bluuebunny/crossref_metadata_2025 huggingface dataset:
Canine MHC‐class II antigens on B and T lymphocytes1
Authors: Doveren R. F. C. , VAN DER Linden C. J. , Spronken E. E. M. , Groenewegen G. , Buurman W. A.
Published: July 2010

MHC‐class II antigens on canine lymphoid cells were detected with monoclonal antibodies (Mabs). On the basis of reactivity with resting or activated T lymphocytes two groups of Mabs were reported earlier. Non‐activated T lymphocytes expressed MHC‐class II antigens recognized by the first group whereas the second group recognized only MHC‐class II antigens on activated T lymphocytes. In this study we analysed the reactivity pattern of both groups of Mabs with purified canine B lymphocytes. One‐ and two‐colour immunoflowcytometric analysis, immu‐noprecipitation, immunohistology and MLC inhibition were performed. The Mabs which only reacted with activated T lymphocytes appeared to stain also purified slg+ lymph node cells. Two‐colour fluorescence and immunohistology confirmed the reactivity of these Mabs with B lymphocytes. Immunoprecipitation showed the bimolecular structure of these antigens. It was concluded that two subsets of MHC‐class II antigens can be detected on canine lymphoid cells. One subset showed an aberrant distribution being expressed on both nonactivated and activated T and on B lymphocytes. The second subset of MHC‐class II antigens could only be detected on B lymphocytes and activated T lymphocytes, a distribution pattern similar to that found in most other species, for instance man.
Natural autoreactive H‐2‐specific serum antibodies in a group of BALB/cBy (H‐2d) mice
Authors: ČErný‐Provaznik Radka , Kloosterman Tinie , Verkerk Door , Vroom Thea M. , Iványi Pavol
Published: July 2010

Natural autoreactive H‐2‐specific antibodies were detected by lymphocytotoxic test in sera of 15 BALB/cBy (H‐2d) mice maintained in the same cage. The antibodies could be detected only for a short period of time; they reacted strongly with H‐2d and H‐2s and weakly with H‐2k,q,r cells. Such antibodies could not be identified in sera of other groups of mice of the same strain maintained in the same environment. All serum‐positive mice had a shorter life span than control mice. However, neither a real link between the antibodies and the disease nor a clear understanding of the disease was achieved.
DR2 short antigen in Japanese
Authors: Matsuki Kazumasa , Watanabe Shozo , Nanzai Yorohide , Nakatate Manroku , Juji Takeo
Published: July 2010

A variant of the DR2 antigen, DR2 short (DR2S), was investigated in Japanese subjects by using a 9th International Histocompatibility Workshop reagent and locally‐obtained alloantisera. A significant positive association between DR2S. Bw67 and TB23 was demonstrated. Haplotype analysis on four Japanese families showed that DR2S was segregated with the A11‐Cw7‐Bw67‐DR2S‐DQw1‐TB23 haplotype.
Interaction between HLA antigens and immunoglobulin (Gm) allotypes in susceptibility to type I diabetes
Authors: Tait B. D. , Propert D. N. , Harrison L. , Mandel T. , Martin F. I. R.
Published: July 2010

HLA‐A,B,C and DR typing was performed on 108 Caucasian type I diabetic patients, 68 being Gm typed. The expected association with B8, B18, Bw62, DR3 and DR4 was observed as well as an excess of DR3/4 heterozygotes. DR2 was decreased in frequency.

In the total patient group, no Gm association was observed but when the patients were subgrouped according to HLA type, HLA/Gm interactive effects were seen. An increase in Gm (1,3;5) was observed in DR3 positive, DR4 negative patients. This association occurred predominantly in females (compared with DR4 and DR3/4 patients of the same Gm phenotype who were predominantly male). Further genetic heterogeneity was identified within DR3/4 patients. Within this group, Bw62 was increased (strongly suggestive of Bw62‐DR4 haplotypes) within B8, Gm heterozygotes compared with B8, Gm homozygotes. This finding can be interpreted as indicating a three‐way interaction between genes on two HLA haplotypes and Gm‐linked genes.

These results reflect the genetic heterogeneity and complexity of insulin‐dependent diabetes mellitus and explain in part the previous failure of simple genetic models to adequately explain inheritance patterns observed.
Test of prolongation of skin graft survival by blood injections provides evidence for presence of a new histocompatibility locus in the B‐G region of chicken MHC
Authors: Vilhelmová M.
Published: July 2010

When used for pretransplantation treatment, blood of congenic chicken lines CB and CB.R1, incompatible only in the B‐G region of the major histocompatibility complex (MHC), differed in their ability to induce prolonged survival of skin grafts transferred from either of these lines onto recipients of a third congenic line, CC. Moreover, skin grafts from CB and CB.R1 donors displayed a difference in survival time, irrespective of blood pretreatment. Graft survival time after pretreatment of recipients with CB blood could be prolonged by prior induction of neonatal tolerance to the B‐G product; this could be done with injections of whole blood or of separated erytrocytes or leucocytes of line CC.R1 chickens (incompatible with CC recipients in the B‐G region). The results indicate that a new histocompatibility locus is present in the B‐G region of the chicken MHC.
Haplotype frequencies in South‐East Scotland
Authors: Jazwinska E. C. , Kilpatrick D. C.
Published: July 2010

One hundred and thirty‐two families consisting of healthy babies born after normal pregnancies at an Edinburgh maternity unit and their parents were tissue‐typed for HLA‐A, B and DR antigens. The antigen frequencies and the commonest haplotype frequencies are reported.
The HLA‐Dw HAG specificity is defined by DRβ cDNA hybridization as a hybrid haplotype carrying DR5 and DRw6 determinants
Authors: Tilanus Marcel G. J. , Schreuder Geziena M. Th. , Pawelec Graham , Giphart Marius J.
Published: July 2010

The serological and cellular class II definition of HTC9W1802 HAG was difficult to establish. RFLP obtained with a DRβ cDNA probe indicated that HAG could be a hybrid haplotype composed of fragments characteristic for DR5 and DRw6 specificities.
Addison's disease: immunological aspects*
Authors: Latinne D. , Vandeput Y. , Bruyere M. De , Bottazzo F. , Sokal G. , Crabbe J.
Published: July 2010

The frequency of HLA DR3 in patients with Addison's disease is increased and the relative risk factor rises to 10 when adrenocortical failure is part of a polyendocrinopathy
A genetic study of Behçet's disease in Taiwan Chinese
Authors: Chung Y‐M. , Tsai S‐T. , Liao F. , Liu J.‐H.
Published: July 2010

The frequency of HLA‐A, B and C antigen in 53 patients and HLA‐DR, DQ and DN antigen in 31 patients of Behest's disease was studied. All patients were Chinese, and diagnosis was made according to the Japanese Research Committee on Behcet's disease. A significantly increased incidence of HLA‐B51 (P <0.001) and a significantly decreased incidence of HLA‐B16 (P <0.01) was found. No significant difference was found in HLA‐DR, DQ and DN antigens.
Functional characterization of HLA‐DRA11 0101/ DRB1* 0401 molecules expressed in Drosophila melanogaster cells
Authors: Hansen Bjarke Endel , Andersson Ellen Christina , Madsen Lars Siim , Engberg Jan , Søndergaard Leif , Svejgaard Arne , Fugger Lars
Published: July 2010

Abstract: We have expressed the human MHC class II molecule, HLA‐DRA1*0101/‐DRB1*0401 (DRB1 *0401), in Drosophila melanogaster Schneider 2 cells under control of the Drosophila metallothionein promoter. Upon induction with CuSO4, flow cytometry revealed expression of DRBl *0401 on the surface of the Drosophila cells at high levels. The membrane‐bound class II molecules could present peptides specifically to DRB1 *0401‐restricted T cells. Drosophila‐expressed DRBl *0401 molecules revealed a decreased N‐linked glycosylation as compared to DRB1 *0401 molecules purified from a human B‐cell line. The purified DRB1*0401 molecules from Drosophila cells were dissociated into subunits in SDS‐PAGE but could be stabilized with a peptide known to bind DRBl*0401 with a high affinity, indicating that the recombin‐ant class II molecules from Drosophila cells are either empty or occupied by low affinity endogenous peptides. This assumption was further substantiated by the observation that the class II molecules from Drosophila cells had a much higher peptide‐binding capacity than DRBl*0401 molecules derived from the human B‐cell line. Otherwise, the two species of DRB1 *0401 had similar peptide‐binding specificities and affinities. The purified recombinant DRB1*0401 molecules also showed biological activity because immobilized complexes of DRB1*0401 and synthetic peptides specifically stimulated DRB1*0401‐restricted T cells.
The expression and differentiation pattern of cell antigens and adhesion molecules on the nonadherent cell population in canine long‐term marrow culture: a biphasic development of myeloid and lymphoid cells
Authors: Krizanac‐Bengez L. , Moore P.F. , Barsoukov A. , Sandmaier B.M.
Published: July 2010

Abstract: During maturation of normal hematopoietic progenitors, there appears to be differentiation‐dependent expression of adhesion receptors, which may contribute to the homing and lodging of stem progenitor cells into the marrow and for the eventual release of mature effector cells from the marrow cavity. Using a model of long‐term marrow culture, we studied the expression pattern of different lineage cell antigens and cell adhesion molecules on the nonadherent cells in canine long‐term marrow culture. CD4+ cells became a major proportion of both the small and large cell subsets by day 8 of culture. Small CD4+ cells, the majority of which are negative for other T‐cell antigens during the first 2 weeks of culture, express low levels of CD4 (CD41°) and coexpress granulocytic and/or monocytic markers. These CD41° cells have progenitor potential as measured by the long‐term culture‐initiating cell assay and differentiate into myeloid (first wave) and lymphoid (second wave) cells. The T cells, which appear in 2‐week‐old long‐term marrow culture, respond to Con A but not to allo‐antigen. At the same time, most of the large cells are CD14+, CD11b+, DLA‐DR+ and CD4lo+, while granulocytes are not observed. This phenotypic pattern closely resembles that found on myelomonocytic cells developing from fetal thymic and fetal liver CD34+ precursors in a model of human fetal thymic organ culture. The cell adhesion molecules ‐ CD44, CD18, l‐selectin, CDlla‐c as well as VLAα4, dramatically increase from the first week of long‐term marrow culture, while ICAM‐1 and a new β2 cell adhesion molecule, αdβ2, increased slightly from the third week on. In the large (“monocytic”) cell population, αdβ2 was exclusively expressed by CD4+ cells. The differentiation pattern of T‐cell antigens and adhesion molecules seen in the canine long‐term marrow culture appear to mimic those required for developmental interactions between leukocytes and endothelial cells; that is, an early expression of L‐selectin and CD44, followed by the integrins, and later on by ICAM‐1 and αdβ2. Our data support the view that in a model of canine long‐term marrow culture hematopoietic precursors retain their intrinsic developmental potential.
Allelic diversity at the primate MHC‐DMB locus: presence of a conserved tyrosine inhibitory motif in the cytoplasmic tail
Authors: Alvarez M. , Recio M.J. , Martinez‐Laso J. , Pérez‐Bias M. , Garcia‐de‐la‐Torre C. , Vargas‐Alarcón G. , Alegre R. , Gomez‐Casado E. , Arnaiz‐Villena A.
Published: July 2010

Abstract: Ten new primate Mhc‐DMB complete cDNA sequences have been obtained in chimpanzee (n=four), gorilla (n=three) and orangutan (n=three); this gene has not been previously studied in these species. Exon‐ic allelism has been recorded all along the molecule domains and also in the leader peptide, but not in the transmembrane segment. An analysis of the residues critical in the conformation of the Mhc‐DR peptide‐binding site was done in order to look for a Mhc‐DR homologue site; synonymous substitutions are favoured in this homologous HLA‐DM region. This is another finding that supports the possibility that DM could not be typically presenting molecules. The immunoreceptor inhibition motif Tyr 230‐Thr/Ser 231‐Pro 232‐Leu 233 (ITIM) is invariantly present in apes for at least 15 million years, and may have a double function: 1) To direct DMB‐DMA molecules from the endoplasmic reticulum or cell surface towards the endosom‐al/lysosomal class II compartment and 2) to send an inhibitory signal to the cell in order to stop synthesis of unnecessary HLA‐DR molecules, once all available antigenic peprides are loaded. Other molecules, like NK‐cell receptors and Fc receptors, bear this type of tyrosine‐based inhibitory motifs in order to switch off specific cell functions. DMB molecules (as previously shown in C4d molecules) do not present species‐specific motifs in common chimpanzee, suggesting that this species is very close to gorilla or man; also, DMB, like C4d molecules, do not show a trans‐species evolution pattern, suggesting the existence of extensive homogenization of DMB genes within each species or a recent generation of alleles. Finally, a clade grouping human and gorilla DMB cDNA sequences is obtained using a dendrogram (as for C4d trees); this is in contrast to others' results that obtain a human/ chimpanzee clade using different DNA sequences.
A first map of the porcine major histocompatibility complex class I region
Authors: Velten F. , Rogel‐Gaillard C. , Renard C. , Chardon P. , Pontarotti P. , Tazi‐Ahnini R. , Vaiman M.
Published: July 2010

Abstract: A map of the SLA complex, or swine major histocompatibility complex (MHC), class I region was constructed by alignment of yeast artificial chromosomes (YACs) harboring MHC class I genes as well as anchor genes already mapped within the human MHC complex (HLA). Five YACs containing 9 anchor genes built a contig of about 1.0–1.2 Mb between the SLA class HI BAT1 locus and the olfactory receptor‐like genes OLF42. Ten different SLA class I sequences, including putative allelic forms of published classical and non‐classical SLA class I genes, were assigned to the 400‐kb enclosing centromeric part of the contig. Three additional YACs comprising the OLF89 genes and two YACs containing the butyrophilin gene were located telomeric to the contig. Comparison between the human and porcine MHC complexes showed a perfect conserved order of anchor genes, whereas no orthologous relationships were found for the class I loci.
Characterization of the ABO blood group genes in macaques: evidence for convergent evolution
Authors: Doxiadis G.G.M. , Otting N. , Antunes S.G.M. , de Groot N.G. , Harvey M. , Doxiadis I.I.N. , Jonker M. , Bontrop R.E.
Published: July 2010

Abstract: The ABO blood group system is known to act as a major transplantation barrier in primates. Different primate species share the presence of A and B antigens. The polymorphism of the macaque ABO blood group genes was analyzed by cloning and sequencing the exon 7 region. In the case of the rhesus macaque (Macaca mulatto) and cynomolgus monkey (Macaca fascicularis) we were able to identify ABO blood group gene segments which cluster into two lineages, namely: *A/*O1 and *B. In addition allelic variation was observed. The 2 amino acid replacements at positions 266 and 268, which are thought to be crucial for A or B transferase activity, could be confirmed for both macaque species. Comparison of primate sequences shows that A and B reactivity was generated independently from each other in the hominoids and Old World monkey lineages. Hence, the primate A and B blood group genes are subject to convergent evolution.
HSP70 gene polymorphisms in ankylosing spondylitis
Authors: Fraile A. , Nieto A. , Matarán L. , Martin J.
Published: July 2010

Abstract: Despite the strength of the association of ankylosing spondylitis (AS) with HLA‐B27, other genetic elements could play a possible role in the pathophysiology of AS. Because of the localization, in the proximity of the HLA‐B locus, and the involvement of heat shock proteins (HSP) in the immune response, we analyzed the influence of HSP70 gene polymorphism on the susceptibility to AS. HSP70‐1, HSP70‐2 and HSP70‐hom genotypes were analyzed by PCR‐RFLP in patients with AS and in healthy controls. The results obtained in the present study showed that there are not significant differences in the distribution of HSP70‐hom genotypes, whereas significant differences in HSP70‐1 and HSP70‐2 genotypes between AS patients and random controls were found. However, when the distribution of these genotypes were compared in B*27‐matched AS patients and controls, the differences disappeared. These data suggest that the polymorphism of HSP70 genes was not independently associated with AS, and that the differences in HSP70‐1 and HSP70‐2 genotypes among AS patients and controls appears to be due to the linkage disequilibrium between HSP70 alleles and HLA‐B*27.
Nucleotide and amino acid sequence alignment for human killer cell inhibitory receptors (KIR), 1998
Authors: Steffens U. , Vyas Y. , Dupont B. , Selvakumar A.
Published: July 2010

Abstract: We present alignments of nucleotide sequences and deduced amino acid sequences for all currently identified killer cell inhibitory receptors (KIR). The genes for these receptors have been localized to human chromosome 19q13.4 and constitute a large gene family. They all encode structures typical of type I transmembrane molecules belonging to the immunoglobulin superfamily (Ig‐SF). Extensive polymorphism exists within the genes and many of the currently identified cDNA clones represent alternatively spliced forms of previously reported full‐length clones. The sequence alignments have been posted on the World Wide Web and are accessible at the Tissue Antigens web site at: http:www.tissue‐antigens.dkkir‐align.html. The alignments will be updated at intervals.
Intracellular signal transduction mediated by ligation of MHC class I molecules
Authors: Skov S.
Published: July 2010

Abstract: A great deal of knowledge has accumulated regarding signal transduction after ligation of MHC class I (MHC‐I) molecules. In recent years focus has been given to delineation of the intracellular signal pathways activated after MHC‐I ligation. Activation of tyrosine kinases leading to a rise in the intracellular free calcium concentration ([Ca2+]i) is the major initial event occurring after MHC‐I ligation of T cells. Curiously, the MHC‐I‐induced signaling is not dependent upon the cytoplasmic tail of the MHC‐I molecule, suggesting that the MHC‐I molecule induces intracellular signaling through association with other membrane‐embedded molecules. More distal signaling events after MHC‐I ligation includes activation of the Jak/Stat pathway leading to Stat‐3 activation, and activation of the PI3‐kinase leading to JNK activation and apoptosis. This review will sum up what is currently known about signaling induced by ligation of MHC‐L
Genomic structure of PIR‐B, the inhibitory member of the paired immunoglobulin‐like receptor genes in mice
Authors: Alley T.L. , Cooper M.D. , Chen M. , Kubagawa H.
Published: July 2010

Abstract: The genes encoding the murine paired immunoglobulin‐like receptors PIR‐A and PIR‐B are members of a novel gene family which encode cell‐surface receptors bearing immunoreceptor tyrosine‐based inhibitory motifs (ITIMs) and their non‐inhibitory/activatory counterparts. PIR‐A and PIR‐B have highly homologous extracellular domains but distinct trans‐membrane and cytoplasmic regions. A charged arginine in the transmembrane region of PIR‐A suggests its potential association with other transmembrane proteins to form a signal transducing unit. PIR‐B, in contrast, has an uncharged transmembrane region and several ITIMs in its cytoplasmic tail. These characteristics suggest that PIR‐A and PIR‐B which are coordinately expressed by B cells and myeloid cells, serve counter‐regulatory roles in humoral and inflammatory responses. In the present study we have determined the genomic structure of the single copy PIR‐B gene. The gene consists of 15 exons and spans approximately 8 kilobases. The first exon contains the 5′ untranslated region, the ATG translation start site, and approximately half of the leader peptide sequence. The remainder of the leader peptide sequence is encoded by exon 2. Exons 3–8 encode the six extracellular immunoglobulin‐like domains and exons 9 and 10 code for the extracellular membrane proximal and transmembrane regions. The final five exons (exons 11–15) encode for the ITIM‐bearing cytoplasmic tail and the 3′ untranslated region. The intron/exon boundaries of PIR‐B obey the GT‐AG rule and are in phase I, with the notable exception of the three boundaries determined for ITIM‐containing exons. A microsatellite composed of the trinucleotide repeat AAG in the intron between exons 9 and 10 provides a useful marker for studying population genetics.
Human monoclonal antibody with T‐cell‐like specificity recognizes MHC class I self‐peptide presented by HLA‐DR1 on activated cells
Authors: Wölpl A. , Haider T. , Kalbacher H. , Neumeyer H. , Siemoneit K. , Goldmann S.F. , Eiermann T.H.
Published: July 2010

Abstract: Alloreactive T cells recognize peptides presented in the binding groove of major histocompatibility complex molecules (MHCs), whereas B cells mainly recognize the MHCs independent of bound peptides. Here, we demonstrate that the human B‐cell repertoire comprises B cells which can be stimulated during pregnancy to produce antibodies reacting with MHCs in a way similar to T cells. The human monoclonal antibody UL‐5A1 recognizes DR1PRA/DRB1*0101) molecules on lymphoblastoid cell lines only if they co‐express HLA‐A2 or if they have been loaded with HLA‐A2‐derived peptides. The effect of the HLA‐A2 peptide 105–117 on UL‐5A1 reactivity was specific, time and dose‐dependent Reactivity increased when naturally processed peptides were removed from DR1 molecules before the HLA‐A2 peptide 105–117 was loaded. UL‐5A1 reacted specifically with cells that had been activated. The results imply a role of activation of cells in peptide processing and/or loading.
HFE codon 63/282 (H63D/C282Y) dimorphism in German patients with genetic hemochromatosis
Authors: Gottschalk R. , Seidl C. , Löffler T. , Seifried E. , Hoelzer D. , Kaltwasser J.P.
Published: July 2010

Abstract: Genetic hemochromatosis (GH) is closely associated with genes of the major histocompatibility complex (MHC) on chromosome 6. Recently, a candidate gene for GH, with structural similarities to MHC class I genes, designated HLA‐H and presently named HFE, has been cloned. The HFE gene is localized telomeric to the MHC and several reports have indicated that the HFE gene is mutated in GH patients. In the present study we have analyzed the relationship of HFE gene variants and disease manifestation in GH patients and family members. Fifty‐seven patients with GH, 73 family members and 153 healthy blood donors were studied for the amino acid dimorphism at codon 63 (His63Asp=H63D) and codon 282 (Cys282Tyr= C282Y) of the HFE gene. The codon 63 and 282 dimorphism were defined by PCR amplification of genomic DNA samples and restriction enzyme digestion using RsaI/SnaBI for C282Y and Bcll/Mbo1 for H63D. Ferritin, transferrin serum levels and total iron‐binding capacity were determined prior to therapeutic intervention. The Tyr‐282 substitution occurred in 53 (93%) of patients compared with 8 (5.2%) of controls (OR=169, P>0.0001). Fifty‐one (90%) patients were Tyr‐282 homozygous. In contrast, the Asp‐63 substitution was present in 5 (8.8%) of the patients compared with 34 (22%) of controls (OR=0.39, P=NS) with none of the patients being homozygous. In Tyr‐282 homozygous GH patients serum ferritin levels, transferrin saturation, liver iron and liver iron index were elevated significantly compared to Tyr‐282‐negative patients, whereas no difference was observed between Tyr/Cys‐282 heterozygous and Tyr‐282‐negative patients.
HLA‐DR and ‐DQ alleles in Italian patients with melanoma
Authors: Lulli P. , Grammatico P. , Brioli G. , Catricalà C. , Morellini M. , Roccella M. , Mariani B. , Pennesi G. , Roccella F. , Cappellacci S. , Trabace S.
Published: July 2010

Abstract: Controversial data have been reported about HLA alleles and susceptibility to melanoma. Our investigation was undertaken to analyze the relationship between HLA alleles distribution in patients with melanoma and susceptibility to the tumor, in order to study the possible correlation between HLA class II DQA1, DQB1 and DRB1 genes involved in immune recognition, and melanoma, usually considered a highly immunogenic tumor. We therefore typed by means of PCR‐SSP (sequence‐specific primers) 53 Italian patients and 53 healthy random controls coming from the same geographic area. We observed a decrease of all haplotypes bearing DQB1*0301, DQB1*0302 and DQB1*0303 alleles but not of haplotype DRB1*11;DQA1*0501;DQB1*0301. Our results seem to support the hypothesis of a protective role of some DQ3‐bearing haplotypic combinations in melanoma.
Soluble HLA class I and class II antigens in patients with multiple sclerosis
Authors: Ott M. , Stecker K. , Seidl C. , Seifried E. , Westhoff U. , Grosse‐Wilde H. , Fischer P.‐A.
Published: July 2010

Abstract: Soluble HLA class I (sHLA‐I) and soluble HLA class II (sHLA‐II) antigen levels during different stages of disease were investigated in paired serum and cerebrospinal fluid (CSF) samples from 37 patients with multiple sclerosis (MS) using ELISA and Western blot analysis. Soluble HLA‐II antigens in the serum of untreated patients with the relapsing‐remitting type of MS (RRMS) were found to be significantly elevated in acute relapse as compared to values obtained from patients under steroid treatment, in remission or healthy controls. No significant differences in circulating sHLA‐I levels could be detected. In contrast, a trend towards increased intrathecal production of sHLA‐I molecules in the CSF was observed in untreated RRMS patients in acute relapse, whereas the levels of soluble HLA‐II antigens in the CSF were below the detection limit of the ELISA method. Our observations underline the presence of systemic immune activation in MS patients, as reflected in elevated serum sHLA‐II antigen levels, and reveal a dichotomy between sHLA class I and II antigen production in the peripheral blood versus CSF in acute MS. Serial measurements of sHLA‐II antigen levels might represent a non‐invasive method to assess disease activity in MS patients.
HLA‐A*02172* adds to the heterogeneity of HLA‐A*02 alleles
Authors: Fischer G.F. , Faé I. , Frey E. , Mayr W.R.
Published: July 2010

Abstract: We have characterized a novel HLA*02 allele by nucleotide sequencing.
Constitutive nitric oxide synthase gene polymorphisms and house dust mite respiratory allergy in an Algerian patient group
Authors: Djidjik R. , Ghaffor M. , Brun M. , Gharnaout M. , Salah S. S. , Boukouaci W. , Djidjik H. , Benyounes A. , Koumaravelou K. , Krishnamoorthy R. , Abbadi M. C. , Charron D. , Tamouza R.
Published: July 2010

Genetic polymorphisms in neuronal nitric oxide synthase (NOS1) and calmodulin‐dependent endothelial NOS (NOS3) genes are known to influence the course of allergic respiratory disorders. We investigated the role of NOS1 −84 G→A and NOS3 −786 T→C, 894 G→T and 27 base pair (bp) repeat polymorphisms in 125 patients suffering from asthma and/or rhinitis and monosensitized against Dermatophagoides pteronyssinus (Dpter) and 111 controls from Algeria. We found a higher frequency of the −786 C NOS3 allele in patients than in controls [corrected P value (Pc) = 0.04], especially in female cases (Pc = 0.02) and that the ‘ab’ genotype of the 27‐bp polymorphism was significantly associated with specific immunoglobulin E production against Dpter (P = 0.006). This study brings further support for the participation of NOS3 gene polymorphism in the pathogenesis of respiratory allergic disorders.
Interleukin‐10 gene polymorphisms influence the clinical course of non‐Hodgkin’s lymphoma
Authors: Bogunia‐Kubik K. , Mazur G. , Wróbel T. , Kuliczkowski K. , Lange A.
Published: July 2010

The pathophysiology of Non‐Hodgkin’s lymphoma (NHL) is still unknown and clinical course is very unpredictable. Many cytokines, including interleukin‐10 (IL‐10), play a role in the perpetuation of this disease. The IL‐10‐producing capability has been found to be influenced by the IL‐10 gene promoter polymorphisms. The aim of the present study was to assess whether any of IL‐10 (−1082 A/G, −819 C/T and −592 A/C) genotypes prevails in Polish patients with NHL and whether IL‐10 promoter polymorphisms may be associated with less or more favourable course of the disease. IL‐10 gene promoter polymorphisms were assessed in 105 individuals, including 55 NHL patients and 50 ethically matched controls. The frequency of the IL‐10 low‐producing −1082 AA homozygous genotype was significantly higher in patients with aggressive NHL as compared with patients with indolent forms of the disease (0.57 vs 0.28, P < 0.05) and controls [0.57 vs 0.32, odds ratio (OR) = 2.69, P < 0.05]. Also, the presence of the ACC genotype was more frequently detected among patients with more aggressive disease than in those with indolent forms (0.74 vs 0.47, P < 0.05) and healthy controls (0.74 vs 0.42, OR = 3.69, P < 0.05). In multivariate analyses, the AA homozygosity (OR = 6.33, P < 0.05) and ACC genotype (OR = 3.57, P = 0.05) appeared as independent risk factors of more aggressive manifestation of NHL in addition to the elevated lactate dehydrogenase 480 level. Although no direct association was found between IL‐10 promoter polymorphisms and NHL, IL‐10 (−1082) AA homozygosity and IL‐10 ACC genotype were found to be associated with unfavourable prognosis in patients with NHL.
Follicular associated T cells and their B‐cell helper qualities
Authors: Haynes Nicole M.
Published: July 2010

The immune system utilizes sophisticated cellular surveillance mechanisms to maintain the integrity of the multicellular host. Adaptive immunosurveillance in particular constitutes a powerful branch of the immune system that houses the capacity to mount exquisitely specific responses against a diverse array of foreign antigens. Central to the development of adaptive immunity is the activation of T and B cells. Upon antigen engagement, T and B cells have been observed to undergo striking changes in their migratory status and distribution within secondary lymphoid organs, a phenomenon that is to a large extent controlled through their altered responsiveness to homeostatic T‐ and B‐zone chemokines. Changes in their chemokine receptor expression and/or sensitivity to their respective ligands assist in bringing rare antigen‐specific T and B lymphocytes, dendritic cells and CD4+CD3− accessory cells together. Cognate interaction between these cells at the T–B junction can support the generation of extrafollicular foci of antibody producing plasma cells and the formation of germinal centers. Such T‐dependent antibody responses are highly dependent on the functional properties and activity of a specialized subset of CXCR5+ICOS+ CD4 T cells referred to as T follicular helper cells (TFH). This review presents an overview of some of the defining characteristics of this subset of T‐helper cells and the chemokine receptors and their ligands that help dictate the migratory activity of TFH cells within secondary lymphoid organs.
LeERF‐1, a novel AP2/ERF family gene within the B3 subcluster, is down‐regulated by light signals in Lithospermum erythrorhizon
Authors: Zhang W. , Zou A. , Miao J. , Yin Y. , Tian R. , Pang Y. , Yang R. , Qi J. , Yang Y.
Published: July 2010

We previously showed that ethylene might be involved in the process of shikonin biosynthesis regulated by light signals. Here, we cloned a full‐length cDNA of LeERF‐1, a putative ethylene response factor gene, from Lithospermum erythrorhizon using the RACE (rapid amplification of cDNA ends) method. Phylogenetic analysis revealed that LeERF‐1 was classified in the B3 subfamily, together with ERF1 and ORA59 of Arabidopsis. Heterologous expression of LeERF‐1 in Arabidopsis showed that LeERF‐1:eGFP fusion protein was precisely localised to the nucleus, implying that it might function as a transcription factor. Detailed expression analysis with real‐time PCR showed that LeERF‐1 was significantly down‐regulated by white, blue and red light, although the inhibitory effect of red light was relatively weak compared to other light conditions. Tissue‐specific expression analysis also indicated that LeERF‐1 was dominantly expressed in the roots, which grow in soil in darkness. These patterns are all consistent with the effects of different light signals on regulating formation of shikonin and its derivatives, indicating that LeERF‐1 might be a crucial positive regulator, like other B3 subfamily proteins (such as ORCA3 and ORA59), in regulating biosynthesis of secondary metabolites.
Ausgedehnte menschliche Mäusefavusendemie in der ungarisdien Tiefebene
Authors: SZATHMARY S.
Published: July 2010

Verfasser hat eine, ein großs Gebiet umfassende Mäusefavusendemie beobach–tet, deren Herkunft er auf den Boden zurückführt. Er beschreibt die Infektions–quellen der Endemie und die Infektionsformen. Er ist der Meinung, daß die In–fektion von den durch den Boden inflzierten Feldäusen auf Hausäuse und von diesen auf Menschen und Katzen übertragen wird. Der Verfasser berichtet über die menschlichen Mäusefavusfälle in einer Verteilung nach Altersstufen und stellt dabei den Infektionsgrad der Bevölkerung einiger Städte der Ungarischen Tiefebene vor und während der Endemie fest. Er fand, daß das Ausmaß der Ansteckung in den Kleinstädten während der latenten Endemie zehnmal größer war als in den Großstädten. Aus den Angaben des Graphikons der durch Trichophyton quinckeanum und Trichophyton gypseum verursachten Fälle zieht er die Schlußfolgerung, daß die Mäuse an der Verbreitung der von diesem Pilz stam–menden Infektion keinen Anteil haben.

Zum Schluß beschäftigt sich der Verfasser mit den besonderen Krankheitser–scheinungen der favösen Mäuse und mit den Varietäten des die Endemie ver–ursachenden Pilzes.
Mold infection of imported smoked herring
Authors: Refai M. , Elmossalami E. , Loot A.
Published: July 2010

Aus einer Partie von 6 420 kg importierter Räucherheringe wurden Proben entnommen und mykologisch untersucht. Die Heringe wiesen weiße und schwarze Schimmelflecke auf und rochen schimmlig, ebenso die Holzkisten, in denen sie verpackt waren. Die oberste Lage Heringe war am stärksten verschimmelt.

Mikroskopisch konnte bei der Direktuntersuchung festgestellt werden, daß es sich um Aspergillus und Penicillium handelte. Die kulturelle Identifizierung ergab als Ursache der schwarzen Flecke Aspergillus niger, Typ Awamori, und als Ursache der hellen Flecke Penicillium funiculosum.

Zur Bekämpfung wird, neben hygienischen Maßnahmen, vorgeschlagen, die Heringe mit 20–25 %iger Salzlösung oder mit 3% iger Essiglösung zu behandeln und anschließend an der Luft zu trocknen. In leichten Fällen kann die Oberfläche der Heringe auch mit Öl eimgerieben werden.
Ein gepufferter Nährboden für Mikropilze
Authors: Lührs K.
Published: July 2010

Es wird ein gepufferter Nährboden besdirieben, auf dem Mikropilze ihre makroskopi‐schen und mikroskopischen Strukturen sehr gut ausbilden, ohne überschießendes Wachstum zu zeigen. Der Nährboden eignet sich zur Anzucht wie audi zur anschließenden unmittel‐baren Aufbewahrung der Mikropilze.

A buffered agar culture medium is described on which the macroscopic and microscopic structures of microfungi form well without showing exaggerated growth. The culture medium is suitable for both the culture and the following maintenance of the microfungi.
Schimmelpilze im Haushalt/Moulds in the Domestic Environment
Authors: Reiß J.
Published: July 2010

Zusammenfassung: An 77 Meßstellen in Küchen, Badezimmern sowie in Wohn‐ und Schlafräu‐men von Wohnungen wurde der Gesamtgehalt der Luft an Schimmelpilzen (mit Malzextrakt‐agar) sowie selektiv an Aspergillus parasiticus, A. flavus und Penicillium roqueforti (mit diffe‐renzierenden Nährböden) bestimmt; die übrigen Schimmelpilze wurden nicht differenziert. Der Keimgehalt war besonders hoch (bis zu 60 koloniebildende Elemente je 30 Liter Luft) bei höhe‐ren Temperaturen, Luftbewegungen (z. B. Klopfen von Teppichen, Bettenmachen) sowie über textilen Unterlagen (Teppichen, Sofas). A. parasiticus und A. flavus traten gehäuft auf bei Temperaturen von über 24°C in Badezimmern (insbesondere über den Vorlegern vor Toilettenschüsseln) und in Wohnräumen in der Nähe von Sofas, Gardinen und Läufern. P. roqueforti war nur in Küchen zu finden (Kühlschrank, verschimmeltes Brot, Brotschneidemaschinen, Mülleimer).

Summary: The mould content of the air at 77 sites in kitchens, bathrooms, living‐rooms and bedrooms in houses was measured using malt extract agar (total mould content) and differentiating media for Aspergillus parasiticus/A. flavus and for Penicillium roqueforti; other moulds have not been differentiated. The mould content was especially high (up to 60 colony forming elements in 301 air) at higher temperatures, in currents of air (e. g. brushing out of carpets, shaking of beds) as well as above textile materials (carpets, sofas). A. parasiticus/A. flavus were frequent at temperatures of more than 24°C in bathrooms (especially above WC mats) and in living‐rooms near curtains, sofas and carpets. P. roqueforti was only found in kitchens (refrigerator, moulded bread, bread‐cutting machines, waste‐bins).
The Effect of Cilofungin (LY 121019) in Combination with Amphotericin B or Flucytosine Against Candida Species: Die Wirkung von Cilofungin (LY 121019) in Kombination mit Amphotericin B oder Flucytosin auf Candida‐Arten
Authors: Bulo A.N. , Bradley Suzanne F. , Kauffman Carol A.
Published: July 2010

Summary: Cilofungin was combined with amphotericin B or flucytosine to determine if synergistic inhibition or killing occurred against 50 strains of various Candida species. Synergistic inhibition of growth occurred only once with amphotericin B and cilofungin and only 2 times with flucytosine and cilofungin. Synergistic killing occurred in 5 strains with the amphotericin B‐cilofungin combination and in 7 strains with the flucytosine‐cilo‐fungin combination. Antagonism occurred frequently with both the amphotericin B‐cilofungin and the flucytosine‐cilofungin combinations.

Zusammenfassung: Cilofungin wurde mit Amphotericin B oder Flucytosin kombi‐niert, um eine etwaige synergistische Wachstumshemmung oder Inaktivierung von 50 Stämmen unterschiedlicher Candi‐da‐Arten zu untersuchen. Eine synergisti sche Wachstumshemmung wurde nur ein‐mal mit Amphotericin B und Cilofungin und zweimal rnit Flucytosin und Cilofungin beobachtet. Eine synergistische Abtötung trat an 5 Stämmen mit der Amphotericin B‐Cilofungin‐ und an 7 Stämmen mit der Flucytosin‐Cilofungin‐Kombination auf. Häufiger wurden bei beiden Kombinatio‐nen Antagonismen gefunden.
Feasibility of high‐density electrophysiological study using multiple‐electrode array in isolated small animal atria
Authors: Lau Dennis H , Mackenzie Lorraine , Shipp Nicholas J , Kuklik Pawel , Dimitri Hany , Lobb Bruce LW , Alasady Muayad , Lim Han S , Kelly Douglas R , Brooks Anthony G , Saint David A , Sanders Prashanthan
Published: July 2010

1. High‐density cardiac electrophysiological study (EPS) of small animal atria has been limited to optical mapping techniques, which require complex and expensive equipment setup. We aim to evaluate the feasibility of carrying out EPS in isolated atrial tissues using a custom made high‐density multiple‐electrode array (MEA).

2. Isolated rat atrial preparations were studied. The MEA (4 × 5 mm) consisted of 90 silver chloride coated electrodes (0.1 mm diameter, 0.5 mm pitch) and was connected to a conventional EP system yielding 80 bipolar signals. Atrial tissues were placed over the MEA in a dish bubbled with 100% oxygen and superfused with modified HEPES solution at pH 7.35 and 37°C. Then, 1 mmol of 2,3‐butanedione monoxime was added to suppress motion artifacts from muscle contractions. Custom plaque analysis software was used for offline conduction analysis.

3. Isolated atrial tissues showed good viability of > 30 min, allowing ample time for complete EPS. High quality electrograms with excellent signal to noise ratio were obtained. All electrophysiological parameters showed good reproducibility: effective refractory period, conduction velocity and heterogeneity index. Tachycardia was also inducible in these normal atria.

4. The present study shows the feasibility of performing high‐density EPS of small isolated atrial tissues with a conventional electrode‐based technique. The MEA system is compatible with standard electrophysiology recording systems and provides a novel, inexpensive option for detailed EPS in small animal models. In particular, it presents new research avenues to further explore the mechanisms of atrial arrhythmias in various transgenic and knockout rodent models.
Involvement of mitogen‐activating protein kinase and intracellular pH in the duration of the metaphase I (MI) pause of starfish oocytes after spawning
Authors: Usui Kana , Hirohashi Noritaka , Chiba Kazuyoshi
Published: July 2010

The metaphase I (MI) arrest of starfish oocytes is released after spawning. In this study using starfish Asterina pectinifera, the duration of MI after spawning was ~20 min and ~30 min in fertilized and unfertilized oocytes, respectively. This prolongation of MI in unfertilized oocytes, referred to as the MI pause, was maintained by mitogen‐activating protein kinase (MAPK) as well as low intracellular pH (~7.0). Contrary to previous reports, MI arrest was not maintained by MAPK, since it was inactive in the oocytes arrested at MI in the ovary and activated immediately after spawning. Also, cyclin B was not degraded at pH 6.7 in the cell‐free preparation without MAPK activity, whereas it was degraded at pH 7.0, suggesting that MI arrest was solely maintained by lower pH (< 7.0). Normal development occurred when the spawned oocytes were fertilized before the first polar body formation, whereas fertilization after the first polar body formation increased the rate of abnormal development. Thus, due to MI pause and MI arrest, the probability for fertilization before the polar body formation might be increased, leading to normal development.
Left ventricular geometry and cardiovascular mortality based on haemodialysis patient autopsy analyses
Authors: MIMURA IMARI , NISHI HIROSHI , MISE NAOBUMI , MORI MASAYA , SUGIMOTO TOKUICHIRO
Published: July 2010

Aim:  In end‐stage renal disease (ESRD) patients, left ventricular hypertrophy (LVH) is common and a risk for cardiovascular events. LVH is geometrically classified into two major groups, concentric and eccentric, and accumulating evidence suggests eccentric LVH has a more negative effect than concentric LVH on ESRD outcome. However, there have been very few studies on the cardiac findings from ESRD patient autopsy in which the relationship between LVH geometry and mortality was analyzed.

Methods:  An observational study was performed with the autopsy findings in 30 haemodialysis patient cases between 2001 and 2006 at Mitsui Memorial Hospital, Tokyo. Between those who died of a cardiovascular cause and those who died of non‐cardiovascular causes, we compared the heart/bodyweight ratio, left ventricular dilatation, and the extent of fibrosis of the left ventricle.

Results:  Heart/bodyweight ratio was significantly higher (P < 0.0001) in the cardiovascular mortality group (n = 11, 11.7 ± 2.5 g/kg) compared to the non‐cardiac cause of death group (n = 19, 8.05 ± 0.7 g/kg). The dilatation of the left ventricle was significantly more frequent in the cardiovascular than the non‐cardiac cause of death group (P = 0.016). Additionally, the fibrotic area of left ventricular cross‐section was larger in the cardiovascular (1.63 ± 1.6%) than the non‐cardiac group (0.83 ± 1.7%, P = 0.04).

Conclusion:  This autopsy study indicates that eccentric LVH in haemodialysis patients is closely associated with cardiovascular mortality. LVH geometry, as well as LVH severity, is worthy of consideration as a clinical predictor for cardiovascular mortality.
Immunoglobulin A1 protease: A new therapeutic candidate for immunoglobulin A nephropathy
Authors: XIE LIN‐SHEN , HUANG JUN , QIN WEI , FAN JUN‐MING
Published: July 2010

Immunoglobulin A nephropathy (IgAN), characterized by predominant or exclusive deposition of IgA1 in glomerular mesangium, is the most common primary glomerulonephritis worldwide. At present, the treatment is always limited due to the incomplete understanding of the pathogenesis of IgAN. Mesangial deposited IgA1 is the common final pathway leading to glomerulonephritis and renal injury. IgA1 protease, a proteolytic enzyme with strict substrate specificity for human IgA1, may be an effective therapeutic candidate for IgAN by removing the mesangial deposited IgA1.
Serotonin‐transporter‐linked promoter region polymorphism and serotonin transporter binding in drug‐naïve patients with major depression
Authors: Joensuu Mikko , Lehto Soili Marianne , Tolmunen Tommi , Saarinen Pirjo Irmeli , Valkonen‐Korhonen Minna , Vanninen Ritva , Ahola Pasi , Tiihonen Jari , Kuikka Jyrki , Pesonen Ullamari , Lehtonen Johannes
Published: July 2010

Aims:  Both the serotonin transporter and its genetic regulation by the serotonin‐transporter‐linked polymorphic region have a role in the pathophysiology of depression. Most of the previous studies have found no influence of serotonin‐transporter‐linked polymorphic region allelic variation on serotonin transporter binding in healthy controls or patients with major depression. Due to the inconsistency of the previous findings, we compared single photon emission computed tomography imaging with the serotonin‐transporter‐linked polymorphic region genotype in patients with major depressive disorder.

Methods:  A total of 23 drug‐naïve patients with major depressive disorder were genotyped and brain imaged with [123I]nor‐β‐CIT single photon emission computed tomography. The severity of depression was evaluated with the 17‐item Hamilton depression rating scale.

Results:  Depressed patients homozygous for the short allele had lower [123I]nor‐β‐CIT binding in the medial prefrontal cortex, but not in the midbrain, compared with the other genotypes.

Conclusion:  The decreased medial prefrontal cortical serotonin transporter binding in the patients homozygous for the short allele may be linked to altered function of the serotonin‐transporter‐linked polymorphic region gene expressed in these patients, especially in the medial prefrontal cortex.
Urodynamic effects of solifenacin in untreated female patients with symptomatic overactive bladder
Authors: Tanaka Yoshinori , Masumori Naoya , Tsukamoto Taiji
Published: July 2010

Objectives:  To investigate the urodynamic effects of solifenacin in untreated female patients with symptomatic overactive bladder (OAB).

Methods:  A total of 52 untreated female patients with OAB symptoms were given 5 mg solifenacin once daily for 12 weeks. Before and after treatment, the frequency volume chart, overactive bladder symptom score (OABSS), postvoid residual volume, filling cystometry and adverse events were evaluated.

Results:  After solifenacin treatment, OAB symptoms were improved, voided volume was increased and voiding number was decreased. Bladder capacities at the first sensation of bladder filling, first desire to void and strong desire to void were significantly increased. Intravesical pressure at the first sensation of bladder filling was significantly decreased. Detrusor overactivity (DO) disappeared in five patients. For 28 patients with persisting DO after treatment, bladder capacity at DO was significantly increased. Both groups with and without DO at baseline had significant improvements of OAB symptoms.

Conclusions:  Solifenacin urodynamically increases bladder capacity in female patients with symptomatic OAB.