra
Published: March 2003

Aim
: To study the effect of rotavirus infection on amino acid uptake in the small intestine in an experimental mouse model.

Methods
: Infant mice (7–8 days of age) were orally infected with the EB serotype 3 strain of rotavirus and animals (both infected and control) were killed on days 0, 1, 3, 5, 7 and 10 post inoculation (PI) after recording their bodyweights. Gamma‐glutamyltranspeptidase (GGT), leucine amino peptidase (LAP), glutathione (GSH) and leucine amino acid uptake in the jejunum and ileum were assessed.

Results
: Infected animals showed significant reduction in their bodyweights and intestinal lengths on the third day PI compared with controls. Leucine amino peptidase, GGT, GSH and leucine uptake were significantly reduced in the ileum on the third and fifth day PI compared with controls while uptake in the jejunum was only reduced on third day PI. The LAP, GGTP, GSH and leucine uptake attained normal levels on the seventh day when diarrhoea stopped. Histology showed damage to the villi in the jejunum and prominent cytoplasmic vacuolation in the ileum of infected animals on the third and fifth day PI.

Conclusion
: Rotavirus affects amino acid uptake in the small intestine at the time of peak infection.
Manifestations of hypercholesterolaemia, hypoglycaemia, erythrocytosis and hypercalcaemia in patients with hepatocellular carcinoma: Report of two cases
Authors: Chu Chen‐Wei , Hwang Shinn‐Jang , Luo Jiing‐Chyuan , Tsay Shyh‐Haw , Li Chung‐Pin , Chang Full‐Young , Lee Shou‐Dong , Lui Wing‐Yiu , Chiang Jen‐Huey
Published: March 2003

Background
: Hypercholesterolaemia, hypoglycaemia, hypercalcaemia and erythrocytosis, are well‐known paraneoplastic manifestations in patients with hepatocellular carcinoma (HCC). Hepatocellular carcinoma patients manifesting with two or three paraneoplastic manifestations have been previously reported. However, HCC patients presenting with four paraneoplastic syndromes have not been previously reported.

Methods and Results
: This manuscript describes two HCC patients who manifested with hypercholesterolaemia, hypoglycaemia, hypercalcaemia and erythrocytosis during their clinical course. Erythrocytosis appeared early when HCC was diagnosed and declined to within normal range after optimal therapy for HCC. Hypercholesterolaemia manifested initially after the diagnosis in case 1, declined to within normal range after lobectomy and was re‐elevated after tumour recurred. With disease progression, hypercalcaemia and hypoglycaemia occurred 1–3 months after diagnosis and the both patients subsequently died several days later.

Conclusions
: Similar features found in both patients were large tumour burden, high serum alpha‐fetoprotein level and rapid downhill clinical course even with optimal therapy. The clinical significance of these paraneoplastic manifestations is discussed.
Effect of butyrate on paracellular permeability in rat distal colonic mucosa ex vivo
Authors: Mariadason John M , Kilias Diana , Catto‐Smith Anthony , Gibson Peter R
Published: March 2003

Background and Aims
: The effects of butyrate on colonic epithelial barrier function are poorly understood. The aim of this study was to examine the short‐term effects of butyrate on paracellular permeability of rat distal colonic epithelium.

Methods
: Mucosa mounted in Ussing chambers was treated with butyrate (1–10 mmol/L) for 4 h. Transepithelial conductance, [51Cr]‐EDTA flux, mucosal brush border hydrolase activity and epithelial kinetics, using proliferating cell nuclear antigen (PCNA) staining, were measured.

Results
: On exposure to butyrate (10 mmol/L, but not 1 or 5 mmol/L), transepithelial conductance was 65 ± 2% higher (mean ± SEM; n = 8, P < 0.05, paired t‐test) and the rate coefficient for [51Cr]‐EDTA flux was 65 ± 25% higher (P = 0.03) than those of control tissue. Histologically, the epithelium exhibited no signs of injury, but butyrate‐treated tissue exhibited interstitial oedema consistent with water uptake in association with butyrate absorption. Butyrate caused a reduction in crypt column height to 30.6 ± 1.6 cells from 33.4 ± 1.8 cells in controls (n = 10, P < 0.03), but the number of cells per crypt column staining with PCNA was unchanged. Butyrate significantly reduced the mucosal activities of alkaline phosphatase by 40 ± 16%, maltase by 54 ± 12% and dipeptidyl peptidase IV by 41 ± 14%.

Conclusions
: Acute exposure to butyrate increased paracellular permeability in rat distal colon. The mechanism involved may relate to the loss of differentiated surface epithelial cells, or as a physiological response to Na+‐coupled butyrate uptake.
PREVALENCES OF HELICOBACTER PYLORI AMONG NSAID USERS AND NON USERS
Authors: Djumhana  , Hadi S , Abdurachman SA , Widjojo J , Saketi JR
Published: March 2003

Background:

The main etiology of gastroduodenal ulcer are NSAID and Hp. The role if Hp infection to the patients who use NSAID is still controversy. We compare the prevalence of Hp infection among ulcer and non ulcer patients in those who used NSAID and who didn’t use.

Material & Methods:

A retrospective study had been done from 1995 ‐ 1988 to 248 patients who were proven to have ulcer and non ulcer by endoscopic examination. Infection of Hp was tested by CLO and histopathology. Base on the history of NSAID consumption, the patients were divided into NSAID users group and non users group.

Result:

Between 1995 and 1998, 248 patients were studied, they consisted of 95 ulcer patients (50 GU, 40DU, 5 GU+DU) and 163 non ulcer patients. Age ranged from 16‐78 years old. The median age of GU;DU and NU wee 61;49 and 44 yrs respectively. Among 95 ulcer patients, 67.4% were NSAID user and 32.6% were non users, the prevalence of Hp among NSAID users and non users were 20.3% and 81.7% respectively (p<0.01).Among 163 non ulcer patients 36.8% were NSAID users and 63.2% were non users, the prevalence of Hp among NSAID users and non users were 33.1% and 60.2% respectively (p<0.05). Ninety percent of 50 GU patients were NSAID users, the prevalence of Hp among them was 11.1%. The prevalence of Hp among GU patients who didnít use NSAID was 4/5(80%). Among 40 patients with DU,35% were NSAID users and 65% were non users, the prevalence of Hp among users and non users were 42.9% and 92.3% respectively (p<0.01). All patients with GU+DU were NSAID users, 40% of them had Hp positive.

Conclusion:

The prevalence of Hp among NSAID users was lower than non users. In NSAID users group who had ulcer the prevalence of Hp was lower than those who had non ulcer. This finding support that Hp infection may not increase the risk of ulcer in patient who use NSAID.
ENDOSCOPIC AND HISTOPATHOLOGIC PICTURE OF GASTRIC MUCOSA WITH HELICOBACTER PYLORI INFECTION
Authors: B Marpaung , Hakim Zain Lukman , P Tarigan , S Pardede , G Tambunan
Published: March 2003

Background

Helicobacter pylori (HP) can colonise beneath layer of mucous on the surface of gastric epithelial cells caused chronic infection more than 95% at antrum (chronic antral inflamation) besides corpus with spreading inequitably. This inflamation can cause gastric lession as a Gastritis, Gastric Ulcer (GU), Cancer of Duodenal Ulcer (DU). Absence of chronic antral inflamation (increased number of mononuclear cells in lamina propia) is a highly specific methode to exclude H. pylori infection.

Objective

To investigated endoscopic mucosal lesion (Gastritis, GU, Cancer or DU) and histologic picture of gastric mucosal H. pylori infection.

Methods

This study was performed in 50 patient with gastroscopic lesion (Gastritis, GU,Cancer or DU) and CLO test positive. H. pylori was evaluated by modified Giemsa staining and gastritis by Haemotoxiline and eosin (H and E) staining in the antrum and corpus.

Result

Reported in The Third Western Pasific Helicobacter Congress, June 22‐24 Bali Indonesia.
CORRELATION OF GASTRIC INTESTINAL METAPLASIA AND HELICOBACTER PYLORI INFECTION AMONG FUNCTIONAL DYSPEPTIC PATIENTS
Authors: Abdullah Murdani , Rani A Aziz
Published: March 2003

Background:

It is generally accepted that intestinal metaplasia (IM) is a pre cursor of gastric cancer and is associated with Helicobacter pylori (Hp) infection. But still little data available about association of IM and Hp in different clinical groups of patients, especially in areas with high Hp prevalence.

Aim:

to evaluate the IM and itís correlation with Hp infection in consecutive patients with functional dyspepsia (FD).

Methods:

a retrospective review of our endoscopy database and histological data from January 1997 to December 1999 was made. In this period we performed 3083 upper intestinal endoscopy in patients with FD. Endoscopy procedure was done without any specific preparation for Hp evaluation. Biopsy specimen were taken from antrum and corpus and were stained with Giemsa, H&E and Alcian Blue. Histological data was evaluated by pathologist from Department of Pathology, Medical Faculty, University of Indonesia according to the Sydney System. IM was evaluated as present or absent. One hundred and fourteen consecutive data were eligible for statistical analysis.

Results:

Histological data of 114 patients with FD was analyzed. Average age was 45.47 years (SD 14.32), male 62.3 % (71/114), and female 37.7 % (43/114). Forty‐eight (42.11%) patients with FD were Hp positive on histology and were significantly older than Hp negative. (48.74 +12.65/43.25+15.04; p < 0.05). IM was present in 13 ( 11.4%) patients with FD. They were significantly older than the patients without IM (mean age 55.08+11.98/44.23+14.18; p <0.05) Frequency of IM was similar both in Hp positive and Hp negative patients with FD (12.5%/10.6%; p>0.05).

Conclusions:

IM among patients with FD was 11.4%. IM was significantly more frequent found in older age but our data suggest that IM is not related to Hp status in FD patients.
ORAL THERAPEUTIC IMMUNIZATION WITH EXTRACT OF HELICOBACTER MURIDARUM AND CHOLERA TOXIN SUB UNIT B FOR ERADICATION OF HELICOBACTER PYLORI IN INFECTED MICE
Authors: Wibawa I D.n , Suata K. , Mulyadi K. , S Suwigyo
Published: March 2003

Objective

Helicobacter muridarum is one of specific spiral bacterial that inhabits stomach and intestine of mice and rats. Microbiologically this pathogen was almost similar with Helicobacter pylori. This research was the first experimental study in oral therapeutic immunization for eradication of Helicobacter pylori on infected mice by using the extract of Helicobacter muridarum with cholera toxin sub unit B.

Material & Method

Mice were divided into three different group of treatment. The first group consist of 12 mice received therapeutic oral immunization with Helicobacter muridarum bacterial protein and cholera toxin sub unit B (CT+Ag). The second group consist of 12 mice received the same treatment with cholera toxin sub unit B (CT). The third group consist of 5 mice as control without vaccination.

Result

Of 12 mice known to have Helicobacter pylori infection and received immunization with 250 μg extract to Helicobacter muridarum in combination with 10 μg cholera toxin sub unit B, the eradication rate on day‐7, 14, and 21post immunization were 2 (16.7%), 3 (25%), and 5 (41.7%) mice, respectively. One week after the third immunization, of 12 mice that received the first treatment (CT+Ag) we found 7 (58.34%) mice were eradicated. From 12 mice vaccinated with cholera toxin sub unit B (CT), at day‐7, 14, and 21 post immunization there were 0 (0%), 1 (8.4%), and 2 (18.19%) mice showed negative faecal culture for Helicobacter pylori. However, in untreated control group all showed positive faecal culture for Helicobacter pylori throughout the experiment. The immune response serologically proved by the increase of IgG anti‐Helicobacter muridarum titre that statistically significant difference among treated group after the second week of the experiment.

Conclusion

Results of this study suggest that oral therapeutic immunization using extract of Helicobacter muridarum combined with cholera toxin sub unit B eradicated 58.34% mice infected by Helicobacter pylori. The successful of this oral therapeutic immunization showed cross immune reaction between Helicobacter muridarum and Helicobacter pylori.
CHARACTERISTIC OF GASTRIC CANCER IN INDONESIA: THE ROLE OF HELICOBACTER PYLORI INFECTION
Authors: Abdullah Murdani , Rani A Aziz , Daldiyono
Published: March 2003

Background

Gastric cancer is the second most common fatal malignancy in the world. In 1996, approximately one million new cases of gastric cancer were found. It is generally agreed that the pathogenesis is multifactorial which may include, dietary factors, environmental factors, bacterial and viral infections.

Aim

to evaluate the frequent of gastric cancer in Indonesia and itís relating factors.

Methods

A sample size of 7902 subjects were determined based on hospital data of dyspeptic patients following gastroduodenoscopy procedure from January 1997 to September 1999. Patients were recruited from 9 endoscopic centers located in 5 cities in Indonesia. Endoscopic biopsy specimens were taken 2 specimens from the antrum (2 cm from pylorus) and 2 specimens from the corpus. Helicobacter pylori infections were determined by serology (ELISA), rapid urea test (CLO test), or histopathology examination using Haematoxyline Eosin and Giemsa staining. The criteria used to diagnose Helicobacter pylori infection were a positive result either from one of these tests and/or in combination.

Results

The frequent of proximal gastric cancer and distal gastric cancer finding were 0.63 % and 0.54 %, consecutively. In the proximal and distal gastric cancer groups the present of Helicobacter pylori were 55.77 % and 85.36 %, consecutively (p>0.05). The finding of gastric cancer among ethnic groups were 0.65 % for Chinese ethnicity and 0.81 % for Non‐Chinese ethnicity, statistically has no significant different (p=0,9514). The distal‐to‐proximal gastric cancer ratio was 0.85. The proximal gastric cancer more frequent to be found in the age group of 41‐60 years old (47.83%), while the distal gastric cancer in the age group of 51‐70 years old (61.54%).

Conclusion

The distal‐to‐proximal gastric cancer ratio was 0.85. The present of Helicobacter pylori were lower in proximal gastric cancer rather than distal gastric cancer, but statistically has of no significant.