bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual expression of mouse and rat VRL‐1 in the dorsal root ganglion derived cell line F‐11 and biochemical analysis of VRL‐1 after heterologous expression
Authors: Jahnel Ricarda , Bender Olaf , Münter Lisa M. , Dreger Mathias , Gillen Clemens , Hucho Ferdinand
Published: October 2003

The vanilloid‐like TRP‐channel VRL‐1 (TRPV2) is a nonselective cation channel expressed by primary sensory neurons and non‐neuronal tissues [Caterina, M.J., Rosen, T.A., Tominaga, M., Brake, A.J and Julius, D. (1999) Nature398, 436–441]. It is one of the six members of the vanilloid‐like TRP‐channel family which is now termed the TRPV family [Montell, G., Birnbaumer, L., Flockerzi, V., Bindels, R.J., Brutford, E.A., Caterina, M.J., Clapham, D.E., Harteneck, C., Heller, S., Julius, D., Kojima, I., Mori, Y., Penner, R., Prawitt, D., Scharenberg, A.M., Schultz, G., Shimizu, N. and Zhu, M.X. (2002) Mol. Cell2, 229–231]. As it is a temperature‐gated channel, VRL‐1 appears to be functionally related to VR1. In contrast to VR1, VRL‐1 is activated at a higher temperature threshold and it does not respond to capsaicin or protons. Here we describe the expression of VRL‐1 in the rat dorsal root ganglion‐derived cell line F‐11, a hybridoma of mouse neuroblastoma (N18TG2) and rat dorsal root ganglion cells. We found by RT‐PCR that F‐11 cells express not only the rat VRL‐1, but also its mouse orthologue in a single cell. The F‐11 parental cell line N18TG2 also expressed murine VRL‐1. Due to its neuronal character, the DRG‐derived F‐11 cell line provides an experimental system for the study of VRL‐1 biochemistry. However, one has to be aware that both the mouse and the rat protein are expressed simultaneously. Furthermore we cloned VRL‐1 from rat brain and analyzed its glycosylation and localization in comparison to the endogenously expressed protein in F‐11 cells. In contrast to the endogenous VRL‐1 the overexpressed protein is glycosylated. Similar to VR1 the glycosylation is N‐linked as shown by an deglycosylation assay. Immunofluorescence analysis of the endogenous VRL‐1 in F‐11 cells gives only weak signals in the cytoplasm whereas the overexpressed rat VRL‐1 appears mainly at the plasma membrane.
Thioredoxin reductase from the malaria mosquito Anopheles gambiae
Authors: Bauer Holger , Gromer Stephan , Urbani Andrea , Schnölzer Martina , Schirmer R. Heiner , Müller Hans‐Michael
Published: October 2003

The mosquito, Anopheles gambiae, is an important vector of Plasmodium falciparum malaria. Full genome analysis revealed that, as in Drosophila melanogaster, the enzyme glutathione reductase is absent in A. gambiae and functionally substituted by the thioredoxin system. The key enzyme of this system is thioredoxin reductase‐1, a homodimeric FAD‐containing protein of 55.3 kDa per subunit, which catalyses the reaction NADPH + H+ + thioredoxin disulfide→NADP+ + thioredoxin dithiol. The A. gambiae trxr gene is located on chromosome X as a single copy; it represents three splice variants coding for two cytosolic and one mitochondrial variant. The predominant isoform, A. gambiae thioredoxin reductase‐1, was recombinantly expressed in Escherichia coli and functionally compared with the wild‐type enzyme isolated in a final yield of 1.4 U·ml−1 of packed insect cells. In redox titrations, the substrate A. gambiae thioredoxin‐1 (Km = 8.5 µm, kcat = 15.4 s−1 at pH 7.4 and 25 °C) was unable to oxidize NADPH‐reduced A. gambiae thioredoxin reductase‐1 to the fully oxidized state. This indicates that, in contrast to other disulfide reductases, A. gambiae thioredoxin reductase‐1 oscillates during catalysis between the four‐electron reduced state and a two‐electron reduced state. The thioredoxin reductases of the malaria system were compared. A. gambiae thioredoxin reductase‐1 shares 52% and 45% sequence identity with its orthologues from humans and P. falciparum, respectively. A major difference among the three enzymes is the structure of the C‐terminal redox centre, reflected in the varying resistance of catalytic intermediates to autoxidation. The relevant sequences of this centre are Thr–Cys–Cys–SerOH in A. gambiae thioredoxin reductase, Gly–Cys–selenocysteine–GlyOH in human thioredoxin reductase, and Cys–X–X–X–X–Cys–GlyOH in the P. falciparum enzyme. These differences offer an interesting approach to the design of species‐specific inhibitors. Notably, A. gambiae thioredoxin reductase‐1 is not a selenoenzyme but instead contains a highly unusual redox‐active Cys–Cys sequence.
β‐Amyloid protein oligomers induced by metal ions and acid pH are distinct from those generated by slow spontaneous ageing at neutral pH
Authors: Klug Genevieve M. J. A. , Losic Dusan ,   Supundi, Subasinghe S. , Aguilar Marie‐Isabel , Martin Lisandra L. , Small David H.
Published: October 2003

Amyloid protein (Aβ1–40) aggregation and conformation was examined using native and sodium dodecyl sulfate/polyacrylamide gel electrophoresis, and the results compared with those obtained by atomic force microscopy, and with Congo red binding, sedimentation and turbidity assays. The amount of Aβ aggregation measured was different, depending upon the method used. Incubation for 15 min at pH 5.0 or in the presence of Fe2+, Cu2+ or Zn2+ did not alter the level of Aβ oligomers observed on SDS and native gels. However, the slow aggregation of Aβ to form high molecular mass species over 5 days was inhibited. In contrast, when Aβ aggregation was monitored using a Congo red binding assay or sedimentation assay, a rapid increase in Aβ aggregation was observed after incubation for 15 min at pH 5.0, or in the presence of Fe2+, Cu2+ or Zn2+. The low pH‐, Zn2+‐ or Cu2+‐induced Aβ aggregation measured in a turbidity assay was reversible. In contrast, a considerable proportion of the Aβ aggregation measured by native and SDS/PAGE was stable. Atomic force microscopy studies showed that Aβ aged at pH 5.0 or in the presence of Zn2+ produced larger looser rod‐shaped aggregates than at pH 7.4. Aβ that had been aged at pH 7.4 was more cytotoxic than Aβ aged at pH 5.0. Taken together, the results suggest that Aβ oligomerizes via two mutually exclusive mechanisms to form two different types of aggregates, which differ in their cytotoxic properties.
Molecular and functional characterization of adenylate kinase 2 gene fromLeishmania donovani
Authors: Villa Héctor , Pérez‐Pertejo Yolanda , García‐Estrada Carlos , Reguera Rosa M. , Requena José María , Tekwani Babu L. , Balaña‐Fouce Rafael , Ordóñez David
Published: October 2003

ATP‐regenerating enzymes may have an important role in maintaining ATP levels in mitochondria‐like kinetoplast organelle and glycosomes in parasitic protozoa. Adenylate kinase (AK) (ATP:AMP phosphotransferase) catalyses the reversible transfer of the γ‐phosphate group from ATP to AMP, releasing two molecules of ADP. This study describes cloning and functional characterization of the gene encoding AK2 from a genomic library ofLeishmania donovaniand also its expression in leishmania promastigote cultures.AK2was localized on an ≈ 1.9‐Mb chromosomal band as a single copy gene.L. donovani AK2gene is expressed as a single 1.9‐kb mRNA transcript that is developmentally regulated and accumulated during the early log phase. The overexpression ofL. donovani AKgene inEscherichia coliyielded a 26‐kDa polypeptide that could be refolded to a functional protein with AK activity. The recombinant protein was purified to apparent homogeneity. Kinetic analysis of purifiedL. donovaniAK showed hyperbolic behaviour for both ATP and AMP, withKmvalues of 104 and 74 µm, respectively. The maximum enzyme activity (Vmax) was 0.18 µmol·min−1· mg−1protein. P1,P5‐(bis adenosine)‐5′‐pentaphosphate (Ap5A), the specific inhibitor of AK, competitively inhibited activity of the recombinant enzymes with estimatedKivalues of 190 nmand 160 nmfor ATP and AMP, respectively. Ap5A also inhibited the growth ofL. donovanipromastigotesin vitrowhich could be only partially reversed by the addition of ADP. Thus, presence of a highly regulated AK2, which may have role in maintenance of ADP/ATP levels inL. donovani, has been demonstrated.
Dimer asymmetry and the catalytic cycle of alkaline phosphatase from Escherichia coli
Authors: Orhanović Stjepan , Pavela‐Vrančič Maja
Published: October 2003

Although alkaline phosphatase (APase) from Escherichia coli crystallizes as a symmetric dimer, it displays deviations from Michaelis–Menten kinetics, supported by a model describing a dimeric enzyme with unequal subunits [Orhanović S., Pavela‐Vrančič M. and Flogel‐Mršić M. (1994) Acta. Pharm.44, 87–95]. The possibility, that the observed asymmetry could be attributed to negative cooperativity in Mg2+ binding, has been examined. The influence of the metal ion content on the catalytic properties of APase from E. coli has been examined by kinetic analyses. An activation study has indicated that Mg2+ enhances APase activity by a mechanism that involves interactions between subunits. The observed deviations from Michaelis–Menten kinetics are independent of saturation with Zn2+ or Mg2+ ions, suggesting that asymmetry is an intrinsic property of the dimeric enzyme. In accordance with the experimental data, a model describing the mechanism of substrate hydrolysis by APase has been proposed. The release of the product is enhanced by a conformational change generating a subunit with lower affinity for both the substrate and the product. In the course of the catalytic cycle the conformation of the subunits alternates between two states in order to enable substrate binding and product release. APase displays higher activity in the presence of Mg2+, as binding of Mg2+ increases the rate of conformational change. A conformationally controlled and Mg2+‐assisted dissociation of the reaction product (Pi) could serve as a kinetic switch preventing loss of Pi into the environment.
Wyerone Acid Phytoalexin Synthesis and Peroxidase Activity as Markers for Resistance of Broad Beans to Chocolate Spot Disease
Authors: Nawar H. F. , Kuti J. O.
Published: October 2003

Infection of broad bean (Vicia faba L.) leaves with Botrytis fabae (Sard.) resulted in wyerone acid phytoalexin accumulation and increase in peroxidase activities in resistant and susceptible broad bean cultivars. Rapid wyerone acid accumulation was observed in leaves of resistant cultivars that reached levels greater than twofold of the susceptible cultivars. Following infection of broad bean cultivars, either resistant or susceptible to B. fabae, wyerone acid synthesis in resistant cultivars peaked at 5 days then declined, whereas in susceptible cultivars synthesis gradually decreased. While the ethanol‐extract of wyerone acid significantly reduced B. fabae spore germination with increased concentrations, the phytoalexin had no effect on in vitro B. fabae germ‐tube growth. Peroxidase activity in infected leaves of resistant was 10 times higher than the susceptible cultivars and eight times higher in uninfected leaves of the resistant than the susceptible cultivars. Peroxidase activity in infected leaves was greater than twofold in resistant cultivars and less than twofold in susceptible cultivars, when compared with uninfected leaves. The ratio of peroxidase activity in infected to uninfected leaves increased over time in susceptible cultivars but remained unchanged in resistant cultivars. Peroxidase activity in uninfected and infected leaves and wyerone acid biosynthesis in infected broad bean plants were successfully used to ascertain the resistance and susceptibility of four broad bean cultivars to B. fabae. Using wyerone acid synthesis and peroxidase activity as preliminary markers for resistance of broad bean to chocolate spot disease, caused by B. fabae, is suggested in this study.
Fungal Endophytic Communities in Healthy and Declining Quercus robur L. and Q. cerris L. Trees in Northern Italy
Authors: Gennaro M. , Gonthier P. , Nicolotti G.
Published: October 2003

Healthy and declining English oak (Quercus robur) and Turkey oak (Q. cerris) in north‐western Italy, in a plain oak forest showing decline for oak puzzle disease, were tested to assess possible variations in the composition of their fungal endophytic communities and their relation to the health status of trees. Samples collected in spring (buds) and in autumn (leaves, annual shoots and twigs) were surface‐sterilized, cut into fragments and placed on potato dextrose agar for a month; 26 fungal species were isolated, the most frequent being Tubakia dryina, Dendrodochium sp., Eutypella sp. and a sterile mycelium. Correspondence analysis showed significant qualitative differences between assemblages inhabiting twigs and herbaceous tissues that were due to the low frequency of Tubakia dryina in twigs and its higher frequency in buds, leaves and shoots. Tubakia dryina was isolated more frequently from leaves of declining oaks and from buds of healthy oaks; Monochaetia monochaeta showed a preference for healthy trees, especially leaves and buds. According to the Shannon–Wiener index, endophytic fungal communities of leaves, twigs and buds of declining English oak were poorer than those of declining Turkey oak, but there were no significant differences between healthy hosts.
The Effects of Oligosaccharide and Spores from Aspergillus niger on the Defence Responses of Taxus chinensis Leaves In vitro
Authors: Li M. Y. , Lan W. Z. , Chen C. , Yu L. J.
Published: October 2003

Spores and oligosaccharide of a strain of Aspergillus niger, which had been isolated from the inner bark of Taxus chinensis, were used to treat T. chinensis leaves. The spores decreased the dry weight and chlorophyll content of the leaves, but increased their malondialdehyde content; oligosaccharide induced similar but more moderate changes. The changes in soluble protein, phenolic content, and peroxidase and phenylalanine ammonia‐lyase activity were also analysed. Oligosaccharide significantly increased all these, whereas the spores had contrary effects. Results indicate that oligosaccharide, but not the fungal spores, elicited a defence reaction in T. chinensis. Possible reasons for these different effects on T. chinensis leaves in vitro are discussed.
Effect of Crinipellis perniciosa Infection on Abscission of Cacao Cotyledons, Reserve Mobilization and Dry Matter Partitioning
Authors: Motilal L. A. , Sirju‐Charran G. , Sreenivasan T. N.
Published: October 2003

Infection by Crinipellis perniciosa on cacao seedlings prevented the abscission of cotyledons which normally abscise within 32–61 days from seed sowing. The early growth and development of control and artificially inoculated seedlings was investigated for root dry mass (RDM), shoot dry mass (SDM), shoot‐to‐root ratio (SRR), total dry mass (TDM), cotyledonary dry mass (CDM) and cotyledonary water content (CWC). Cotyledonary reserve mobilization was estimated at 69 and 56% at 5 weeks and 79 and 64% at 8 weeks in control and infected seedlings, respectively. Infection induced the enlargement of tissues but was not accompanied by an increase in dry mass. Infection both delayed and reduced the utilization of cotyledonary food reserves resulting in slower accumulation of RDM, SDM and TDM culminating in a reduction of growth by a factor of 1.6 at 8 weeks. However, the SRR of inoculated plants was similar to that of control plants, suggesting that the balance between the root and shoot systems exists which is unchanged by the effect of the pathogen. CWC was decreased upon senescence to an average of 65% at abscission. The prevention of cotyledonary abscission in infected seedlings is suggested to be due in part to the CDM remaining above a critical level of 20% of the initial CDM. The implication of this response in relation to the infection biology of the pathogen is discussed.
Adequacy of support for new graduates during their transition into the workplace: A Queensland, Australia study
Authors: Parker Victoria , Plank Ashley , Hegney Desley
Published: October 2003

In 2001, a study into issues of concern to assistant‐in‐nursing, registered and enrolled nurse members of the Queensland Nurses Union was undertaken. Approximately equal numbers of nurses from each of the aged care, acute private and acute public sectors were surveyed. Overall, 1477 nurses responded, representing a response rate of 53%. This article focuses on one aspect of the study—the perceived adequacy of support offered to new nursing graduates as they exit university and begin their transition into the workplace. In particular, responses from nurses are compared with professional level or current role designation, age, time spent in the workplace and health sector. Considerable divergence of opinion among the respondents, particularly across designation, age and years of experience, was found within the three sectors. For example, in the public and private employment sectors, older and more experienced nurses were more likely to perceive the support for new nurses as adequate compared to younger and less experienced nurses. Additionally, in the acute private sector, the more senior the nurse the more likely the perception that there was adequate preparation for new graduates entering the workforce.
Agitated older patients: Nurses’ perceptions and reality
Authors: Poole Julia , Mott Sarah
Published: October 2003

Management of agitation is an increasingly common duty in the nursing care of older patients. Agitation describes a range of behavioural symptoms including aggressiveness and hyperactivity, and can be a sign of severe illness. In a series of focus groups in a large teaching hospital, nurses’ feelings and actions in regard to nursing agitated older people were recorded and analysed. The results demonstrated that agitation is not well understood and is often not well‐managed. Despite recent efforts to provide more supportive staffing structures, nurses felt particularly stressed and unsupported in relation to this phenomenon. Recommendations are made for the instigation of enhanced education programmes as well as ongoing attention to improved workload initiatives.
Predictors of psychological well‐being of nurses in Alexandria, Egypt
Authors: Arafa Mostafa Ahmed , Nazel Mervat Wagdy Abou , Ibrahim Nahla Khamis , Attia Ashraf
Published: October 2003

As nursing has been previously identified as a stressful occupation, sources of job stress and levels of job satisfaction were extensively investigated. However, studies addressing issues of nurses’ mental health are scarce. This work aims to assess psychological well‐being of nurses in different job settings in Alexandria and to identify sociodemographic, psychosocial and workplace predictors. A total sample of 412 nurses represented nurses working in five different health organizations in Alexandria. A self‐administered questionnaire was used to collect sociodemographic, occupational and health data, and the Standardized Arabic Version of General Health questionnaire (GHQ‐30 items), Job Descriptive Index (JDI), and Social Support Scale (SSS) were also used. Results revealed that 21.67% of nurses recorded moderate to severe psychological symptoms on GHQ. Fewer years of experience, negative family and friend support, and negative total work satisfaction were found to be significant predictors of psychological ill health among nurses in a descending rank order. Implications for nursing intervention will be discussed.
The spiritual dimensions of care in military nursing practice
Authors: Ormsby Andrew , Harrington Ann
Published: October 2003

Spirituality has been the subject of numerous journal articles and books in recent years. Research into this topic has been conducted in many spheres of nursing practice with the notable exception of military nursing. This article goes a small way to addressing the apparent lack of research into spirituality in a military nursing setting by summarizing the findings of one study into this significant area of nursing care. The findings are derived from a mixed method quantitative/qualitative study of registered nurses in the Royal Australian Air Force. The major finding indicated that two distinct concepts of ‘family’ define the way in which this small group of nurses perceive, assess and implement care for the spiritual needs of their patients. These concepts comprise a traditional family structure and an extended military family structure that includes the person's unit and comrades‐in‐arms.
Coexistence of focal nodular hyperplasia and pseudotumor caused by focal spared lesion in the liver of a young man
Authors: WU WEN‐CHIH , CHEN SHINN‐CHERNG , DIA CHIA‐YEN , YU MING‐LUNG , HSIEH MING‐YUH , LIN ZU‐YAU , WANG LIANG‐YEN , TSIA JUNG‐FA , CHANG WEN‐YU , CHUANG WAN‐LONG
Published: October 2003

Abstract  We report a case of 19‐year‐old male with an underlying case of chronic hepatitis C infection who suffered from two types of benign liver tumor: focal nodular hyperplasia (FNH) and pseudotumor due to focal fatty spared area in a fatty liver. These two kinds of lesions rarely occur simultaneously. The spectral Doppler ultrasound (US) images of these lesions were also provided. We suggest that spectral Doppler US provides an alternative diagnostic tool for the differentiation of liver tumors regarding their vascular pattern, which might help ensure a correct diagnosis.

© 2003 Blackwell Publishing Asia Pty Ltd
Is acupuncture a risk factor for hepatitis? Systematic review of epidemiological studies
Authors: ERNST E , SHERMAN Kj
Published: October 2003

Objective:  Acupuncture has been repeatedly associated with infectious hepatitis. The aim of the present systematic review was therefore to critically evaluate such data from epidemiological investigations.

Methods:  Four independent literature searches were carried out to identify all epidemiological evidence linking acupuncture with hepatitis. All studies were validated by the authors and data extracted according to predefined criteria.

Results:  Fifteen investigations fulfilled our inclusion criteria. Most studies originated from Asia. One study included markers to hepatitis A virus, three to hepatitis B virus, and 13 to hepatitis C virus. Five investigations reported associations between acupuncture and seropositivity to hepatitis C virus. In those studies, acupuncture increased the risk only modestly.

Conclusion:  A modest association between hepatitis C and acupuncture has been reported in some countries. This emphasizes the importance of exclusively using disposable acupuncture needles.
Parenchymal transforming growth factor beta‐1: Its type II receptor and Smad signaling pathway correlate with inflammation and fibrosis in chronic liver disease of viral etiology
Authors: CALABRESE FIORELLA , VALENTE MARIALUISA , GIACOMETTI CINZIA , PETTENAZZO ELENA , BENVEGNU LUISA , ALBERTI ALFREDO , GATTA ANGELO , PONTISSO PATRIZIA
Published: October 2003

Background and Aims:  Transforming growth factor‐beta (TGF‐beta) system is involved in the control of cell growth and extracellular matrix formation. Previous studies in patients with chronic liver disease have shown that increased TGF‐beta expression significantly correlates with the degree of hepatic fibrosis. The aim of our study was to define TGF‐beta system expression in hepatic parenchymal cells and its significance in patients with differing extents of chronic liver disease of viral etiology.

Methods:  Expression of  TGF‐beta 1, TGF‐beta 1 type II receptor (TGF‐beta RII) and the Smad signaling pathway was evaluated in consecutive liver sections of 77 patients with chronic liver disease (65 HCV positive and 12 HBV positive). Results were correlated with histological scores and apoptotic activity.

Results:  TGF‐beta 1 was demonstrated in the liver of 30/56 (53.6%) patients with chronic hepatitis and 20/21 (95%) patients with cirrhosis, but in none of the 20 normal livers. Positive cytokine reaction was seen both in stromal cells and hepatocytes. Expression of TGF‐beta RII and Smad proteins showed a distribution pattern similar to that of  TGF‐beta, with a direct correlation in terms of immunoreactivity extent. A significant correlation was found between parenchymal expression of  TGF‐beta system and inflammatory and fibrosis scores. No correlation was found with apoptotic index and other morphological, clinical or virological parameters.

Conclusions:  The TGF‐beta system is up‐regulated at the ligand, receptor and signaling level in the liver of patients with more active disease. The strong expression of  TGF‐beta and the Smad pathway in parenchymal cells suggests that hepatocytes, in addition to mesenchymal cells, may play an important role in the progression of liver disease.
Analysis of CYP2E1 polymorphism for the determination of genetic susceptibility to gastric cancer in Koreans
Authors: PARK GEUN TAE , LEE OH YOUNG , KWON SUNG JOON , LEE CHUN GEUN , YOON BYUNG CHUL , HAHM JOON SOO , LEE MIN HO , HOO LEE DONG , KEE CHOON SUHK , SUN HEE SIK
Published: October 2003

Background:  Interindividual genetic differences in susceptibility to chemical carcinogens are among the most important host factors in human cancer. The present study was undertaken to reveal the association between the polymorphism of CYP2E1 (CYP2E1/PstI and CYP2E1/DraI) with genetic susceptibility to gastric cancer development in Koreans.

Methods:  In the present study, 120 gastric cancer patients and 145 controls with no history of tumors were analyzed. CYP2E1 was determined by polymerase chain reaction‐restriction fragment length polymorphisms (PCR‐RFLP), or PCR and direct gel electrophoresis.

Results:  The overall genotype distribution of CYP2E1 was not significantly different from that of controls. However, the genotype distribution of the patient subgroups with a history of heavy cigarette smoking (>30 pack/year) in the CYP2E1/PstI and CYP2E1/DraI polymorphisms were significantly different from those of non‐smoking patients (P = 0.0122 and P = 0.0029, respectively). The difference was also noticeable in the younger patient subgroup (aged ≤50 years) compared with normal controls (P = 0.0414) in the CYP2E1/PstI. The relative risk estimation for the combination of the CYP2E1/PstI and CYP2E1/DraI polymorphisms revealed that the odds ratio for individuals with homozygotes of rare alleles (c2/c2, C/C) was 5.6 (95% confidence interval = 0.9–39.1).

Conclusions:  : These results suggest the possible involvement of the CYP2E1 polymorphism in smoking‐induced gastric cancer development in Koreans as one of the risk factors which increases genetic susceptibility.
Obstetric cholestasis with elevated gamma glutamyl transpeptidase: Incidence, presentation and treatment
Authors: MILKIEWICZ PIOTR , GALLAGHER RUTH , CHAMBERS JENNY , EGGINGTON ENID , WEAVER JUDITH , ELIAS ELWYN
Published: October 2003

Background:  Obstetric cholestasis (OC) may cause severe pruritus in the mother and lead to fetal distress and stillbirth. The etiology of OC is multifactorial, but includes inherited dysfunction of bile canalicular transporters. One of these, multidrug resistant protein 3 (MDR3), a phospholipid transporter, when dysfunctional is associated with elevated levels of gamma glutamyl transpeptidase (GGT). The aim of the present study was to assess the incidence of OC associated with elevated GGT. We compared the natural history of a cholestatic pregnancy and the efficacy of ursodeoxycholic acid (URSO) in OC patients grouped according to a normal or raised GGT level.

Methods:  Eighty‐one patients with OC were analyzed. OC was diagnosed in patients with pruritus and elevated serum bile acids (SBA). Fifty‐seven consenting volunteer patients (70%) were treated with URSO.

Results:  Elevated GGT at presentation was found in 21 patients (30%) and was associated with significantly higher serum levels of aspartate transaminase (AST), bilirubin (BIL) and SBA. OC presented at approximately the same gestation week in both groups of patients. In patients not treated with URSO, liver function tests (LFT) showed no significant change from the time of diagnosis to delivery. Patients from both groups responded to URSO with significant improvement in their AST and alanine aminotransferase (ALT) levels, but SBA fell significantly only in the normal GGT group.

Conclusions:  An elevated GGT occurs in less than one‐third of patients with OC in the UK and, when present, is associated with greater impairment of LFT, but no difference in gestational age at onset. Treatment with URSO appears to be safe and significantly improves LFT in patients with OC, with the exception of SBA in the high GGT group.
Expression of hepatoma‐derived growth factor in hepatocarcinogenesis
Authors: YOSHIDA KENYA , NAKAMURA HIDEJI , OKUDA YORIHIDE , ENOMOTO HIRAYUKI , KISHIMA YOSHIHIKO , UYAMA HIROKAZU , ITO HIROAKI , HIRASAWA TSUTOMU , INAGAKI SHUICHIRO , KAWASE ICHIRO
Published: October 2003

Background and Aim:  The present study investigated the expression of hepatoma‐derived growth factor (HDGF) in human hepatocellular carcinoma (HCC) and in the liver during hepatocarcinogenesis in two rodent models.

Methods:  Expression of HDGF was analyzed using northern blotting and immunohistochemistry in the human and rodent models.

Results:  Hepatoma‐derived growth factor was more highly expressed in HCC than in the adjacent liver in humans with hepatitis, as shown by northern blotting. Using immunohistochemistry with the specific anti‐HDGF antibody, HDGF was more strongly and frequently expressed in the nucleus and cytoplasm of HCC cells than in the adjacent normal hepatocytes. Hepatoma‐derived growth factor was also more strongly expressed in the tumors than in the adjacent fatty liver of fatty liver Shionogi (FLS) mice, than in the cirrhotic liver of choline‐deficient amino acid feeding rats, as shown by northern blotting and immunohistochemistry. In the liver of FLS mice, HDGF expression increased gradually from the age of 24 weeks through to 52 weeks after birth, showing that HDGF expression was already increased at an early stage before tumor development. In the non‐tumorous liver with fatty change, the foci expressing HDGF appeared at 24 weeks of age, which were the activated macrophage clusters with enhanced DNA synthesis and fat droplets. It is suggested that HDGF was secreted or released from these foci and stimulated hepatocyte proliferation in a paracrine manner in FLS mice, and stimulated the proliferation of hepatic tumor cells in an autocrine manner.

Conclusions:  The present findings suggest that HDGF plays an important role in the development or progression of HCC in humans and rodents.
Optimization of dialysate sodium in sodium profiling haemodialysis
Authors: KIM Moon‐jae , SONG Joon ho , KIM Gyeong a , LIM Hee jung , LEE Seoung woo
Published: October 2003

SUMMARY:  Sodium profiling haemodialysis is a modified method of sodium gradient dialysis during which dialysate sodium follows a time‐dependent profile. Sodium profiling haemodialysis has claimed to reduce intradialytic discomforts such as hypotension, muscle cramps, and disequilibrium syndrome. Having the low sodium period is an essential part of the sodium profiling haemodialysis to compensate for the sodium gain during the high sodium period. In spite of this, however, the incidence of interdialytic complications that results from the excessive sodium gain has been reported in previous literature. Making the prediction of optimal dialysate sodium concentration for isonatric dialysis is practically very difficult since too many variables influence the sodium gradient, including the initial plasma sodium and tonicity and/or dialysis dynamics that differ from patient to patient and from treatment to treatment. As for sodium profiling haemodialysis, complexities are added further since details of profile, such as type and form of profile, or initial, terminal, or time‐distribution of dialysate sodium are varied considerably. We have recently reported that the intradialytic sodium balance and interdialytic weight gain are directly related to the time‐averaged concentration of dialysate sodium (TACNa). The dialysate sodium can be optimized using this concept of TACNa for sodium profiling dialysis. TACNa should be approximately 0.5–0.8 mmol/L lower than patient's predialysis serum sodium concentrations to achieve a sodium balance neutral dialysis. In that study the optimal TACNa, seems to be between 137.8 and 143.5 mmol/L. Such an optimal value should be defined for the individual centres based on their profile protocols for clinical use. In the future, dialysate sodium should be optimized based on the exact prediction of the postdialysis plasma sodium levels.
Anticoagulation during haemodialysis in patients at high‐risk of bleeding
Authors: KIM Yoon‐Goo
Published: October 2003

SUMMARY:  Routine haemodialysis is performed with systemic anticoagulation, usually with heparin, to prevent thrombosis in the extracorporeal blood circuit. However, systemic anticoagulation can produce haemorrhagic complications in patients at high risk of bleeding. To minimize the risk of bleeding, a number of alternative regimens have been proposed: regional heparinization with protamine reversal; minimal heparinization; no heparin with saline flushes; regional anticoagulation with citrate; or prostacyclin anticoagulation. Although the incidence of bleeding complications has been reduced, each of these methods has its own limitations and complications. Among the types of membrane used in dialysers, cellulose membranes have been made more biocompatible by attaching N,N‐diethyl‐aminoehtyl (DEAE) groups to cellulose backbone. Positively charged DEAE groups on Hemophan enable negative charged heparin to be bound with the membrane. Haemodialysis using heparin‐bound Hemophan has been reported to be a possible modality for patients at risk of bleeding. We designed more simplified heparin binding technique and have performed haemodialysis using heparin‐bound Hemophan in patients at risk of bleeding during the past 7 years. In this review, current strategies to minimize bleeding complications and our experience of haemodialysis using heparin‐bound Hemophan will be discussed.
Low glucose degradation products dialysis solution modulates the levels of surrogate markers of peritoneal inflammation, integrity, and angiogenesis: preliminary report
Authors: KIM Yong‐Lim , DO Junyoung , PARK Sun‐Hee , CHO Kyuhyang , PARK Jongwon , YOON Kyungwoo , CHO Dong‐Kyu , LEE Eun‐Gyui , KIM In‐San
Published: October 2003

SUMMARY:  The presence of glucose degradation products (GDPs) in peritoneal dialysis (PD) fluids has many adverse effects, namely clinically significant abdominal pain or discomfort during infusion, inhibition of cell proliferation, impairment of inflammatory cell function, cytotoxicity, and the induction of vascular endothelial growth factor (VEGF). In a prospective, randomized, controlled trial comparing a low GDP PD solution (pH 7.0, two compartment bag: low GDP) to conventional PD solution (pH 5.5: high GDP), the overnight dialysate levels of the markers of inflammation/wound healing (hyaluronic acid (HA)), mesothelial cell mass/membrane integrity (cancer antigen 125 (CA125)), and angiogenesis (VEGF) were assessed over a 12‐month period. Twenty‐six newly commencing continuous ambulatory peritoneal dialysis (CAPD) patients were randomly assigned to either the Low GDP group (n = 16) or the High GDP group (n = 10). Standard peritoneal permeability analysis for membrane transport characteristics and dialysis adequacy with nutritional status (serum albumin, nPCR) were evaluated at 1, 6, and 12 months. In patients treated with high GDP solution, there was significant increase in VEGF with time (time = 1 month, 67.2 ± 10.8; time = 6 months, 189.8 ± 90.2; and time = 12 months, 169.3 ± 83.1 pg/mg of protein; P < 0.05). There was no significant change of VEGF with time in the low GDP group. Significantly higher concentrations of CA125 (65.5 ± 10.4 vs. 19.7 ± 2.6 at 1 month, P < 0.0001; 66.6 ± 9.8 vs. 29.7 ± 5.0 at 6 months, P < 0.01; 68.7 ± 10.5 vs. 30.7 ± 10.0 U/mL at 12 months, P < 0.01) and lower concentrations of HA (114.6 ± 18.8 vs. 254.3 ± 69.2 at 1 month, P < 0.05; 417.5 ± 57.2 vs. 1277.5 ± 367.9 ng/mg of protein at 12 month, P < 0.05) were observed in the low GDP group compared with the high GDP group. In conclusion, continuous therapy with the low GDP solution modulates the levels of surrogate markers of peritoneal inflammation, integrity and angiogenesis. The results strongly suggest that the use of a low GDP solution would be beneficial to maintain the function and structural integrity of the peritoneal membrane.
Genetic risk factors for cerebral infarction using data from a large‐scale genetic epidemiological study: the Ohasama Study
Authors: Katsuya Tomohiro , Sugimoto Ken , Hozawa Atsushi , Ohkubo Takayoshi , Yamamoto Koichi , Matsuo Akiko , Ishikawa Kazuhiko , Matsubara Mitsunobu , Rakugi Hiromi , Tsuji Ichiro , Imai Yutaka , Ogihara Toshio
Published: October 2003

Background:  With the imminent advent of an extremely aged society, there will be an increasing requirement for the prediction, early detection and treatment of cerebral infarction. Involved in the etiological mechanisms of cerebral infarction are a number of complex genetic and environmental factors related to the onset and progression of hypertension and arteriosclerosis. Elucidation of the significance of the various risk factors will require definite identification of phenotypes using large numbers of subjects.

Methods:  The present study was conducted as part of a cohort study with subjects from the general population of a rural community (the Ohasama Study). Blood pressure (BP) patterns were assessed through random home‐based and clinical measurements, as well as 24 h ambulatory BP monitoring. Magnetic resonance imaging of the brain was carried out in some subjects in order to detect asymptomatic cerebral infarcts, the maximum intima–media thickness was determined by carotid high‐resolution ultrasonography, and cognitive function was assessed using the mini mental state examination. Correlation analysis of these parameters and the candidate hypertensive genotypes was then performed.

Results:  Significant associations were seen between (i) gene polymorphisms in the renin–angiotensin system and asymptomatic cerebral infarction and the non‐dipper pattern of circadian blood pressure variation; and (ii) endothelial nitric oxide synthase (eNOS) gene polymorphism and arterial pressure, lacunar score and cognitive function. An association was seen between the endothelin‐1 polymorphism and hypertension, but only in obese subjects.

Conclusion:  There are interactions between genes and the environment in the etiology of cerebral infarction.
Influence of sex and estrogen on vitamin D‐induced arterial calcification in rats
Authors: Nakamura Tetsuro , Akishita Masahiro , Kozaki Koichi , Toba Kenji , Orimo Hajime , Ouchi Yasuyoshi
Published: October 2003

Background:  It is known that the process of arteriosclerosis is affected by sex and estrogen. The present study was thus undertaken to examine the effects of these factors on arterial calcification, a form of arteriosclerosis, using a rat model of vitamin D toxicity.

Methods and results:  Vehicle or 5 µg/kg per day 1α(OH)D3 was given to male and female 30‐week‐old Fisher rats for 2 weeks. Arterial calcification, evaluated by calcium content in the aorta, was 70% more marked in male rats compared to that in female rats, whereas calcium content in the aorta was similar in vehicle‐treated male and female rats. Next, the effects of ovariectomy and estrogen replacement (estradiol dipropionate 20 µg/kg per week) were examined in female rats given 5 µg/kg per day 1α(OH)D3 for 2 weeks. Calcium content in the aorta was significantly higher in ovariectomized rats than in sham‐operated rats and in ovariectomized and estrogen‐replaced rats. No difference between the groups was seen when vehicle was given to the animals.

Conclusions:  These results suggest that sex and estrogen can modify the process of arterial calcification. The mechanisms remain to be determined, although the effects were independent of serum calcium level.
Elderly case of non‐mucinous bronchioloalveolar carcinoma showing diffuse ground‐glass changes on chest computed tomography
Authors: Kikawada Masayuki , Hirao Kentarou , Shimizu Takeshi , Uno Masanori , Iwamoto Toshihiko , Nagao Toshitaka , Takasaki Masaru
Published: October 2003

An 83‐year‐old man was diagnosed as having recurrent spinal canal stenosis and was admitted to his local hospital on 13 July 2001. Because interstitial changes were detected on the chest X‐ray, he was transferred to our hospital after 3 days. Chest computed tomography showed diffuse ground‐glass attenuation and a right pleural effusion. To make a diagnosis, transbronchial lung biopsy of right B3, B4 and B8 was performed. Histological examination of specimens from B4 and B8 revealed non‐mucinous bronchioloalveolar carcinoma. It seems that a bilateral diffuse ground‐glass appearance is one of the radiographic features of progressive bronchioloalveolar carcinoma.
Initial experience of abdominal aortic aneurysm repairs in Borneo
Authors: Yii Ming Kon
Published: October 2003

Background:  Abdominal aortic aneurysms (AAA) repairs are routineoperations with low mortality in the developed world. There arefew studies on the operative management of AAA in the Asian population.This study reports the initial results from a unit with no previousexperience in this surgery by a single surgeon on completion oftraining.

Methods:  All patients with AAA repair from a prospective databasebetween 1996 and 1999 in the south‐east Asian state of Sarawak inBorneo Island were analyzed. Three groups were identified on presentationaccording to clinical urgency of surgery. Elective surgery was offeredto all good risk patients with AAA of ≥ 5 cm.All symptomatic patients were offered surgery unless contraindicatedmedically.

Results:  AAA repairs were performed in 69 patients: 32 (46%)had elective repairs of asymptomatic AAA; 20 (29%) hadurgent surgery for symptomatic non‐ruptured AAA; and 17 (25%)had surgery for ruptured AAA. The mortality rate for elective surgery was6%; the two deaths occurred early in the series with thesubsequent 25 repairs recorded no further mortality. The mortalityrates for the urgent, symptomatic non‐ruptured AAA repair and rupturedAAA repair were 20% and 35%, respectively. Cardiacand res­piratory complications were the main morbidities.Sixty‐three patients seen during this period had no surgery; threepresented and died of ruptured AAA, 34 had AAA of ≤ 5 cmin diameter, and 26 with AAA of ≥ 5 cmdiameter had either no consent for surgery or serious medical contraindications.

Conclusion:  This study showed that AAA can be repaired safely byhighly motivated and adequately trained surgeons in a hospital withlittle previous experience.
Analysis of the outcomes of a visiting surgical service to small rural communities
Authors: Hughes‐Anderson Wayne , House Jill , Aitken Robert J. , Rankin Sarah L. , House Anthony K.
Published: October 2003

Background:  A team of visiting surgeons has provided regular clinics and day surgery to rural locations in country towns away from resident surgical centres. This format has provided continuity of care for 7 years despite a constantly changing medical workforce. The aim of the present study was to review the results of the group and to compare them against national standards and to provide a model for future outreach programmes.

Methods:  All patient diagnoses, procedures and clinical outcomes were recorded prospectively. This record of activity was then collated. District hospital records and clinical notes have been rechecked for complications over a discrete 4 year period.

Results:  There have been 7419 items of service provided, including 2676 procedures. The diagnostic grouping and subsequent day‐surgery activity are consistent with the top 30 surgical separations from all Australian hospitals. These patients have been found suitable to remain in their own home environment for treatment.

Conclusion:  Experienced surgeons operating on selected patients with careful nursing care, in small country hospitals have outcomes similar to urban hospitals.
Role of community diagnostic ultrasound examination in the diagnosis of full‐thickness rotator cuff tears
Authors: Goldberg Jerome A. , Bruce Warwick J. M. , Walsh William , Sonnabend David H.
Published: October 2003

Background:  Diagnostic ultrasound examination has become the most commonly used investigation in Australia for diagnosing rotator cuff tears. The authors felt that the results of such investigations were often inaccurate in their clinical practices.

Methods:  The diagnostic ultrasound findings in 336 cases were compared to arthrography, and in 225 cases findings at surgery.

Results:  A very poor accuracy rate of 0.38 was found for diagnostic ultrasound examination. The sensitivity was 0.24 and specificity was 0.61.

Conclusions:  Extreme caution is recommended in the use of diagnostic ultrasound, as currently practised in a general community setting, in diagnosing full‐thickness rotator cuff tears.
Effect of transdermal glyceryl trinitrate and anti‐inflammatory gel in infusion phlebitis
Authors: Çökmez Atilla , Gür Serhat , Genç Hüdai , Deniz Sümer , Tarcan Ercüment
Published: October 2003

Background:  Phlebitis is the commonest complication of intravenous infusion. It has been suggested that it is initiated by venoconstriction at the infusion site, hence treatment with a vasodilator may reduce its incidence.

Methods:  A prospective controlled study was carried out on the effect of transdermal glyceryl trinitrate (GTN) and topical anti‐inflammatory gel (non‐steroidal anti‐inflammatory drug; NSAID) on the survival of peripheral intravenous infusion in 386 patients.

Results:  A total of 34.9% (43 out of 123) of the infusions failed in the control group compared with 14.1% (18 out of 127) in the NSAID group (P < 0.05) and 30.8% (43 out of 136) in the GTN group (P < 0.05). In the control group 31 positive cultures were obtained. Twenty‐one positive cultures were obtained in the GTN group and four cases of bacterial proliferation were observed in the NSAID group.

Conclusions:  Infusion phlebitis is a common problem in hospitalized patients and its incidence can be effectively reduced by NSAI gel and GTN but NSAI gel is more effective than GTN.
Bereavement in paediatric intensive care
Authors: Stack Charles G.
Published: October 2003

The death of a child is a very sad event in anyone's life. It also affects all staff in paediatric intensive care units in different ways at different times. The publication of standards of bereavement care in paediatric intensive care hopes to be able to assist medical and nursing staff to understand and feel more confident in this emotionally difficult area of medicine. The aim of this article is to summarize some of the major points made in the document.
A rare cause of upper airway obstruction in a 5‐year‐old girl: a laryngeal web
Authors: Siggers B.R.C. , Ross O. , Randall C. , Connett G.
Published: October 2003

A case is described of a 5‐year‐old girl with respiratory distress. She was intubated without difficulty, but developed respiratory distress on extubation. Laryngoscopy/bronchoscopy via a laryngeal mask airwayTM revealed an extensive layngeal web which was removed with laser therapy. The causes and differential diagnosis of laryngeal web are discussed.