bluuebunny/crossref_metadata_2025_split 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

SummarySingle 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

SummaryDay 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

AimsTo 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.MethodsThirty 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.ResultsPharmacokinetic 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.ConclusionThe 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

SummaryGaucher 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

SummaryBortezomib 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

SummaryObjective  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

SummaryMacrophages 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

SummaryEmbryonic 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

SummaryFOXP3 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

SummaryHeat 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

SummaryCollagen 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.
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

SummaryThe 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.
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.