bluuebunny/crossref_metadata_2025 huggingface dataset:
Genotypic effects of calpain 1 and calpastatin on the tenderness of cooked M. longissimus dorsi steaks from Jersey × Limousin, Angus and Hereford‐cross cattle
Authors: Morris C. A. , Cullen N. G. , Hickey S. M. , Dobbie P. M. , Veenvliet B. A. , Manley T. R. , Pitchford W. S. , Kruk Z. A. , Bottema C. D. K. , Wilson T.
Published: July 2006

Single nucleotide polymorphisms (SNPs) in the calpain 1 (CAPN1) and calpastatin (CAST) genes were studied to determine their effects on meat tenderness in Bos taurus cattle. Strip loins (M. longissimus dorsi) were removed from cattle in four resource populations after slaughter (n = 1042), aged under controlled conditions until fixed times after rigor mortis, cooked and measured using a tenderometer. Animals were genotyped for the CAPN1 SNP c.947C>G (p.Ala316Gly; AF252504) and for the CAST SNP c.2959A>G (AF159246). Frequencies of CAPN1 C alleles ranged from 23% to 68%, and CAST A alleles from 84% to 99.5%. From all data combined, the CAPN1 CC genotype (compared with the GG genotype) was associated with a 20.1 ± 1.7% reduced average shear force at intermediate stages of ageing (P < 0.001) and with a 9.5 ± 1.3% reduction near ultimate tenderness (P < 0.001). The heterozygote was intermediate. For CAST, corresponding values for AA compared with AG genotypes were reductions of 8.6 ± 2.0% and 5.1 ± 1.6% respectively (both P < 0.001), but there were too few GG genotypes for comparison. There were small interactions between the CAPN1 and CAST genotypes. For the CAPN1 and CAST genotypes combined, the maximal genotype effect in average shear force was 25.7 ± 5.5% (P < 0.001) at intermediate stages and 15.2 ± 4.8% near ultimate tenderness (P < 0.01).
Genetic heterogeneity of day blindness in Alaskan Malamutes
Authors: Seddon J. M. , Hampson E. C. G. M. , Smith R. I. E. , Hughes I. P.
Published: July 2006

Day blindness is a progressive and specific degeneration of cone photoreceptors in the retina of young dogs. This disorder has been associated with a breed‐specific non‐synonymous substitution in exon 6 of the cyclic nucleotide gated channel β3 (CNGB3) gene in German Shorthaired Pointer dogs and a genomic deletion removing the entire gene in Alaskan Malamute dogs from the USA. To further investigate this disorder, we characterized CNGB3 in a three‐generation pedigree of Alaskan Malamute dogs from Australia segregating for day blindness. Fifteen of the dogs showed clinical signs of day blindness. Four of these were definitively diagnosed by standardized electroretinography. Polymerase chain reaction amplification of exon 6 of CNGB3 was attempted, and as expected, amplification was successful in the 18 unaffected or carrier dogs. However, a non‐mutated exon 6 was also amplified and sequenced in six of the 15 affected dogs. On sequencing each exon and exon/intron boundary in two such affected individuals and two unaffected individuals, three exonic substitutions and 12 intronic changes were noted. These sequence variations in affected individuals were also present in one or both unaffected dogs and so appear to have no obvious effect on the protein's function. Hence, day blindness shows genetic heterogeneity within the Alaskan Malamute population of Australia, a result that is somewhat unexpected given the relatively small effective population size of this breed.
Plasma concentrations of inhaled corticosteroids in relation to airflow obstruction in asthma
Authors: Mortimer Kevin J. , Harrison Tim W. , Tang Yufei , Wu Kai , Lewis Sarah , Sahasranaman Srikumar , Hochhaus Gunther , Tattersfield Anne E.
Published: July 2006

Aims

To compare the pharmacokinetic profiles of beclometasone, budesonide, fluticasone and mometasone following inhalation in patients with asthma, and explore the relationship between lung function and plasma drug concentrations.

Methods

Thirty subjects with asthma and a forced expiratory volume in 1 s (FEV1) ranging from 36 to 138% predicted, inhaled 800 µg beclometasone, budesonide and mometasone and 1000 µg fluticasone in random order. Plasma drug concentrations were measured over 8 h and the relationship between the area under the plasma concentration–time curve (AUC0−8) and lung function was modelled using linear regression. Estimated AUC0−8 values at 50 and 100% predicted FEV1 were compared for each drug.

Results

Pharmacokinetic profiles differed markedly between the drugs. Correlation coefficients for the relation between FEV1% predicted and AUC0−8 values for beclometasone, budesonide, fluticasone and mometasone were 0.37 (P = 0.05), 0.33 (P = 0.08), 0.25 (P = 0.2) and 0.52 (P = 0.004), respectively, and estimated AUC0−8 values were 1.3 [95% confidence interval (CI) 1.0, 1.8], 1.3 (95% CI 1.0, 1.8), 1.4 (95% CI 0.9, 2.2) and 2.2 (95% CI 1.3, 3.5) times higher for the four drugs, respectively, at 100 compared with 50% predicted FEV1.

Conclusion

The higher plasma concentrations of inhaled corticosteroids in patients with a higher FEV1% predicted suggests that, for any given dose, these patients will be at greater risk of developing adverse systemic effects with long‐term use.
Aggregation of red blood cells in patients with Gaucher disease
Authors: Adar Tomer , Ben‐Ami Ronen , Elstein Deborah , Zimran Ari , Berliner Shlomo , Yedgar Saul , Barshtein Gershon
Published: July 2006

Gaucher disease is associated with increased red blood cell (RBC) aggregation, but the pathophysiological significance of this phenomenon and its correlation with disease manifestations are unclear. RBC aggregation was evaluated in 43 patients with Gaucher disease and 53 healthy controls. Dynamic RBC aggregation was examined in a narrow‐gap flow chamber at varying shear stress. Compared with the controls, RBC aggregation in Gaucher disease was increased by 25%. Comparison of RBC aggregation in autologous plasma and in dextran (500 kDa) showed an increase both in plasma‐dependent (extrinsic) and ‐independent (intrinsic) RBC aggregation. Subgroup analysis revealed that increased RBC aggregation was limited to patients with an intact spleen. RBC aggregation in patients did not correlate with plasma fibrinogen concentration, disease severity, enzyme replacement therapy or genotype. We conclude that RBC aggregation is increased in patients with Gaucher disease and an intact spleen, possibly reflecting the accumulation of glucocerebroside and other substances in the plasma and RBC membranes of these patients. Our results do not support a role for RBC aggregation in the pathogenesis of vascular complications of Gaucher disease.
Drug‐induced cutaneous vasculitis in patients with non‐Hodgkin lymphoma treated with the novel proteasome inhibitor bortezomib: a possible surrogate marker of response?
Authors: Gerecitano John , Goy Andre , Wright John , MacGregor‐Cortelli Barbara , Neylon Ellen , Gonen Mithat , Esseltine Dixie , Boral Anthony , Schenkein David , Busam Klaus , Teruya‐Feldstein Julie , Sachs Dana , O'Connor Owen A.
Published: July 2006

Bortezomib is the first proteasome inhibitor to be approved for use in haematological malignancies. Although a rash has been described as a common adverse event associated with the drug, it has not been well characterised. Based on three phase II studies of bortezomib in patients with non‐Hodgkin lymphoma (140 assessable patients), we identified 26 patients who developed a unique erythematous maculopapular rash during treatment, six of whom underwent cutaneous biopsy. Punch biopsy in six patients revealed a perivascular lymphocytic infiltrate without evidence of lymphoma, consistent with a non‐necrotising cutaneous vasculitis. The combined overall response rate was 41%. The response in the 26 patients who developed a rash was 73%, compared with 33% in patients who did not. The odds ratio for response given the development of a rash was 4·6 (95% CI, 1·7–12·4, P = 0·001). This is the first report to characterise a vasculitic rash associated with bortezomib, and to show a relationship between development of the rash and response to treatment. Unlike classic hypersensitivity type reactions, this vasculitic rash may not necessarily prompt cessation of drug. In fact, the development of an isolated cutaneous vasculitis may portend a better clinical response to bortezomib in some patients.
Hypothyroidism as a protective factor in acute stroke patients
Authors: Alevizaki Maria , Synetou Margaret , Xynos Konstantinos , Alevizaki Calliope C. , Vemmos Kostas N.
Published: July 2006

Objective  It has been reported that hypothyroidism is associated with better survival in elderly persons. We investigated possible associations of thyroid status with clinical outcome in patients with acute stroke.

Design  Retrospective analysis.

Patients  Consecutive patients (median age 70 years) admitted for acute stroke.

Measurements  Total T3, T4 and TSH levels. Stroke severity evaluation using the Scandinavian Stroke Scale (SSS) and the Glasgow Coma Score (GCS). Handicap and survival assessment over 12 months.

Results  Of 744 patients where thyroid function tests were available within the first 24 h of stroke, 13 had elevated TSH (≥ 10 µU/ml; range 10–42 µU/ml) (hypo‐group), 51 had mildly elevated TSH (3·3–9·9 µU/ml) and 680 had nonelevated TSH < 3·3 µU/ml. In the hypo‐group transient ischaemic attacks (TIA's) were more prevalent (46·2%) compared to the groups of mildly elevated TSH (11·8%) and nonelevated TSH (12·4%, P < 0·002). Hypo‐group had more frequently an adequate level of consciousness (GCS 14–15 = fully alert): 92·3%vs 74·5% and 63·7% (P = 0·033), a milder neurological deficit (SSS score 45–58) 76·9%vs 39·2% and 38·7% (P = 0·02) compared to the other two groups, respectively, and a tendency for lower glucose levels on admission. One year outcome tended to be better with respect to survival and handicap.

Conclusions  Acute stroke patients with laboratory findings compatible with pre‐existing hypothyroidism on admission, appear to have better clinical presentation and outcome; we speculate that a reduced response to stress and previous TIA's, possibly related to endogenous ‘preconditioning’, may contribute to this phenomenon.
Gene expression profiling of human macrophages at late time of infection with Mycobacterium tuberculosis
Authors: Volpe Elisabetta , Cappelli Giulia , Grassi Manuela , Martino Angelo , Serafino Annalucia , Colizzi Vittorio , Sanarico Nunzia , Mariani Francesca
Published: July 2006

Macrophages play an essential role in the immune response to Mycobacterium tuberculosis (Mtb). Previous transcriptome surveys, by means of micro‐ and macroarrays, investigated the cellular gene expression profile during the early phases of infection (within 48 hr). However, Mtb remains within the host macrophages for a longer period, continuing to influence the macrophage gene expression and, consequently, the environment in which it persists. Therefore, we studied the transcription patterns of human macrophages for up to 7 days after infection with Mtb. We used a macroarray approach to study 858 human genes involved in immunoregulation, and we confirmed by quantitative real‐time reverse transcriptase polymerase chain reaction (q‐rt RT‐PCR) and by enzyme‐linked immunosorbent assay the most relevant modulations. We constantly observed the up‐regulation in infected macrophages versus uninfected, of the following genes: interleukin‐1β and interleukin‐8, macrophage inflammatory protein‐1α, growth‐related oncogene‐β, epithelial cell‐derived neutrophil‐activating peptide‐78, macrophage‐derived chemokine, and matrix metalloproteinase‐7; whereas macrophage colony‐stimulating factor‐receptor and CD4 were down‐regulated in infected macrophages. Mtb is able to withstand this intense cytokine microenvironment and to survive inside the human macrophage. Therefore we simultaneously investigated by q‐rt RT‐PCR the modulation of five mycobacterial genes: the alternative sigma factors sigA, sigE and sigG, the α‐crystallin (acr) and the superoxide dismutase C (sodC) involved in survival mechanisms. The identified host and mycobacterial genes that were expressed until 7 days after infection, could have a role in the interplay between the host immune defences and the bacterial escape mechanisms.
Immune‐privileged embryonic Swiss mouse STO and STO cell‐derived progenitor cells: major histocompatibility complex and cell differentiation antigen expression patterns resemble those of human embryonic stem cell lines
Authors: Koch Katherine S. , Son Kyung‐Hwa , Maehr Rene , Pellicciotta Illenia , Ploegh Hidde L. , Zanetti Maurizio , Sell Stewart , Leffert Hyam L.
Published: July 2006

Embryonic mouse STO (S, SIM; T, 6‐thioguanine resistant; O, ouabain resistant) and 3(8)21‐enhanced green fluorescent protein (EGFP) cell lines exhibit long‐term survival and hepatic progenitor cell behaviour after xenogeneic engraftment in non‐immunosuppressed inbred rats, and were previously designated major histocompatibility complex (MHC) class I‐ and class II‐negative lines. To determine the molecular basis for undetectable MHC determinants, the expression and haplotype of H‐2K, H‐2D, H‐2L and I‐A proteins were reassessed by reverse transcriptase–polymerase chain reaction (RT‐PCR), cDNA sequencing, RNA hybridization, immunoblotting, quantitative RT‐PCR (QPCR), immunocytochemistry and flow cytometry. To detect cell differentiation (CD) surface antigens characteristic of stem cells, apoptotic regulation or adaptive immunity that might facilitate progenitor cell status or immune privilege, flow cytometry was also used to screen untreated and cytokine [interferon (IFN)‐γ]‐treated cultures. Despite prior PCR genotyping analyses suggestive of H‐2q haplotypes in STO, 3(8)21‐EGFP and parental 3(8)21 cells, all three lines expressed H‐2K cDNA sequences identical to those of d‐haplotype BALB/c mice, as well as constitutive and cytokine‐inducible H‐2Kd determinants. In contrast, apart from H‐2Ld[LOW] display in 3(8)21 cells, H‐2Dd, H‐2Ld and I‐Ad determinants were undetectable. All three lines expressed constitutive and cytokine‐inducible CD34; however, except for inducible CD117[LOW] expression in 3(8)21 cells, no expression of CD45, CD117, CD62L, CD80, CD86, CD90·1 or CD95L/CD178 was observed. Constitutive and cytokine‐inducible CD95[LOW] expression was detected in STO and 3(8)21 cells, but not in 3(8)21‐EGFP cells. MHC (class I+[LOW]/class II–) and CD (CD34+/CD80–/CD86–/CD95L–) expression patterns in STO and STO cell‐derived progenitor cells resemble patterns reported for human embryonic stem cell lines. Whether these patterns reflect associations with mechanisms that are regulatory of immune privilege or functional tissue‐specific plasticity is unknown.
Splice variants of human FOXP3 are functional inhibitors of human CD4+ T‐cell activation
Authors: Smith Emma L. , Finney Helene M. , Nesbitt Andrew M. , Ramsdell Fred , Robinson Martyn K.
Published: July 2006

FOXP3 has been identified as a key regulator of immune homeostasis. Mutations within the FOXP3 gene result in dysregulated CD4+ T‐cell function and elevated cytokine production, leading to lymphoproliferative disease. FOXP3 expression in CD4+ T cells is primarily detected with the CD4+ CD25+ regulatory T‐cell population. In humans the protein is detected as a doublet following immunoblot analysis. The lower band of the doublet has been identified as a splice isoform lacking a region corresponding to exon 2. The aim of this study was to investigate whether the splice variant form lacking exon 2 and a new novel splice variant lacking both exons 2 and 7, were functional inhibitors of CD4+ T‐cell activation. The data generated showed that full‐length FOXP3 and both splice variant forms of the protein were functional repressors of CD4+ T‐cell activation.
Heat shock protein 27: its potential role in vascular disease
Authors: Ferns Gordon , Shams Sedigheh , Shafi Shahida
Published: July 2006

Heat shock proteins are molecular chaperones that have an ability to protect proteins from damage induced by environmental factors such as free radicals, heat, ischaemia and toxins, allowing denatured proteins to adopt their native configuration. Heat shock protein‐27 (Hsp27) is a member of the small Hsp (sHsp) family of proteins, and has a molecular weight of approximately 27 KDa. In addition to its role as a chaperone, it has also been reported to have many additional functions. These include effects on the apoptotic pathway, cell movement and embryogenesis. In this review, we have focused on its possible role in vascular disease.
Regulation of granuloma fibrosis by nitric oxide during Mycobacterium avium experimental infection
Authors: Lousada Susana , Flórido Manuela , Appelberg Rui
Published: July 2006

Collagen deposition within granulomas formed after Mycobacterium avium infection was analysed on histological sections stained with Masson's trichrome using acquired computerized image analysis and a program that was specifically designed for that purpose. Comparison was made between immunocompetent C57BL/6 mice and mice genetically deficient in the inducible nitric oxide (NO) synthase gene (iNOS–/– mice) infected with either a highly virulent strain or a moderately virulent strain of M. avium. iNOS‐deficient mice were more resistant to the highly virulent strain than control C57B1/6 mice, but both strains were equally susceptible to the less virulent M. avium strain. Collagen distribution in the granuloma was found in the cuff surrounding the granuloma in an area rich in lymphoid cells as well as inside the granuloma itself, conferring a mesh‐like structure within that lesion. It was seen that iNOS–/– mice induced a higher collagen deposition than C57BL/6 mice and that such collagen deposition varied with the mycobacterial strain used to infect the animals.
HCV‐related advanced fibrosis/cirrhosis: randomized controlled trial of pegylated interferonα‐2a and ribavirin
Authors: Helbling Beat , Jochum Wolfram , Stamenic Ivan , Knöpfli Marina , Cerny Andreas , Borovicka J. , Gonvers Jean‐Jacques , Wilhelmi Martin , Dinges Sabine , Müllhaupt Beat , Esteban Alicia , Meyer‐Wyss Beat , Renner Eberhard L. ,   on behalf of the Swiss Association for the Study of the Liver (SASL)
Published: July 2006

Summary. In patients with hepatitis C virus (HCV)‐related advanced fibrosis/cirrhosis, 30% of sustained HCV clearance has been reported with pegylated interferonα‐2a (PEG‐IFN) alone, but the efficacy and tolerability of the PEG‐IFN/ribavirin (RBV) combination remain poorly defined. A total of 124 treatment‐naïve patients with biopsy proved HCV‐related advanced fibrosis/cirrhosis (Ishak score F4–F6, Child–Pugh score ≤7) were randomized to 48 weeks of PEG‐IFN (180 μg sc weekly) and standard dose of RBV (1000/1200 mg po daily, STD) or PEG‐IFN (180 μg sc weekly) and low‐dose of RBV (600/800 mg po daily, LOW). Sustained virologic response (SVR) rates with PEG‐IFN/STD RBV (52%) were higher – albeit not significantly – than that with PEG‐IFN/LOW RBV (38%,P = 0.153). In multivariate analysis, genotype 2/3 and a baseline platelet count ≥150 × 109/L were independently associated with SVR. The likelihood of SVR was <7% if viraemia had not declined by ≥2 log or to undetectable levels after 12 weeks. Nine adverse events in the STD RBV and 15 in the LOW RBV group were classified as severe (including two deaths); dose reductions for intolerance were required in 78% and 57% (P = 0.013), and treatment was terminated early in 23% and 27% of patients (P = n.s.). The benefit/risk ratio of treating compensated HCV‐cirrhotics with STD PEG‐IFN/RBV is favourable.
A brassinolide‐suppressed rice MADS‐box transcription factor, OsMDP1, has a negative regulatory role in BR signaling
Authors: Duan Ke , Li Li , Hu Peng , Xu Shu‐Ping , Xu Zhi‐Hong , Xue Hong‐Wei
Published: July 2006

The MADS‐box transcription factor‐encoding genes are expressed mainly during plant reproductive development, where they play important roles in controlling floral organ initiation and identity. Few previous reports have investigated the functions of MADS‐box transcription factors expressed in vegetative tissues. Here we describe the functional characterization of a rice AG‐like MADS‐box protein, OsMDP1 (Oryza sativa MADS‐domain‐containing protein 1). A partial cDNA encoding a MADS‐box domain was identified via high‐throughput screening of rice brassinolide‐regulated genes, and the full‐length cDNA was subsequently isolated via screening of a cDNA library constructed from rice materials at tillering stage. Expression pattern analyses indicated that OsMDP1 is transcribed mainly in vegetative tissues, including the mature leaf, coleoptile, root‐elongation zone, culm internode, and especially the joint region between the leaf blade and sheath. Further studies revealed that transcription of OsMDP1 is stimulated by darkness and suppressed by brassinolide treatment. OsMDP1 deficiency resulted in shortened primary roots, elongated coleoptiles and enhanced lamina joint inclinations. Moreover, transgenic plants showed hypersensitivities to exogenous brassinolide in terms of lamina joint inclination and coleoptile elongation. OsMDP1 deficiency resulted in enhanced expression of OsXTR1, which encodes xyloglucan endotransglycosylase, the cell‐wall loosening enzyme necessary for cell elongation, and modulated expressions of multiple genes involved in cell signalling and gene transcription, indicating the key negative regulatory role of OsMDP1 in BR signalling.
Can allergic diseases be prevented prenatally?
Authors: Boyle R. J. , Tang M. L. K.
Published: July 2006

Allergic diseases continue to increase in prevalence, and now affect over a third of the population in many countries. There is evidence that the increase in such diseases has its origins in early life exposures. Pregnancy or early childhood may therefore be critical periods for preventing the onset of allergic disease, and prenatal interventions are an attractive possibility for a population‐based preventive approach. Here we review the data suggesting that prenatal exposures are important in the development of allergic disease, and that interventions during this time might be effective in prevention. We find evidence from both animal and human studies that prenatal interventions can influence the future development of allergic disease. There are a number of mechanisms through which such interventions may act to prevent allergic sensitization. We conclude that prenatal interventions have the potential to reduce the burden of allergic disease, and merit continued investigation. Further research in this area may lead to significant public health initiatives.
Overexpression of RCI2A decreases Na+ uptake and mitigates salinity‐induced damages in Arabidopsis thaliana plants
Authors: Mitsuya Shiro , Taniguchi Mitsutaka , Miyake Hiroshi , Takabe Tetsuko
Published: July 2006

We have investigated whether the overexpression of RCI2A gene causes an enhanced salt‐tolerant phenotype in Arabidopsis thaliana. Although the growth of RCI2A‐overexpressing transgenic plants was comparable with that of wild type under normal conditions, high salinity treatment caused decreased accumulation of Na+ and ameliorated suppression of the shoot growth of transgenic plants than that of wild type. Under high salinity treatment, the chlorophyll content of the shoots of wild‐type plants significantly decreased compared with transgenic plants. The increases of malondialdehyde (MDA) and of H2O2 production caused by high salinity were greater in the shoots of wild type than in that of transgenic plants. These results suggest that overexpression of RCI2A can alleviate salinity‐induced growth suppression and photooxidative damages via reducing Na+ uptake into the shoots.
Genetics of flower initiation and development in annual and perennial plants
Authors: Tan Fui‐Ching , Swain Steve M.
Published: July 2006

Flowering is an integral developmental process in angiosperms, crucial to reproductive success and continuity of the species through time. Some angiosperms complete their life cycle within a year (annual plants), and others have a longer reproductive life, which is characterized by the generation of new flowering and vegetative shoots every year (perennial plants). Despite the differences in their lifespan, the underlying genetics of flower induction and floral organ formation appears to be similar among these plants. Hence, the knowledge gained from the study of flowering mechanism in Arabidopsis thaliana can be used to better understand similar processes in other plant species, especially the perennials, which usually have a long generation time and are not amenable to genetic analysis. Using Arabidopsis as a model, we briefly discuss the current understanding of the transition from vegetative to reproductive growth and the subsequent formation of individual floral organs, and how this knowledge has been successfully applied to the identification of homologous genes from perennial crops. Although annuals appear to share many similarities with perennials in terms of gene function, they differ in their commitment to flowering. Once an annual reaches the reproductive phase, all meristems are typically converted into either floral or inflorescence meristems. In contrast, each year, each meristem of a mature perennial has the choice to produce either a vegetative or a reproductive shoot. The physiology and genetics of flowering in Citrus are used to highlight the complexity of reproductive development in perennials, and to discus possible future research directions.
Response of physiologic metabolism and cell structures in mango fruit to exogenous methyl salicylate under low‐temperature stress
Authors: Han Jin , Tian Shi‐Ping , Meng Xiang‐Hong , Ding Zhan‐Sheng
Published: July 2006

We explored the effects of exogenous methyl salicylate (MeSA) on the development of chilling injury symptom, and the structure and composition of the pericarp, in mango (Mangifera indica L. cv. ‘Red 6’) fruit under low‐temperature stress using histochemical analysis and scanning electron microscopy together with Fourier transform infrared (FTIR) analysis. The results indicated that chilling injury symptom was remarkably limited in the fruit treated with MeSA at 0.1 mM as compared to the 5°C control, demonstrating the positive effects of MeSA in reducing chilling injury of mango fruit in low‐temperature storage. In MeSA‐treated fruit, the pericarp wax surface showed many cracks, and exocarp cells exhibited normal separation. The cell wall of exocarp contained lower amounts of pectic substances, aliphatics and phenolics in MeSA‐treated fruit. In addition, MeSA‐treated fruit contained more esterified substances and less carboxylate and carboxyl substances. Our work revealed the importance of MeSA in enhancing fruit tolerance to low‐temperature stress and suggested a contribution of cellular structure and composition to this effect, which has not been reported previously.
Investigation of selenium tolerance mechanisms in Arabidopsis thaliana
Authors: Zhang Li‐Hong , Abdel‐Ghany Salah E. , Freeman John L. , Ackley Ashley R. , Schiavon Michela , Pilon‐Smits Elizabeth A. H.
Published: July 2006

To investigate selenium tolerance mechanisms in Arabidopsis thaliana, genetic and physiologic studies were performed in the three Arabidopsis accessions Landsberg erecta (Ler), Columbia (Col) and Wassilewskija (Ws). Accession Ler was significantly less tolerant to selenate than Ws and Col, whereas Ws was less tolerant to selenite than the others. Analysis of selenium tolerance in F1 and F2 plants obtained from crosses between these accessions suggest that multiple genes are involved in selenate tolerance and a single major gene controls selenite tolerance in these populations. Bulked segregant analysis in two F2 populations indicated that molecular marker ciw7 on chromosome 4 is linked to selenite tolerance, and three molecular markers on chromosomes 1, 3 and 5 (nga111, ciw4 and ciw8, respectively) are linked to selenate tolerance. The ecotypic variation in selenite tolerance appeared to be correlated with root levels of non‐protein thiols. Also, the shoot tissue levels of selenocysteine (SeCys) and selenocystine were correlated with tolerance to both selenate and selenite. Judging from RT‐PCR results, several sulfate transporters and S assimilatory enzymes appear to be upregulated by selenate and selenite at the transcriptional level. A potential SeCys methyltransferase was expressed at lower levels in selenite‐sensitive Ws than in the other two, when grown on selenite. Together, these studies show that there is substantial intraspecific variation in tolerance to selenate and selenite in Arabidopsis, and provide insights into the genetic and biochemical mechanisms underlying the observed ecotypic differences.
Effect of pre‐hospital advanced life support with rapid sequence intubation on outcome of severe traumatic brain injury
Authors: Klemen P. , Grmec Š.
Published: July 2006

Background:  The role of pre‐hospital trauma care and the effect of pre‐hospital rapid sequence intubation (RSI) on patient outcome are still not clear. This study evaluated the impact of pre‐hospital trauma care by emergency physicians (EP) on mortality from severe traumatic brain injury (TBI) and a 180‐day Glasgow Outcome Scale (GOS).

Methods:  A 48‐month parallel non‐controlled cohort study compared a group of 64 patients with severe TBI [Glasgow Coma Scale (GCS) < 9; Injury Severity Score (ISS) > 15] who received pre‐hospital advanced life support (ALS) with RSI and were transported to the hospital by EPs (EP group), with a group of 60 patients who did not receive pre‐hospital ALS with RSI [emergency medical technicians (EMT) group].

Results:  There were no significant statistical differences between the groups in age (P= 0.79), mechanism of injury (P= 0.68), gender (P= 0.82), initial GCS (P= 0.63), initial SaO2 in the field (P= 0.63), initial systolic blood pressure in the field (P= 0.47) and on‐scene time (P= 0.41). In the EP group, there was significantly better first hour survival (97% vs. 79%, P= 0.02), first day survival (90% vs. 72%, P= 0.02), better functional outcome (GOS 4–5: 53% vs. 33%, P < 0.01; GOS 2–3: 8% vs. 20%, P < 0.01) and shortened hospitalization time in intensive care unit (ICU) (P= 0.03) and other departments (P= 0.04). In total hospital mortality, we detected no differences between both groups [EP group: 40% (95% CI: 34–45%) vs. EMT group 42% (95% CI: 36–47%, P= 0.76], except in a subgroup of patients with GCS 6–8 where there was significantly lower total hospital mortality in the EP group (24% vs. 78%, P < 0.01).

Conclusion:  After starting the trauma care system with emergency physicians in our region, there was a decrease in the number of deaths on hospital admission, a reduction in hospital mortality in the GCS group 6–8, a change in the temporal distribution of deaths, an improvement in functional neurological outcome and shortened hospitalization time.
Effects of cigarette smoking on serum fluoride concentrations and renal function integrity after 1 MAC‐h sevoflurane anaesthesia
Authors: Laisalmi M. , Kokki H. , Soikkeli A. , Markkanen H. , Yli‐Hankala A. , Rosenberg P. , Lindgren L.
Published: July 2006

Background:  Tobacco smoke contains various chemicals which may affect drug metabolism. Sevoflurane is metabolized to inorganic fluoride, and elevated serum fluoride concentrations (S‐F−) may cause deterioration of renal function. Whether smokers develop high S‐F− and associated disturbances in renal function is not known.

Methods:  We investigated sevoflurane metabolism in 25 non‐smoking and 25 smoking (> 10 cigarettes/day) generally healthy women, aged 19–68 years, undergoing gynaecological elective surgery under one minimum alveolar concentration‐hour (1 MAC‐h) standardized sevoflurane anaesthesia. S‐F− was measured for 24 h. Glomerular and tubular function was assessed by measuring serum and urine tumour‐associated trypsin inhibitor (TATI), β2‐microglobulin and serum creatinine for 48 h after sevoflurane inhalation.

Results:  There were no differences between the two study groups with regard to S‐F−. It increased significantly in both groups: in non‐smokers, from a baseline between 1.0 and 11 μmol/l (median, 1.6 μmol/l) to a maximum between 8.2 and 40 μmol/l (26 μmol/l) (P < 0.001) and, in smokers, from a baseline between 0.5 and 5.2 μmol/l (1.7 μmol/l) to a maximum between 19 and 71 μmol/l (25 μmol/l) (P < 0.001). In both groups, S‐F− remained elevated for the entire sampling period (P < 0.001). In all five women (one non‐smoker and four smokers) with a maximum S‐F− of 40 μmol/l or higher and an area under the serum fluoride concentration–time curve (AUCF0–24) of 500 μmol/h/l or higher, serum TATI increased above the pathological concentration of 3.0 nmol/l, whereas only six of the 45 patients with S‐F− below 40 μmol/l had serum TATI above 3.0 nmol/l (P < 0.001). β2‐Microglobulin increased significantly (> 1 mg/l) in two patients with high S‐F− relative to two of the 45 patients with S‐F− below 40 μmol/l (P= 0.005). None of the patients developed clinically detectable renal dysfunction.

Conclusion:  Smoking did not affect S‐F− after sevoflurane anaesthesia. Glomerular dysfunction, seen as increased serum TATI, was noted in five women with S‐F− above 40 μmol/l. Our results suggest that the renal toxic threshold of S‐F− seems to be lower than the earlier reported value of 50 μmol/l.
Expression of cyclo‐oxygenase‐2 in gastrointestinal carcinoid tumors
Authors: Mizuno Shigeaki , Kato Kimitoshi , Hashimoto Akemi , Sugitani Masahiko , Sheikh Aleemuzzaman , Komuro Sachiko , Jike Toyoharu , Iwasaki Ariyoshi , Arakawa Yasuyuki , Nemoto Norimichi
Published: July 2006

Background:  Cyclo‐oxygenase (COX)‐2 overexpression is observed in various neoplasms and COX‐2 inhibition has been attempted as prevention and/or therapy in these neoplasms. Carcinoid tumors are thought to arise from neuroendocrine cells and originate mainly in the gastrointestinal tract. Cyclo‐oxygenase‐2 is reportedly expressed in neuroendocrine cells of normal colorectal mucosa. The role of COX in carcinoids has not previously been investigated. The aim of the present paper was to clarify the expression of COX‐1 and ‐2, and their role in human gastrointestinal carcinoids.

Methods:  Expression of COX‐1 and ‐2 was studied immunohistochemically in 38 gastrointestinal carcinoids. Five bronchopulmonary and seven metastatic carcinoids were also examined, for comparison with gastrointestinal carcinoids. The immunohistochemical score (IHS) was calculated from staining intensity and immunoreactive cell population, and ranked according to four grades (negative to strong).

Results:  Cyclo‐oxygenase‐2 was expressed in all gastrointestinal carcinoids (weak, 1; moderate, 13; strong, 24) and bronchopulmonary carcinoids (weak, 1; moderate, 4), as well as their metastases (moderate, 3; strong, 4). The IHS of COX‐2 in larger tumors was significantly lower than that in smaller tumors. However, the IHS of COX‐2 at the advancing tumor edge was significantly higher than that at the centers of tumors ≥10 mm in size. Faint COX‐1 expression was detected in only one duodenal, one rectal and four bronchopulmonary carcinoids.

Conclusions:  Enhanced COX‐2 expression was observed in gastrointestinal as well as bronchopulmonary carcinoids and their metastases, especially at the advancing edges of the tumors. Cyclo‐oxygenase‐2 may play a role in carcinoid progression.
Polymorphisms in the promoter region of the angiotensinogen gene are associated with liver cirrhosis in patients with chronic hepatitis B
Authors: Xiao Fan , Wei Hongshan , Song Shujing , Li Guoli , Song Chuan
Published: July 2006

Background and Aims:  It is known that the renin‐angiotensin system (RAS) regulates fibrosis. Polymorphisms in the genes of the RAS may contribute to the outcome of liver cirrhosis. Angiotensinogen (AGT), mainly produced in the liver, is the substrate of renin. The aim of this study was to determine whether polymorphisms in the promoter region of the AGT gene are associated with liver cirrhosis in patients with chronic hepatitis B.

Methods:  Restriction fragment length polymorphism PCR was used to study polymorphisms in the promoter region of the AGT gene in patients with liver cirrhosis and in a control population. Four polymorphisms were assayed: G‐217A, G‐152A, A‐20C and A‐6G.

Results:  A statistically significant relationship was seen between polymorphisms of the AGT core promoter region and liver cirrhosis in patients with chronic hepatitis B (A‐20C, P = 0.007; A‐6G, P = 0.042). However, the distributions of the AGT‐217 and AGT‐152 genotypes were not significantly different from the control population (P = 0.615 and P = 0.170, respectively).

Conclusions:  Polymorphisms of the core promoter region of the AGT gene (AGT‐20 and AGT‐6) were associated with liver cirrhosis in patients with chronic hepatitis B.
East Asian‐type Helicobacter pylori cytotoxin‐associated gene A protein has a more significant effect on growth of rat gastric mucosal cells than the Western type
Authors: Fu Hai Ying , Asahi Kayoko , Hayashi Yujiro , Eguchi Hiroshi , Murata Hiroaki , Tsujii Masahiko , Tsuji Shingo , Azuma Takeshi , Kawano Sunao
Published: July 2006

Background and Aim:  Cytotoxin‐associated gene A (CagA) protein from H. pylori was reported to be injected into host gastric epithelial cells via a bacterial type IV secretion system, thereby modifying signal transduction. It is classified into two major subtypes, Western and East Asian. The present study aimed to compare the effects of East Asian‐type and Western‐type CagA on host cell growth.

Methods:  A tetracycline (tet)‐off system and cagA genes from Western and East Asian‐type H. pylori (NCTC 11637 and F32) were transfected into untransformed rat gastric mucosal (RGM1) cells to establish RGM1‐CagA cell lines in which CagA expression could be controlled by tetracycline. These cell lines were used to investigate the effect of CagA protein expression on cell growth with BrdU and water‐soluble tetrazolium reagent (WST‐8) assays. CagA expression, phosphorylation and extracellular signal‐regulated kinase (ERK) activation were examined with immunoprecipitation and Western blotting analysis.

Results:  5‐Bromo‐2′deoxyuridine (BrdU) and WST‐8 assays demonstrated significant increases in DNA replication and RGM1 cell growth after CagA protein expression. ERK phosphorylation was enhanced when CagA protein was expressed in RGM1‐CagA cells. Moreover, the East Asian‐type CagA showed a significantly greater effect on ERK activation and host cell growth than the Western type. PD98059, a mitogen‐activated protein kinase kinase (MEK) inhibitor, suppressed ERK phosphorylation and the CagA protein‐induced increase in RGM1‐CagA cell growth.

Conclusions:  CagA protein expression induces an increase in RGM1‐CagA cell proliferation via the mitogen‐activated protein kinase (MAPK) signal pathway. The East Asian‐type CagA showed a significantly greater effect on cell growth than the Western type, suggesting that the East Asian CagA‐positive strain may have an important role in pathogenesis.
High dose probiotic and prebiotic cotherapy for remission induction of active Crohn’s disease
Authors: Fujimori Shunji , Tatsuguchi Atsushi , Gudis Katya , Kishida Teruyuki , Mitsui Keigo , Ehara Akihito , Kobayashi Tsuyoshi , Sekita Yoshihisa , Seo Tsuguhiko , Sakamoto Choitsu
Published: July 2006

Background:  Clinical trials of probiotic treatment for Crohn’s disease (CD) have yielded conflicting results. This study assessed the clinical usefulness of combined probiotic and prebiotic therapy in the treatment of active CD.

Method:  Ten active CD outpatients without history of operation for CD were enrolled. Their mean (±SD) age was 27 ± 7 years and the main symptoms presented were diarrhea and abdominal pain. Patients’ initial therapeutic regimen of aminosalicylates and prednisolone failed to achieve remission. Patients were thus initiated on a synbiotic therapy, consisting of both probiotics (75 billion colony forming units [CFU] daily) and prebiotics (psyllium 9.9 g daily). Probiotics mainly comprised Bifidobacterium and Lactobacillus. Patients were free to adjust their intake of probiotics or prebiotics throughout the trial. Crohn’s disease activity index (CDAI), International Organization for the Study of Inflammatory Bowel Disease (IOIBD) score and blood sample variables were evaluated and compared before and after the trial.

Results:  The duration of the trial was 13.0 ± 4.5 months. By the end of therapy, each patient had taken a 45 ± 24 billion CFU daily probiotic dose, with six patients taking an additional 7.9 ± 3.6 g daily psyllium dose. Seven patients had improved clinical symptoms following combined probiotic and prebiotic therapy. Both CDAI and IOIBD scores were significantly reduced after therapy (255–136, P = 0.009; 3.5–2.1, P = 0.03, respectively). Six patients had a complete response, one had a partial response, and three were non‐responders. Two patients were able to discontinue their prednisolone therapy, while four patients decreased their intake. There were no adverse events.

Conclusion:  High‐dose probiotic and prebiotic cotherapy can be safely and effectively used for the treatment of active CD.
Recovery of temperate Desulfovibrio vulgaris bacteriophage using a novel host strain
Authors: Walker Christopher B. , Stolyar Sergey S. , Pinel Nic , Yen Huei‐Che B. , He Zhili , Zhou Jizhong , Wall Judy D. , Stahl David A.
Published: July 2006

A novel sulfate‐reducing bacterium (strain DePue) closely related to Desulfovibrio vulgaris ssp. vulgaris strain Hildenborough was isolated from the sediment of a heavy‐metal impacted lake using established techniques. Although few physiological differences between strains DePue and Hildenborough were observed, pulse‐field gel electrophoresis (PFGE) revealed a significant genome reduction in strain DePue. Comparative whole‐genome microarray and polymerase chain reaction analyses demonstrated that the absence of genes annotated in the Hildenborough genome as phage or phage‐related contributed to the significant genome reduction in strain DePue. Two morphotypically distinct temperate bacteriophage from strain Hildenborough were recovered using strain DePue as a host for plaque isolation.
MICROETHICS IN ACTION1
Authors: NIKKU NINA , ERIKSSON BENGT ERIK
Published: July 2006

The future development of bioethics has been discussed in a number of articles in recent years, principally with regard to the trend towards empirical studies. However, what is meant by empirical studies in this context and how it is to be used concretely have been subject to varying interpretations. The purpose of this article is to develop what we term the microethical approach as a concrete method for an empirically driven bioethics. By adopting a microethical perspective, we will illustrate an analytical concept for describing and demonstrating how, as a result of contextual circumstances and forms of understanding, different individuals in their everyday life adopt different coping strategies and behavior patterns in relation to ethical values. From a deepened perspective, the complexity of human behavior becomes apparent, and knowledge is gained about how moral problems are perceived and construed by those whom they in fact affect.

We intend first and foremost to develop the microethical methodology by elucidating the methods and approaches that can help in clarifying moral dilemmas on a microethical level, and how the relationship between the empirical material and the ethical analysis evolves over the course of the analysis. This is exemplified by a study of caregivers’ entrance into patients’ private lives through the provision of care and assistance in the home.
LAY CONCEPTS IN INFORMED CONSENT TO BIOMEDICAL RESEARCH: THE CAPACITY TO UNDERSTAND AND APPRECIATE RISK
Authors: ILTIS ANA
Published: July 2006

Persons generally must give their informed consent to participate in research. To provide informed consent persons must be given information regarding the study in simple, lay language. Consent must be voluntary, and persons giving consent must be legally competent to consent and possess the capacity to understand and appreciate the information provided. This paper examines the relationship between the obligation to disclose information regarding risks and the requirement that persons have the capacity to understand and appreciate the information. There has been insufficient attention to the extent to which persons must be able to understand and appreciate study information in order to have their consent deemed valid when the information is provided in simple, lay language. This paper argues that (1) the capacity to understand and appreciate information that should be deemed necessary to give valid consent should be defined by the capacity of the typical, cognitively normal adult and (2) the capacity of the typical, cognitively normal adult to understand and appreciate the concept of risk is limited. Therefore, (3) all things being equal, potential subjects must possess a limited capacity to understand and appreciate risk to be deemed competent to consent to research participation. (4) In some cases investigators ought to require that persons possess a greater than typical capacity to understand and appreciate risk.
MAKING THE CASE FOR HUMAN LIFE EXTENSION: PERSONAL ARGUMENTS
Authors: SCHLOENDORN JOHN
Published: July 2006

In the close to medium future, the life sciences might permit a vast extension of the human life span. I will argue that this is a very desirable development for the individual person. The question whether death is a harm to the dying is irrelevant here. All it takes is that being alive is good for the living person and not being alive is not good for anyone. Thus, living persons who expect to live on happily are rationally required to want to stay alive. Eventual uncertainty whether it will be possible to be happy in the future provides no objection, but rather an incentive to try. This view, however, may be naive in assuming that persons are unchanging entities that exist separately from their psychological information. Objections have been derived from reductionistic views that value our future experiences in a way that declines with time, so that there will be a future point beyond which only negligible value accrues. If we adopt such a view, then we cannot now be concerned to have experiences beyond that point. I argue that these arguments fail to take into account all the reasons we might have to be concerned for the future and all the kinds of such concern that come from them. The adoption of a plausible reductionistic account can arguably weaken our concern for the future and certainly change its quality in important ways. But this provides no objection to the desire to live forever, nor to live at all.
CHINESE CONCEPTS OF EUTHANASIA AND HEALTH CARE1
Authors: SLEEBOOM‐FAULKNER MARGARET
Published: July 2006

This article argues that taking concepts of euthanasia out of their political and economic contexts leads to violations of the premises on which the Stoic ideal of euthanasia is based: ‘a quick, gentle and honourable death’.2 For instance, the transplantation of the narrowly defined concept of euthanasia developed under the Dutch welfare system into a developing country, such as the People’s Republic of China (PRC), seems inadequate. For it cannot deal with questions of anxiety about degrading forms of dying and suffering without reference to its economic rationale, demanded by a scarcity (unequal distribution) of health care resources.

The weakness of health care provisions for the terminally ill in Mainland China has become increasingly poignant since the collapse of collective health care institutions in the countryside since the reforms of the late‐1980s. As in most cases where health care facilities are wanting, it is difficult to apply the criteria of gentleness and dignity at reaching death. Its solution lies not in a faster relief from suffering by euthanasia, but in extending the quality of life through distributive justice within Chinese healthcare policy‐making.

This paper begins with a brief description of the Dutch euthanasia law, after which it discusses Chinese conceptions of euthanasia in biomedical textbooks, the media and in surveys. It concludes by pointing out the need for a transnational framework in which both the specifics and generalities of euthanasia can be discussed.