bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protease research in the era of systems biology
Authors: Keller Ulrich auf dem , Doucet Alain , Overall Christopher M. 
Published: November 2007

Abstract
Proteases are specific modulators of signaling molecules and their underlying pathways in addition to their degradative roles. However, proteases do not act alone, but form cascades, circuits and networks that all dynamically interconnect to form the protease web, which defines the proteolytic potential of a cell or tissue in a defined condition. To describe the protease web and its net activity several novel high-throughput proteomic techniques, in the field termed degradomics, have been developed. Emerging systems biology methods to evaluate the expression, activity and substrate discovery of proteases are presented. Understanding the protease web and its perturbations in pathology will help to develop new therapeutics for the treatment of diseases, such as cancer, arthritis and chronic obstructive pulmonary diseases.
Association of cathepsin E with tumor growth arrest through angiogenesis inhibition and enhanced immune responses
Authors: Shin Masashi , Kadowaki Tomoko , Iwata Jun-ichi , Kawakubo Tomoyo , Yamaguchi Noriko , Takii Ryosuke , Tsukuba Takayuki , Yamamoto Kenji 
Published: November 2007

Abstract
Cathepsin E (CE) is an intracellular aspartic proteinase implicated in various physiological and pathological processes, yet its actual roles in vivo remain elusive. To assess the physiological significance of CE expression in tumor cells, human CE was stably expressed in human prostate carcinoma ALVA101 cells expressing very little CE activity. Tumor growth in nude mice with xenografted ALVA101/hCE cells was slower than with control ALVA101/mock cells. Angiogenesis antibody array and ELISA assay showed that this was partly due to the increased expression of some antiangiogenic molecules including interleukin 12 and endostatin in tumors induced by CE expression. In vitro studies also demonstrated that, among the cathepsins tested, CE most efficiently generated endostatin from the non-collagenous fragment of human collagen XVIII at mild acidic pH. Histological examination revealed that tumors formed by ALVA101/hCE cells were partitioned by well-developed membranous structures and covered with thickened, well-stratified hypodermal tissues. In addition, both the number and extent of activation of tumor-infiltrating macrophages were more profound in ALVA101/hCE compared to ALVA101/mock tumors. The chemotactic response of macrophages to ALVA101/hCE cells was also higher than that to ALVA/mock cells. These results thus indicate that CE expression in tumor cells induces tumor growth arrest via inhibition of angiogenesis and enhanced immune responses.
Two decades of thyroglobulin type-1 domain research
Authors: Mihelič Marko , Turk Dušan 
Published: November 2007

AbstractThyroglobulin type-1 repeats are primarily found in thyroglobulin and several other functionally unrelated proteins. Because a few of them exhibit inhibitory activity against cysteine proteases they were named thyropins (thyroglobulin type-1 domain protease inhibitors). In contrast to cystatins, the best-characterized group of papain-like protease inhibitors, they exhibit greater selectivity in their interactions with target proteases. Interestingly, a few members inhibit aspartic protease cathepsin D and metalloproteases. In contrast to the inhibitory fragment of the major histocompatibility complex class II-associated p41 form of invariant chain, whose structural integrity appears mandatory for its inhibitory properties, short polypeptides derived from insulin-like growth factor-binding proteins exhibit the same activity as the structure of the whole fragment. Taken together, the results indicate that the thyroglobulin type-1 repeat is a structural motif occasionally employed as an inhibitor of proteases.
Human and mouse homo-oligomeric meprin A metalloendopeptidase: substrate and inhibitor specificities
Authors: Bylander John E. , Bertenshaw Greg P. , Matters Gail L. , Hubbard Simon J. , Bond Judith S. 
Published: November 2007

Abstract
Meprin metalloproteinases have been implicated in the susceptibility to and progression of diabetic nephropathy and inflammatory bowel diseases. Our studies with experimental models of these diseases in mice are congruent with the conclusion that meprins modulate the inflammatory responses and tissue damage. To determine whether the mouse and human enzymes differ, recombinant forms of meprin A from the two species were compared with respect to structure, substrates and inhibitors. Human homo-oligomeric meprin A formed oligomers ranging from 950 000 to 1 500 000 Da vs. 900 000 Da for mouse meprin A. Human and mouse meprin A exhibited similar activity against azocasein, fibronectin, collagen IV, and peptides such as parathyroid hormone, ghrelin, and gastrin-releasing peptide. The human enzyme had lower activity against gelatin, bradykinin, α-melanocyte-stimulating hormone and neurotensin, and higher activity against secretin and orcokinin. Human meprin A showed a preference for acidic residues in the P1′ position of the substrate, unlike mouse meprin A. Several metalloproteinase inhibitors had IC50 values in the nanomolar range, but potency ranged from similar values to a difference of several orders of magnitude for meprins from the two species. This work provides valuable data to improve predictability for human systems based on meprin functions in mouse models.
A Cross-National Comparison of Racial and Ethnic Disparities in Low Birth Weight in the United States and England
Authors: Teitler Julien O. , Reichman Nancy E. , Nepomnyaschy Lenna , Martinson Melissa 
Published: November 2007

OBJECTIVE. We used 2 new nationally representative surveys to compare racial and ethnic differences in low birth weight in the United States and England.METHODS. Risk factors and rates of low birth weight were compared across groups for singleton births within each country (white, black, Hispanic, Asian, and American Indian mothers in the United States; white, black, and Asian mothers in England). Crude rates and rates adjusted for socioeconomic status and behaviors were compared. Additional comparisons were limited to native-born mothers.RESULTS. Racial and ethnic disparities in low birth weight are as large in England as in the United States. Socioeconomic status and behaviors explain little of the variation across racial and ethnic groups in either country.CONCLUSIONS. Health disadvantages associated with being a minority do not seem to be a uniquely American phenomenon. Universal health care, as provided in the United Kingdom, alone may be insufficient to reduce racial and ethnic disparities in low birth weight.
Voices of Asian American Youth: Important Characteristics of Clinicians and Clinical Sites
Authors: Vo Dzung X. , Pate Olivia Lee , Zhao Huaqing , Siu Philip , Ginsburg Kenneth R. 
Published: November 2007

OBJECTIVE. The purpose of this work was to explore clinician and site characteristics that are important to Chinese and Vietnamese immigrant and first-generation youth.
METHODS. A 3-stage mixed qualitative-quantitative design consisting of exploratory focus groups, a survey, and explanatory focus groups was used to ensure that all of the ideas were generated, prioritized, and explained by youth. Adolescents of Chinese and/or Vietnamese descent and aged 13 to 18 years were recruited in community centers and schools. In stage 1, 55 adolescents in 8 focus groups shared their views on factors that attract or deter them from seeking care. In stage 2, youth responded to a survey including 27 teen-generated items regarding clinicians and sites. In stage 3, 87 teens in 11 groups explained the top-rated items and offered suggestions on how to meet their needs. All of the stages were conducted in English, Mandarin Chinese, and Vietnamese.
RESULTS. Most of the 245 survey respondents (77%) were born in Asia, and 70% had lived in the United States for &lt;3 years. The 27 items were divided into 6 priority ranks by the marginal homogeneity test. Clinician cleanliness and experience shared first rank. Second rank was shared by Asian teens being treated like other teens, site cleanliness, clinician honesty, and clinician friendliness and attitude. The third rank was shared by respect, privacy, completeness, clinicians explaining their actions, and lower health care costs. Interspersed among ranks 5 and 6 were items specific to the needs of Asian youth: the clinician would offer more explanation because Asian families might not ask questions; the clinician would not assume that Asian teens are drug and sex free; the clinician would understand that Asian families may use traditional healing; the clinician would not assume that Asians do not know English; adolescents would not translate for parents; and the teen would be able to choose an Asian clinician. There was little variation in ratings by age, gender, ethnicity, or socioeconomic status. However, 11 of 27 items differed by acculturation. Examples include the greater importance ascribed by more acculturated youth to not being judged, to not having to translate, and to the clinician addressing behavioral issues. Acculturation also affected the youths' views regarding confidentiality and translation.
CONCLUSIONS. Asian American adolescents value the same concerns as all adolescents: respect, honesty, competency, cleanliness, privacy, and nonjudgmental service. However, they also have unique perspectives, and youth at varying levels of acculturation differ in some of their views.
A duodeno-gastrooesophagealis refluxbetegség sebészi kezelése: duodenal switch műtétr
Authors: Varga Gábor , Cseke László , Kalmár Katalin , Horváth Örs Péter 
Published: November 2007

Absztrakt
A duodeno-gastrooesophagealis refluxbetegség komplex motilitási zavar, melynek kezelése (gyógyszeres és sebészi) mind a mai napig nem egységesen elfogadott. Tanulmányunk célja, hogy ismertessük a duodeno-gastrooesophagealis refluxbetegség kezelésével kapcsolatos tapasztalatainkat.
A tanulmányba azok a gastrooesophagealis refluxos betegek kerültek, akiknél terápiarezisztens epigastrialis panaszok, epés regurgitáció hátterében 24 órás kétcsatornás gyomor-, nyelőcső-Bilitec-vizsgálat kóros mértékű duodenogastricus refluxot igazolt. Mind a négy nőbetegnél (átlagéletkor 41,75 év (32–53)) duodenal switch műtétet végeztünk. A betegek 75%-ában korábban cholecystectomia történt. Az átlagos utánkövetési idő 24,25 (21–30) hónap volt.
Mind a 4 betegnél korábban gastrooesophagealis reflux betegség miatt antirefluxműtétre került sor. Közülük egy betegnél recidív gastrooesophagealis reflux is igazolódott, nála refundoplicatiót is végeztünk. Perioperatív szövődményt, mortalitást nem észleltünk. Utánkövetés során mind a négy beteg panaszmentessé vált, azonban egy betegnél az egyéves kontrollvizsgálat során végzett 24 órás nyelőcső-pH-monitorozás kóros mértékű savas refluxot igazolt.
Gastrooesophagealis reflux betegeknél antirefluxműtét után jelentkező epigastrialis panaszok hátterében kóros mértékű duodenogastricus reflux állhat. Erre prediszponáló tényező lehet a korábban elvégzett cholecystetomia. Gyógyszeres kezelésre nem javuló, funkcionális vizsgálatokkal igazolt kóros mértékű duodenogastricus reflux kezelésére duodenal switch műtét jó eredménnyel alkalmazható.
Hematopoietic Mixed Chimerism Derived from Allogeneic Embryonic Stem Cells Prevents Autoimmune Diabetes Mellitus in NOD Mice
Authors: Verda Larissa , Kim Duck An , Ikehara Susumu , Statkute Laisvyde , Bronesky Delphine , Petrenko Yevgeniya , Oyama Yu , He Xiang , Link Charles , Vahanian Nicholas N. , Burt Richard K. 
Published: November 2007

AbstractEmbryonic stem cell (ESC)-derived hematopoietic stem cells (HSC), unlike HSC harvested from the blood or marrow, are not contaminated by lymphocytes. We therefore evaluated whether ESC-derived HSC could produce islet cell tolerance, a phenomenon termed graft versus autoimmunity (GVA), without causing the usual allogeneic hematopoietic stem cell transplant complication, graft-versus-host disease (GVHD). Herein, we demonstrate that ESC-derived HSC may be used to prevent autoimmune diabetes mellitus in NOD mice without GVHD or other adverse side effects. ESC were cultured in vitro to induce differentiation toward HSC, selected for c-kit expression, and injected either i.v. or intra-bone marrow (IBM) into sublethally irradiated NOD/LtJ mice. Nine of 10 mice from the IBM group and 5 of 8 from the i.v. group did not become hyperglycemic, in contrast to the control group, in which 8 of 9 mice developed end-stage diabetes. All mice with &gt;5% donor chimerism remained free of diabetes and insulitis, which was confirmed by histology. Splenocytes from transplanted mice were unresponsive to glutamic acid decarboxylase isoform 65, a diabetic-specific autoantigen, but responded normally to third-party antigens. ESC-derived HSC can induce an islet cell tolerizing GVA effect without GVHD. This study represents the first instance, to our knowledge, of ESC-derived HSC cells treating disease in an animal model.Disclosure of potential conflicts of interest is found at the end of this article.
Morphological and Functional Characterization of Predifferentiation of Myelinating Glia-Like Cells from Human Bone Marrow Stromal Cells Through Activation of F3/Notch Signaling in Mouse Retina
Authors: Lu Li , Chen Xue , Zhang Cheng-Wu , Yang Wu-Lin , Wu Ya-Jun , Sun Li , Bai Li-Min , Gu Xiao-Song , Ahmed Sohail , Dawe Gavin S. , Xiao Zhi-Cheng 
Published: November 2007

Abstract
Recently, we have demonstrated that F3/contactin and NB-3 are trans-acting extracellular ligands of Notch that promote differentiation of neural stem cells and oligodendrocyte precursor cells into mature oligodendrocytes (OLs). Here, we demonstrate that human bone marrow stromal cells (hBMSCs) can be induced to differentiate into cells with myelinating glial cell characteristics in mouse retina after predifferentiation in vitro. Isolated CD90(+) hBMSCs treated with β-mercaptoethanol for 1 day and retinoic acid for 3 days in culture changed into myelinating glia-like cells (MGLCs). More cells expressed NG2, an early OL marker, after treatment, but expression of O4, a mature OL marker, was negligible. Subsequently, the population of O4(+) cells was significantly increased after the MGLCs were predifferentiated in culture in the presence of either F3/contactin or multiple factors, including forskolin, basic fibroblast growth factor, platelet-derived growth factor, and heregulin, in vitro for another 3 days. Notably, 2 months after transplantation into mouse retina, the predifferentiated cells changed morphologically into cells resembling mature MGLCs and expressing O4 and myelin basic protein, two mature myelinating glial cell markers. The cells sent out processes to contact and wrap axons, an event that normally occurs during early stages of myelination, in the retina. The results suggest that CD90(+) hBMSCs are capable of morphological and functional differentiation into MGLCs in vivo through predifferentiation by triggering F3/Notch signaling in vitro.
Disclosure of potential conflicts of interest is found at the end of this article.
Efficient In Vitro Labeling of Human Neural Precursor Cells with Superparamagnetic Iron Oxide Particles: Relevance for In Vivo Cell Tracking
Authors: Neri Margherita , Maderna Claudio , Cavazzin Chiara , Deidda-Vigoriti Vivien , Politi Letterio S. , Scotti Giuseppe , Marzola Pasquina , Sbarbati Andrea , Vescovi Angelo L. , Gritti Angela 
Published: November 2007

AbstractRecent studies have raised appealing possibilities of replacing damaged or lost neural cells by transplanting in vitro-expanded neural precursor cells (NPCs) and/or their progeny. Magnetic resonance (MR) tracking of superparamagnetic iron oxide (SPIO)-labeled cells is a noninvasive technique to track transplanted cells in longitudinal studies on living animals. Murine NPCs and human mesenchymal or hematopoietic stem cells can be efficiently labeled by SPIOs. However, the validation of SPIO-based protocols to label human neural precursor cells (hNPCs) has not been extensively addressed. Here, we report the development and validation of optimized protocols using two SPIOs (Sinerem and Endorem) to label human hNPCs that display bona fide stem cell features in vitro. A careful titration of both SPIOs was required to set the conditions resulting in efficient cell labeling without impairment of cell survival, proliferation, self-renewal, and multipotency. In vivo magnetic resonance imaging (MRI) combined with histology and confocal microscopy indicated that low numbers (5 × 103 to 1 × 104) of viable SPIO-labeled hNPCs could be efficiently detected in the short term after transplantation in the adult murine brain and could be tracked for at least 1 month in longitudinal studies. By using this approach, we also clarified the impact of donor cell death to the MR signal. This study describes a simple protocol to label NPCs of human origin using SPIOs at optimized low dosages and demonstrates the feasibility of noninvasive imaging of labeled cells after transplantation in the brain; it also evidentiates potential limitations of the technique that have to be considered, particularly in the perspective of neural cell-based clinical applications.Disclosure of potential conflicts of interest is found at the end of this article.
Trafficking of Multipotent Mesenchymal Stromal Cells from Maternal Circulation Through the Placenta Involves Vascular Endothelial Growth Factor Receptor-1 and Integrins
Authors: Chen Chie-Pein , Lee Ming-Yi , Huang Jian-Pei , Aplin John D. , Wu Yi-Hsin , Hu Cing-Siang , Chen Pei-Chun , Li Hung , Hwang Shiaw-Min , Liu Shu-Hsiang , Yang Yuh-Cheng 
Published: November 2007

AbstractMaternal cells can become engrafted in various fetal organs during pregnancy. The nature of the cells and the mechanisms of maternofetal cell trafficking are not clear. We demonstrate that human lineage-negative, CD34-negative (Lin−CD34−) multipotent mesenchymal stromal cells express α2, α4, α5, and β1 integrins, which mediate their adhesion to endothelium, and vascular endothelial growth factor receptor-1 (VEGFR-1), which mediates their response to vascular endothelial growth factor A (VEGF-A). A maternal-fetal VEGF-A concentration gradient exists across the placental barrier, and cord blood plasma induces transendothelial and trans-Matrigel migration of stem cells in vitro. Migration is inhibited by a VEGF-A-neutralizing antibody or antibodies against VEGFR-1 or integrin α2, α4, α5, or β1. When Lin−CD34− multipotent mesenchymal stromal cells are transferred to rat maternal venous blood, they traffic through the placenta, engraft in various fetal organs, and persist in offspring for at least 12 weeks. Cell proliferation ability is retained in the xenogeneic placenta. Maternofetal trafficking is significantly reduced by blocking antibodies against integrins α2, α4, α5, and β1 or VEGFR-1. These results suggest that maternal microchimerism arises by the trafficking of multipotent mesenchymal stromal cells via VEGF-A- and integrin-dependent pathways across the hemochorial placenta to fetal tissues.Disclosure of potential conflicts of interest is found at the end of this article.
Characterization of Transplanted Green Fluorescent Protein+ Bone Marrow Cells into Adipose Tissue
Authors: Tomiyama Koji , Murase Noriko , Stolz Donna Beer , Toyokawa Hideyoshi , O'Donnell Daniel R. , Smith Darren M. , Dudas Jason R. , Rubin J. Peter , Marra Kacey G. 
Published: November 2007

Abstract
Following transplantation of green fluorescent protein (GFP)-labeled bone marrow (BM) into irradiated, wild-type Sprague-Dawley rats, propagated GFP+ cells migrate to adipose tissue compartments. To determine the relationship between GFP+ BM-derived cells and tissue-resident GFP− cells on the stem cell population of adipose tissue, we conducted detailed immunohistochemical analysis of chimeric whole fat compartments and subsequently isolated and characterized adipose-derived stem cells (ASCs) from GFP+ BM chimeras. In immunohistochemistry, a large fraction of GFP+ cells in adipose tissue were strongly positive for CD45 and smooth muscle actin and were evenly scattered around the adipocytes and blood vessels, whereas all CD45+ cells within the blood vessels were GFP+. A small fraction of GFP+ cells with the mesenchymal marker CD90 also existed in the perivascular area. Flow cytometric and immunocytochemical analyses showed that cultured ASCs were CD45−/CD90+/CD29+. There was a significant difference in both the cell number and phenotype of the GFP+ ASCs in two different adipose compartments, the omental (abdominal) and the inguinal (subcutaneous) fat pads; a significantly higher number of GFP−/CD90+ cells were isolated from the subcutaneous depot as compared with the abdominal depot. The in vitro adipogenic differentiation of the ASCs was achieved; however, all cells that had differentiated were GFP−. Based on phenotypical analysis, GFP+ cells in adipose tissue in this rat model appear to be of both hematopoietic and mesenchymal origin; however, infrequent isolation of GFP+ ASCs and their lack of adipogenic differentiation suggest that the contribution of BM to ASC generation might be minor.
Disclosure of potential conflicts of interest is found at the end of this article.
Early growth response gene-1 plays a pivotal role in down-regulation of a cohort of genes in uterine leiomyoma
Authors: Ishikawa Hiroshi , Shozu Makio , Okada Masahiko , Inukai Mai , Zhang Bo , Kato Keiichi , Kasai Tadayuki , Inoue Masaki 
Published: November 2007

AbstractMicroarray studies have identified many genes that are down-regulated in uterine leiomyoma compared with myometrium, including early growth response gene-1 (EGR1). However, the mechanisms underlying coordinated down-regulation of this gene cohort remain unknown. To address the transcriptional role of EGR1 in leiomyoma, EGR1 binding to promoter sequences on target genes was assessed by chromatin immunoprecipitation (ChIP) assay in leiomyoma tissues and myometrium-derived KW cells. Computer analysis demonstrated that 50 out of 135 genes listed as down-regulated in array reports possessed potential binding sites for EGR1 within 1 kb promoter sequence. ChIP assay was performed for a random selection of 13 genes possessing potential binding sites for EGR1 (Group A), 3 genes known as EGR1 targets in other tissues (Group B), and 4 control genes. Decreased EGR1 bindings were significant for 11 out of 16 genes (Group A+B) in leiomyoma tissues compared with myometrium, and mRNA levels in tissue samples were actually decreased for 7 out of the 11 genes. ChIP analyses performed on KW cells showed induction of EGR1 binding to the promoter region of all genes except one Group A+B gene, but for none of the control genes. These results indicate that EGR1 is a key player in coordinated down-regulation of genes in leiomyoma. Application of ChIP–quantitative PCR assay with the aid of computer-assisted analysis of genome databases appears useful for the comprehensive interpretation of array data.