bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial DNA variation of an isolated population of the Adriatic brook lamprey Lampetra zanandreai (Agnatha: Petromyzontidae): phylogeographic and phylogenetic inferences
Authors: Caputo V. , Giovannotti M. , Nisi Cerioni P. , Splendiani A. , Marconi M. , Tagliavini J.
Published: January 2010

Two mitochondrial genes were examined to compare an isolated population of the Adriatic brook lamprey Lampetra zanandreai in central Italy with other populations in the species range (Po plain) and with parasitic and freshwater lampreys. A single haplotype, identical to one in a Venetian sample, was found in 10 individuals from the isolated population. The reduced variability is consistent with a history of dispersal after the Pleistocene expansion of the Po basin. The results support the hypothesis of an origin of L. zanandreai and L. fluviatilis–L. planeri from a common anadromous ancestor.
Landscape genetic patterns of the rainbow darterEtheostoma caeruleum: a catchment analysis of mitochondrial DNA sequences and nuclear microsatellites
Authors: Haponski A. E. , Bollin T. L. , Jedlicka M. A. , Stepien C. A.
Published: January 2010

Catchment population structure and divergence patterns of the rainbow darterEtheostoma caeruleum(Percidae: Teleostei), an eastern North American benthic fish, are tested using a landscape genetics approach. Allelic variation at eight nuclear DNA microsatellite loci and two mitochondrial DNA regions [cytochrome (cyt)bgene and control region; 2056 aligned base pairs (bp)] is analysed from 89 individuals and six sites in the Lake Erie catchment (Blanchard, Chagrin, Cuyahoga and Grand Rivers)v.the Ohio River catchment (Big Darby Creek and Little Miami River). Genetic and geographic patterning is assessed using phylogenetic trees, pair‐wiseFSTanalogues, AMOVA partitioning, Mantel regression, Bayesian assignment, 3D factorial correspondence and barrier analyses. Results identify 34 cytbhaplotypes, 22 control region haplotypes and 137 microsatellite alleles whose distributions demonstrate marked genetic divergence between populations from the Lake Erie and Ohio River catchments.Etheostoma caeruleumpopulations in the Lake Erie and Ohio River catchments divergedc.1·6 mya during the Pleistocene glaciations. Greater genetic separations characterize the Ohio River populations, reflecting their older habitat age and less recent connectivity. Divergence levels within the Lake Erie catchment denote more recent post‐glacial origins. Notably, the western Lake Erie Blanchard River population markedly differs from the three central basin tributary samples, which are each genetically distinguishable using microsatellites. Overall relationships among the Lake Erie sites refute a genetic isolation by geographic distance hypothesis.Etheostoma caeruleumpopulations thus exchange few genes and have low migration among tributaries and catchments.
Shallow phylogeographic structuring of Vimba vimba across Europe suggests two distinct refugia during the last glaciation
Authors: Hänfling B. , Dümpelmann C. , Bogutskaya N. G. , Brandl R. , Brändle M.
Published: January 2010

Genetic variation and geographical structuring of vimba Vimba vimba were analysed across 26 sites (80 individuals) by means of mtDNA sequences (cyt b gene, mitochondrial control region) to localize hypothesized glacial refugia and to reconstruct postglacial recoloniation routes. Although genetic diversity among sequenced individuals was low, a combined analysis of the two sequenced fragments revealed a western (central and northern Europe: Danube, Elbe and lakes of Sweden) and an eastern clade (eastern Europe: Dnieper–South Bug, Don, Neman). Furthermore, a number of divergent ancestral haplotypes distributed around the Black and Caspian Seas became apparent. Mismatch analyses supported a sudden expansion model for the populations of the western clade between 50 and 10 000 bp. Overall, the study provides strong evidence for a northward and westward expansion of V. vimba from two refugial regions located in the Danubian drainage and the northern Pontic regions respectively.
Development and characterization of microsatellite markers to study population genetic diversity of Przewalski's naked carp Gymnocypris przewalskii in China
Authors: Zhang Y. , Jiang P. , Gang H. , Shi J.‐Q. , Sun X.
Published: January 2010

Two populations of Przewalski's naked carp Gymnocypris przewalskii, 30 individuals per population, were screened for 10 microsatellite loci. Moderate allele variation was found in these loci with two to eight alleles per locus. The expected and observed heterozygosity ranged from 0·019 to 0·805 and from 0·160 to 0·575, respectively.
Molecular data reveal a diverse Astyanax species complex in the upper Iguaçu River
Authors: Pie M. R. , Baggio R. A. , Boeger W. A. , Patella L. A. , Ostrensky A. , Vitule J. R. S. , Abilhoa V.
Published: January 2010

Astyanax is among the most speciose genera in the Characidae. In this study, molecular markers were used to assess the extent to which some of the commonly recognized Astyanax species of the upper Iguaçu River correspond to natural groups. These results indicate that the diversity of Astyanax has been severely underestimated with several potential cryptic species.
Spermatic cell characteristics in Gymnotiformes (Teleostei: Ostariophysi) and their phylogenetic meaning
Authors: França G. F. , Oliveira C. , Quagio‐Grassiotto I.
Published: January 2010

Spermatic characteristics were studied in representatives of the families Rhamphichthyidae, Sternopygidae and Apteronotidae, and compared with pre‐existent data from Gymnotidae and Hypopomidae. The spermatic characteristics found in Gymnotiformes were also compared with data from other Ostariophysi spermatic cells. The spermatic characteristics as the type of spermiogenesis and the structural pattern of the sperm, considering nuclear form, pattern of chromatin condensation, nuclear fossa and its relation with the centriolar complex, form and localization of mitochondria, form of midpiece, presence or absence of cytoplasmic canal and cytoplasmic sleeve, and flagellar fins were utilized. The comparative analysis of the spermatic cell of Gymnotiformes better support the previous proposals for the order considering Gymnotidae as a derived group, than the more recent ones that located Gymnotidae in a basal position as the sister group of the remaining Gymnotiformes. Regarding the Ostariophysi, the comparative analyses based on the spermatic cell characteristics is consistent with a recent systematic proposal that consider Gymnotiformes as a sister group of Characiformes.
Mitochondrial DNA divergence in the critically imperilled pygmy madtom, Noturus stanauli (Siluriformes: Ictaluridae)
Authors: Bennett M. G. , Heath Howell J. , Kuhajda B. R. , Wood R. M.
Published: January 2010

The mitochondrial cytochrome b gene was sequenced for six individuals of the pygmy madtom, Noturus stanauli, a globally imperilled catfish, from both known localities in Tennessee (U.S.A.) separated by over 1055 river km. Phylogenetic and population genetic analyses revealed little divergence between these populations for this locus.
Normal development of the tomato clownfish Amphiprion frenatus: live imaging and in situ hybridization analyses of mesodermal and neurectodermal development
Authors: Ghosh J. , Wilson R. W. , Kudoh T.
Published: January 2010

The normal embryonic development of the tomato clownfish Amphiprion frenatus was analysed using live imaging and by in situ hybridization for detection of mesodermal and neurectodermal development. Both morphology of live embryos and tissue‐specific staining revealed significant differences in the gross developmental programme of A. frenatus compared with better‐known teleost fish models, in particular, initiation of somitogenesis before complete epiboly, initiation of narrowing of the neurectoderm (neurulation) before somitogenesis, relatively early pigmentation of melanophores at the 10–15 somite stage and a distinctive pattern of melanophore distribution. These results suggest evolutionary adaptability of the teleost developmental programme. The ease of obtaining eggs, in vitro culture of the embryo, in situ staining analyses and these reported characteristics make A. frenatus a potentially important model marine fish species for studying embryonic development, physiology, ecology and evolution.
Formation of chromosome aberrations in androgenetic rainbow trout Oncorhynchus mykiss
Authors: Ocalewicz K. , Dobosz S. , Kuzminski H. , Goryczko K.
Published: January 2010

Residues of maternal nuclear DNA in the form of chromosome fragments were observed in the healthy and morphologically normal androgenetic rainbow trout Oncorhynchus mykiss. A hypothetical model for formation of chromosome re‐arrangements caused by the incomplete maternal nuclear DNA inactivation in the androgenetic rainbow trout was proposed in the present paper.
MHC class IIB additive and non‐additive effects on fitness measures in the guppy Poecilia reticulata
Authors: Fraser B. A. , Neff B. D.
Published: January 2010

The genetic architecture of fitness at the class IIB gene of the major histocompatibility complex (MHC) in the guppy Poecilia reticulata was analysed. Diversity at the MHC is thought to be maintained by some form of balancing selection; heterozygote advantage, frequency‐dependent selection or spatially and temporally fluctuating selection. Here these hypotheses are evaluated by using an algorithm that partitions the effect of specific MHC allele and genotypes on fitness measures. The effect of MHC genotype on surrogate measures of fitness was tested, including growth rate (at high and low bulk food diets), parasite load following a parasite challenge and survival. The number of copies of the Pore_a132 MHC allele was inversely related to infection by Gyrodactylus flukes and it appeared to be positively related to faster growth. Also, genotypes combining the Pore_a132 or other relatively common alleles paired with rare MHC alleles produced both advantageous and detrimental non‐additive effects. Thus, the genetic architecture underlying fitness at the MHC is complex in the P. reticulata.
Mechanisms of chromosomal evolution and its possible relation to natural history characteristics in Ancistrus catfishes (Siluriformes: Loricariidae)
Authors: De Oliveira R. R. , Feldberg E. , Dos Anjos M. B. , Zuanon J.
Published: January 2010

Ancistrus is the most speciose genus of the tribe Ancistrini, with 58 valid species and many yet to be described. Cytogenetic studies were conducted on five apparently undescribed species from the Amazon basin, which showed different diploid numbers: Ancistrus sp. Purus (2n = 34); Ancistrus sp. Macoari (2n = 46); Ancistrus sp. Dimona (2n = 52); Ancistrus sp. Vermelho (2n = 42) and Ancistrus sp. Trombetas (2n = 38). All species possessed only one pair of NOR‐carrying chromosomes, but with extensive variation in both the location on the chromosome as well as in the position of the ribosomal sites on the karyotype. The karyotypic evolution of Ancistrus species seems to be based on chromosomal rearrangements, with a tendency to a reduction of the diploid number. Two new instances of XX/XY sex chromosomes for Ancistrus species, based on the heteromorphism in the male karyotype, were also recorded. The large karyotypic diversity among Ancistrus species may be related to biological and behavioural characteristics of these fish that include microhabitat preferences, territoriality and specialized reproductive tactics. These characteristics may lead to a fast rate of fixation of chromosomal mutations and eventually speciation across the basin.
Differentiated ZZ/ZW sex chromosomes in Apareiodon ibitiensis (Teleostei, Parodontidae): cytotaxonomy and biogeography
Authors: Bellafronte E. , Vicari M. R. , Artoni R. F. , Margarido V. P. , Moreira‐Filho O.
Published: January 2010

Conventional and molecular chromosomal analyses were carried out on three populations of Apareiodon ibitiensis sampled from the hydrographic basins of the São Francisco River and Upper Paraná River (Brazil). The results reveal a conserved diploid number (2n = 54 chromosomes), a karyotype formula consisting of 50 m‐sm + 4st and a ZZ/ZW sex chromosome system that has not been previously identified for the species. C‐banding analysis with propidium iodide staining revealed centromeric and terminal bands located in the chromosomes of the specimens from the three populations and allowed the identification of heteromorphism of heterochromatin regions in the Z and W chromosomes. The number of 18S sites located through fluorescent in situ hybridization (FISH) varied between the populations of the São Francisco and Upper Paraná Rivers. The location of 5S rDNA sites proved comparable in one pair of metacentric chromosomes. Thus, the present study proposes a ZZ/ZW sex chromosome system for A. ibitiensis among the Parodontidae, and a hypothesis is presented regarding possible W chromosome differentiation stages in this species through DNA accumulation, showing geographical variations for this characteristic, possibly as a consequence of geographical reproductive isolation.
Molecular and karyotypic phylogeography in the NeotropicalHoplias malabaricus(Erythrinidae) fish in eastern Brazil
Authors: Santos U. , Völcker C. M. , Belei F. A. , Cioffi M. B. , Bertollo L. A. C. , Paiva S. R. , Dergam J. A.
Published: January 2010

The sedentary, predatory characinHoplias malabaricushas one of the widest distributions of freshwater fishes in South America and is characterized by seven karyomorphs (A–G) that occur in sympatric and allopatric populations. Karyotypical patterns of variation in wild populations have been interpreted as evidence of multiple lineages within this nominal species, a possibility that may limit the validity of experimental data for particular karyomorphs. This study used the phylogeographic and genealogical concordance between cytogenetic (N= 49) and molecular (mitochondrial DNA) (N= 73) data on 17 samples, collected in 12 basins from south‐eastern and north‐eastern Brazil, to assess the systematic value of cytogenetic data. Cytogenetic patterns show a sex chromosome system in the 2n= 40F karyomorph. Molecular and cytogenetic data indicate a long, independent evolutionary history of karyomorphs and a coastal origin of continental populations in south‐eastern Brazil. The lack of fit with molecular clock expectations of divergence between groups is likely to be due to strong demographic fluctuations during the evolution of this species complex. The results indicate that karyotypical identification provides a reliable baseline for placing experimental studies onHopliasspp. in a phylogenetic context.
Mechanisms of skin fibrosis in systemic sclerosis
Authors: JINNIN Masatoshi
Published: January 2010

Systemic sclerosis (SSc) or scleroderma is an acquired disorder which typically results in fibrosis of the skin and internal organs. Skin fibrosis, the hallmark of this disease, is defined as excess deposition and accumulation of extracellular matrix, mainly type I collagen, in the dermis. Dermal fibroblasts isolated from lesional skin of SSc patients and culturedin vitroexhibit increased synthesis of collagen and decreased collagenase activity, consistent with the disease phenotype. This review focuses on the recent progress in the research for molecular mechanisms of skin fibrosis in SSc. The upregulated collagen production at transcriptional level in SSc fibroblasts involves various regulators including cytokines or transcription factors. Among them, transforming growth factor (TGF)‐β/Smad signaling is likely to play a key role in the pathogenesis of SSc, and the autocrine TGF‐β signaling hypothesis can explain intrinsic activation of collagen promoter in SSc fibroblasts. Imbalance between matrix metalloproteinases and tissue inhibitor of metalloproteinases might also contribute to the excess accumulation of collagen in the dermis.
Combinational effect of low‐dose oral corticosteroid and mizoribine for ulcerative colitis in a patient with systemic sclerosis
Authors: OHTSUKA Tsutomu
Published: January 2010

The combinational effect of oral corticosteroid and mizoribine for ulcerative colitis is presented in a patient with systemic sclerosis (SSc). A 64‐year‐old woman came to our clinic complaining of a 30‐year history of Raynaud’s phenomenon. She had past history of ulcerative colitis with the continued medication of mesalazine without success. She was presented with sclerodactyly and finger joint swelling. She also showed epigastric discomfort. Laboratory study showed positive anti‐nuclear antibody and positive anti‐centromere antibody. Histological examination showed mild perivascular mononuclear cell infiltrates in the whole dermis and increased deposition of collagen fibers in the middle and lower dermis. Chest X‐ray film showed mild bibasilar pulmonary fibrosis. An upper gastrointestinal series study showed reflux esophagitis and atrophic gastritis. These findings led to the diagnosis of systemic sclerosis (limited type) complicated with ulcerative colitis. Treatment with oral corticosteroid (5 mg/day) and mizoribine (150 mg/day) in the morning was started. She showed remarkable improvement for sclerodactyly and lower intestinal bleeding stopped after 6 months. She is under the same treatment without exaggeration and adverse effect of the drug until now.
Case of localized scleroderma successfully treated with bath psoralen and ultraviolet A therapy
Authors: UCHIYAMA Masaki , OKUBO Yukari , KAWASHIMA Hisashi , YAMAMOTO Kengo , MITSUHASHI Yoshihiko , TSUBOI Ryoji
Published: January 2010

The patient was a 12‐year‐old girl with linear scleroderma distributed on the right abdomen, dorsal aspect of the right thigh, lower leg and foot. The initial regimen of oral prednisolone and methotrexate, or i.v. methylprednisolone failed in the treatment of the scleroderma. Then bath psoralen and ultraviolet A therapy (bath‐PUVA) therapy of 0.2 J–4.0 J/cm2 daily to total doses 62.8 J/cm2 combined with oral prednisolone was started. After bath‐PUVA therapy, regression of the skin sclerosis was observed, the possible mobile range of the right ankle was increased and histological examination confirmed improvement of the sclerosis. The successful results of bath‐PUVA therapy in this case suggest its utility for localized scleroderma.
Case of localized scleroderma associated with osteomyelitis
Authors: MUROI Eiji , OGAWA Fumihide , YAMAOKA Toshifumi , SUEYOSHI Fumiko , SATO Shinichi
Published: January 2010

We report a 4‐year‐old girl presenting with progressive linear scleroderma affecting the right leg. Biopsy specimen disclosed typical histopathological findings of localized scleroderma. Right leg magnetic resonance imaging (MRI) showed high signal areas on T2‐weighted images on the subcutaneous fatty tissue, muscles and bone marrow, suggesting that skin inflammation extended to the bone marrow. Oral corticosteroid therapy was instituted with improvement of both skin sclerosis and MRI findings. Our observations suggest that MRI examination should be considered in patients with localized scleroderma to evaluate the extension of the inflammation.
Cutaneous polyarteritis nodosa: A report of 16 cases with clinical and histopathological analysis and a review of the published work
Authors: ISHIGURO Naoko , KAWASHIMA Makoto
Published: January 2010

Sixteen cases of cutaneous polyarteritis nodosa referred to our Department from 1985 to 2003 were studied clinically and histopathologically. Laboratory data, treatments and clinical courses were also evaluated retrospectively. All cases had nodules and/or indurated erythemas on their lower extremities. All cases showed necrotizing vasculitis of small muscular arteries in the subcutaneous tissues and/or occlusion of those arteries histopathologically. Fifteen cases also had accumulation of plasma protein in vessels of the dermis and subcutaneous tissues. Laboratory data showed high activity of platelets and coagulation in some cases. Eleven cases had been effectively treated with non‐steroidal anti‐inflammatory drugs. Eight cases were observed for at least 5 years (the longest for ∼19 years) and had good prognoses and no systemic involvement. Cutaneous polyarteritis nodosa seems to be a benign disease, and differs from systemic polyarteritis nodosa although their histopathological features are common. Cutaneous polyarteritis nodosa might involve local dysfunction of the circulation from the dermis to the subcutaneous area. A review of the published work shows that the cause(s) of most cases of cutaneous polyarteritis nodosa is unknown, that no controlled trials for treatment of cutaneous polyarteritis nodosa compared to polyarteritis nodosa have been reported, and that no definitively effective therapy for cutaneous polyarteritis nodosa has been established.
Case of livedoid vasculopathy with extensive dermal capillary thrombi
Authors: SHIMIZU Akira , TAMURA Atsushi , YAMANAKA Masayoshi , AMANO Hiroo , NAGAI Yayoi , ISHIKAWA Osamu
Published: January 2010

Livedoid vasculopathy (LV) is thought to be a thrombogenic disorder. Here, we report a case of LV presenting livedo reticularis with leg ulcers clinically and many thrombogenic cutaneous vessels histologically. These features strongly suggested the presence of thrombogenic factors involved with the development of the lesions. After examination of various possible thrombogenic factors including phosphatidylserine‐dependent anti‐prothrombin antibody, we failed to detect any responsible thrombogenic factors for this case of LV. Recently, diverse thrombogenic factors have been reported to be involved in LV. This case may suggest that unknown thrombogenic factors are additionally related to LV pathogenesis.
Case of livedoid vasculopathy with peripheral neuropathy successfully treated with low‐dose warfarin
Authors: OSADA Shin‐Ichi , KIMURA Yoichi , KAWANA Seiji
Published: January 2010

We report herein a case of a 28‐year‐old woman with persistent livedo racemosa and recurrent ulcerations on the lower extremities. The clinical presentation, together with histopathological findings of vascular occlusion without overt vasculitis in the dermis, led to the diagnosis of livedoid vasculopathy. The patient experienced recurrence of ulcerations and developed peripheral neuropathy affecting the distal extremities during the course of treatment with sarpogrelate hydrochloride. The skin lesions and neurological symptoms improved dramatically after adding low‐dose warfarin potassium to the treatment regimen. This case suggests that administration of low‐dose warfarin is an effective therapy of choice for patients with livedoid vasculopathy.
Case of remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome) showing dermatomyositis‐like eruption
Authors: TAKEDA Kiminobu , FUJITA Jun , FUJII Toshiki , TANABE Hiroshi , MOCHIZUKI Takashi , YANAGIHARA Makoto
Published: January 2010

A 73‐year‐old woman developed linear erythema at the sites of scratching‐induced scars on the bilateral thighs 2 weeks before the initial consultation. Subsequently, edematous erythema developed in the upper eyelids, dorsum of the nose and the face, and pitting edema in the dorsum of the bilateral hands and feet. The C‐reactive protein (CRP) level was 8.2 mg/dL and erythrocyte sedimentation rate (ESR) 121 mm/h. The antinuclear antibody titer was 1:160, and rheumatoid factor (RF) and anti‐Jo‐1 antibody were negative. X‐ray examination of the bilateral hands showed neither narrowing of the joint spaces nor bone erosion. Ga scintigraphy showed synovitis of the bilateral wrists. A diagnosis of remitting seronegative symmetrical synovitis with pitting edema syndrome (RS3PE) was made. The erythema disappeared after diclofenac sodium administration. However, because the joint swelling and pitting edema did not improve, p.o. administration of prednisolone (20 mg/day) was initiated. The CRP and ESR levels normalized 2 months after the initiation of administration, and pitting edema disappeared after 3 months. We report this case because linear erythema like that observed in dermatomyositis has not been described as eruptions associated with RS3PE.
Pyoderma gangrenosum on the breast: A case presentation and review of the published work
Authors: MANSUR Ayşe Tülin , BALABAN Deniz , GÖKTAY Fatih , TAKMAZ Sezen
Published: January 2010

We present a case of pyoderma gangrenosum localized on the breast, without a preceding surgical intervention and associated systemic disorder. The ulcer had rapidly developed and covered a large portion of the breast. The patient responded well to systemic steroids and salicylazosulfapyridine and the ulcer completely healed with scarring after 3 months of treatment. Pyoderma gangrenosum rarely involves the breasts. A published work survey disclosed only 31 reported cases up to date. In most of these cases the lesions were related to previous surgical interventions, probably as the result of a pathergy phenomenon. The main differential diagnoses were skin and soft tissue infections including necrotizing fasciitis, and malignant neoplasms. Negative initial wound cultures and the relative sparing of nipple/areola complex helped to eliminate these disorders. Though an unusual site for pyoderma gangrenosum, lesions on the breast showed the characteristic clinical features of the disease. The types of associated disorders were also similar to those of the cases with classical pyoderma gangrenosum. As most of the lesions healed with significant scarring, early recognition and treatment of pyoderma gangrenosum located on the breast is important to prevent serious physical and psychological morbidity.
Future treatments in systemic sclerosis
Authors: ASANO Yoshihide
Published: January 2010

Systemic sclerosis (SSc) is an autoimmune disorder with clinical manifestations resulting from immune activation, fibrosis development and damage of small blood vessels. Although there have been no established treatments for SSc, lots of new treatments targeting organ and pathogenesis are in the process of development. Transforming growth factor (TGF)‐β is a major cytokine involved in the pathogenesis of fibrosis in SSc. The blockade of cell surface molecules capable of activating latent TGF‐β, blockade of ligand by the pan‐isoform‐specific antibody, soluble TGF‐β receptors and a recombinant latency associated peptide, as well as inhibitors for ALK5 and Smad3 are the potential strategies to abolish the pathological activation of TGF‐β signaling in SSc fibroblasts. Besides TGF‐β, connective tissue growth factor (CTGF)/CCN2, platelet‐derived growth factor (PDGF) and endothelin‐1 are the candidates for the new therapeutic targets. As for immune dysfunction in SSc, i.v. immunoglobulin infusion, stem cell transplantation and B‐cell depletion are potential new therapies under or awaiting a randomized, double‐blind, placebo‐controlled trial, although their efficacies are still controversial. Phosphodiesterase‐5 inhibitors, endothelin receptor antagonists and inhibitors for serotonin signaling are the new therapeutic targets for Raynaud’s phenomenon, digital ulceration and pulmonary arterial hypertension in SSc. Imatinib mesylate may be a novel new therapy for fibrosis and vasculopathy in SSc because it reverses the expression levels ofFli1, which is a transcription factor downregulated in SSc through an epigenetic mechanism and is likely to be involved in the development of fibrosis and vasculopathy in this disease. Potential therapeutic targets other than those described above are also reviewed.
Autoantibody profiles in systemic sclerosis: Predictive value for clinical evaluation and prognosis
Authors: HAMAGUCHI Yasuhito
Published: January 2010

Systemic sclerosis (SSc) is thought to be an autoimmune disease, as autoantibodies against a variety of extractable nuclear antigens can be detected in patient sera. Subgrouping patients based on the type of autoantibodies present can be useful in diagnosis and management. Anti‐centromere antibodies (ACA) and anti‐topoisomerase I antibodies (anti‐topo I) are the classic autoantibodies associated with SSc. ACA are associated with limited cutaneous involvement and isolated pulmonary hypertension, whereas anti‐topo I are associated with diffuse skin involvement and pulmonary fibrosis. ACA are predictors for a favorable prognosis, while anti‐topo I are correlated with a poor prognosis and SSc‐related mortality. Additionally, anti‐RNA polymerase antibodies (anti‐RNAP) are associated with diffuse cutaneous disease and renal involvement. Anti‐nucleolar antibodies define multiple subgroups of patients with SSc. Of these, anti‐Th/To antibodies (anti‐Th/To) and anti‐PM‐Scl antibodies (anti‐PM‐Scl) are associated with limited cutaneous SSc (lSSc), whereas anti‐U3RNP antibodies (anti‐U3RNP) are associated with diffuse cutaneous SSc (dSSc). In addition, anti‐Th/To and anti‐U3RNP can be predictors for a less favorable prognosis with a higher frequency of organ involvement, such as pulmonary fibrosis, pulmonary hypertension and renal crisis. Other autoantibodies are less frequently reported: anti‐Ku antibodies, anti‐U1RNP antibodies, anti‐human upstream‐binding factor, and anti‐U11/U12 antibodies. These antibodies are generally less specific to SSc, but also define clinically distinct patient subsets. Thus, characterization of autoantibodies in SSc together with knowledge of disease characteristics intrinsic to distinct patient populations is helpful for assessing the clinical presentation and prognosis of this disease, and for monitoring patients with SSc.
B lymphocytes: Shedding new light on the pathogenesis of systemic sclerosis
Authors: HASEGAWA Minoru
Published: January 2010

Systemic sclerosis (SSc) is a connective tissue disease characterized by autoimmunity and tissue fibrosis. In patients with SSc, there is a close association between the presence of specific autoantibodies and the development of clinical features. Although it is known that cytokines, including transforming growth factor‐β, can modulate the synthesis of extracellular matrix by fibroblasts, it is not clear how autoimmunity and tissue fibrosis are interrelated. Several recent lines of evidence indicate a potential role for B cells in the development of SSc. CD19 is a critical regulator of B‐cell signaling thresholds, and B cells from SSc patients exhibit increased expression of CD19, a molecule that induces SSc‐specific autoantibody production in transgenic mice. Both SSc patients and tight‐skin mice, a genetic model of SSc, have intrinsic B‐cell abnormalities characterized by chronic B‐cell activation. Remarkably, CD19 loss or B‐cell depletion using antimouse CD20 antibody suppresses the development of skin hyperplasia and autoimmunity in tight‐skin mice. Additionally, a recent study revealed a possible beneficial effect of antihuman CD20 antibody (rituximab) therapy for SSc patients. As B cells have a variety of functions, further investigation into the pathogenic roles of B cells, as well as trials of B‐cell‐targeting therapies, may shed new light on the pathogenesis of SSc.
Animal model of systemic sclerosis
Authors: YAMAMOTO Toshiyuki
Published: January 2010

Scleroderma is a fibrotic condition characterized by immunological abnormalities, vascular injury and increased accumulation of extracellular matrix proteins in the skin. Although the etiology of scleroderma has not yet been fully elucidated, a growing body of evidence suggests that extracellular matrix overproduction by activated fibroblasts results from a complex interaction among endothelial cells, lymphocytes, macrophages and fibroblasts, through a number of mediators, such as cytokines, chemokines and growth factors. For a better understanding of the pathophysiology of scleroderma, animal models are important tools. These models reproduce several histological as well as biochemical aspects of human scleroderma, and we can learn a lot through animal studies. On the other hand, it must be emphasized that studying animal models cannot answer all the problems of human scleroderma. In this review, I introduce current insights into the pathogenesis and also recent updates of therapeutic approaches using several animal models of SSc, and discuss their contribution to our understanding of the pathogenesis of, and treatments for, human scleroderma.
Overexpression of yes‐associated protein contributes to progression and poor prognosis of non‐small‐cell lung cancer
Authors: Wang Yang , Dong Qianze , Zhang Qingfu , Li Zixuan , Wang Enhua , Qiu Xueshan
Published: January 2010

Yes‐associated protein (YAP), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene. This study aimed to assess the clinical significance and biological functions of YAP in non‐small‐cell lung cancer (NSCLC). We investigated the expression of YAP in 92 cases of NSCLC tissue by immunohistochemistry and found that YAP was expressed in 66.3% (61/92) cases and predominantly presented in the nucleus. The expression of YAP in NSCLC was significantly correlated with p‐TNM stage (P = 0.0037) and lymph node metastasis (P = 0.0093). Importantly, YAP expression was associated with short overall survival. Further study in NSCLC cell lines in which YAP was either overexpressed or depleted confirmed that YAP markedly promoted cell proliferation and invasion. These results indicate that YAP plays an important role in NSCLC and might be a useful therapeutic target of NSCLC.

(Cancer Sci 2010; 101: 1279–1285)
ORIGINAL ARTICLE: Associations of the growth hormone receptor (GHR) gene polymorphisms with adiposity and IGF‐I activity in adolescents
Authors: Mong Janice L. Y. , Ng Maggie C. Y. , Guldan Georgia S. , Tam Claudia H. T. , Lee Heung Man , Ma Ronald C. W. , So Wing Yee , Wong Gary W. K. , Kong Alice P. S. , Chan Juliana C. N. , Waye Mary M. Y.
Published: January 2010

Objective:  To explore the genetic effect of the GH receptor (GHR) on obesity and related metabolic parameters in Hong Kong Chinese adolescents.

Context:  Obesity is a growing global epidemic. Increasing evidence suggests that the GH‐IGF‐I axis plays an important role in regulating adiposity and insulin sensitivity.

Design:  We examined the associations of genetic variants of GHR with serum IGF‐I and IGFBP‐3 levels as well as obesity‐related metabolic traits in Hong Kong Chinese adolescents.

Patients:  Nine hundred and eighty‐one randomly selected Hong Kong Chinese adolescents from 14 schools.

Measurements:  We genotyped 17 single nucleotide polymorphisms (SNP) at GHR and measured serum IGF‐I and IGFBP‐3 levels as well as obesity‐related metabolic traits including fasting plasma glucose, insulin and lipid levels.

Results:  There were significant associations between rs4410646 and the body composition (P = 0·0044) and blood pressure factor scores (P = 0·00017). Carriers of the CC genotype had lower body mass index, percentage body fat, waist and hip circumferences than AC and AA genotype carriers (P = 0·00030–0·0094). There was also association between rs7703713 and the IGF‐I activity factor score (P = 0·0033). The GA and AA carriers of rs7703713 had higher serum IGF‐I, higher serum IGFBP‐3 and higher IGF‐I/IGFBP‐3 molar ratio (P = 0·00069–0·025). Haplotype analysis did not increase the significance of associations.

Conclusion:  Our results support the role of GHR gene polymorphisms in modulating adiposity and IGF‐I activity in adolescents. Examination of interactions of these SNPs with lifestyle, environmental and perinatal factors may provide further insights into their long‐term effects on obesity and metabolic risks.
Clinical outcomes of persistent radioiodine uptake in the neck shown by diagnostic whole body scan in patients with differentiated thyroid carcinoma after initial surgery and remnant ablation
Authors: Kim Eui Young , Kim Won Gu , Kim Won Bae , Kim Tae Yong , Ryu Jin‐Sook , Gong Gyungyub , Yoon Jong Ho , Hong Suck Joon , Lee Jeong Hyun , Baek Jung Hwan , Shong Young Kee
Published: January 2010

Objectives  To evaluate the clinical outcomes of persistent radioiodine uptake (RAIU) in the neck by diagnostic whole body scan (DxWBS) after initial therapy and the efficacy of the second ablation in patients with differentiated thyroid carcinoma (DTC).

Design  Patients with DTC who underwent bilateral surgery and high‐dose remnant ablation between 2000 and 2004 were included. Patients with elevated serum stimulated thyroglobulin (sTg) or extensive lateral neck lymph node involvement at initial surgery underwent a second ablation, and patients with undetectable sTg or in very low‐risk groups were observed.

Results  Among 572 patients, 25 had persistent RAIU in the neck at first DxWBS. After a median 65·7 months of follow‐up, five of these patients (20%) had persistent disease, whereas another 20 patients had no abnormal findings by ultrasonography (US) or other imaging modalities. Seven of 20 patients underwent second ablation and 13 were observed. RAIU disappeared spontaneously in about half of the patients in the observation group. There were no significant between‐group differences in change of RAIU at follow‐up DxWBS (P = 0·62). Serum sTg decreased and eventually disappeared over a few years in both groups. Ablation failure was not an independent risk factor for recurrence (P = 0·169).

Conclusions  Neck US and serum sTg, but not DxWBS, were useful diagnostic tools during follow‐up of patients with persistent uptake in the neck at DxWBS. A second ablation was not necessary when neck US showed no evidence of disease, especially in patients with very low sTg concentration.
The effect of oxandrolone on body proportions and body composition in growth hormone‐treated girls with Turner syndrome
Authors: Menke Leonie A. , Sas Theo C. J. , Zandwijken Gladys R. J. , De Ridder Maria A. J. , Stijnen Theo , De Muinck Keizer‐Schrama Sabine M. P. F. , Otten Barto J. , Wit Jan M.
Published: January 2010

Objective  Untreated girls with Turner syndrome (TS) have short stature, relatively broad shoulders, a broad pelvis, short legs, a high fat mass and low muscle mass. Our objective was to assess the effect of the weak androgen oxandrolone (Ox) on body proportions and composition in growth hormone (GH)‐treated girls with TS.

Design/Patients  133 patients were included in a randomized, placebo‐controlled, double‐blind study.

Methods  Patients were treated with GH (1·33 mg/m2 per day) from baseline, combined with placebo (Pl) or Ox in a low (0·03 mg/kg per day) or previously conventional (0·06 mg/kg per day) dose from the age of eight, and oestrogens from the age of twelve. Sitting height, biacromial and biiliacal distances compared with height (i.e. shape values), BMI, waist circumference, sum of 4 skinfolds (sum4skin) and upper arm muscle area (UAMA) SD scores (SDS) were assessed half‐yearly.

Results  Compared with GH + Pl, adult shape values on GH + Ox tended to be higher for sitting height (Ox 0·03, P = 0·2; Ox 0·06, P = 0·02) and biacromial distance (Ox 0·03, P = 0·2; Ox 0·06, P = 0·07) and lower for biiliacal distance (Ox 0·03, P = 0·004; Ox 0·06, P = 0·08). Sum4skin SDS tended to decrease more (Ox 0·03, P = 0·2; Ox 0·06, P = 0·005) while UAMA SDS increased more (Ox 0·03, P < 0·001; Ox 0·06, P < 0·001) than on GH + Pl. The increase in BMI and waist circumference SDS was comparable between the dosage groups.

Conclusions  In GH‐treated girls with TS, Ox 0·06 increases sitting height and tends to increase biacromial distance and decrease biiliacal distance, while Ox 0·03 significantly decreases biiliacal distance compared with height. Furthermore, Ox 0·06 reduces subcutaneous fat mass, and both Ox dosages increase muscle mass.
Interaction between cigarette smoking and iodine intake and their impact on thyroid function
Authors: Cho Nam H. , Choi Hoon Sung , Kim Kyung Won , Kim Hyung‐Lae , Lee Soo‐Youn , Choi Sung Hee , Lim Soo , Park Young Joo , Park Do Joon , Jang Hak C. , Cho Bo Youn
Published: January 2010

Objective  Several population‐based studies in iodine‐deficient areas have shown an association between smoking and thyroid function. There are no population‐based studies about the effects of smoking in iodine‐sufficient areas. We examined the effect of smoking on thyroid function and the association with iodine intake in Korea, an area with sufficient iodine intake, much more than recommended by the World Health Organization (WHO).

Design  Of 5018 subjects in a population‐based cohort, we included 3399 who had no history of thyroid disease were not taking thyroid medication and whose blood samples were available for measurement of thyroid function.

Measurements  Thyroid function test, questionnaire about smoking status and dietary intake.

Results  Of 3399 subjects, 397(11·7%) had subclinical hypothyroidism (SCH). Female sex was an independent risk factor for SCH. Multivariate analysis in female subjects showed the following were independent risk factors for SCH: older age, positive antithyroid peroxidase (anti‐TPO) antibody status and iodine intake, whereas current smoking was inversely related with SCH. However, in male subjects, only age showed a weak association with SCH. When the interaction between smoking and other risk factors was analysed, smoking showed no association with anti‐TPO antibody status, whereas it showed a significant negative interaction with iodine intake (odds ratio, 0·930; 95% CI, 0·869–0·996; P = 0·037). Furthermore, the risk for SCH was observed only in the never‐smoker group; however, it was abolished in current‐ and ex‐smoker groups.

Conclusion  Cigarette smoking was associated with a lower prevalence of SCH in a negative interaction with iodine intake.
Hypopituitarism is uncommon after aneurysmal subarachnoid haemorrhage
Authors: Klose Marianne , Brennum Jannick , Poulsgaard Lars , Kosteljanetz Michael , Wagner Aase , Feldt‐Rasmussen Ulla
Published: January 2010

Objective  Aneurysmal subarachnoid haemorrhage (SAH) has recently been reported as a common cause of chronic hypopituitarism, and introduction of routine neuroendocrine screening has been advocated. We aimed at estimating the risk of hypopituitarism after SAH using strict criteria including confirmatory testing in case of suggested insufficiency.

Design  Cross‐sectional evaluation with a nested prospective subgroup.

Patients and measurements  Endocrine evaluation was performed at a median of 14 months (range 11–26) post‐SAH in 62 patients with SAH and 30 healthy controls. Twenty‐six patients were followed prospectively (median 7 days, and 12 months post‐SAH). Endocrine evaluation included baseline evaluation, which was combined with an insulin tolerance test (ITT) or, if contraindicated, GHRH + arginine tests and a standard ACTH test at evaluation 1–2 years post‐SAH. Pituitary insufficiencies were confirmed by re‐evaluation.

Results  Early post‐SAH hormone alterations mimicking central hypogonadism were present in 58% of the patients and associated with a worse clinical state (P < 0·05). One to 2 years post‐SAH, initial neuroendocrine evaluation identified seven patients (11%) with abnormal results; three had free T4 and TSH suggestive of central hypothyroidism, three men had testosterone below 10 nm, and one had an insufficient GH and cortisol response to the ITT. None of these abnormalities was confirmed upon confirmatory testing.

Conclusion  In the largest reported cohort of patients with SAH to date, with early and late endocrine evaluation, none of the patients had chronic hypopituitarism. Based on these findings, the introduction of routine neuroendocrine screening is not justified, and the data suggest the importance of using strict diagnostic criteria in patients with a low pretest probability of hypopituitarism.
High cortisol levels in the offspring of parents with bipolar disorder during two weeks of daily sampling
Authors: Ellenbogen Mark A , Santo Jonathan B , Linnen Anne‐Marie , Walker Claire‐Dominique , Hodgins Sheilagh
Published: January 2010

Ellenbogen MA, Santo JB, Linnen A‐M, Walker C‐D, Hodgins S. High cortisol levels in the offspring of parents with bipolar disorder during two weeks of daily sampling. Bipolar Disord 2010: 12: 77–86. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  The hypothalamic‐pituitary‐adrenal (HPA) axis is compromised in major depression, bipolar disorder (BD), and in the offspring of parents with major depression. Less is known about the offspring of parents with BD (FH+). The present project provides follow‐up to a previous study showing that the adolescent (mean age 16.7 years) FH+ offspring had higher salivary cortisol levels than the offspring of parents with no mental disorder (FH−) throughout the day in their natural environment, and that girls had higher cortisol levels than boys (Ellenbogen MA, Hodgins S, Walker C‐D, Adam S, Couture S. Daytime cortisol and stress reactivity in the offspring of parents with bipolar disorder. Psychoneuroendocrinology 2006; 31: 1164–1180). The goal of the present study was to determine whether FH+ offspring, approximately two years later, continued to exhibit elevated cortisol levels relative to FH− offspring during two weeks of daily sampling.

Methods:  The present study examined salivary cortisol levels in 24 (18.3 ± 2.6 years) FH+ and 22 (18.0 ± 2.3 years) FH− offspring who are part of the same longitudinal cohort as the previous study. Saliva was collected at 1300h and 1500h in the natural environment of the offspring during 14 consecutive days.

Results:  Multilevel modelling analyses indicated that FH+ offspring had higher afternoon levels of cortisol in their natural environment than FH− offspring, but group differences in slope and gender differences were not found.

Conclusions:  The FH+ offspring exhibited increased daytime secretion of cortisol that, at the level of the group, persisted into late adolescence and young adulthood. Perhaps this change in HPA functioning is associated with an increased vulnerability for the development of an affective disorder.
Higher striatal dopamine transporters in euthymic patients with bipolar disorder: a SPECT study with [99mTc] TRODAT‐1
Authors: Chang Ting Ting , Yeh Tzung Lieh , Chiu Nan Tsing , Chen Po See , Huang Hsiang Yu , Yang Yen Kuang , Lee I Hui , Lu Ru Band
Published: January 2010

Chang TT, Yeh TL, Chiu NT, Chen PS, Huang HY, Yang YK, Lee IH, Lu RB. Higher striatal dopamine transporters in euthymic patients with bipolar disorder: a SPECT study with [99mTc] TRODAT‐1. Bipolar Disord 2010: 12: 102–106. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  Dopamine has been implicated in the etiology of bipolar disorder. The aim of this study was to explore striatal dopamine transporter (DAT) availability in euthymic bipolar patients.

Methods:  Seventeen drug‐free euthymic bipolar patients were recruited. The availability of DAT was approximated using single photon emission computed tomography (SPECT) with [99mTc] TRODAT‐1.

Results:  Compared to the controls, the euthymic bipolar patients had significantly higher availability of striatal DAT.

Conclusions:  Even for patients in the euthymic state, the DAT availability is still higher than that of the controls.