bluuebunny/crossref_metadata_2025 huggingface dataset:
Paradoxical inheritance of HLA‐Iinked susceptibility to rheumatoid arthritis
Authors: De Vries R. R. P. , Nijenhuis L. E. , Khan M. A. , Mehra N. K.
Published: July 2010

In order to clarify the discrepancy between population studies showing association of rheumatoid arthritis (RA) with HLA‐DR4/‐Dw4 and family studies failing to show linkage with HLA, we analysed 16 multicase families in which RA and DR4 status of both parents was known. 120 HLA‐haplotypes of affected and unaffected children could be analysed for co‐segregation with RA. In a combined analysis of both affected and unaffected children co‐segregation of RA with the DR4 carrying haplotype was observed when both parents were unaffected (p=0.001). Co‐segregation of RA with one of the two haplotypes of affected parents was observed (p=0.01), but in this case there was no preference for the DR4 carrying haplotype. In both cases preferential inheritance of the other (not associated with RA) haplotype was observed in unaffected siblings.

These data indicate that susceptibility to RA is controlled by an HLA‐linked gene. This gene is often but not always identical to the gene coding for a product carrying the DR4 epitope or in strong linkage disequilibrium with it. Combined with previous population data, the present data provide evidence for genetic heterogeneity of RA. Finally, they contain a paradox, based on which a new hypothesis for HLA‐linked susceptibility to RA is formulated.
HLA polymorphisms in a Han Chinese population of Sichuan
Authors: Pei J. , Tokunaga K. , Araki C. , Yang C. L. , Sun S. X. , Mi X. Y. , Saji H. , Xiao X. F. , Liang W. X. , Tokunaga E.
Published: July 2010

This study reports the phenotype frequencies (PF) and gene frequencies (GF) of a homogeneous Sichuan Han Chinese population by typing of unrelated 229 individuals and 16 families for HLA‐A, B, C., DR and DQ antigens. The frequencies of Bw67, Bw71, DRwl2, DRwl3 and DRwl4 are the first to be reported in Chinese. The two‐locus haplotypes with significant linkage disequilibrium among the Sichuan have also been listed.
HLA typing and autoantibodies in hepatitis B surface antigen‐negative chronic active hepatitis
Authors: Kilby Alan E. , Albertini Richard J. , Krawitt Edward L.
Published: July 2010

HLA types, serum autoantibodies and serum globulin levels were surveyed in 46 patients with HBsAg‐negative chronic active hepatitis. Patients with chronic active hepatitis with viral risk factors were less likely than those without viral risk factors to be HLA type B8 (10% vs 44%) or to have autoantibodies (antinuclear and/or anti‐smooth muscle antibodies) (38% vs 84%). Thirty patients (10 with and 20 without viral risk factors) were treated with glucocorticosteroids. Of the 11 patients who were HLA‐B8, 100% responded to treatment. Of the 20 patients who were ANA positive, 80% responded. The data suggest that the presence of HLA‐B8 may be a useful predictor of response to anti‐inflammatory treatment and may define a genetic subset of HBsAg‐negative chronic active hepatitis that will benefit from glucocorticosteroid therapy.
An HLA‐DR/DP recombinant family involving DPw6. Evidence for cross‐reactivity between DPw6 and GNN2B
Authors: ØDum Niels , Hartzman Robert , Jakobsen Bodil K. , Morling Niels , Platz Per , Robbins Fu‐Meei , Ryder Lars P. , Shaw Steven , Svejgaard Arne
Published: July 2010

HLA typing of an HLA‐B/GLO recombinant family using bulk‐expanded DP(SB) alloreactive T‐cells (GNN1 to 6) as well as conventional HLA‐ABC, D, DR. and DQ typing showed that a paternal recombination had taken place between HLA‐DR and DQ on the one hand and HLA‐DP(SB) on the other. The recombinant child was DPw4, 6‐heterozygous and differed in terms of class II determinants only for DPw6 from two otherwise HLA identical siblings, who were probably DPw4/4‐homozygous. These siblings did not stimulate the recombinant in MLC whereas they responded to his cells indicating that DPw6 can stimulate in primary MLC. Moreover, it was possible to generate and bulk‐expand DPw6‐reactive lymphocytes (PLs) between MT and MA as responders and BN as stimulator. The correlation coefficient (r) between the reaction of these PLs and the GNN6 (anti‐DPw6) reagents was 1.0 when tested against a panel of 71 individuals.

This is the first report demonstrating that the DPw6 gene, like the DPw1‐w5 genes, is located between DR/DQ and GLO.

The frequency of the DPw6 antigen in 41 unrelated, randomly selected Danes was 7%. HLA‐DP typing of the BN family revealed that the DPw6 positive but not DPw6 negative family members gave intermediate responses with one (GNN2B) but not with another (GNN2A) anti‐DPw2‐reagent. Studies of 63 healthy individuals (unrelated to the BN family) revealed seven similar discrepancies between GNN2A and GNN2B. Strikingly, all four DPw6 positive stimulators gave rise to such discrepancies indicating that the GNN2B reagent is cross‐reactive and recognize a common part of the DPw2 and DPw6 molecules. No cases of GNN2A+/GNN2B‐ stimulators were found.
Gamma ray‐induced mutants as a tool for the production and characterisation of monoclonal antibodies against HLA‐alloantigens
Authors: Spring Bärbel , Pawelec Graham , Ziegler Andreas
Published: July 2010

To simplify the screening procedure for murine monoclonal antibodies specific for polymorphic HLA determinants, spleen cells from a mouse immunized with the human cell line BJAB‐B95.8.6 were fused with NSI mouse myeloma cells, and hybridoma supernatants were screened for their reactivity on BJAB‐B95.8.6 and two gamma ray‐induced HLA‐loss mutants of this line.

The use of these HLA‐loss mutants allowed the rapid identification of two new al‐lospecific MOABs designated TÜ160 and TÜ161. Serological as well as biochemical studies revealed TÜ160 to be specific for HLA‐A2, and TÜ161 for HLA‐B13 molecules, respectively. Both MOABs were determined to be antibodies of the IgG class and were able to precipitate their antigens from lysates of radioactively labeled cells.
Linkage disequilibrium involving three loci
Authors: Green Jack , Woodrow J. C.
Published: July 2010

A formula for the estimation of “three‐locus interaction delta” given by Nijenhuis & D'Amaro (1985) is considered and found to be unsatisfactory. An alternative symmetrical formula is given. Other features of the analysis of Nijenhuis & D'Amaro are criticized and it is emphasized that a more suitable method of analysis of interactions of different orders is given by the use of the empirical logistic method (Green et al. 1983).
A European workshop to investigate technical problems of using HLA monoclonal antibodies in microcytotoxicity assays
Authors: Kennedy L. J. , Bourel D. , Dejour G. , Fauchet R. , Bodmer J. G.
Published: July 2010

Various methods for controlling carryover from monoclonal antibodies (MCA) used in the microcytotoxicity assay to detect HLA antigens were investigated by 45 European laboratories. Carryover was demonstrated in most laboratories when using standard techniques (i.e. as for allo‐antisera). Taking into consideration factors such as technical ease, time, accuracy and reagent availability, nearly half the participants selected the “no‐touch” technique for adding cells and complement as being the best method for controlling carryover in their laboratory. (This method allows the needle of the Hamilton syringe to touch the oil but not the antibody in each well). Most participants (75%) thought that at least one diluent well was still necessary between each MCA well, even when using their preferred technique.
Increased frequency of HLA‐DPw3 in severe aplastic anemia (AA)
Authors: ØDum N. , Platz P. , Morling N. , Jacobsen N. , Jakobsen B. K. , Ryder L. P. , Svegaard A.
Published: July 2010

Thirteen patients with severe aplastic anemia (AA) were HLA‐DP typed using primed lymphocyte typing (PLT). The frequency of HLA‐DPw3 was significantly increased to 69% in AA as compared to 22% in 160 controls (p < 0.001; corrected p < 0.01, RR = 8.0).
Production of an HLA‐DRw13 antibody in a DRw14 positive multiparous woman
Authors: Darke C. , Street J.
Published: July 2010

A lymphocytotoxic HLA‐DR alloantiserum (Ma159) which reacts with DR7, DR5 and DRw13 positive lymphocytes is described. It was non‐cytotoxic against 27 DRw14 positive subjects and was not absorbed by DRw14 positive cells. The anti‐serum was produced by pregnancy alone in a DR4, DRw14 positive woman whose husband possesses DR7 and DRw13. Absorption and titration studies suggested that the antiserum contains separate antibodies directed towards DR7, DRw13 and a determinant shared by DR5 and DRw13. The implications of finding a specific anti‐DRw13 antiserum and its production in a donor positive for the alternative subdivision of DRw6 are discussed.
HLA antigens in South India: II. Selected caste groups of Tamil Nadu
Authors: Rajasekar R. , Kakkanaiah V. N. , Pitchappan RM.
Published: July 2010

HLA‐A, B antigen and haplotype frequencies were studied in four different caste groups of Tamil Nadu living in Madurai. A total number of 101 Nadars, 36 Kallars, 54 Iyers and 57 Telugu‐speaking Naidus were studied. HLA A3 and B15 were significantly higher in Nadars; A10 & B8 in Kallars and Aw19, B12 & B35 in Iyers. HLA A‐B haplotypes A10‐B7, A28‐B17 & A24‐B‐ were characteristic of Nadars; A10‐B8 & A1‐B‐, Kallars; Aw19‐B12 & A1‐B15, Iyers and A2‐B‐, Naidus. Negative linkage disequilibria for Aw19‐B7, A28‐B15 & A9‐B51 were significant in Nadars; A1‐B5, A1‐B12 & Aw19‐B‐ in Iyers and A2‐B17 in Naidus. Heterogeneity chi‐square based on antigen frequency and genetic distance also suggest the heterogeneous nature of the population of South India. Will these caste groups with such diverse haplotypic combinations differ from one another in their immune response and susceptibility to a given epidemic or infection?
HLA‐DP, DQ and DR gene expression in Graves' disease and normal thyroid epithelium
Authors: Piccinini L. A. , Goldsmith N. K. , Roman S. H. , Davies T. F.
Published: July 2010

HLA class II antigen expression by human thyroid epithelium may influence the pathogenesis of autoimmune thyroid disease. HLA‐DP, DQ and DR alpha chain‐specific RNA probes and monoclonal antibodies specific for the three HLA‐D subregion products were used to analyze class II antigen expression in thyroid epithelial cells from normal thyroid tissue and thyroid tissue obtained from patients with Graves’autoimmune thyroid disease. Class II alpha chain RNA transcripts, as well as immunoreactive protein representing all three HLA class II antigens, were detected in Graves’thyroid tissue, and the levels of class II antigen expression appeared to correlate with the degree of lymphocytic infiltration within the gland. Thyroid epithelial cells from normal thyroid glands contained low or absent levels of HLA class II alpha chain mRNA and contained no detectable immunoreactive HLA class II antigen. Thyroid cell monolayer cultures prepared from both Graves' disease and normal thyroid glands exhibited coordinate induction by lectin or human recombinant gamma interferon of HLA‐DP, DQ and DR gene expression. These data demonstrate the potential for HLA‐DP, DQ and DR antigen expression in thyroid epithelium, and imply a dose relationship between lymphocytic infiltration and coordinate transcription and translation of HLA class II genes.
HLA antigens in chronic pancreatitis
Authors: Forbes A. , Schwarz G. , Mirakian R. , Drummond V. , Chan C‐K. , Cotton P. B. , Bottazzo G. F.
Published: July 2010

Since immunological and hereditary factors may be important in chronic pancreatitis, histocompatibility antigens of classes I and II were studied in 50 British Caucasian patients, after exclusion of insulin‐dependent diabetics for whom HLA associations are recognised. Chronic pancreatitis was defined by at least two independent criteria, and only subjects with alcohol‐related and idiopathic disease were included. In 22 patients (21 male), weekly ethanol intake had chronically exceeded 100 g (usually substantially so); the remaining 28 had idiopathic chronic pancreatitis (ICP). Twenty patients (40%) had autoantibodies, in 11 (22%) to gastric parietal cells. Nine of those with ICP (three male) had parietal cell antibody, more than expected for the age/sex distribution. There were overall increased frequencies of HLA Cw5 and B44. In ICP there were increased frequencies of HLA A25 and Cw1, and a decreased frequency of B7. In patients with alcohol‐related disease there were increased frequencies of Cw5 (50.0% vs control 15.9%), B44 (54.5% vs 29.4%), and DR4 (61.1% vs 33.6%). The increased frequency of Cw5 in alcohol‐related disease alone remained significant after correction (p <0.05). A hypothesis that hereditary and possibly immunological factors may contribute to the aetiology of chronic pancreatitis is supported.
HLA‐DR and DQ antigens in insulin‐dependent diabetics in Ethiopia
Authors: Ottenhoff T. H. M. , Mengistu M. , Tadesse G. , De Vries R. R. P. , Converse P. J.
Published: July 2010

Thirty‐one Ethiopian insulin‐dependent (or type I) diabetes mellitus (IDDM) patients and thirty‐three healthy controls from the same ethnic background were typed for HLA‐A, B, C, DR and DQ specificities. The frequencies of both DR3 and DR4 were significantly increased among IDDM patients (resp. p = 0.02, p = 0.01), confirming results in other populations. In contrast to observations in Caucasians, no significant negative association was found with TA10, a newly recognized DQ specificity, at least in the population studied here, whereas DQw1 was more frequently observed among healthy controls (p = 0.01). Although this latter difference does not retain statistical significance after correction for the number of comparisons made, these findings may support previous results suggesting the existence of IDDM susceptibility genes associated with DR3 and DR4 and of IDDM resistance genes associated with DQ antigens.
HLA‐DPw antigens in Danes and Eskimos as determined by local bulk PLT‐reagents
Authors: Petersen C. Munck , Mösller B. K. , Lamm L. U.
Published: July 2010

Primed Lymphocyte Typing cells (PLT‐cells) with specificities for HLA‐DP w1‐w6 were generated. Responder and stimulator lymphocytes were from highly selected donors. Responder cells were primed twice (for 10 and 6 days respectively) prior to a third priming and bulk expansion in IL‐2 containing medium.

The coefficient of correlation between typing results obtained with local PLT‐reagents and results based on 9th International Histocompatibility Workshop reagents was 0.91. As determined by batch to batch and day to day variations (different batch on different day), the reproducibility of +/‐ scorings and assignments obtained with local reagents was 0.87 (range 0.64–1.0) and 0.9 (range 0.69–1.0) respectively.

The HLA‐DPw gene frequencies in a population of 88 unrelated Danes and a population of 48 unrelated Greenland Eskimos were determined. The DPw gene frequencies observed in Danes were very similar to those reported in other Caucasian populations. Compared to Caucasians, a significantly lower frequency of DPw3 and a somewhat higher frequency of DPw2 were found in Eskimos. The findings did not differ from the Hardy‐Weinberg expectations. No linkage disequilibrium between DR and DP was observed in the Eskimo population, whereas the DR3 ‐ DPw1 association in Danes (Caucasians) was confirmed.

With regard to HLA‐DR, DR1, DR4 and DR7 were found to be more frequent in Eskimos than in Danes (not significant using corrected p values).

The genetic distance between the Danish and the Eskimo population was 0.21 as determined by DPw and 0.24 as determined by DR gene frequencies.
Development and characterization of mouse anti‐human LMP2, LMP7, TAP1 and TAP2 monoclonal antibodies
Authors: Kishore R. , Hicklin D.J. , Dellaratta D.V. , Golde U. , Kageshita T. , Seliger B. , Ferrone S.
Published: July 2010

Abstract: Low molecular mass polypeptides (LMP) 2 and LMP7 and transporter associated with antigen processing (TAP) subunits TAP1 and TAP2 play a crucial role in antigen processing and cell surface expression of HLA class I molecules. Since monoclonal antibodies (mAb) to these molecules will facilitate the analysis of their expression, structure and function in normal and transformed cells, in the present study we have developed these reagents. Specifically anti‐LMP2 and LMP7 mAb were generated from BALB/c mice immunized with specific peptides, and anti‐TAPl and TAP2 mAb from BALB/c mice immunized with respective recombinant proteins. mAb VF101–39F7 and VF1O1–39G5 were shown to be specific for LMP2, mAb VF103–5D5 and VF103–8C2 for LMP7, mAb VF108–1B3 and VF108–12D6 for TAP1 and mAb VF118–1E4 and VF118–2C5 for TAP2, since they reacted specifically with the corresponding immunogens in ELISA and with the corresponding LMP and TAP subunits when tested in Western blotting with human lymphoid cell extracts. Furthermore, the mAb immunoprecipitated components with the characteristic electrophoretic mobility from lymphoid cells. Both anti‐LMP and anti‐TAP mAb stained keratinocytes and infiltrating lymphocytes in frozen and formalin‐fixed, paraffin embedded sections of normal skin in indirect immunoperoxidase reactions. Furthermore, all the mAb except mAb VF103–5D5 stained the cytoplasm of lymphoid cells in an intracytoplasmic staining reaction. The specificity and reactivity pattern of the mAb we have characterized indicate that they will be valuable reagents to analyze the cellular expression and tissue distribution of LMP and TAP subunits.
HLA class II allele and haplotype frequencies in Ethiopian Amhara and Oromo populations
Authors: Fort M. , de Stefano G.‐F. , Cambon‐Thomsen A. , Giraldo‐Alvarez P. , Dugoujon J.‐M. , Ohayon E. , Scano G. , Abbal M.
Published: July 2010

Abstract: HLA class II alleles were identified in 181 healthy unrelated Ethiopian children of both sexes and in 350 European controls from the South of France. The Ethiopian individuals belonged to the two major ethnic groups of the country: Oromo (N=83) and Amhara (N=98). In both panels, genetic polymorphism of HLA class II alleles was analysed for the first time by molecular typing of DRB1, DQA1 and DQB1 loci. Allelic and phenotypic frequencies were compared with those of European controls and other African populations. Construction of HLA class II three‐locus haplo‐types was also performed. The study revealed some differences between the two groups. Characteristic features of Central and North African populations appeared on the Ethiopian HLA genotypes. Surprisingly, DRB1*11 presented one of the lowest gene frequencies in both Ethiopian ethnic groups in contrast to Europeans and West Africans. Furthermore, this decrease was more marked than those observed using serological techniques in other geographically close East African countries. Oromo and Amhara only showed minor differences in spite of their different origins and histories. One significant difference consisted of a lower DRB1*01 gene frequency in Oromo as reported in most West African people. Some new or rare haplotypes were also observed in the Oromo group. Our results underline the distinctive features of the Ethiopian populations among the few HLA genotyping data available for East African groups and emphasise the major interest of such investigations in this region of Africa.
DQA‐DQB linkage in Old World monkeys
Authors: Gaur L.K. , Pandarpurkar M. , Anderson J.
Published: July 2010

Abstract: The MHC DQ region in nonhuman primates, as in humans, consists of a and β chains that are polymorphic with strong linkage disequilibrium between certain DQA‐DQB alleles. Not only are contemporary HLA class II allelic variants present in evolutionarily distant species, but we demonstrate that linkages between loci also bear ancient roots. In unrelated baboons (Papio cynocephalus anubis) and family segregation analysis of pig‐tailed macaques (Macaca nemestrina) we found cis‐linkages between DQA1*O1 and DQB1*05 or *06, between DQA1*05 and DQB1*03, and between DQA1*03 and DQB1*03 alleles, all of which are also prominent in modern humans. In contrast, one linkage that has not been seen in humans, between DQA1*05 and DQB1*06 alleles, was also found. These patterns of selective linkage disequilibrium imply evolutionary mechanisms following the divergence of species that constrain the diversity of haplotypes which evolve.
Extended HLA haplotypes in Japanese homozygous typing cells
Authors: Naruse T.K. , Nose Y. , Ando R. , Araki N. , Shigenari A. , Ando A. , Ishihara M. , Kagiya M. , Nabeya N. , Isshiki G. , Inoko H.
Published: July 2010

Abstract:We have defined extended HLA haplotypes including the HLA class II genes, the non‐HLA genes such as TAP1, TAP2 and LMP2, and the (CTG)nmicrosatellite repeats within theN0TCH4gene between DRA and 21OH in 33 Japanese HLA homozygous typing cells (HTC). These conserved haplotypes characterized by unique linkage might be maintained as a result of functional co‐operation among them in the antigen presentation pathway. These HTCs can be served as an original and ethnic‐specific standard panel, providing useful genetic markers in haplotypic diversity, disease association, and anthropology studies.
IL‐12Bpro and GSTP1 polymorphisms in association with silicosis
Authors: Stanilova S. , Miteva L. , Prakova G.
Published: July 2010

To assess the role of IL‐12Bpro and GSTP1 polymorphisms on induced interleukin (IL)‐12p40 production in respect to silicosis development, we examined their distribution in 63 silicosis patients and 165 healthy donors. Decreased frequencies of IL‐12Bpro‐2 allele (42% vs 62.5%, P = 0.0042) and genotype 22 (19% vs 40%, P = 0.02) in patients compared with exposed healthy donors suggested their protective role in silicosis susceptibility. The GSTP1 A/G polymorphism was also associated with silicosis susceptibility. The allele G and genotype GG were overrepresented among patients than among healthy men (36% vs 23%, P = 0.013; 14% vs 2%, Pc = 0.012). Also, patients’ peripheral blood mononuclear cell (PBMC) produced higher IL‐12p40 than healthy donors’ depending on both IL‐12Bpro and GSTP1 polymorphisms. In conclusion, homozygosity of high producer IL‐12p40 genotype IL‐12Bpro‐11 and GSTP1‐GG had the highest genetic risk of silicosis development in Bulgarian miners.
Influenza A (H1N1) virus‐induced hepatocellular injury in a kidney transplant patient
Authors: Daudé M. , Mansuy J.M. , Guitard J. , Basse G. , Esposito L. , Izopet J. , Rostaing L. , Kamar N.
Published: July 2010

M. Daudé, J.M. Mansuy, J. Guitard, G. Basse, L. Esposito, J. Izopet, L. Rostaing, N. Kamar. Influenza A (H1N1) virus‐induced hepatocellular injury in a kidney transplant patient. Transpl Infect Dis 2011: 13: 70–72. All rights reserved.

Abstract: The swine‐origin influenza A (H1N1) virus is mainly responsible for flu. No hepatitis attributable to H1N1 virus has been previously documented. Herein, we report on a kidney transplant patient who developed influenza H1N1 virus‐induced hepatocellular injury. The patient's body temperature was only somewhat elevated, and pulmonary and flu symptoms were mild. H1N1 virus was detected by polymerase chain reaction assay in nasopharyngeal and bronchoalveolar swabs, as well as in the serum. The hepatocellular injury episode resolved after the patient had been placed on oseltamivir therapy. This observation suggests that acute hepatocellular injury could be linked to the influenza H1N1 virus.
Variations in oil palm (Elaeis guineensis Jacq.) progeny response to high aluminium concentrations in solution culture
Authors: Cristancho R. J. A. , Hanafi M. M. , Syed Omar S. R. , Rafii M. Y.
Published: July 2010

Aluminium (Al) phytotoxicity is an important soil constraint that limits crop yield. The objectives of this study were to investigate how growth, physiology, nutrient content and organic acid concentration is affected by Al, and to assess the degree of Al tolerance in different oil palm progeny (OPP). Four OPPs [‘A’ (Angola dura × Angola dura), ‘B’ (Nigerian dura × Nigerian dura), ‘C’ (Deli dura × AVROS pisifera) and ‘D’ (Deli dura × Dumpy AVROS pisifera)] were grown in different Al concentrations (0, 100 and 200 μm) in aerated Hoagland solution, pH 4.4, for 80 days. We observed a severe reduction (57.5%) in shoot dry weight, and root tips were reduced by 46.5% in 200 μm Al. In ‘B’ and ‘C’, the majority of macro‐ and micronutrients in plants were reduced significantly by 200 μm Al, with Mg being lowered by more than 50% in roots and shoots. The 200 μm Al treatment resulted in a 56.50% reduction in total leaf area, a 20% reduction in net photosynthesis and a 17% reduction in SPAD chlorophyll value in the third leaf. Root tips (0–5 mm) showed a significant increase in oxalic acid content with increasing Al concentration (∼5.86‐fold); progeny ‘A’ had the highest concentration of oxalic acid. There was a significant interaction between Al concentration × OPP on total leaf number, root volume, lateral root length, Mg and K in root and shoot tissues, and Ca and N in shoots. The OPPs could be ranked in their tolerance to Al as: ‘A’ > ‘D’ > ‘B’ > ‘C’.
Genetic and physiological analysis of biennialism in Hyoscyamus niger
Authors: Schläppi M.
Published: July 2010

A genetic and physiological study of biennialism in the diploid selfer Hyoscyamus niger (black henbane), an obligate long‐day plant, is described. Three annual and two biennial accessions that were homozygous for their respective growth habits were selected. The early‐flowering trait of two annual accessions was dominant over the late‐flowering trait of the third annual accession. The late‐flowering annual accession, but not the early‐flowering ones, responded to vernalization. Two biennial accessions remained vegetative after more than 1 year in soil and thus had an obligate vernalization requirement. Crosses between annual and biennial accessions showed that biennialism was conferred through a single dominant gene. However, plants containing only one copy of this dominant gene were transformed from biennials into very late‐flowering winter‐annual plants that responded more rapidly to vernalization than biennials. Taken together, these results indicated that there were allelic differences in photoperiod‐specific flowering time genes and that biennialism was a dose‐dependent trait with incomplete dominance. Models for flowering time regulation in henbane involving photoperiod‐, vernalization‐, and most likely gibberellin‐specific pathways are discussed.
Cerebral phaeohyphomycosis caused by an Exophiala. species
Authors: Tintelnot Kathrin , de Hoog G. S. , Thomas E. , Steudel W. I. , Huebner K. , Seeliger H. P. R.
Published: July 2010

Summary. A 45‐year‐old woman was found to have cerebral phaeohyphomycosis caused by an Exophiala species. The portal of entry of the fungus remained unknown. Despite surgery and antimy‐cotic therapy the patient died from circulation failure. The fungus is compared to several related Exophiala species.

Zusammenfassung. Eine 45jährige Frau er‐krankte an einer zerebalen Phaeohyphomykose, hervorgerufen durch eine Exophiala‐Art. Die Ein‐trittspforte dieses Schwärzepilzes wurde nicht ge‐funden. Trotz chirurgischer und antimykotischer Therapie starb die Patientin an Komplikationen des großen Kreislaufs. Der Stamm wird mit einigen ver‐wandten Exophiala‐Arten verglichen.
Specific digestive deficiency of phagocytes in paracoccidioidomycosis. Its absence in peripheral blood neutrophils of members of the nuclear family of patients. An initial report
Authors: Urquiola G. , Goihman‐Yahr M. , de Albornoz M. C. Bastardo , Istúriz G. , Viloria N. , Saavedra N. , Carrasquero M. , Pereira J. , de Gómez M. H. , Román A. , Martín B. San
Published: July 2010

Summary. Paracoccidioidomycosis (PARA) affects only a minority of individuals, who have presumably been exposed to the causative fungus (Paracoccidioides brasiliensis). Neutrophils (PMNs) from patients with PARA show a significant and specific digestive deficiency phagocytosed P. brasiliensis in vitro. It is not known whether the defect is acquired after contact with the fungus, or precedes it. We studied the spouses and offspring of three patients with PARA. Individuals studied stayed in the same house as their husband or father. None of the relatives had evidence of PARA, and their PMNs showed no defect in their ability to digest or kill the fungus. Relatives showed no indication of sensitization against P. brasiliensis. These results are compatible with the view that effective contact with P. brasiliensis may occur only under restricted conditions and that the defect in digestive ability is an infrequent and specific occurrence.

Zusammenfassung. An Paracoccidioidomykose erkrankt vermutlich nur eine Minderheit aller Individuen, die dem Erreger Paracoccidioides brasiliensis exponiert sind. Die neutrophilen Granulozyten (PMN) der Patienten mit Paracoccidioidomykose zeigen eine signifikante Abbauhemmung fir phagozytierte P. brasiliensis in vitro. Es ist nicht bekannt, ob dieser Defekt erst nach dem Erregerkontakt erworben wird, oder ob er schon vorher bestand. Wir haben Ehegatten und Nachkommen von drei Paracoccidioidomykose‐Patienten untersucht. Die Probanden lebten gemeinsam in einer Wohnung mit den Patienten. Bei keinem der verwandten Probanden bestand irgendein Hinweis auf eine Paracoccidioidomykose, und ihre PMN zeigten keine Hemmung im intrazellu‐laren Abbau und der Abtötung des Pilzes. Bei den Probanden wurde auch keine Sensibilisierung gegen P. brasiliensis aufgedeckt. Diese Ergebnisse sind vereinbar mit der Ansicht, daß ein sensibili‐sierender Kontakt mit P. brasiliensis nur unter eingeschränkten Bedingungen statthat und daß der Defekt in der intrazellulären Abbaufahigkeit ein seltenes und spezifisches Ereignis ist.
Efficient transient rescue of hematopoietic mutant phenotypes in zebrafish usingTol2‐mediated transgenesis
Authors: Takeuchi Miki , Kaneko Hiroshi , Nishikawa Keizo , Kawakami Koichi , Yamamoto Masayuki , Kobayashi Makoto
Published: July 2010

Phenotypic rescue experiments have been commonly used in zebrafish since it is convenient to study the causality of mutant phenotypes just by injecting mRNA into embryos. However, this strategy is only effective for phenotypes at early embryonic stages due to mRNA instability. For later developmental stages, DNA constructs are used to express exogenous genes, while it is usually ineffective owing to the problem of mosaicism. This study attempted to solve the problem by usingTol2‐mediated transgenesis. As a model case, we usedvlad tepes(vlt), a zebrafishgata1mutant, whose phenotypes have never been able to be rescued at later stages by transient rescue experiments. Blood cell‐specific transgenic expression ofgata1was driven by its own promoter/enhancer elements. The co‐injection of aTol2‐donor plasmid containinggata1cDNA and transposase mRNA efficiently rescued the bloodless phenotypes ofvlteven in day 12 larvae when definitive erythropoiesis took place with primitive erythropoiesis. ThisTol2‐mediated rescue is therefore considered to be a quick and easy method for analyzing the mutant phenotypes in zebrafish.
Anxiety, neuroticism and oxidative stress: Cross‐sectional study in non‐smoking college students
Authors: Matsushita Masateru , Kumano‐Go Takayuki , Suganuma Nakamori , Adachi Hiroyoshi , Yamamura Schuhei , Morishima Hiroko , Shigedo Yoshihisa , Mikami Akira , Takeda Masatoshi , Sugita Yoshiro
Published: July 2010

Aims:  Oxidative stress has gained attention recently in psychiatric medicine and has been reported to be associated with various diseases. However, the psychosocial factors involved in oxidative stress are still not well understood. Thus, the aim of this study was to examine whether anxiety levels and neuroticism were associated with serum oxidative and anti‐oxidative status in healthy college students.

Methods:  Participants in this cross‐sectional study were 54 non‐smoking college students. Their serum oxidative status was determined by reactive oxygen metabolites (ROM) and the biological anti‐oxidant potential. Anxiety levels and neuroticism were assessed using the State–Trait Anxiety Inventory and the NEO Five‐Factor Inventory, respectively.

Results:  Correlation analysis showed an association of increased ROM concentration with elevated anxiety levels (State, ρ = 0.39, P = 0.046; Trait, ρ = 0.44, P = 0.024) and the personality trait of neuroticism (ρ = 0.47, P = 0.016) in female students. However, the ROM concentration in male students was not associated with the anxiety level or any personality trait.

Conclusion:  Although these findings suggest that neurotic and anxious female students tend to be exposed to oxidative stress, these linkages should be confirmed by multivariate analysis in future research.
Brain‐derived neurotrophic factor as a biomarker for mood disorders: An historical overview and future directions
Authors: Hashimoto Kenji
Published: July 2010

Mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BPD), are the most prevalent psychiatric conditions, and are also among the most severe and debilitating. However, the precise neurobiology underlying these disorders is currently unknown. One way to combat these disorders is to discover novel biomarkers for them. The development of such biomarkers will aid both in the diagnosis of mood disorders and in the development of effective psychiatric medications to treat them. A number of preclinical studies have suggested that the brain‐derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of MDD. In 2003, we reported that serum levels of BDNF in antidepressant‐naive patients with MDD were significantly lower than those of patients medicated with antidepressants and normal controls, and that serum BDNF levels were negatively correlated with the severity of depression. Additionally, we found that decreased serum levels of BDNF in antidepressant‐naive patients recovered to normal levels associated with the recovery of depression after treatment with antidepressant medication. This review article will provide an historical overview of the role played by BDNF in the pathophysiology of mood disorders and in the mechanism of action of therapeutic agents. Particular focus will be given to the potential use of BDNF as a biomarker for mood disorders. BDNF is initially synthesized as a precursor protein proBDNF, and then proBDNF is proteolytically cleaved to the mature BDNF. Finally, future perspectives on the use of proBDNF as a novel biomarker for mood disorders will be discussed.
Treatment outcomes of sorafenib for first line or cytokinerefractory advanced renal cell carcinoma in Japanese patients
Authors: Ueda Takeshi , Imamura Yusuke , Komaru Atsushi , Fukasawa Satoshi , Sazuka Tomokazu , Suyama Takahito , Naya Yukio , Nihei Naoki , Ichikawa Tomohiko , Maruoka Masayuki
Published: July 2010

The objective of the present study was to document the treatment efficacy and safety of sorafenib in Japanese patients with advanced renal cell carcinoma (RCC). A retrospective analysis of 50 consecutive patients with metastatic RCC between January 2005 and December 2009 was carried out. Patients received sorafenib after failed cytokine therapy or first‐line sorafenib treatment. All received 400 mg of sorafenib orally twice daily. Five of 14 patients with bone metastases were also given bisphosphonates. Tumor response was evaluated every 1–2 months according to the Response Evaluation Criteria in Solid Tumors. Adverse events (AE) were evaluated at each visit during and after treatment, and were recorded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 3.0. Dose modification of sorafenib was permitted if grade 3 or 4 AE occurred. Treatment continued until disease progression or treatment intolerance occurred. Partial response, and stable disease as best objective responses were observed in 11 (22%) and 23 (46%) patients, respectively. Median progression‐free survival was 7.3 months and median overall survival was 11.9 months. All patients experienced AE and one or more grade 3/4 AE occurred in 43 of 50 (86%) patients. Although it requires close monitoring, sorafenib treatment seemed to be effective in the present study population.
The persisting presacral sinus after anastomotic leakage following anterior resection or restorative proctocolectomy
Authors: van Koperen P. J. , van der Zaag E. S. , Omloo J. M. T. , Slors J. F. M. , Bemelman W. A.
Published: July 2010

Aim  Despite improvements in anastomotic technique, anastomotic leakage is frequently encountered following anterior resection. This can eventually evolve into a presacral sinus. This study assessed the incidence, the natural course and the outcome of persisting presacral sinus.

Method  Patients who underwent low anterior resection (LAR) for cancer or restorative proctocolectomy (RPC) for ulcerative colitis or familial polyposis were eligible. Patients with anastomotic leakage or a presacral abscess were included. Outcome parameters included a persistent presacral sinus, or its closure and average time to closure and the stoma closure rate.

Results  Twenty‐five patients were identified with a sinus after LAR (n = 20) or RPC (n = 5). A persistent sinus was present in nine (1%) of 834 patients after LAR and two (0.9%) of 229 patients after RPC. Definitive resolution of the sinus occurred in 12 (52%) of 23 assessable patients. This was achieved at a median of 340 days (range 23–731 days). At final follow‐up, nine of the 23 patients had permanent faecal diversion because of recurrent abscess or persistent sinus formation, seven after LAR and two after RPC.

Conclusion  A significant proportion of patients with anastomotic leakage after rectal surgery develop a chronic sinus, of which only half heal over time. Persisting sinus is the main reason for a permanent stoma.
Multimodality in the individual size distributions of bird communities
Authors: Thibault Katherine M. , White Ethan P. , Hurlbert Allen H. , Ernest S. K. Morgan
Published: July 2010

Aim Body size often plays a significant role in community assembly through its impacts on the life history and ecological attributes of species. Insight into the importance of size in structuring communities can be gained by examining the distribution of sizes of individuals [i.e. the individual size distribution (ISD) or size spectrum] in a community. ISDs have been studied extensively in aquatic and tree communities, but have received little attention in terrestrial animal communities. Here, we conduct the first macroecological analysis of ISDs in terrestrial animal communities to determine whether they show broad‐scale consistency in shape.

Location North America, north of Mexico.

Methods Using likelihood‐based methods and Gaussian mixture modelling, coupled with data from the Breeding Bird Survey and Christmas Bird Count, we determine whether the ISDs for thousands of breeding and wintering North American bird communities are: (1) monotonically decreasing, (2) unimodal or (3) multimodal.

Results We find that avian ISDs are consistently multimodal, with most characterized by more than five modes in both breeding and wintering communities from local to continental scales. In addition, the positions of these modes along the size axis are remarkably consistent.

Main conclusions The striking consistency in the ISD within bird communities, as with tree and aquatic communities, indicates that the ISD is an important and informative characterization of resource utilization within an ecological assemblage. The differences in shape of the ISD among these groups also suggest that differences in body size‐related constraints affect interactions within a group and with the environment. Our results confirm that avian assemblages do exhibit structure along the body size axis, and therefore it will be fruitful to explore this pattern in greater detail.
Organizational Accidents: A Systemic Model of Production versus Protection
Authors: Goh Yang Miang , Love Peter E. D. , Brown Helen , Spickett Jeffery
Published: July 2010

abstract

Production pressure is often cited as an underlying contributory factor of organizational accidents. The relationship, however, between production and safety protection is complex and has not been adequately addressed by current theories regarding organizational accident. In addressing this gap, this paper uses the methodology of system dynamics to develop a causal model to address the dynamic interaction between management of production and protection, which can accumulate in an organizational accident. A case study of a fatal rock fall accident in Tasmania, Australia was conducted based on the developed model and is used to uncover the intricate dynamics linking production pressure, risk tolerability, perception of safety margin, and protection efforts. In particular, the study demonstrates how a strong production focus can trigger a vicious cycle of deteriorating risk perception and how increased protection effort can, ironically, lead to deterioration of protection.
The Influence of Top Management Team's Corporate Governance Orientation on Strategic Renewal Trajectories: A Longitudinal Analysis of Royal Dutch Shell plc, 1907–2004
Authors: Kwee Zenlin , Van Den Bosch Frans A. J. , Volberda Henk W.
Published: July 2010

abstract

Using the upper echelons perspective together with corporate governance and strategic renewal literature, this paper investigates how top managers' corporate governance orientation influences a firm's strategic renewal trajectories over time. Through both a qualitative analysis (1907–2004) and a quantitative analysis (1959–2004), we investigate this under‐researched question within the context of a large incumbent firm: Royal Dutch Shell plc. Our results indicate that top managers having an Anglo‐Saxon corporate governance orientation are more likely to pursue exploitative and external‐growth strategic renewal trajectories, while those having a Rhine corporate governance orientation are more likely to pursue exploratory and internal‐growth strategic renewal trajectories. We also found a positive moderating effect of the proportion of shareholders from the Anglo‐Saxon countries on exploitative and external‐growth strategic renewal trajectories. Our findings indicate that top managers' corporate governance orientation can be an important antecedent of strategic renewal and of organizational ambidexterity, both of which influence corporate longevity.
Stochastic efficiency analysis with risk aversion bounds: a comment
Authors: Hardaker J. B. , Lien Gudbrand
Published: July 2010

A recent contribution by Meyer et al. (2009, p. 521) corrected an error of fact by Hardaker et al. (2004b, p. 253) about the comparison between stochastic dominance with respect to a function (SDRF) and stochastic efficiency with respect to a function (SERF). While both methods compare risky prospects for a bounded range of degrees of risk aversion, SERF, unlike SDRF, also demands an assumption that a chosen measure of risk aversion is constant over all levels of outcomes being evaluated. It is argued that it is generally reasonable to make such an assumption, especially when the form of the utility function and the bounds on the degree of risk aversion are carefully chosen. Then SERF has the advantage that it can lead to a smaller efficient set than that identified by SDRF. SERF also has advantages of ease and transparency in use.
A.L.P. Industrial Groups‐A Reassessment1
Authors: CAMPBELL IAN
Published: July 2010

Over many years the industrial wing of the ALP has had many fights with the political wing on two main issues. The first is the deviation of the political wing from the pledged policy of the party…the second issue is the attempt of the political wing to dictate union policy and interfere in union affairs. this was the main issue on which Lang parted company, first with the trade union movement and then with the ALP.
Political Culture, Konrad Adenauer, and the Reunification of Germany: an Attempt at Sorting Out a Number of Problems in a Current Debate.
Authors: SUNDHAUSSEN ULF
Published: July 2010

Alfred Heuss, Versagen und Verhaengnis, Vom Ruin deutscher Geschichte und ihres Verstaendnisses (Failure and Disaster, On the Ruin of German History and its Comprehension), Berlin: Siedler, 1984, 213 pp.; Herbert Ammon and Theodor Schweisfurth, Friedensvertrag, Deutsche Konfoederation, Europaeisches Sicherheitssystem (Peace Treaty, German Confederacy, European Security System), Starnberg: IBF Verlag, 1985, 95 pp.;

Hans‐Peter Schwarz, Die gezaehmten Deutschen, von der Machtbesessenheit zur Machtvergessenheit (The Tamed Germans, From the Obsession with Power to the Oblivion of Power), Stuttgart: Deutsche Verlagsanstalt, 1985, 191 pp.;

Hans‐Peter Schwarz, Adenauer, Der Aufstieg: 1876–1952 (Adenauer, The Rise: 1876–1952). Stuttgart: Deutsche Verlagsanstalt, 1986, 1021 pp.;

Dieter Blumenwitz and Boris Meissner (eds.), Die Uebenvindung der europaeischen Teilung und die deutsche Frage (The Surmounting of the Division of Europe and the German Question), Cologne: Verlag Wissenschaft und Politik, 1986, 143 pp.;

Wolfgang Seiffert, Das ganze Deutschland, Perspektiven der Wiedervereinigung (The Whole Germany, Perspectives of Re‐Unification), Munich‐Zurich: Piper, 1986, 377 pp.
The Aboriginal Franchise and Its Consequences
Authors: Goot Murray
Published: July 2010

This article traces the expansion (and contraction) of the Aboriginal and Torres Strait Islander franchise for Commonwealth, state and territory elections, and to a lesser extent local government elections; it outlines the arguments made for (and against) Aboriginal enfranchisement; and it examines alternative accounts of what drove the expansion (and contraction) of the vote. It pulls together data on Aboriginal enrolment, political awareness and party support, particularly in the Northern Territory. And it examines divergent views about the consequences of Aborigines having the vote: claims that the franchise is an empty formality; claims that it has allowed Aborigines to be manipulated; and claims that it has generated benefits — symbolic, expressive and instrumental.
Between a Rock and a Hard Place: the Case of Papuan Asylum‐Seekers
Authors: Palmer David
Published: July 2010

It is perilous to look to history to provide guidance for the present. Nonetheless the political controversy surrounding the granting of temporary protection to forty‐two asylum‐seekers from West Papua in March 2006 needs to be understood in its wider, historical context. Papua has been a pebble in the region's political shoe since 1949. And national considerations are not new in shaping Australian policy toward asylum‐seekers. Certainly in the 1960s and 1970s Australia played a tactical, often tough game with Papuan asylum‐seekers in order to contain tensions with Indonesia. This article analyses the history of Australia's foreign and immigration policies towards Papuan asylum‐seekers and describes the delicate balancing act that successive Australian governments have needed to perform in handling this issue.
Total War and Genocide: Reflections on the Second World War
Authors: Förster Stig
Published: July 2010

This paper draws on the findings of a series of international conferences on the question of “total war” in the late nineteenth and twentieth centuries to investigate possible connections between “total war” and the problem of genocide. Both “total war” and genocide appear to have reached a terrible culmination in the years 1937‐1945, raising the question of the connection between the two phenomena. This paper considers the usefulness of concepts such as “total war” and “genocide” as social‐scientific ideal types, before going on to reflect on the state of research on the linkage between Nazi Germany's drive for “total war” and its implementation of policies of genocide.