bluuebunny/crossref_metadata_2025 huggingface dataset:
Peginterferon alfa‐2a and ribavirin for chronic hepatitis C genotype 1 infections in black patients: safety, tolerability and impact on sustained virologic response
Authors: Howell C. D. , Jeffers L. S. , Cassidy W. , Reddy K. R. , Hu S. , Lee J. S.
Published: April 2006

Summary.  HCV infections are two‐times more prevalent in black Americans than in whites. We previously reported that treatment with peginterferon alfa‐2a plus ribavirin produced a sustained virologic response (SVR) rate of 26% in blacks, a lower efficacy compared with the SVR in whites. Here we detail the safety profile of peginterferon alfa‐2a plus ribavirin and the relationship between treatment adherence, defined by cumulative drug exposure, and SVR in 78 black patients infected with HCV genotype 1. Sixty‐two (79%) patients completed 48 weeks of combination treatment. Peginterferon alfa‐2a dose was modified for neutropenia in 36 patients (46%), whereas ribavirin dose was modified due to anemia in 31 patients (40%). The SVR rate was related to medication exposure, based on the percentage of the planned doses of peginterferon and ribavirin that the patients received. The SVR rates were 33, 25 and 0% in patients who received >80, 61–80 and ≤60% of the planned peginterferon, respectively. The SVR rates were 28, 33 and 18% in patients who received >80, 61–80 and ≤60% of the planned ribavirin. The SVR rate was 29% (11 of 38) in patients who received >80% of the total planned doses of both peginterferon and ribavirin and 7% (1 of 14) in patients who received ≤80% of both medicines. The SVR was 30% in patients who received >60% exposure to both, and 0% in patients with ≤60% exposure. In conclusion, peginterferon alfa‐2a plus ribavirin demonstrated good safety and tolerability profiles in blacks infected with HCV genotype 1. Adherence to at least >60% of the planned peginterferon alfa‐2a and ribavirin doses for 48 weeks was associated with a greater SVR in black patients with HCV genotype 1 infections.
Association of TNF‐alpha promoter polymorphisms with the outcomes of hepatitis B virus infection in Chinese Han population
Authors: Du T. , Guo X.‐H. , Zhu X.‐L. , Li J.‐H. , Lu L.‐P. , Gao J.‐R. , Gou C.‐Y. , Li Z. , Liu Y. , Li H.
Published: April 2006

Summary.  Host genetic factors and environment factors including hepatitis B virus (HBV) genotypes are widely studied for the different outcomes of HBV infection. Recent studies suggest that tumour necrosis factor‐alpha (TNF‐alpha) plays a pivotal role in the viral clearance and host immune response to HBV, and the capacity for TNF‐alpha production in individuals is influenced by a major genetic component. In this study, we aimed to explore whether the single‐nucleotide polymorphisms (SNPs) of TNF‐alpha promoter are associated with the outcomes of HBV infection in the Chinese Han population. One hundred and forty‐three spontaneously recovered HBV subjects and 196 chronic hepatitis B patients were recruited in this case–control study in the Beijing area of China. Polymerase chain reaction–restriction fragment‐length polymorphism (PCR‐RFLP) and sequence‐specific primer‐PCR (SSP‐PCR) were used to detect the SNPs of five sites in the TNF‐alpha promoter (−238G/A, −308G/A, −857C/T, −863C/A, −1031T/C). The frequency distributions of genotypes and haplotypes in two groups were analysed by EPI and EH programs. The presence of the −238GG genotype was significantly correlated with persistence of HBV infection (OR = 4.08, P = 0.02), and −857TT genotype appeared in relation to the spontaneous clearance of HBV (OR = 0.47, P = 0.03). Frequency of haplotype GGCCT (−238/−308/−857/−863/−1031) in the chronic HB group was significantly lower than that in spontaneously recovered group (P = 0.03), and frequencies of haplotypes GGCAT and GGTAT in the chronic HB group were significantly higher than those in the spontaneously recovered group (P = 0.0001, P = 0.0004). In conclusion, TNF‐alpha promoter polymorphisms are independently associated with different outcomes of HBV infection.
Expressional screening of interferon‐stimulated genes for antiviral activity against hepatitis C virus replication
Authors: Itsui Y. , Sakamoto N. , Kurosaki M. , Kanazawa N. , Tanabe Y. , Koyama T. , Takeda Y. , Nakagawa M. , Kakinuma S. , Sekine Y. , Maekawa S. , Enomoto N. , Watanabe M.
Published: April 2006

Summary.  Type‐I interferons (IFNs) and the interferon‐stimulated genes (ISGs) play a major role in antivirus responses against hepatitis C virus (HCV) infection. In this study, we studied expression profiles of ISGs in cells supporting subgenomic HCV replication (Huh7/Rep), and screened their activities to suppress HCV replication. Real‐time PCR analyses showed that the expression levels of 23 ISGs were significantly lower in Huh7/Rep than naive Huh7 cells due to transcriptional suppression of the interferon‐stimulated response element (ISRE). Furthermore, the expression level of ISGs was also decreased in the cured Huh7 cells in which replicon had been eliminated (cHuh7), indicating adaptation of the cells to support HCV replication by downregulating ISGs. On the other hand, expression of HCV replicon was significantly suppressed by overexpression of several ISGs including PKR, MxA, IRF‐9, GBP‐1, IFI‐6‐16, IFI‐27, 25OAS and IRF‐1. Knock down of GBP‐1, IFI‐6‐16 and IFI‐27 by short hairpin RNA resulted in increase of HCV replication. Thus, we conclude that downregulation of ISG expression is required in the host cells supporting HCV replication and that several ISGs directly suppress HCV replication. The search for ISGs that regulate HCV replication may help to elucidate the cellular antiviral defence mechanisms against HCV infection.
A catalogue of RR Lyrae stars from the Northern Sky Variability Survey
Authors: Wils Patrick , Lloyd Christopher , Bernhard Klaus
Published: April 2006

A search for RR Lyrae stars has been conducted in the publicly available data of the Northern Sky Variability Survey. Candidates have been selected by the statistical properties of their variation; the standard deviation, skewness and kurtosis with appropriate limits determined from a sample 314 known RRab and RRc stars listed in the General Catalogue of Variable Stars. From the period analysis and light-curve shape of over 3000 candidates 785 RR Lyrae have been identified of which 188 are previously unknown. The light curves were examined for the Blazhko effect and several new stars showing this were found. Six double-mode RR Lyrae stars were also found of which two are new discoveries. Some previously known variables have been reclassified as RR Lyrae stars and similarly some RR Lyrae stars have been found to be other types of variable, or not variable at all.
Strategies for development of vaccines for control of ixodid tick species
Authors: DE LA FUENTE J. , KOCAN K. M.
Published: April 2006

Ticks are distributed worldwide and impact human and animal health, as well as food animal production. Control of ticks has been primarily by application of acaricides, which has resulted in selection of resistant ticks and environmental pollution. Vaccines have been shown to be a feasible tick control method that offers a cost‐effective, environmentally friendly alternative to chemical control. However, identification of tick‐protective antigens remains the limiting step in vaccine development. Tick antigens exposed naturally to the host during tick feeding and those concealed have both shown promise as candidate vaccine antigens. Development of vaccines against multiple tick species may be possible using highly conserved tick‐protective antigens or by antigens showing immune cross‐reaction to different tick species. Vaccines made from a combination of key protective antigens may greatly enhance vaccine efficacy. Preliminary studies have suggested the possibility of vaccine strategies directed toward both tick control and the blocking of pathogen transmission. Characterization of the tick genomes will have a great impact on the discovery of new protective antigens. The future of research directed toward tick vaccine development is exciting because of new and emerging technologies for gene discovery, and vaccine formulation and delivery.
Intraperitoneal Echinococcus multilocularis infection in C57BL/6 mice affects CD40 and B7 costimulator expression on peritoneal macrophages and impairs peritoneal T cell activation
Authors: MEJRI N. , GOTTSTEIN B.
Published: April 2006

One of the most important immunopathological consequence of intraperitoneal alveolar echinococcosis (AE) in the mouse is suppression of T cell‐mediated immune responses. We investigated whether and how intraperitoneal macrophages (MØs) are, respectively, implicated as antigen‐presenting cells (APCs). In a first step we showed that peritoneal MØs from infected mice (AE‐MØs) exhibited a reduced ability to present a conventional antigen (chicken ovalbumin, C‐Ova) to specific responder lymph node T cells. In a subsequent step, AE‐MØs as well as naïve MØs (positive control) proved their ability to uptake and process C‐Ova fluorescein isthiocyanate (FITC). Furthermore, in comparison with naïve MØs, the surface expression of Ia molecules was up‐regulated on AE‐MØs at the early stage of infection, suggesting that AE‐MØs provide the first signal via the antigen–Ia complex. To study the accessory activity of MØs, AE‐MØs obtained at the early and late stages of infection were found to decrease Con A‐induced proliferation of peritoneal naïve T cells as well as of AE‐sensitized peritoneal T cells, in contrast to stimulation with naïve MØs. The status of accessory molecules was assessed by analysing the expression level of costimulatory molecules on AE‐MØs, with naïve MØs as controls. It was found that B7‐1 (CD80) and B7‐2 (CD86) expression remained unchanged, whereas CD40 was down‐regulated and CD54 (= ICAM‐1) was slightly up‐regulated. In a leucocyte reaction of AE‐MØs with naïve or AE‐T cells, both types of T cells increased their proliferative response when CD28 – the ligand of B7 receptors – was exposed to anti‐CD28 in cultures. Conversely to naïve MØs, pulsing of AE‐MØs with agonistic anti‐CD40 did not even partially restore their costimulatory activity and failed to increase naïve or AE‐T cell proliferation. Neutralizing anti‐B7‐1, in combination with anti‐B7‐2, reduced naïve and AE‐T cell proliferation, whereas anti‐CD40 treatment of naïve MØs increased their proliferative response to Con A. These results point at the key role of B7 receptors as accessory molecules and the necessity of the integrity of CD40‐expression by naïve MØs to improve their accessory activity. Taken together, the obstructed presenting‐activity of AE‐MØs appeared to trigger an unresponsiveness of T cells, contributing to the suppression of their clonal expansion during the chronic phase of AE‐infection.
A tomato mutant that shows stunting, wilting, progressive necrosis and constitutive expression of defence genes contains a recombinant Hcr9 gene encoding an autoactive protein
Authors: Barker Claire L. , Talbot Stephen J. , Jones Jonathan D. G. , Jones David A.
Published: April 2006

The tomato Cf‐9 gene confers resistance to races of the leaf mould fungus Cladosporium fulvum that carry the Avr9 avirulence gene. Cf‐9 resides at a locus containing five paralogous genes and was isolated by transposon tagging using a modified maize Dissociation (Ds) element. The tagging experiment generated an allelic series of Ds‐induced mutations of Cf‐9, most of which were wild type in appearance. However, one mutant, designated M205, showed stunted growth, wilting, progressive leaf chlorosis and necrosis and constitutive expression of defence genes. The phenotype of M205 was caused by a semidominant, Avr9‐independent mutation that co‐segregated with a Ds element insertion at the Cf‐9 locus. Molecular genetic analysis indicated that the Cf‐9 locus of M205 had undergone recombination, generating a chimeric gene, designated Hcr9‐M205, that comprised an in‐frame fusion between the 5′ coding region of the Cf‐9 paralogue, Hcr9‐9A, and the 3′ coding region of Cf‐9. The presence of a possible excision footprint adjacent to the junction between Hcr9‐9A and Cf‐9, and a Ds insertion at the homologous position in the downstream paralogue Hcr9‐9D, is consistent with recombination between Hcr9‐9A and Cf‐9 promoted by transposition of Ds from Cf‐9 into Hcr9‐9D. Agrobacterium tumefaciens‐mediated transient expression of Hcr9‐M205 in Nicotiana tabacum caused chlorosis and the accumulation of defence gene transcripts, indicating that the protein encoded by this novel Hcr9 gene is autoactive.
Mutations in the Diageotropica (Dgt) gene uncouple patterned cell division during lateral root initiation from proliferative cell division in the pericycle
Authors: Ivanchenko Maria G. , Coffeen Warren C. , Lomax Terri L. , Dubrovsky Joseph G.
Published: April 2006

In angiosperms, root branching requires a continuous re‐initiation of new root meristems. Through some unknown mechanism, in most eudicots pericycle cells positioned against the protoxylem change identity and initiate patterned division, leading to formation of lateral root primordia that further develop into lateral roots. This process is auxin‐regulated. We have observed that three mutations in the Diageotropica (Dgt) gene in tomato prevent primordium formation. Detailed analysis of one of these mutants, dgt1‐1, demonstrated that the mutation does not abolish the proliferative capacity of the xylem‐adjacent pericycle in the differentiated root portion. Files of shortened pericycle cells found in dgt1‐1 roots were unrelated to primordium formation. Auxin application stimulated this unusual proliferation, leading to formation of a multi‐layered xylem‐adjacent pericycle, but did not rescue the primordium formation. In contrast to wild type, auxin could not induce any cell divisions in the pericycle of the most distal dgt1‐1 root‐tip portion. In wild‐type roots, the Dgt gene promoter was expressed strongly in lateral root primordia starting from their initiation, and on auxin treatment was induced in the primary root meristem. Auxin level and distribution were altered in dgt1‐1 root tissues, as judged by direct auxin measurements, and the tissue‐specific expression of an auxin‐response reporter was altered in transgenic plants. Together, our data demonstrate that the Dgt gene product, a type‐A cyclophilin, is essential for morphogenesis of lateral root primordia, and that the dgt mutations uncouple patterned cell division in lateral root initiation from proliferative cell division in the pericycle.
Genome‐wide analysis of spatial and temporal gene expression in rice panicle development
Authors: Furutani Ikuyo , Sukegawa Shin , Kyozuka Junko
Published: April 2006

The basic structure of a rice inflorescence (the panicle) is determined by the pattern of branch formation, which is established at the early stages of panicle development. In this study we conducted global transcriptome profiling of the early stages of rice panicle development from phase transition to floral organ differentiation. To generate a meristem‐specific gene‐expression profile, shoot apical meristems (SAMs) and subsequently formed, very young panicles were collected manually and used for cDNA microarray analysis. We identified 357 out of 22 000 genes that are expressed differentially in the early stages of panicle development, and the 357 genes were classified into seven groups based on their temporal expression patterns. The most noticeable feature is that a fairly small number of genes, which are extensively enriched in transcription factors, are upregulated in the SAM immediately after phase transition. In situ hybridization analysis showed that each gene analysed exhibits a unique and interesting localization of mRNA. Remarkably, one of the transcription factors was proven to be a close downstream component of the pathway in which LAX, a major regulator of panicle branching, acts. These results suggest that our strategy – careful collection of meristems, global transcriptome analysis and subsequent in situ hybridization analysis – is useful not only to obtain a genome‐wide view of gene expression, but also to reveal genetic networks controlling rice panicle development.
A chloroplast‐localized dual‐specificity protein phosphatase in Arabidopsis contains a phylogenetically dispersed and ancient carbohydrate‐binding domain, which binds the polysaccharide starch
Authors: Kerk David , Conley Terry R. , Rodriguez Flor A. , Tran Hue T. , Nimick Mhairi , Muench Douglas G. , Moorhead Greg B. G.
Published: April 2006

Dual‐specificity protein phosphatases (DSPs) are important regulators of a wide variety of protein kinase signaling cascades in animals, fungi and plants. We previously identified a cluster of putative DSPs in Arabidopsis (including At3g52180 and At3g01510) in which the phosphatase domain is related to that of laforin, the human protein mutated in Lafora epilepsy. In animal and fungal systems, the laforin DSP and the beta‐regulatory subunits of AMP‐regulated protein kinase (AMPK) and Snf‐1 have all been demonstrated to bind to glycogen by a glycogen‐binding domain (GBD). We present a bioinformatic analysis which shows that these DSPs from Arabidopsis, together with other related plant DSPs, share with the above animal and fungal proteins a widespread and ancient carbohydrate‐binding domain. We demonstrate that DSP At3g52180 binds to purified starch through its predicted carbohydrate‐binding region, and that mutation of key conserved residues reduces this binding. Consistent with its ability to bind exogenous starch, DSP At3g52180 was found associated with starch purified from Arabidopsis plants and suspension cells. Immunolocalization experiments revealed a co‐localization with chlorophyll, placing DSP At3g52180 in the chloroplast. Gene‐expression data from different stages of the light–dark cycle and across a wide variety of tissues show a strong correlation between the pattern displayed by transcripts of the At3g52180 locus and that of genes encoding key starch degradative enzymes. Taken together, these data suggest the hypothesis that plant DSPs could be part of a protein assemblage at the starch granule, where they would be ideally situated to regulate starch metabolism through reversible phosphorylation events.
Arabidopsis homologue of human transcription factor IIH/nucleotide excision repair factor p44 can function in transcription and DNA repair and interacts with AtXPD
Authors: Vonarx Edward J. , Tabone Emma K. , Osmond Megan J. , Anderson Heather J. , Kunz Bernard A.
Published: April 2006

Eukaryotic general transcription factor (TF) IIH is composed of 10 proteins, seven of which are also required for nucleotide excision repair (NER) of UV radiation‐induced DNA damage in human cells and yeast. Plant homologues of the human TFIIH subunits XPB and XPD that function in NER have been isolated but none has been shown to operate in transcription. Here we address the capabilities of Arabidopsis thaliana AtGTF2H2 and AtXPD, homologues of the essential interacting human/yeast TFIIH components p44/Ssl1 and XPD/Rad3, respectively. Expression of AtGTF2H2 or AtXPD cDNAs in yeast ssl1 or rad3 mutants temperature‐sensitive for growth due to thermolabile transcription of mRNA restored growth and so transcription at the non‐permissive temperature. AtGTF2H2 also complemented the NER deficiency of the corresponding yeast mutant, as measured by full recovery of UV resistance, whereas AtXPD did not despite being necessary for NER in Arabidopsis. UV treatment did not upregulate transcription of AtGTF2H2 or AtXPD in Arabidopsis. Suppression of a yeast translation initiation defect by the ssl1‐1 mutation was prevented by expression of AtGTF2H2. Deletion of SSL1 in a yeast strain expressing AtGTF2H2 did not affect growth or confer UV sensitivity, demonstrating that AtGTF2H2 can perform all essential transcription functions and UV damage repair duties of Ssl1 in its absence. Furthermore, AtGTF2H2 interacted with AtXPD and yeast Rad3, and AtXPD also interacted with yeast Ssl1 in two‐hybrid assays. Our results indicate that AtGTF2H2 can act in transcription and NER, and suggest that it participates in both processes in Arabidopsis as part of TFIIH.
Nuclear suppressors define three factors that participate in both 5′ and 3′ end processing of mRNAs in Chlamydomonas chloroplasts
Authors: Rymarquis Linda A. , Higgs David C. , Stern David B.
Published: April 2006

Chloroplast RNA processing and degradation are orchestrated by nucleus‐encoded factors. Although several transcript‐specific factors have been identified, those involved in global RNA metabolism have mostly remained elusive. Using Chlamydomonas reinhardtii, we have identified three pleiotropic nuclear mutations, mcd3, mcd4 and mcd5, which cause quantitative variation between polycistronic transcripts and accumulation of transcripts with novel 3′ ends. The mcd3, mcd4 and mcd5 mutants were initially isolated as photoautotrophic suppressors of the petD 5′ mutants LS2 and LS6, which harbour four nucleotide linker‐scanning mutations near the 5′ end of the mature transcript. The LS mutants accumulate 1–3% of the wild‐type (WT) petD mRNA level and no cytochrome b6/f complex subunit IV, which is the petD gene product and required for photosynthesis. Each suppressor restores approximately 15% of the WT petD mRNA and subunit IV levels. Genetic analysis showed mcd4 to be recessive, and suggested that MCD4 interacts with the petD mRNA stability factor MCD1. To assess the specificity of mcd3, mcd4 and mcd5, transcripts from 32 chloroplast genes were analysed by RNA filter hybridizations. mcd3 and mcd4 displayed aberrant transcript patterns for 17 genes, whereas only three were altered in mcd5. Since the mutations affect multiple RNAs in a variety of ways, our data suggest that MCD3, MCD4 and MCD5 may participate in a series of multiprotein complexes responsible for RNA maturation and degradation in Chlamydomonas chloroplasts.
WRKY70 modulates the selection of signaling pathways in plant defense
Authors: Li Jing , Brader Günter , Kariola Tarja , Tapio Palva E.
Published: April 2006

Cross‐talk between signal transduction pathways is a central feature of the tightly regulated plant defense signaling network. The potential synergism or antagonism between defense pathways is determined by recognition of the type of pathogen or pathogen‐derived elicitor. Our studies have identified WRKY70 as a node of convergence for integrating salicylic acid (SA)‐ and jasmonic acid (JA)‐mediated signaling events during plant response to bacterial pathogens. Here, we challenged transgenic plants altered in WRKY70 expression as well as WRKY70 knockout mutants of Arabidopsis with the fungal pathogens Alternaria brassicicola and Erysiphe cichoracearum to elucidate the role of WRKY70 in modulating the balance between distinct defense responses. Gain or loss of WRKY70 function causes opposite effects on JA‐mediated resistance to A. brassicicola and the SA‐mediated resistance to E. cichoracearum. While the up‐regulation of WRKY70 caused enhanced resistance to E. cichoracearum, it compromised plant resistance to A. brassicicola. Conversely, down‐regulation or insertional inactivation of WRKY70 impaired plant resistance to E. cichoracearum. Over‐expression of WRKY70 resulted in the suppression of several JA responses including expression of a subset of JA‐ and A. brassicicola‐responsive genes. We show that this WRKY70‐controlled suppression of JA‐signaling is partly executed by NPR1. The results indicate that WRKY70 has a pivotal role in determining the balance between SA‐dependent and JA‐dependent defense pathways.
ABERRANT TESTA SHAPE encodes a KANADI family member, linking polarity determination to separation and growth of Arabidopsis ovule integuments
Authors: McAbee Jessica Messmer , Hill Theresa A. , Skinner Debra J. , Izhaki Anat , Hauser Bernard A. , Meister Robert J. , Venugopala Reddy G. , Meyerowitz Elliot M. , Bowman John L. , Gasser Charles S.
Published: April 2006

The Arabidopsis aberrant testa shape (ats) mutant produces a single integument instead of the two integuments seen in wild‐type ovules. Cellular anatomy and patterns of marker gene expression indicate that the single integument results from congenital fusion of the two integuments of the wild type. Isolation of the ATS locus showed it to encode a member of the KANADI (KAN) family of putative transcription factors, previously referred to as KAN4. ATS was expressed at the border between the two integuments at the time of their initiation, with expression later confined to the abaxial layer of the inner integument. In an inner no outer (ino) mutant background, where an outer integument does not form, the ats mutation led to amorphous inner integument growth. The kan1kan2 double mutant exhibits a similar amorphous growth of the outer integument without affecting inner integument growth. We hypothesize that ATS and KAN1/KAN2 play similar roles in the specification of polarity in the inner and outer integuments, respectively, that parallel the known roles of KAN proteins in promoting abaxial identity during leaf development. INO and other members of the YABBY gene family have been hypothesized to have similar parallel roles in outer integument and leaf development. Together, these two hypotheses lead us to propose a model for normal integument growth that also explains the described mutant phenotypes.
Skin cancer trends in northern Jordan
Authors: Omari Abdel K. , Khammash Muhammad R. , Matalka Ismail
Published: April 2006

Background  The Jordan Cancer Registry was established in 1996, since which time all cases of cancer have been reported and registered. We have used this registry to perform the first analysis of skin cancer in northern Jordan and to compare our findings with those of published reports from other regions.

Methods  All histopathologically proven cases of skin cancer, reported during the years 1997 through 2001, were reviewed. Information regarding tumor type, age, gender, and anatomical location was collected.

Results  A total of 272 cases of malignant skin tumors were diagnosed between the years 1997 and 2001. Basal cell carcinoma (BCC) was the commonest type, representing 52.9% of all skin cancers. Females were more frequently affected than males, with age‐adjusted incidence rates of 23.3 and 19.7 per 100,000 of population, respectively. Squamous cell carcinoma (SCC) comprised 26.4% of the total, its age‐adjusted incidence rate per 100,000 of population being 14.2 for males and 6.18 for females. the incidence rate increased in males and decreased in females during the study period. The incidence of both BCC and SCC increased with age. The head and neck region was the commonest site affected by both types of cancer. Malignant melanoma (MM) comprised 11.39% of all skin cancer cases, with a female to male ratio of 1.2 : 1. The median age at onset for female patients was 49 years while that for males was 70 years, and the commonest site affected was the lower limbs, followed by the trunk.

Conclusions  In Jordan, sun‐related skin cancers have relatively low incidences and a rather stable pattern, compared with other areas with similar climate and skin phenotypes.
Levocetirizine is an effective treatment in patients suffering from chronic idiopathic urticaria: a randomized, double‐blind, placebo‐controlled, parallel, multicenter study
Authors: Kapp Alexander , Pichler Werner J.
Published: April 2006

Background  Chronic idiopathic urticaria (CIU) is defined by the almost daily presence of urticaria for at least 6 weeks without an identifiable cause. Symptoms include short‐lived wheals, itching, and erythema. CIU impedes significantly a patient's quality of life (QoL). Levocetirizine is an antihistamine from the latest generation approved for CIU.

Aim  To investigate the efficacy of levocetirizine, 5 mg, and placebo for the symptoms and signs of CIU, as well as for the QoL and productivity.

Methods  The primary criteria of evaluation were the pruritus severity scores over 1 week of treatment and over 4 weeks. The QoL was assessed via the Dermatology Life Quality Index (DLQI).

Results  Baseline pruritus severity scores were comparable in the two treatment groups (2.06 ± 0.58). After 1 week, levocetirizine was superior to placebo and demonstrated a considerable efficacy (difference = 0.78, P < 0.001). This efficacy was maintained over the entire study period (4 weeks, P < 0.001). The number and size of wheals were considerably reduced compared with placebo over 1 week and over the total treatment period (P ≤ 0.001). This was paralleled by an improvement in the QoL (DLQI: 7.3 units in the levocetirizine group and 2.4 units in the placebo group) and a higher productivity at work in the levocetirizine group (3.0 workdays lost per patient per month in the placebo group, 0.3 in the levocetirizine group). No unexpected adverse events occurred.

Conclusions  Levocetirizine, 5 mg once daily, is an effective treatment for CIU, characterized not only by a rapid and sustained response, but also by an important improvement in QoL.
Dermatosurgical techniques for repigmentation of vitiligo
Authors: Rusfianti Marsia , Wirohadidjodjo Yohanes Widodo
Published: April 2006

There are a number of dermatosurgery techniques available to achieve repigmentation of vitiligo, such as suction blister grafting, split‐thickness skin grafting, punch grafting, follicular grafting, cultured‐melanocytes transplantation, and noncultured‐melanocytes transplantation. Each method has advantages and disadvantages. As there are no specific data available from the prospective studies in this field it is uneasy to recommend which surgical approach to vitiligo offers the best result. According to a systematic review by Njoo et al.,17 suction blister and split‐thickness skin grafting have the highest rates of success (87%), while the average success rates for other methods varied from 13% to 53%. Punch grafting has the highest rate of adverse effects, including cobblestoning appearance (27%) and scar formation (40%) in the donor site. Accordingly, it is also mandatory to appropriately select vitiligo patients in order to achieve a complete and permanent repigmentation.
Frontal fibrosing alopecia versus lichen planopilaris: a clinicopathological study
Authors: Poblet Enrique , Jiménez Francisco , Pascual Alejandro , Piqué Enric
Published: April 2006

Background  Frontal fibrosing alopecia (FFA) is an acquired scarring alopecia currently considered a clinical variant of lichen planopilaris (LPP). Our purpose was to examine the clinicopathological features of FFA. In addition, we investigated the similarities and differences between FFA and LPP.

Methods  Biopsies from the scalp lesions of eight patients with FFA and eight patients with LPP were microscopically analyzed. Two cases of FFA and four cases of LPP were studied using direct immunofluorescence.

Results  In spite of the completely different clinical characteristics of FFA and LPP patients, the histopathological findings for the two entities were similar. Common microscopic findings for both FFA and LPP included an inflammatory lymphocytic infiltrate involving the isthmus and infundibulum of the hair follicles, the presence of apoptotic cells in the external root sheath, and a concentric fibrosis surrounding the hair follicles that resulted in their destruction with subsequent scarring alopecia. Biopsies taken from FFA patients showed less follicular inflammation and more apoptotic cells than those from LPP patients. In some cases of LPP, the inflammatory infiltrate involved the interfollicular epidermis, a finding never present in our FFA cases. Direct immunofluorescence was negative in the two cases of FFA studied and showed deposits of immunoglobulins and/or complement in two of the four LPP cases examined.

Conclusions  The characteristic findings for FFA were more prominent apoptosis and less inflammation than found in LPP, along with spared interfollicular epidermis. FFA cases showed a rather characteristic histopathological pattern, although we could not find any clear‐cut histological differences between FFA and LPP.
Porokeratosis of Mibelli following bone marrow transplantation
Authors: Alexis Andrew F. , Busam Klaus , Myskowski Patricia L.
Published: April 2006

Background  Porokeratosis is a rare disorder of keratinization with both autosomal dominant and acquired forms. Immunosuppression has been associated with the development of porokeratosis in numerous case reports and series. To our knowledge, however, only five cases of porokeratosis have been reported following bone marrow transplantation.

Results  We report five cases of porokeratosis of Mibelli following bone marrow transplantation. The diagnosis of porokeratosis was made between 1 and 13 years post‐transplantation. The underlying malignancy in four of the five cases was leukemia, while the fifth patient had non‐Hodgkin's lymphoma. Porokeratosis developed during remission in the four leukemia patients, whereas, in the fifth patient, it occurred during a relapse of lymphoma.

Conclusions  Porokeratosis may develop following bone marrow transplantation. Our five cases double the number reported in the medical literature, and the incidence of porokeratosis following bone marrow transplantation may be significantly higher than previously recognized. As cutaneous carcinomas have been reported in association with porokeratosis, careful surveillance for porokeratosis in bone marrow transplant recipients is warranted.
Importance of carbohydrate in the interaction of Tamm‐Horsfall protein with complement 1q and inhibition of classical complement activation
Authors: Rhodes Diana CJ
Published: April 2006

Tamm‐Horsfall protein (THP) binds strongly to complement 1q (C1q), a key component of the classical complement pathway. The goals of this study were to determine whether THP altered the activation of the classical complement pathway and whether the carbohydrate portion of THP was involved in this glycoprotein's binding to C1q and alteration of complement activation. The ability of THP to prevent complement activation in diluted serum or plasma incubated at 37°C was assessed using both a haemolytic assay with antibody‐sensitized sheep RBC and a C4d ELISA. Both these methods showed that THP inhibited activation of the classical complement pathway in a dose‐dependent manner. Glycosidases were used to remove most of the carbohydrate from THP. This partially deglycosylated THP bound human IgG with a higher affinity (KD1= 1.4 nmol/L;KD2= 0.31 μmol/L) than did intact THP (KD1= 33.4 nmol/L;KD2= 31.0 μmol/L). An ELISA showed that removal of carbohydrate from THP reduced, but did not eliminate, the ability of this protein to inhibit binding of C1q to intact THP. Haemolysis assays using antibody‐sensitized sheep RBC showed that removal of THP carbohydrate eliminated the ability of THP to protect against complement activation. In conclusion, THP inhibited the activation of the classical complement pathway that occurred in diluted serum or plasma. The carbohydrate moieties of THP appeared to be important in this inhibitory activity.
Inhibition of nuclear factor‐κB activation is essential for membrane‐associated TNF‐α‐induced apoptosis in HL‐60 cells
Authors: Shi Wenfang , Li Lingyun , Shi Xu , Zheng Fang , Zeng Jingyang , Jiang Xiaodan , Gong Feili , Zhou Muxiang , Li Zhuoya
Published: April 2006

The killing of tumour cells that are resistant to soluble TNF‐α (sTNF‐α) by the membrane‐bound form of TNF‐α (mTNF‐α) suggests that different intracellular signalling pathways are involved. We found that mTNF‐α induced apoptosis in HL‐60 cells and failed to cause degradation of inhibitor of kappa B alpha (IκB‐α) and translocation and activation of nuclear factor kappa B (NF‐κB), whereas sTNF‐α failed to induce apoptosis, but lowered cytoplasmic inhibitor of kappa B alpha, induced translocation of NF‐κB to the nucleus and experimentally increased activity of the regulated luciferase. Furthermore, mTNF‐α upregulated the expression of TNF receptor associated factor (TRAF) 1 and failed to induce TRAF1 and TRAF2 membrane translocation, but led to cytoplasmic colocalization. In contrast, sTNF‐α stimulated the expression of TRAF1 and TRAF2, recruiting both molecules onto the cell membrane poststimulation. These results suggest that the increased susceptibility of HL‐60 cells to mTNF‐α may be due to the failure of TRAF2 membrane translocation caused by the upregulation of TRAF1 expression and formation of a TRAF1/TRAF2 complex in the cytoplasm, thereby inhibiting NF‐κB activation and inducing apoptosis.
Hypothesis: A biological role for germline transcription in the mechanism of V(D)J recombination – implications for initiation of allelic exclusion
Authors: Franklin Andrew
Published: April 2006

The sequences that encode the antigen‐binding sites of IgH and IgL chains – variable (V), diversity (D, H chain loci only) and joining (J) sequences – are configured as separate DNA segments at the germline level. Expression of an Ig molecule requires V(D)J assembly. Productive V(D)J recombination is monoallelic. How rearrangement is initiated differentially at maternal and paternal alleles is unclear. The products of recombination activating gene (RAG)1 and RAG2 mediate rearrangement by cleaving the DNA between an unrearranged gene segment and adjacent recombination signal sequences (RSS). It is proposed that supercoiling generated during germline transcription at Ig loci (which occurs concomitantly with rearrangement) is required at RSS for RAG1/2 recognition. Rearrangement might hence initiate sequentially at maternal and paternal alleles where deregulated germline transcription causes RAG1/2 recognition of RSS to become stochastic.
Increased IL‐4 production and attenuated proliferative and pro‐inflammatory responses of splenocytes from wild‐caught rats (Rattus norvegicus)
Authors: Lesher Aaron , Li Bin , Whitt Parker , Newton Nolan , Devalapalli Aditya P , Shieh Karl , Solow Jonathan S , Parker William
Published: April 2006

Wild animals, unlike their laboratory counterparts, live amidst an abundance of pathogens and parasites. The presence of such immune stimulation from the time of birth likely has a profound effect on the development and stasis of the immune system. To probe potential differences between the immune systems of wild and laboratory animals, the response to mitogen (Con A) of splenocytes from wild rats was evaluated in vitro and compared with results from lab‐rat‐derived splenocytes. Although the response to mitogen is ubiquitous in splenocytes from laboratory animals regardless of strain or even species, splenocytes derived from wild rats were unresponsive to mitogen as judged by upregulation of activation markers and proliferation. Further, splenocytes from wild rats produced almost 10‐fold less IL‐2 and TNF‐α in response to mitogen than did splenocytes from laboratory rats. In addition, mitogen stimulation resulted in an almost 100‐fold greater production of IL‐4 in wild‐rat‐derived splenocytes than in lab‐rat‐derived splenocytes. Perhaps surprisingly, these differences were observed in the absence of differences between wild and laboratory animals in the ratio of CD4+/CD8+ T cells or in the relative numbers of T cells, B cells and monocytes in the splenocyte population. These observations may have substantial implications for the hygiene hypothesis and provide considerable insight into the roles played by the environment during immune system development and modulation.
Thermal evolution of the Tertiary Shimanto Belt, Muroto Peninsula, Shikoku, Japan
Authors: Underwood Michael B. , Laughland Matthew M. , Byrne Tim , Hibbard J. P. , DiTullio Lee
Published: April 2006

Abstract
The Shimanto accretionary complex on the Muroto Peninsula of Shikoku comprises two major units of Tertiary strata: the Murotohanto Sub‐belt (Eocene‐Oligocene) and the Nabae Sub‐belt (Oligocene‐Miocene). Both sub‐belts have been affected by thermal overprints following the peak of accretion‐related deformation. Palaeotemperatures for the entire Tertiary section range from ∼ 140 to 315°C, based upon mean vitrinite reflectance values of 0.9–5.0%Rm. Values of illite crystallinity index are consistent with conditions of advanced diagenesis and anchimetamorphism. Illite/mica b0 lattice dimensions indicate that burial pressures were probably no greater than 2.5kbar. In general, levels of thermal maturity are higher for the Murotohanto Sub‐belt than for the Nabae Sub‐belt. The Eocene‐Oligocene strata also display a spatial decrease in thermal maturity from south to north and this pattern probably was caused by regional‐scale differential uplift following peak heating. Conversely, the palaeothermal structure within the Nabae Sub‐belt is fairly uniform, except for the local effects of mafic intrusions at the tip of Cape Muroto. There is a paleotemperature difference of ∼ 90°C across the boundary between the Murotohanto and Nabae Sub‐belts (Shiina‐Narashi fault), and this contrast is consistent with approximately 1200 m of post‐metamorphic vertical offset.

Subduction prior to Middle Miocene probably involved the Kula or fused Kula‐Pacific plate and the background geothermal gradient during the Eocene‐Oligocene phase of accretion was ∼ 30–35°C/km. Rapid heating of the Shimanto Belt evidently occurred immediately after a Middle Miocene reorganization of the subduction boundary. Hot oceanic lithosphere from the Shikoku Basin first entered the subduction zone at ∼ 15 Ma; this event also coincided with the opening of the Sea of Japan and the rapid clockwise rotation of southwest Japan. The background geothermal gradient at that time was ∼ 70°C/km. Whether or not all portions of the inherited (Eocene‐Oligocene) palaeothermal structure were overprinted during the Middle Miocene remains controversial.
A deep section of accretionary complex: Susunai Complex in Sakhalin Island, Northwest Pacific Margin
Authors: Kimura Gaku , Sakakibara Masayuki , Ofuka Hisashi , Ishizuka Hideo , Miyashita Sumio , Okamura Makoto , Melinikov Olex A. , Lushchenko Vilera
Published: April 2006

Abstract
A deep section of accretionary complex, the metamorphosed Susunai Complex, is observed on Sakhalin Is., Russia. High pressure part of pumpellyite‐actinolite facies metavolcanics, metacherts and metapelites are well exposed and constitute a tectonic pile preserving primary structures related to underplating of the oceanic crust. Three stages of deformation, D1 through D3, suggest successive deformation during subduction, underplating and exhumation of the complex. Oceanic material in the complex is more abundant than other well documented ancient accretionary complexes (e.g. the Shimanto Belt in southwest Japan and the Ghost Rocks Formation in Alaska), which were shallowly underplated. At Susunai, deep down‐stepping of a décollément has scraped off the upper part of the oceanic crust, primarily the pillowed basalt horizon. This down‐stepping results from crustal weakening as overpressured water is released from the fractured oceanic crust during metamorphism.
Ash layers in deep‐sea sediments as tracers of arc volcanic activity: Japan and Central America as case studies
Authors: Cambray Herve , Cadet Jean‐Paul , Pouclet André
Published: April 2006

Abstract
Arc volcanic activity on opposite sides of the Pacific Ocean (Japan and Central America) has been investigated by examining the number of volcanic ash layers recorded in Neogene and Quaternary deep‐sea sediments. The data suggest that ash layers counted in deep‐sea sediments may provide a reliable record of arc volcanism. The study is based on a quantitative analysis of arc volcanic activity using cores collected on DSDP (Deep‐Sea Drilling Project) and ODP (Ocean Drilling Program) legs. Five distinct parameters which might affect ash distribution in marine sediments were reviewed: nature of the eruption, wind influence, settling conditions, diagenesis, and plate motion. Of these five, past atmospheric circulation was the most significant. The main constraint on the analysis is that temporal scattering of ash is not directly related to wind pattern variations. Results of this analysis are correlated with dating of terrestrial volcanic sequences. Although marine tephra records for individual regions reveal minor differences in the episodes of volcanic activity, a general correlation exists between activity of arc volcanism in Japan and in Central America. Two important pulses of arc volcanism occurred during Middle Miocene times (18–13 Ma) and Plio‐Quaternary times (5–0 Ma). These episodes of intense volcanism are separated by a well recorded quiescent period during Late Miocene times. These correlating episodes of the volcanic record indicate a direct link between arc volcanism and the global tectonic evolution of the Pacific ocean margins.
Shifting of the volcanic fronts during Early to Late Miocene in the Northeast Japan arc
Authors: Ohki Jun'ichi , Watanabe Naoki , Shuto Kenji , Itaya Tetsumaru
Published: April 2006

Abstract
Recent advanced chronological studies for the Tertiary volcanic rocks from the Northeast (NE) Japan arc revealed three volcanic fronts which differed in temporal and spatial distribution. These fronts were (i) the Matsumae‐Shizukuishi‐Shiogama line of 22–25 Ma which is obliquely across the Quaternary volcanic front (QVF); (ii) the Tomari‐Shiogama line of 13–16 Ma which exists 30–50 km east of the QVF and (iii) a line of 0–8 Ma which is the same as the QVF. The first shifting of the 22–25 Ma line to the 13–16 Ma one was due to the counterclockwise rotation of the NE Japan arc during 20–12 Ma as proposed by Otofuji et al. (1985), and the second shifting of the 13–16 Ma line to the 0–8 Ma line could have contributed to a decrease in the dip of the slab of the Pacific plate which subducted beneath the NE Japan arc during 13–8 Ma.
The chemical Th‐U‐total Pb isochron ages of Jiaodong and Jiaonan metamorphic rocks in the Shandong Peninsula, eastern China
Authors: Enami Masaki , Suzuki Kazuhiro , Zhai Mingguo , Zheng Xiangshen
Published: April 2006

Abstract
The chemical Th‐U‐total Pb isochron method (CHIME) was applied to determine the age of monazite and thorite in five gneisses and zircon in an ultra high‐pressure (UHP) phengite schist from the Su‐Lu region, eastern China. The CHIME ages and isotopic ages reported in the literature show that gneisses in the Su‐Lu region are divided into middle Proterozoic (1500–1720 Ma) and Mesozoic (100–250 Ma) groups. The Proterozoic group includes paragneiss and orthogneiss of the amphibolite‐granulite facies, and their protolith age is late Archean‐early Proterozoic. The Mesozoic group is mainly composed of orthogneiss of the greenschist‐epidote amphibolite facies, and the protolith age is Middle Paleozoic‐Early Proterozoic. The Proterozoic and Mesozoic gneisses occupy northern and southern areas of the Su‐Lu region, respectively, which are divided by a major Wulian‐Qingdao‐Yantai fault. Ultra high‐pressure metamorphic rocks occur as blocks in the Mesozoic gneisses, and form a UHP complex.

The UHP phengite schist in the Mesozoic orthogneiss contains detrital zircons with late Proterozoic CHIME age (ca 860 Ma). Age of the UHP metamorphism is late Proterozoic or younger, and protolith age of the UHP metamorphic rocks is probably different from that of the surrounding Mesozoic gneisses.