bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pro‐inflammatory signature mediates FGF2‐induced angiogenesis
Authors: Andrés Germán , Leali Daria , Mitola Stefania , Coltrini Daniela , Camozzi Maura , Corsini Michela , Belleri Mirella , Hirsch Emilio , Schwendener Reto A. , Christofori Gerhard , Alcamì Antonio , Presta Marco 
Published: July 2008

AbstractFibroblast growth factor‐2 (FGF2) is a potent angiogenic growth factor. Here, gene expression profiling of FGF2‐stimulated microvascular endothelial cells revealed, together with a prominent pro‐angiogenic profile, a pro‐inflammatory signature characterized by the up‐regulation of pro‐inflammatory cytokine/chemokines and their receptors, endothelial cell adhesion molecules and members of the eicosanoid pathway. Real‐time quantitative PCR demonstrated early induction of most of the FGF2‐induced, inflammation‐related genes. Accordingly, chick embryo chorioallantoic membrane (CAM) and murine Matrigel plug angiogenesis assays demonstrated a significant monocyte/macrophage infiltrate in the areas of FGF2‐driven neovascularization. Similar results were obtained when the conditioned medium (CM) of FGF2‐stimulated endothelial cells was delivered onto the CAM, suggesting that FGF2‐upregulated chemoattractants mediate the inflammatory response. Importantly, FGF2‐triggered new blood vessel formation was significantly reduced in phosphatidylinositol 3‐kinase‐γ null mice exhibiting defective leucocyte migration or in clodronate liposome‐treated, macrophage‐depleted mice. Furthermore, the viral pan‐chemokine antagonist M3 inhibited the angiogenic and inflammatory responses induced by the CM of FGF2‐stimulated endothelial cells and impaired FGF2‐driven neovascularization in the CAM assay. These findings point to inflammatory chemokines as early mediators of FGF2‐driven angiogenesis and indicate a non‐redundant role for inflammatory cells in the neovascularization process elicited by the growth factor.
In vivo engineering of a human vasculature for bone tissue engineering applications
Authors: Steffens Lilian , Wenger Andreas , Stark G. Björn , Finkenzeller Günter 
Published: July 2008

AbstractThe neovascularization of three‐dimensional voluminous tissues, such as bone, represents an important challenge in tissue engineering applications. The formation of a preformed vascular plexus could maintain cell viability and promote vascularization after transplantation. We have developed a three‐dimensional spheroidal coculture system consisting of human primary endothelial cells and human primary osteoblasts (hOBs) to improve angiogenesis in bone tissue engineering applications. In this study, we investigated the survival and vascularization of the engineered implants in vivo. Endothelial cell spheroids were cocultured with hOBs in fibrin and seeded into scaffolds consisting of processed bovine cancellous bone (PBCB). The cell‐seeded scaffolds were evaluated for their angiogenic potential in two different in vivo assays: the chick embryo chorioallantoic membrane (CAM) model and the severe combined immunodeficiency disorder (SCID) mouse model. In both assays, the development of a complex three‐dimensional network of perfused human neovessels could be detected. After subcutaneous implantation into immunodeficient mice, the newly formed human vasculature was stabilized by the recruitment of murine smooth muscle α‐actin‐positive mural cells and anastomoses with the mouse vasculature. We conclude that this endothelial cell spheroid system can be used to create a network of functional perfused blood vessels in vivo. The finding that this process takes place with high efficacy in the presence of co‐implanted primary osteoblasts and in an osteoconductive environment provided by the PBCB scaffold, suggests that this system may be suitable for improving vascularization in bone tissue engineering.
The cleavage of thyroid‐stimulating hormone receptor is dependent on cell–cell contacts and regulates the hormonal stimulation of phospholipase c
Authors: Hai Mai‐Thu Vu , Radu Aurelian , Ghinea Nicolae 
Published: July 2008

AbstractThyroid‐stimulating hormone receptor (TSHR) consists of a hormone‐binding extracellular subunit and a seven‐transmembrane spanning subunit that interacts with the G proteins Gαs and Gαq. The two subunits, generated by proteolytic cleavage of a single polypeptide chain, are held together by disulphide bridges. The receptor is completely cleaved in thyroid tissue, while in cultured cells (thyrocytes and non‐thyroid cells) the cleaved and uncleaved forms coexist. The reasons for these divergent data are not understood. Here we provide an explanation by showing that cleavage depends on cell–cell contacts. An almost complete cleavage was observed in confluent cells, while in sparse cells most of the receptor was in the uncleaved form. We also show that coupling of TSHR to Gαq (as measured by inositolphosphate generation) is markedly reduced when the receptor is not cleaved. In contrast, coupling to Gαs [as measured by cyclic adenosine 3′,5′‐monophosphate (cAMP) synthesis] is unaffected by cleavage of the receptor. These results suggest that the cell–cell contacts are necessary for cleavage of the receptor, which acts as a regulatory step in inositolphosphate production via phospholipase C activation. The latter observation was confirmed using cells that express the uncleavable mutant TSHR‐Δ50‐NET, for which the TSH‐stimulated inositolphosphate production was completely abolished.
Orthodontic extraction of mandibular third molar to avoid nerve injury and promote periodontal healing
Authors: Alessandri Bonetti Giulio , Incerti Parenti Serena , Checchi Luigi 
Published: July 2008

AbstractAim: Impacted mandibular third molar extraction is a common procedure in oral surgery, not without risk of nerve injury and periodontal defects on the distal aspect of the adjacent second molar. The “orthodontic extraction” is proposed as a method to avoid mandibular nerve injury during the extraction of a deeply embedded third molar and to prevent or limit such periodontal problems.Material and Methods: A 28‐year‐old man presented a deeply impacted left mandibular third molar that required extraction. Radiographs revealed a very slight quantity of bone at the distal surface of the adjacent second molar. The third molar was extruded according to the “orthodontic extraction” technique. A 3‐month retention phase elapsed to ensure adequate bone maturation and the tooth was finally extracted.Results: No neurological complications occurred. A minimal residual bone defect at the distal surface of the adjacent second molar was detected radiographically both post‐operatively and at the 3‐year follow‐up.Conclusions: Orthodontic extraction makes third molar removal easier and has no neurological risk. This procedure, followed by a 3‐month retention phase, appears to be effective in preventing or limiting the development of periodontal problems on the distal aspect of the adjacent second molar.
Granuloma annulare – a manifestation of infection with Borrelia?
Authors: Ziemer Mirjana , Grabner Tanja , Eisendle Klaus , Baltaci Mehmet , Zelger Bernhard 
Published: July 2008

Background:  Among the theories of origin of granuloma annulare (GA) are those of infection. Reports gave raise to the assumption that there is evidence for Borrelia as the causing agent.Methods:  To assess the evidence for infection with Borrelia in GA, tissue sections were stained with a polyclonal Borrelia antibody. With focus‐floating microscopy (FFM), slides were scanned at a 200‐ to 400‐fold magnification. Part of the material was also investigated with a Borrelia‐specific polymerase chain reaction (PCR).Results:  A total of 157 biopsies of GA have been investigated. Using FFM, Borrelia were detected in 127 cases of GA (80.9%). Borrelia were more prominent in localized (85.2%) than in diffuse GA (62.1%). In 27 cases of GA analysed by PCR, Borrelia‐specific DNA could be detected in only one case (3.7%), but was positive in 21 cases by FFM (77.8%). About 93.3% of 15 control cases of borreliosis were positive with FFM and 46.7% with PCR, while all controls other than borreliosis remained negative for spirochetes.Conclusion:  FFM is a reliable method to show Borrelia in tissue sections of GA, which is more sensitive than PCR. This underlines the possibility that Borrelia are involved specifically in the aetiology and pathogenesis of GA.
Evaluation of skin biopsies for fungal infections: role of routine fungal staining
Authors: Mohan Harsh , Bal Amanjit , Aulakh Rakhi 
Published: July 2008

Background:  The diagnosis of cutaneous fungal infection is usually made on clinical examination of the lesion and direct microscopic examination of skin scrapings with potassium hydroxide. Histopathological examination is rarely required to confirm dermatophytic infections. There is often a discord between the clinical and histopathological findings and many times clinical appearance can have a poor histopathological correlation.Methods:  This retrospective study was carried out on all skin biopsies received in a period of 1 year. The clinical details of all cases were retrieved and slides were reviewed. Routine fungal staining periodic acid‐Schiff (PAS) stain was performed in all cases.Results:  Of 403 skin biopsies received in 1 year, material for further staining was available in 338. On re‐examining the slides stained with PAS stain, fungi were identified in 34 cases (10%), of which fungal infection had been suspected clinically in five cases.Conclusions:  Use of routine stains like PAS can help to reach a correct diagnosis and initiate appropriate treatment. Fungal staining should be done in skin biopsies with non‐specific clinical details and microscopic findings for best patient management.
Androgen receptor overexpression in Becker nevus: histopathologic and immunohistochemical analysis
Authors: Kim Young Jin , Han Jae Ho , Kang Hee Young , Lee Eun‐So , Kim You Chan 
Published: July 2008

Background:  Becker nevus (BN) is a unilateral, hairy, pigmented cutaneous hamartoma that frequently appears in adolescence. Several features of BN suggest that increased androgen sensitivity plays a role in its pathogenesis. There have been only a few studies of histopathologic and immunohistochemical characteristics of BN, and the etiopathogenesis has not been fully established.Methods:  Two‐millimeter punch biopsies were taken from lesional and perilesional normal skin of 30 patients diagnosed as having BN. Fifteen skin samples each of lentigo and café au lait spots were used as controls. The sections were stained with hematoxylin‐eosin, Fontana‐Masson, antibodies to NKI/beteb, MART‐1 (Melanoma Antigen Recognized by T cells), S‐100 protein and androgen receptor (AR).Results:  Histopathologic features of BN showed frequent acanthosis, papillomatosis, keratotic plugging, irregular rete ridge elongation and flattening in the epidermis. Especially, the shape of the rete ridges in BN had a relatively characteristic appearance, which was the fusion of more than two adjacent rete ridges. Melanocyte counts were significantly increased in BN skin. The extent of AR expression was significantly higher in the epidermis of BN.Conclusions:  Our study indicates that there may be an association between AR and BN, but additional studies will be required to evaluate this further.
Comparison of CD23 staining patterns in Merkel cell carcinoma and non‐cutaneous small cell carcinoma
Authors: Carvalho Jason , Fullen Douglas , Lowe Lori , Su Lyndon , Ma Linglei 
Published: July 2008

Background:  During our daily practice, we observed that cluster designation 23 (CD23) (clone BU38) labels Merkel cells in normal skin. In this study, we examined the expression of CD23 in Merkel cell carcinoma (MCC) and assessed its usefulness in distinguishing MCC from non‐cutaneous small cell carcinoma (SMCC).Methods:  Immunohistochemical staining of CD23 was performed on a total of 33 MCCs, 22 SMCCs and 5 carcinoid tumors.Results:  CD23 reactivity was present in 32 of 33 (97%) MCCs, 18 of 22 (82%) SMCCs and 5 of 5 (100%) carcinoid tumors. In MCC, 19 cases (59%) showed a predominance of perinuclear dot‐like staining similar to cytokeratin 20, 3 (9%) showed mostly cytoplasmic staining and 10 (31%) displayed a combination of perinuclear dot‐like and cytoplasmic staining. In contrast, all CD23‐positive SMCCs and carcinoid tumors showed a diffuse cytoplasmic staining. There was a significant difference in the CD23 staining patterns between MCC and SMCC (p < 0.0001).Conclusion:  CD23 is expressed in the majority of MCC, SMCC and carcinoid tumor irrespective of clinical outcome. The distinct punctate CD23 staining for MCC may be helpful in differentiating it from SMCC. To our knowledge, this is the first study to show the expression of CD23 in neuroendocrine tumors.
Disease burden of chronic lymphocytic leukaemia within the European Union
Authors: Watson Louise , Wyld Peter , Catovsky Daniel 
Published: July 2008

AbstractObjective:  Whilst Chronic lymphocytic leukaemia (CLL) is considered a rare disease, to our knowledge, the current prevalence of CLL within the European Union (EU) member states is not published. Understanding the number of individuals with CLL is vital to assess disease burden within the wider population.Methods:  Using 2002 data from the International Agency for Research on Cancer, we estimated the number of individuals with CLL (ICD‐10 C91.1) from those reported for all leukaemias (C91–95) and extrapolated the figures by the population increase within the EU between 2002 and 2006, the last year with fully updated community population estimates. One‐ and 5‐yr partial prevalence estimates are reported (i.e. the number of individuals still living 1–5 yr post‐diagnosis). We then applied proportional estimates from the literature to assess those requiring immediate treatment, those under observation and their likely progression rates.Results:  We found that within the 27 EU states plus Iceland, Norway and Lichtenstein, 1‐ and 5‐yr CLL partial prevalence estimates totalled approximately 13 952 and 46 633 individuals respectively in 2006. By applying Binet staging to the 1‐yr estimate, 40% of patients will be stage B/C and require immediate treatment. Thus, 5581 individuals may be treated within the first year of diagnosis. Of the 60% (8371) under observation, by 5 yr up to 33% (2763) may have more advanced disease with increased risk of mortality.Conclusion:  Whilst CLL is a rare disease, the number of individuals burdened by the disease within the EU is considerable and thousands of patients require treatment and physician care, which has cost implications for member states.
Hematopoietic progenitor cell colony growth differentiates chronic myelomonocytic leukemia from reactive monocytosis
Authors: Birrer Angelika , Jusufi Florije , Bernimoulin Michael , Tichelli André , Gratwohl Alois , Nissen‐Druey Catherine , Dirnhofer Stephan , Meyer‐Monard Sandrine , Stern Martin 
Published: July 2008

AbstractIn the absence of a cytogenetic abnormality or overt dysplasia, chronic myelomonocytic leukemia (CMML) may be difficult to be distinguished from reactive monocytosis. We have previously described a typical growth pattern in CMML patients, i.e., ‘pseudonormal’ colonies resembling granulocytic colonies but consisting entirely of monocytic cells when stained. To study the utility of the colony forming unit cell assay (CFU‐C) as a diagnostic tool in patients with monocytosis, we analyzed a cohort of 48 consecutive patients referred to our institution with peripheral blood monocytosis. Thirty‐six patients fulfilled the WHO criteria for CMML; 12 were diagnosed with reactive monocytosis. Of the patients with CMML, 28 showed pseudonormal growth with or without leukemic cluster growth, another four showed exclusively leukemic growth. None of the patients with reactive monocytosis showed either leukemic or pseudonormal growth. With a specificity of 100% and a sensitivity of 89%, the CFU‐C assay has a unique potential to distinguish CMML from reactive monocytosis.
CD4+ T‐regulatory cells: toward therapy for human diseases
Authors: Allan Sarah E. , Broady Raewyn , Gregori Silvia , Himmel Megan E. , Locke Natasha , Roncarolo Maria Grazia , Bacchetta Rosa , Levings Megan K. 
Published: July 2008

SummaryT‐regulatory cells (Tregs) have a fundamental role in the establishment and maintenance of peripheral tolerance. There is now compelling evidence that deficits in the numbers and/or function of different types of Tregs can lead to autoimmunity, allergy, and graft rejection, whereas an over‐abundance of Tregs can inhibit anti‐tumor and anti‐pathogen immunity. Experimental models in mice have demonstrated that manipulating the numbers and/or function of Tregs can decrease pathology in a wide range of contexts, including transplantation, autoimmunity, and cancer, and it is widely assumed that similar approaches will be possible in humans. Research into how Tregs can be manipulated therapeutically in humans is most advanced for two main types of CD4+ Tregs: forkhead box protein 3 (FOXP3)+ Tregs and interleukin‐10‐producing type 1 Tregs (Tr1 cells). The aim of this review is to highlight current information on the characteristics of human FOXP3+ Tregs and Tr1 cells that make them an attractive therapeutic target. We discuss the progress and limitations that must be overcome to develop methods to enhance Tregs in vivo, expand or induce them in vitro for adoptive transfer, and/or inhibit their function in vivo. Although many technical and theoretical challenges remain, the next decade will see the first clinical trials testing whether Treg‐based therapies are effective in humans.
A randomized clinical trial of chlorhexidine in the maintenance of oral candidiasis‐free period in HIV infection
Authors: Nittayananta W , DeRouen TA , Arirachakaran P , Laothumthut T , Pangsomboon K , Petsantad S , Vuddhakul V , Sriplung H , Jaruratanasirikul S , Martin MD 
Published: July 2008

Objective:  To determine if chlorhexidine can be used as an intervention to prolong the time to relapse of oral candidiasis.Subjects and methods:  A double‐blinded randomized clinical trial was performed in 75 HIV/AIDS subjects with oral candidiasis. Clotrimazole troche was prescribed, and the subjects were re‐examined every 2 weeks until the lesions were completely eradicated. The subjects were then randomly divided into two groups; 0.12% chlorhexidine (n = 37, aged 22–52 years, mean 34 years) and 0.9% normal saline (n = 38, aged 22–55 years, mean 38 years). They were re‐examined every 2 weeks until the next episode was observed.Results:  The time to recurrence of oral candidiasis between the chlorhexidine and the saline group was not statistically significant (P > 0.05). The following variables were significantly associated with the time of recurrence; frequency of antifungal therapy (P = 0.011), total lymphocyte (P = 0.017), alcohol consumption (P = 0.043), and candidiasis on gingiva (P = 0.048). The subjects with lower lymphocyte showed shorter oral candidiasis‐free periods (P = 0.034).Conclusions:  Chlorhexidine showed a small but not statistically significant effect in maintenance of oral candidiasis‐free period. This lack of significance may be due to the small sample size. Further study should be performed to better assess the size of the effect, or to confirm our findings.
Expression of human β‐defensin ‐1, ‐2, and ‐3 in non‐inflamed pseudocyst, mucoceles
Authors: Frederic MK , Yamaai T , Mizukawa N , Kaneda Y , Katase N , Gunduz M , Nagatsuka H , Sugahara T 
Published: July 2008

Objectives and design:  The expressions of human beta defensin‐1 (HBD‐1), ‐2 (HBD‐2) and ‐3 (HBD‐3) in non‐inflamed pseudocysts such as mucoceles were investigated immunohistochemically in this study.Materials and methods:  Mucocele specimens were obtained from 21 patients. The expression of HBDs was studied immunohistochemically by using antibodies directed against HBD‐1, ‐2, and ‐3. Statistical analyses were carried out on serial sections stained with antibodies.Results:  Cells expressing HBDs were found in mucoceles. The expression of HBD‐2 was observed in floating cells in all the specimens, whereas HBD‐1 and HBD‐3‐expressing cells were detected in 93% and 73% of the mucoceles, respectively. The HBD‐2 signal was the most intense and the HBD‐3 signal intensity was weaker than that of HBD‐1. HBDs were expressed in neutrophils and in other floating cells. Interestingly, the signal intensity and the population of positive cells located close to the centers of cysts were higher than those located in the peripheral areas of cysts.Conclusion:  The expression of HBDs was found even in non‐inflamed pseudocysts such as mucoceles. These results suggest that an unknown mechanism not involved in biophylaxis for the expression of HBDs may exist.
Social Implications of Overweight and Obesity in Children
Authors: Edmunds Laurel D. 
Published: July 2008

PURPOSE.  To elucidate some of the social impacts that overweight and obesity in children has on families. Healthcare practitioners may be unaware of these impacts if not similarly affected. DESIGN.  Qualitative semistructured, interview‐based study. METHODS.  A purposive sample of parents (n = 58) with overweight and obese children (n = 48) from three areas in the United Kingdom was used. Analysis was thematic and iterative, underpinned by Grounded Theory.RESULTS.  There are many social situations that have an impact on the child directly (stigmatization), on parents (blame), and on the family in general (being ostracized). PRACTICE IMPLICATIONS.  Seeing the child and his/her family in a broader context with improved understanding of the complexity of raising an overweight child.
Dietary and Physical Activity Patterns: Examining Fathers’ Perspectives
Authors: Snethen Julia A. , Broome Marion E. , Kelber Sheryl , Leicht Sandra , Joachim Jackie , Goretzke Maribeth 
Published: July 2008

PURPOSE.  Obesity adversely affects children, yet limited information is available on the familial environmental influence of fathers. The purpose of this study was to examine fathers’ influences on their children's eating and activity patterns. DESIGN AND METHODS. Participants for this mixed methods study was a convenience sample of 51 multi‐ethnic fathers of children 8–12 years of age, who completed surveys addressing dietary and physical activity behaviors. RESULTS.  An association was found between fathers’ and children's weight status. Half the children snacked without parental guidance. PRACTICE IMPLICATIONS.  Nurses need to assist children and their families to develop effective weight management strategies.
Genetic diversity pattern of Stipa purpurea populations in the hinterland of Qinghai–Tibet Plateau
Authors: Liu W.‐S. , Dong M. , Song Z.‐P , Wei W 
Published: July 2008

Abstract Stipa purpurea is among constructive endemic species in alpine meadow and steppe on the Qinghai–Tibet Plateau. To reveal the genetic diversity of this species and its relationship with geographic distribution pattern, we sampled eight populations across a northward transect with an increasing aridity gradient in the hinterland of Qinghai–Tibet Plateau. Their genetic diversity was quantified using eight intersimple sequence repeat (ISSR) primers. We found that S. purpurea had relatively low genetic diversity (He = 0.135) but significant genetic differentiation among populations (Gst = 0.391), indicating relatively more genetic diversity retained within populations. A Mantel test revealed a significant relationship between genetic and geographic distance in the S. purpurea populations. The genetic diversity tended to decrease with increasing latitude and longitude, while no significant relationship was found between genetic diversity and altitude, suggesting the possible influences of humidity and temperature on genetic diversity of alpine plant. We propose conservation measures for this plant on the plateau.