bluuebunny/crossref_metadata_2025 huggingface dataset:
BINARY MINOR PLANETS
Authors: Richardson Derek C. , Walsh Kevin J.
Published: November 2005

A review of observations and theories regarding binary asteroids and binary trans-Neptunian objects [collectively, binary minor planets (BMPs)] is presented. To date, these objects have been discovered using a combination of direct imaging, lightcurve analysis, and radar. They are found throughout the Solar System, and present a challenge for theorists modeling their formation in the context of Solar System evolution. The most promising models invoke rotational disruption for the smallest, shortest-lived objects (the asteroids nearest to Earth), consistent with the observed fast rotation of these bodies; impacts for the larger, longer-lived asteroids in the main belt, consistent with the range of size ratios of their components and slower rotation rates; and mutual capture for the distant, icy, trans-Neptunian objects, consistent with their large component separations and near-equal sizes. Numerical simulations have successfully reproduced key features of the binaries in the first two categories; the third remains to be investigated in detail.
In ovo exposure to monochromatic green light promotes skeletal muscle cell proliferation and affects myofiber growth in posthatch chicks
Authors: Halevy Orna , Piestun Yogev , Rozenboim Israel , Yablonka-Reuveni Zipora
Published: November 2005

Our previous studies demonstrated that illumination of chicken embryos with monochromatic green light results in enhanced body and muscle weight at later posthatch stages. In the present study, we investigated the cellular and molecular basis of this phenomenon. First, we showed that on day 6 posthatch, myofibers were more uniform in the in ovo illuminated group than in the control group incubated in the dark, with respect to the number of myofibers displaying diameter values within the range of the mean value. Second, we tested the hypothesis that in ovo illumination causes an increase in the number of myoblasts; this in turn can promote posthatch muscle growth. Indeed, a significant increase in the number of skeletal muscle cells isolated from pectoralis muscle was observed in the in ovo illuminated group on days 1 and 3 posthatch relative to the control group. This increased cell number was accompanied by higher expression levels of Pax7 and myogenin proteins on posthatch days 1 and 3, respectively. A parallel analysis of proliferating cells in the intact muscle further demonstrated a significant increase in the number of cells positive for proliferating cell nuclear antigen in muscle from the in ovo illuminated group. Third, we demonstrated that the transition from fetal- to adult-type myoblasts, normally occurring in late stages of chicken embryogenesis, is initiated earlier in embryos subjected to in ovo green-light illumination. We suggest that the stimulatory effect of in ovo illumination on posthatch muscle growth is the result of enhanced proliferation and differentiation of adult myoblasts and myofiber synchronization.
Effect of low-repetition jump training on bone mineral density in young women
Authors: Kato Takeru , Terashima Toru , Yamashita Takenori , Hatanaka Yasuhiko , Honda Akiko , Umemura Yoshihisa
Published: November 2005

The hypothesis of the present study was that low-repetition and high-impact training of 10 maximum vertical jumps/day, 3 times/wk would be effective for improving bone mineral density (BMD) in ordinary young women. Thirty-six female college students, with mean age, height, and weight of 20.7 ± 0.7 yr, 158.9 ± 4.6 cm, and 50.4 ± 5.5 kg, respectively, were randomly divided into two groups: jump training and a control group. After the 6 mo of maximum vertical jumping exercise intervention, BMD in the femoral neck region significantly increased in the jump group from the baseline (0.984 ± 0.081 vs. 1.010 ± 0.080 mg/cm2; P < 0.01), although there was no significant change in the control group (0.985 ± 0.0143 vs. 0.974 ± 0.134 mg/cm2). And also lumbar spine (L2–4) BMD significantly increased in the jump training group from the baseline (0.991 ± 0.115 vs. 1.015 ± 0.113 mg/cm2; P < 0.01), whereas no significant change was observed in the control group (1.007 ± 0.113 vs. 1.013 ± 0.110 mg/cm2). No significant interactions were observed at other measurement sites, Ward's triangle, greater trochanter, and total hip BMD. Calcium intakes and accelometry-determined physical daily activity showed no significant difference between the two groups. From the results of the present study, low-repetition and high-impact jumps enhanced BMD at the specific bone sites in young women who had almost reached the age of peak bone mass.
Small supernumerary marker chromosomes – progress towards a genotype-phenotype correlation
Authors: Liehr T. , Mrasek K. , Weise A. , Dufke A. , Rodríguez L. , Martínez Guardia N. , Sanchís A. , Vermeesch J.R. , Ramel C. , Polityko A. , Haas O.A. , Anderson J. , Claussen U. , von Eggeling F. , Starke H.
Published: November 2005

Small supernumerary marker chromosomes (sSMC) are still a major problem in clinical cytogenetics as they are too small to be characterized for their chromosomal origin by traditional banding techniques, but require molecular cytogenetic techniques for their identification. Apart from the correlation of about one third of the sSMC cases with a specific clinical picture, i.e. the i(18p), der(22), i(12p) (Pallister Killian syndrome) and inv dup(22) (cat-eye) syndromes, most of the remaining sSMC have not yet been correlated with clinical syndromes. Recently, we reviewed the available >1600 sSMC cases (Liehr T, sSMC homepage: http://mti-n.mti.uni-jena.de/∼huwww/MOL_ZYTO/sSMC.htm). A total of 387 cases (including the 45 new cases reported here) have been molecularly cytogenetically characterized with regard to their chromosomal origin, the presence of euchromatin, heterochromatin and satellite material. Based on analysis of these cases we present the first draft of a basic genotype-phenotype correlation for sSMC for all human chromosomes apart from the chromosomes Y, 10, 11 and 13.
Increased complexity of radiation-induced chromosome aberrations consistent with a mechanism of sequential formation
Authors: Anderson R.M. , Papworth D.G. , Stevens D.L. , Sumption N.D. , Goodhead D.T.
Published: November 2005

Complex chromosome aberrations (any exchange involving three or more breaks in two or more chromosomes) are effectively induced in peripheral blood lymphocytes (PBL) after exposure to low doses (mostly single particles) of densely ionising high-linear energy transfer (LET) α-particle radiation. The complexity, when observed by multiplex fluorescence in situ hybridisation (m-FISH), shows that commonly four but up to eight different chromosomes can be involved in each rearrangement. Given the territorial organisation of chromosomes in interphase and that only a very small fraction of the nucleus is irradiated by each α-particle traversal, the aim of this study is to address how aberrations of such complexity can be formed. To do this, we applied theoretical “cycle” analyses using m-FISH paint detail of PBL in their first cell division after exposure to high-LET α-particles. In brief, “cycle” analysis deconstructs the aberration “observed” by m-FISH to make predictions as to how it could have been formed in interphase. We propose from this that individual high-LET α-particle-induced complex aberrations may be formed by the misrepair of damaged chromatin in single physical “sites” within the nucleus, where each “site” is consistent with an “area” corresponding to the interface of two to three different chromosome territories. Limited migration of damaged chromatin is “allowed” within this “area”. Complex aberrations of increased size, reflecting the path of α-particle nuclear intersection, are formed through the sequential linking of these individual sites by the involvement of common chromosomes.
Molecular characterisation of the t(1;15)(p22;q22) translocation in the prostate cancer cell line LNCaP
Authors: Strefford J.C. , Lane T.M. , Hill A. , LeRoux L. , Foot N.J. , Shipley J. , Oliver R.T.D. , Lu Y.-J. , Young B.D.
Published: November 2005

Although chromosome translocations are well-documented recurrent events in hematological malignancies and soft tissue sarcomas, their significance in carcinomas is less clear. We report here the molecular characterization of the reciprocal translocation t(1;15)(p22;q22) in the prostate carcinoma cell line, LNCaP. The chromosome 1 breakpoint was localized to a single BAC clone, RP11-290M5, by sequential FISH analysis of clones selected from the NCBI chromosome 1 map. This was further refined to a 580-bp region by Southern blot analysis. A 2.85-kb fragment spanning the der(1) breakpoint was amplified by long-range inverse PCR. The breakpoint on chromosome 1 was shown to lie between the CYR61 and the DDAH1 genes with the der(1) junctional sequence linking the CYR61 gene to the TSPAN3 (TM4SF8) gene on chromosome 15. Confirmatory PCR and FISH mapping of the der(15) showed loss of chromosome material proximal to the breakpoint on chromosome 15, containing the PSTPIP1 and RCN2 genes. On the available evidence we conclude that this translocation does not result in an in-frame gene fusion. Comparative expressed sequence hybridization (CESH) and comparative genomic hybridization (CGH) analysis, showed relative down-regulation of gene expression surrounding the breakpoint, but no gross change in genomic copy number. Real-time quantitative RT-PCR for genes around the breakpoint supported the CESH data. Therefore, here we may have revealed a gene down-regulation mechanism associated with a chromosome translocation, either through small deletion at the breakpoint or through another means of chromosome domain related gene regulation.
A molecular cytogenetic study of chromosome evolution in chimpanzee
Authors: Gross M. , Starke H. , Trifonov V. , Claussen U. , Liehr T. , Weise A.
Published: November 2005

We applied multitude multicolor banding (mMCB) in combination with a novel FISH DNA probe set including subcentromeric, subtelomeric and whole chromosome painting probes (subCTM) to characterize a Pan paniscus (PPA) cell line. These powerful techniques allowed us to refine the breakpoints of a pericentric inversion on chimpanzee chromosome 4, and discovered a novel cryptic pericentric inversion in chimpanzee chromosome 11. mMCB provided a starting point for mapping and high resolution analysis of breakpoints on PPA chromosome 4, which are within a long terminal repeat (LTR) and surrounded by segmental duplications, as well as the integration/expansion sites of the interstitial heterochromatin on chimpanzee chromosomes 6 and 14. Moreover, we found evidence at hand for different types of heterochromatin in the chimpanzee genome. Finally, shedding new light on the human/chimpanzee speciation, karyotypes of three members of the genus Pan were studied by mMCB and no cytogenetic differences were found although the phylogenetic distance between these subspecies is suggested to be 2.5 million years.
Porcine PPARGC1A (peroxisome proliferative activated receptor gamma coactivator 1A): coding sequence, genomic organization, polymorphisms and mapping
Authors: Jacobs K. , Rohrer G. , van Poucke M. , Piumi F. , Yerle M. , Barthenschlager H. , Mattheeuws M. , van Zeveren A. , Peelman L.J.
Published: November 2005

We report here the characterisation of porcine PPARGC1A. Primers based on human PPARGC1A were used to isolate two porcine BAC clones. Porcine coding sequences of PPARGC1A were sequenced together with the splice site regions and the 5′ and 3′ regions. Using direct sequencing nine SNPs were found. Allele frequencies were determined in unrelated animals of five different pig breeds. In the MARC Meishan-White Composite resource population, the polymorphism in exon 9 was significantly associated with leaf fat weight. PPARGC1A has been mapped by FISH to SSC8p21. A (CA)n microsatellite (SGU0001) has been localised near marker SWR1101 on chromosome 8 by RH mapping and at the same position as marker KS195 (32.5 cM) by linkage mapping. The AseI (nt857, Asn/Asn489) polymorphism in exon 8 was used to perform linkage analysis in the Hohenheim pedigrees and located the gene in the same genomic region. Transcription of the gene was detected in adipose, muscle, kidney, liver, brain, heart and adrenal gland tissues, which is in agreement with the function of PPARGC1A in adaptive thermogenesis.
Assignment of 204 genes localized on HSA17 to a porcine RH (IMpRH) map to generate a dense comparative map between pig and human/mouse
Authors: Shimogiri T. , Kiuchi S. , Hiraiwa H. , Hayashi T. , Takano Y. , Maeda Y. , Rohrer G.A. , Milan D. , Yasue H.
Published: November 2005

Bi- and uni-directional chromosome painting (ZOO-FISH) and gene mapping have revealed correspondences between human chromosome (HSA) 17 and porcine chromosome (SSC) 12 harboring economically important quantitative trait loci. In the present study, we have assigned 204 genes localized on HSA17 to SSC12 to generate a comprehensive comparative map between HSA17 and SSC12. Two hundred fifty-five primer pairs were designed using porcine sequences orthologous with human genes. Of the 255 primer pairs, 208 (81.6%) were used to assign the corresponding genes to porcine chromosomes using the INRA-Minnesota 7000-rad porcine × Chinese hamster whole genome radiation hybrid (IMpRH) panel. Two hundred three genes were integrated into the SSC12 IMpRH linkage maps; and one gene, PPARBP, was found to link to THRA1 located in SSC12 but not incorporated into the linkage maps. Three genes (GIT1, SLC25A11, and HT008) were suggested to link to SSC12 markers, and the remaining gene (RPL26) did not link to any genes/expressed sequence tags/markers registered, including those in the present study. A comparison of the gene orders among SSC12, HSA17, and mouse chromosome 11 indicates that intra-chromosomal rearrangements occurred frequently in this ancestral mammalian chromosome during speciation.
Assignment of 101 genes localized in HSA10 to a swine RH (IMpRH) map to generate a dense human-swine comparative map
Authors: Yasue H. , Kiuchi S. , Hiraiwa H. , Ozawa A. , Hayashi T.
Published: November 2005

Economically important traits such as growth and backfat in pigs have been shown to be influenced by genes in swine chromosome (SSC) 10q12→qter corresponding to human chromosome (HSA) 10p. However, since gene information in the swine chromosomal region was limited, we attempted to generate a dense comparative map between SSC10 and HSA10 by mapping the 115 genes of HSA10 to a swine RH map (IMpRH map). In the mapping ten genes were assigned to SSC10, 88 to SSC14, and one to SSC3. One gene was suggested to link to SSC3, and another to SSC9. The correspondences between HSA10 and SSC10 and between HSA10 and SSC14 were essentially consistent with the observations obtained from bi/uni-directional chromosome painting or other results. This study further indicated that a large number of intrachromosomal rearrangements occurred in the synteny-conserved regions following species separation.
Unusually extensive karyotype reorganization in four congeneric Gerbillus species (Muridae: Gerbillinae)
Authors: Aniskin V.M. , Benazzou T. , Biltueva L. , Dobigny G. , Granjon L. , Volobouev V.
Published: November 2005

Comparative analysis of the G- and C-banding patterns in four morphologically poorly differentiated Gerbillus species (G. pyramidum, G. perpallidus, G. tarabuli and G. occiduus) was carried out. These gerbils have similar karyotype morphology with 2n and NF equal to 38/76, 40/76, 40/78 and 40/80, respectively. Our study revealed that possibly 70 Robertsonian (Rb) fusions, two pericentric inversions, one tandem translocation and at least 13 non-identified rearrangements have occurred during the karyotypic evolution of these species. The number of chromosomal changes by which any of these species differ from each other ranges from 33 to 49. One Rb fusion was common to two of the species, with only a single autosome-gonosome translocation shared by all four, suggesting a monophyletic origin of these karyotypically highly divergent species. Based on the chromosomal data obtained here, the systematic and geographic implications for these North African species are also discussed.
Chromosomal assignment of LASP1 and LASP2 genes and organization of the LASP2 gene in chicken
Authors: Terasaki A.G. , Suzuki H. , Ando J. , Matsuda Y. , Ohashi K.
Published: November 2005

Lasp-1 and lasp-2 are actin-binding proteins that contain a LIM domain, two nebulin repeats and an SH3 domain with significant identity. We determined the chromosomal locations of the LASP1 and LASP2 genes in chicken by fluorescence in situ hybridization. The LASP1 gene was localized to a pair of microchromosomes and the LASP2 gene was localized to chromosome 2p3.1, indicating that the chromosomal locations of the LASP1 and LASP2 genes are highly conserved between chicken and human. The comparison of genomic and cDNA sequences of chicken lasp-2 and nebulette, a nebulin-related protein in muscle, suggested that both the corresponding mRNAs shared exons in the same manner as their human homologues. When compared with the domain structure of nebulette, another nebulin repeat was predicted for lasp-2, and all the nebulin repeats of lasp-2 were better conserved than those in nebulette. We also found the exon boundaries in nebulin repeats of lasp-2 were similar to those of other nebulin-related proteins.
Identification of the sex-determining locus of Atlantic salmon (Salmo salar) on chromosome 2
Authors: Artieri C.G. , Mitchell L.A. , Ng S.H.S. , Parisotto S.E. , Danzmann R.G. , Hoyheim B. , Phillips R.B. , Morasch M. , Koop B.F. , Davidson W.S.
Published: November 2005

We have integrated data from linkage mapping, physical mapping and karyotyping to gain a better understanding of the sex-determining locus, SEX, in Atlantic salmon (Salmo salar). SEX has been mapped to Atlantic salmon linkage group 1 (ASL1) and is associated with several microsatellite markers. We have used probes designed from the flanking regions of these sex-linked microsatellite markers to screen a bacterial artificial chromosome (BAC) library, representing an 11.7× coverage of the Atlantic salmon genome, which has been HindIII fingerprinted and assembled into contigs. BACs containing sex-linked microsatellites and their related contigs have been identified and representative BACs have been placed on the Atlantic salmon chromosomes by fluorescent in situ hybridization (FISH). This identified chromosome 2, a large metacentric, as the sex chromosome. By positioning several BACs on this chromosome by FISH, it was possible to orient ASL1 with respect to chromosome 2. The region containing SEX appears to lie on the long arm between marker Ssa202DU and a region of heterochromatin identified by DAPI staining. BAC end-sequencing of clones within sex-linked contigs revealed five hitherto unmapped genes along the sex chromosome. We are using an in silico approach coupled with physical probing of the BAC library to extend the BAC contigs to provide a physical map of ASL1, with a view to sequencing chromosome 2 and, in the process, identifying the sex-determining gene.
Molecular investigation of a dicentric 13;17 chromosome found in a 21-week gestation fetus with multiple congenital abnormalities
Authors: Cockwell A.E. , Maloney V.K. , Thomas N.S. , Smith E.L. , Gonda P. , Bass P. , Crolla J.A.
Published: November 2005

We report a 21-week gestation fetus terminated because of multiple congenital abnormalities seen on ultrasound scan, including ventriculomegaly, possible clefting of the hard palate, cervical hemivertebrae, micrognathia, abnormal heart, horseshoe kidney and a 2-vessel umbilical cord. On cytogenetic examination, the fetus was found to have a male karyotype with 45 chromosomes with a dicentric chromosome, which appeared to consist of the long arms of chromosomes 13 and 17. Molecular genetic investigations and fluorescence in situ hybridization (FISH) unexpectedly showed that the derivative chromosome contained two interstitial blocks of chromosome 17 short arm sequences, totalling approximately 7 Mb, between the two centromeres. This effectively made the fetus monosomic for ∼15 Mb of 17p without the concurrent trisomy for another chromosome normally seen following malsegregation of reciprocal translocations. It also illustrates the complexity involved in the formation of some structurally abnormal chromosomes, which can only be resolved by detailed molecular investigations.
Bilateral Video-Assisted Thoracoscopic Thymectomy vs. Extended Transsternal Thymectomy in Myasthenia Gravis: A Prospective Study
Authors: Chang P.C. , Chou S.H. , Kao E.L.. , Cheng Y.J. , Chuang H.Y. , Liu C.K. , Lai C.L. , Huang M.F.
Published: November 2005

The optimal approach to thymectomy remains controversial. This study is designed to prospectively compare the results between bilateral video-assisted thoracoscopic thymectomy (BVTx) and extended transsternal thymectomy (ETTx) in patients with myasthenia gravis (MG) without thymoma. Fifteen patients who had undergone BVTx and 16 patients who had undergone ETTx were compared for age, gender, severity of disease, preoperative duration of disease, operative time, intraoperative blood loss, postoperative complications, hospital stay, duration of chest tube drainage, thymic histopathology, pain perception by visual analog scale (VAS), remission and improvement rate, period of follow-up, and activities of daily living (ADL). Fisher’s exact test, t test and paired t test were used for statistical analysis. BVTx had longer operative time and less intraoperative blood loss than that of the ETTx. Their remission rates and their degree of postoperative ADL improvement were not significantly different. However, the lowering of VAS was significantly greater in the sternotomy group at 3 months. All other parameters were not significantly different. No mortality was noted in the series. We consider BVTx as an effective alternative procedure to the transsternal approach for patients with nonthymomatous MG. As more and more people care about cosmetics, BVTx could become the future trend.
Development of a Special Balloon Occlusion Device to Prevent Adverse Events in High-Risk Patients during Open Aortic Surgery
Authors: Weigang E. , Luehr M. , von Samson P. , Hartert M. , Goebel H. , Wetzig M. , Bernard V. , Siegenthaler M.P. , Beyersdorf F.
Published: November 2005

Objective: To prevent clamp injury that may occur during aortic surgery, we aimed to develop a special balloon occlusion (BO) device to lower the thromboembolic risk in patients with severe atherosclerosis during aortic aneurysm repair. Methods: The study comprised two test phases: a laboratory-testing series focussing on flexible artificial aortas, and an experimental series conducted on 10 pigs. Results: The device proved to be effective during the laboratory tests and the experiments on pigs. No complications such as intraoperative balloon rupture, dislocation, or occlusion leaks occurred. No damage to the aortic vessels was observed in further histological examinations. Conclusions: This BO device has the potential to become an alternative to cross-clamping for vascular surgeons in patients with severely atherosclerotic vessels.
D-Dimer in the Early Diagnosis of Acute Mesenteric Ischemia Secondary to Arterial Occlusion in Rats
Authors: Kurt Y. , Akin M.L. , Demirbas S. , Uluutku A.H. , Gulderen M. , Avsar K. , Celenk T.
Published: November 2005

Background: Early diagnosis of mesenteric ischemia can be life saving. The aim of this study is to investigate the time-dependent diagnostic value of plasma D-dimer and other ancillary laboratory evaluations such as creatine phosphokinase, lactic dehydrogenase, aspartate aminotransferase, alanine aminotransferase, amylase, and leukocyte count in an experimental superior mesenteric arterial occlusion (SMA-O) model in rats. Methods: Forty male Wistar-Albino rats were separated into 4 groups: 2-, 4-, 6-, and 12-hour SMA-O groups. After laparotomy, the SMA was identified and ligated for 2, 4, 6 and 12 h in the 4 respective study groups. Blood samples were taken for laboratory tests 2 h after laparotomy in the control group and at the end of the ischemic period in the study groups. Results: The longer the duration of mesenteric ischemia, the higher were the serum D-dimer levels in the study groups, and statistical significance was obtained at 2 h (p = 0.021). Sensitivity, positive predictive value, negative predictive value, and accuracy of the relation were 88.8, 88.8, 100 and 90%, respectively. Leukocyte count was significantly higher than controls after 12 h. No other laboratory parameter correlated positively with the duration of mesenteric ischemia. Conclusion: Serum D-dimer measurements may be a valuable diagnostic parameter in the early diagnosis of mesenteric ischemia.
Methylene Blue in the Evaluation of Gastrointestinal Tract Integrity: Potential Limitations
Authors: Prosst R.L. , Reinecke Franziska , Geginat G.
Published: November 2005

Introduction: The integrity of the gastrointestinal tract can be evaluated by oral or rectal application of methylene blue. In the presence of anastomotic leaks or fistulas, methylene blue can be recovered in adjacent drains. However, parts of the dye can biochemically be reduced by intestinal bacteria to its colorless form leucomethylene blue, limiting the prediction of the test. Materials and Methods: Diluted methylene blue was added to different concentrations of bacterial suspensions of Escherichia coli and Enterococcus faecalis. The time for discoloration of the suspension was measured. Results: Reduction of methylene blue to leucomethylene blue was observed in both types of bacterial suspension. A 108 bacterial concentration discolorated the dye within 1 h in the E. faecalis suspension, respectively 2.5 h in the E. coli suspension. Longer bacterial interaction with methylene blue reduced the bacterial concentration required to achieve complete discoloration. Discussion: Methylene blue can reliably be used as routine diagnostic test for the assessment of upper gastrointestinal integrity, where bacterial load is low. In the lower gastrointestinal tract, where bacterial load is generally higher, the dye can indicate leaks, only if extended intestinal passage after oral ingestion is avoided. In all other cases, the examiner has to be aware of false-negative results by bacterial discoloration of methylene blue.
Allogeneic Hematopoietic Cell Transplantation as Consolidation Immunotherapy of Cancer after Autologous Transplantation
Authors: Maris Michael B. , Storb Rainer
Published: November 2005

Autologous and allogeneic hematopoietic cell transplantations (HCT) after high-dose conditioning are curative for many patients with hematologic malignancies. The major limitation of autologous HCT is disease recurrence, while the problem with allogeneic HCT is the restriction to relatively young and otherwise medically fit patients because of complications from high-dose therapy coupled with those from graft-versus-host disease (GVHD). The well-described benefits of graft-versus-tumor (GVT) effects have stimulated the development of conditioning regimens with attenuated doses of chemoradiotherapy that may provide both a degree of cytoreduction before allografting (reduced intensity) and facilitate allogeneic cell engraftment through immuno- suppression (nonmyeloablative). Both reduced-intensity and nonmyeloablative approaches seek to exploit GVT activity of donor cells to eradicate cancer. Because of intrinsic or acquired insensitivity of some malignancies to standard dose chemotherapy and the limitations of GVT effects in eradicating large tumor burdens, high-dose autologous HCT has been used before reduced-intensity and nonmyeloablative allogeneic HCT. This approach appears to improve response rates for malignancies such as multiple myeloma and lymphoma, while avoiding morbidity and mortality of high-dose allogeneic HCT. This review details the rationale, benefits and limitations of this approach.
Autologous Hematopoietic Stem Cell Transplantation in Non-Hodgkin’s Lymphomas
Authors: Zinzani Pier Luigi
Published: November 2005

Early studies on high-dose therapy followed by autologous bone marrow transplantation demonstrated the safety and efficacy of this approach in non-Hodgkin’s lymphoma (NHL). As the procedure became easier and safer with the introduction of peripheral blood progenitor cells instead of marrow, the popularity of this procedure declined. In the last decade, autologous hematopoietic stem cell transplantion has played an important role in front-line and salvage treatments of indolent and aggressive NHL.
Long-Term Evolution of Endocrine Disorders and Effect of GH Therapy in 35 Patients with Pituitary Stalk Interruption Syndrome
Authors: Tauber Maïthé , Chevrel Jean , Diene Gwenaelle , Moulin Pierre , Jouret Béatrice , Oliver Isabelle , Pienkowski Catherine , Sevely Annick
Published: November 2005

We report long-term evolution of endocrine functions and the results of GH treatment in 35 patients (26 male and 9 female) with pituitary stalk interruption. At diagnosis, mean chronological age was 4.8 ± 2.7 years, mean SDS for height –3.1 ± 0.8 with a bone age retardation of 2.3 ± 1.3 years and a mean SDS for growth velocity of –0.5 ± 1.1; 80% presented complete GH deficiency (GHD) and 20% partial GHD; thyroid deficiency was present in 47.1% of children with complete GHD but absent in all partial GHD. Diagnosis was made during the first months of life in only 2 patients while 23% presented with severe neonatal distress; neonatal signs were only observed in the group with pituitary height below 2 mm (45.7% of patients). GHD was isolated in 40.6% of patients below 10 years while multiple hormone deficiencies was consistent at completion of growth in all patients. Height gain was significantly higher in patients who started GH treatment before 4 years (p = 0.002). GH treatment is very effective: in 13 patients, final height was –0.4 ± 1.0, total height gain 3.2 ± 1.2 and distance to target height –0.3 ± 1.6 SDS.
Lack of Association between the IL13 Variant Arg110Gln and Susceptibility to Cedar Pollinosis in a Japanese Population
Authors: Cheng Lei , Hirota Tomomitsu , Enomoto Tadao , Tamari Mayumi , Akahoshi Mitsuteru , Matsuda Akira , Shimizu Makiko , Takahashi Naomi , Enomoto Keisuke , Yamasaki Akiko , Mao Xiao-Quan , Hopkin Julian M. , Shirakawa Taro
Published: November 2005

Background:Interleukin (IL)-13 has come to be appreciated as a molecule critically involved in allergic inflammatory responses. Recent studies revealed that a common variant in the coding region of the IL13 gene, Arg110Gln, has been implicated in the development of asthma and atopy. Methods:To assess whether the IL13 variant Arg110Gln is associated with cedar pollinosis, one of the most common atopic diseases in the Japanese population, we examined the Arg110Gln variant using PCR-RFLP to compare the genotype and allele frequencies between 95 patients with cedar pollinosis and 95 healthy control subjects. Relationships between the Arg110Gln variant and the pollinosis-related traits, e.g. rhinitis severity, eosinophil counts in nasal secretion and serum total and allergen-specific IgE levels, were also investigated. Results: The frequencies of the minor allele Gln110 were 25.8% in patients with cedar pollinosis and 30.9% in healthy control subjects (p > 0.05). There was also no significant difference in the genotype frequencies between cases and controls (p > 0.05). In addition, we found no significant association of the Arg110Gln variant with any of the pollinosis-related phenotypes (p > 0.05). Conclusions: Our data suggest lack of evidence for identifying the variant Arg110Glnat the IL13 locus as a genetic risk factor involved in the development of Japanese cedar pollinosis.
Macrophage Apolipoprotein E Reduces Atherosclerosis and Prevents Premature Death in Apolipoprotein E and Scavenger Receptor–Class BI Double-Knockout Mice
Authors: Yu Hong , Zhang Wenwu , Yancey Patricia G. , Koury Mark J. , Zhang Youmin , Fazio Sergio , Linton MacRae F.
Published: November 2005

Objective—

Mice null for both apolipoprotein (apo)E and scavenger receptor (SR)-BI (DKO) develop severe hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarction, and premature death. The current study examines the ability of macrophage apoE to improve the dyslipidemia, reduce atherosclerosis, and rescue the lethal phenotype of DKO mice.

Methods and Results—

Initially, bone marrow transplantation (BMT) was unsuccessful, because the DKO mice died from a rapidly fatal anemia 3 to 5 days after lethal irradiation. Therefore, probucol was used to rescue the DKO mice during BMT and was discontinued 2-weeks after BMT, allowing successful reconstitution with donor marrow. Twelve male apoE
−/−
SR-BI
−/−
mice fed 0.5% probucol in a chow diet were lethally irradiated and transplanted with either wild-type (WT) or DKO bone marrow. Two-weeks after BMT, apoE was detected in serum in WT→DKO mice, and mean serum cholesterol levels were reduced by 70% versus DKO→DKO mice. Lipoprotein profiles and HDL subpopulations in WT→DKO mice were similar to apoE
+/+
SR-BI
−/−
→DKO mice and resembled those of SR-BI
−/−
mice. In WT→DKO mice, aortic atherosclerosis was reduced by 88% to 90% versus DKO→DKO mice. Furthermore, the DKO→DKO mice died &8 weeks after BMT, whereas WT→DKO mice exhibited a life span >40 weeks after BMT.

Conclusions—

Macrophage apoE is able to rescue the lethal phenotype of apoE
−/−
SR-BI
−/−
mice by improving the dyslipidemia and dramatically reducing atherosclerotic lesion development.
Cyclic Strain–Mediated Regulation of Vascular Endothelial Occludin and ZO-1
Authors: Collins Nora T. , Cummins Philip M. , Colgan Olga C. , Ferguson Gail , Birney Yvonne A. , Murphy Ronan P. , Meade Gerardene , Cahill Paul A.
Published: November 2005

Objective—

The vascular endothelium constitutes a highly effective fluid/solute barrier through the regulated apposition of intercellular tight junction complexes. Because endothelium-mediated functions and pathology are driven by hemodynamic forces (cyclic strain and shear stress), we hypothesized a dynamic regulatory link between endothelial tight junction assembly/function and hemodynamic stimuli. We, therefore, examined the effects of cyclic strain on the expression, modification, and function of 2 pivotal endothelial tight junction components, occludin and ZO-1.

Methods and Results—

For these studies, bovine aortic endothelial cells were subjected to physiological levels of equibiaxial cyclic strain (5% strain, 60 cycles/min, 24 hours). In response to strain, both occludin and ZO-1 protein expression increased by 2.3±0.1-fold and 2.0±0.3-fold, respectively, concomitant with a strain-dependent increase in occludin (but not ZO-1) mRNA levels. These changes were accompanied by reduced occludin tyrosine phosphorylation (75.7±8%) and increased ZO-1 serine/threonine phosphorylation (51.7±9% and 82.7±25%, respectively), modifications that could be completely blocked with tyrosine phosphatase and protein kinase C inhibitors (dephostatin and rottlerin, respectively). In addition, there was a significant strain-dependent increase in endothelial occludin/ZO-1 association (2.0±0.1-fold) in parallel with increased localization of both occludin and ZO-1 to the cell–cell border. These events could be completely blocked by dephostatin and rottlerin, and they correlated with a strain-dependent reduction in transendothelial permeability to FITC-dextran.

Conclusions—

Overall, these findings indicate that cyclic strain modulates both the expression and phosphorylation state of occludin and ZO-1 in vascular endothelial cells, with putative consequences for endothelial tight junction assembly and barrier integrity.
Angiotensin II Type 1 Receptor Agonistic Antibodies Reflect Fundamental Alterations in the Uteroplacental Vasculature
Authors: Walther Thomas , Wallukat Gerd , Jank Alexander , Bartel Sabine , Schultheiss Heinz-Peter , Faber Renaldo , Stepan Holger
Published: November 2005

Abnormal uterine perfusion detected by Doppler sonography reflects impaired trophoblast invasion, a factor involved in the pathogenesis of pregnancy complications such as preeclampsia or intrauterine growth retardation. Recent studies have demonstrated an autoantibody against the angiotensin type 1 (AT
1
) receptor in pregnant women with preeclampsia. Our aim was to determine whether the AT
1
autoantibody precedes the clinical symptoms and is thus predictive of preeclampsia. We therefore detected this antibody in serum from second trimester pregnancies with abnormal uterine perfusion because these women show an indirect sign of inadequate trophoblast invasion. Then the AT
1
autoantibody distribution/concentration was compared with that of women at term with or without pregnancy pathology. The AT
1
autoantibody was already detectable in second trimester pregnant women with abnormal uterine perfusion before the clinical manifestation of preeclampsia (80%). However, it was also found in second trimester pregnant women with abnormal uterine perfusion who later developed intrauterine growth retardation (60%) or even had a normal course of pregnancy (62%). In the third trimester, the AT
1
autoantibody was demonstrated in 89% of patients with manifest preeclampsia, 86% of those with manifest intrauterine growth retardation, and even in healthy pregnant women at term with a history of abnormal uterine perfusion in the second trimester. We conclude that the AT
1
autoantibody is an early but nonspecific marker for preeclampsia. The generation of this antibody seems to be associated with distinct types of pregnancy disorders resulting from impaired placental development. The AT
1
autoantibody may thus be causative for pathological uteroplacental perfusion.
FcγRIIB Mediates C-Reactive Protein Inhibition of Endothelial NO Synthase
Authors: Mineo Chieko , Gormley Andrew K. , Yuhanna Ivan S. , Osborne-Lawrence Sherri , Gibson Linda L. , Hahner Lisa , Shohet Ralph V. , Black Steven , Salmon Jane E. , Samols David , Karp David R. , Thomas Gail D. , Shaul Philip W.
Published: November 2005

C-reactive protein (CRP) is an acute-phase reactant that is positively correlated with cardiovascular disease risk and endothelial dysfunction. Whether CRP has direct actions on endothelium and the mechanisms underlying such actions are unknown. Here we show in cultured endothelium that CRP prevents endothelial NO synthase (eNOS) activation by diverse agonists, resulting in the promotion of monocyte adhesion. CRP antagonism of eNOS occurs nongenomically and is attributable to blunted eNOS phosphorylation at Ser1179. Okadaic acid or knockdown of PP2A by short-interference RNA reverses CRP antagonism of eNOS, indicating a key role for the phosphatase. Aggregated IgG, the known ligand for Fcγ receptors, causes parallel okadaic acid–sensitive loss of eNOS function, FcγRIIB expression is demonstrable in endothelium, and heterologous expression studies reveal that CRP antagonism of eNOS requires FcγRIIB. In FcγRIIB
+/+
mice, CRP blunts acetylcholine-induced increases in carotid artery vascular conductance; in contrast, CRP enhances acetylcholine responses in FcγRIIB
−/−
mice. Thus FcγRIIB mediates CRP inhibition of eNOS via PP2A, providing a mechanistic link between CRP and endothelial dysfunction.
Soluble Vascular Endothelial Growth Factor Receptor-1 (sFLT-1) Mediates Downregulation of FLT-1 and Prevents Activated Neutrophils From Women With Preeclampsia From Additional Migration by VEGF
Authors: Krysiak Oliver , Bretschneider Anja , Zhong Enhong , Webb Jessie , Hopp Hartmut , Verlohren Stefan , Fuhr Norbert , Lanowska Malgorzata , Nonnenmacher Andreas , Vetter Roland , Jankowski Joachim , Paul Martin , Schönfelder Gilbert
Published: November 2005

Neutrophil activation and increased migration is associated with preeclampsia and is resolved after delivery. Preeclampsia is an inflammatory disorder where altered levels of vascular endothelial growth factor (VEGF) and the circulating soluble fms-like tyrosine kinase 1 (sFlt-1) have a pathogenic role. VEGF, by binding to FLT-1, induces leukocytic chemotaxis. We studied expression and function of FLT-1 in maternal neutrophils during preeclampsia and normal pregnancies. Analysis of maternal neutrophils showed the relationship between FLT-1 expression and week of gestation. Preeclamptic women express lower FLT-1 and sFLT-1 in neutrophils. In contrast, serum levels of sFLT-1 in patients with preeclampsia are increased and, therefore, inhibit upregulation of FLT-1 in neutrophils by neutralizing VEGF. VEGF-dependent FLT-1 expression is regulated by changing FLT-1-promoter activity. Promoter activity is decreased by sFLT-1. In vitro experiments demonstrated that migration of neutrophils is regulated by VEGF via FLT-1 and excess of sFLT-1. Thus, VEGF-dependent migration of neutrophils is decreased during preeclampsia as a consequence of excess circulating sFlt1. But, they still increase migration by fMLP and, therefore, migration of neutrophils from preeclamptic women is highly activated when compared with the normotensive group. In conclusion, besides being involved in inducing an antiangiogenic state in the serum, excess of sFLT-1 seems to prevent activated neutrophils from women with preeclampsia from additional migration by VEGF. We provide evidence that neutrophils may be involved in the pathophysiology of pregnancy-related hypertensive disorders.
Adiponectin Inhibits Endothelial Synthesis of Interleukin-8
Authors: Kobashi Chikaaki , Urakaze Masaharu , Kishida Mika , Kibayashi Etsuko , Kobayashi Hideki , Kihara Shinji , Funahashi Tohru , Takata Michiyo , Temaru Rie , Sato Akira , Yamazaki Katsuya , Nakamura Norio , Kobayashi Masashi
Published: November 2005

Adiponectin is an antiatherogenic adipokine that inhibits inflammation by mechanisms that are not completely understood. We explored the effect of adiponectin on endothelial synthesis of interleukin-8 (IL-8), a pro-inflammatory chemokine that plays a role in atherogenesis. Adiponectin decreased the secretion of IL-8 from human aortic endothelial cells (HAEC) stimulated with tumor necrosis factor-α (TNF-α). Adiponectin also inhibited IL-8 mRNA expression induced by TNF-α. Phosphorylation of IκB-α was decreased by adiponectin, but phosphorylation of ERK, SAPK/JNK, and p38MAPK were unaffected. Adiponectin increased intra-cellular cAMP levels in HAEC in a dose-dependent manner; PKA activity was also increased. The inhibitory effect of adiponectin on TNF-α–induced IL-8 synthesis was inhibited by pretreatment with Rp-cAMP, a PKA inhibitor. These observations suggest that adiponectin inhibits IL-8 synthesis through inhibition of a PKA dependent NF-κB signaling pathway. We also showed that adiponectin enhances Akt phosphorylation. The inhibitory effect of adiponectin on TNF-α–induced IL-8 synthesis was abrogated in part by pretreatment with the PI3 kinase inhibitor LY294002 or by Akt siRNA transfection, suggesting that Akt activation might inhibit IL-8 synthesis induced by TNF-α. We conclude that inhibition of NF-κB and activation of Akt phosphorylation may mediate adiponectin inhibition of atherosclerosis.
Potential Applicability of Recombinant Factor VIIa for Intracerebral Hemorrhage
Authors: Flaherty Matthew L. , Woo Daniel , Haverbusch Mary , Moomaw Charles J. , Sekar Padmini , Sauerbeck Laura , Kissela Brett , Kleindorfer Dawn , Broderick Joseph P.
Published: November 2005

Background and Purpose—

To date, there are no proven, effective treatments for intracerebral hemorrhage (ICH) beyond supportive medical care. A recent randomized, blinded, placebo-controlled trial of recombinant factor VIIa (rFVIIa) administered intravenously within 4 hours of ICH onset reported a reduction in morbidity and mortality compared with placebo. We sought to determine the potential applicability of rFVIIa in a large, population-based cohort of ICH patients.

Methods—

All of the patients age ≥18 years hospitalized with nontraumatic ICH in the Greater Cincinnati region were identified from May 1998 to July 2001 and August 2002 to April 2003. Patient demographics were compared with the inclusion and exclusion criteria from the rFVIIa trial to determine eligibility for treatment and reasons for exclusion. Mortality in the eligible patient group was compared with the placebo group in the rFVIIa trial.

Results—

Over 4 calendar years, 1018 ICH patients were identified; of these, 133 (13.1%) had no exclusions and presented within the prescribed time window. An additional 45 patients (4.4%) may have been eligible but had uncertain onset or computed tomography scan times. The most common reasons for exclusion (not mutually exclusive) were late presentation (n=398), vaso-occlusive disease (n=369), deep coma (n=219), and prolonged international normalized ratio or partial thromboplastin time (n=200). Mortality at 90 days among potentially eligible patients was the same as for the placebo group in the rFVIIa trial (29% versus 29%;
P
=0.99).

Conclusions—

In this large, population-based ICH cohort, 13.1% to 17.5% of patients would have qualified for treatment with rFVIIa by trial criteria.
Is White Matter Involved in Patients Entered into Typical Trials of Neuroprotection?
Authors: Ho Prahlad W. , Reutens David C. , Phan Thanh G. , Wright Peter M. , Markus Romesh , Indra Indra , Young Dennis , Donnan Geoffrey A.
Published: November 2005

Background and Purpose—

One of the reasons for the failure of trials of neuroprotection in stroke may be the lack of white matter (WM) protection. However, whether patients entered into typical neuroprotection trials have WM involved in the ischemic process is unknown. We studied patients who were enrolled in neuroprotection trials at our center and used a neuroimaging coregistration approach to determine whether final infarcts involved WM and, if so, in what proportion. We also aimed to provide the first in vivo volume distribution of gray matter (GM) and WM in normal stroke-aged brains.

Methods—

Patients enrolled in trials of neuroprotection had late computed tomography or magnetic resonance scans coregistered in standard stereotaxic coordinate space after segmentation of symptomatic cerebral infarcts. These were then superimposed on a probabilistic map of GM and WM, which was developed from age-matched normal controls in whom GM and WM volumes were assessed.

Results—

Forty-two patients (mean age, 73.7±10.5 years) were studied from 6 trials of neuroprotection. WM formed 41.7% of the brain volume in 37 control subjects (mean age, 73.5±8.4 years). In the segmented infarcts, WM comprised a median of 49% (interquartile range, 36.5 to 77.9) of the infarct volume. Ninety-five percent of infarcts had some involvement of WM tracts.

Conclusions—

WM occupies ≈42% by volume of the normal stroke-aged brain. Patients entered into typical trials of neuroprotection may have significant WM volumes involved in the ischemic process, thus providing a rationale for the development of neuroprotectants for this compartment.