bluuebunny/crossref_metadata_2025_split huggingface dataset:
TNFα blockade prevents the development of inflammatory bowel disease in HLA‐B27 transgenic rats
Authors: Milia Anna Franca , Manetti Mirko , Generini Sergio , Polidori Lucia , Benelli Gemma , Cinelli Marina , Messerini Luca , Ibba‐Manneschi Lidia , Matucci‐Cerinic Marco 
Published: March 2008

AbstractRats transgenic for HLA‐B27 and human β2microglobulin (B27TR) develop a multi‐systemic disease resembling inflammatory bowel disease (IBD) and spondyloarthritis. TNFα has a crucial role in chronic inflammation. Our objective was to evaluate the effect of anti‐TNFα treatment on spontaneous IBD in B27TR. Nine‐week‐old B27TR received monoclonal anti‐TNFα or an isotypic IgG2a,k up to age of 18 weeks. A second group was monitored up to 18 weeks and then randomly assigned to anti‐TNFα or IgG2 a,k treatment. Each rat was monitored for clinical IBD manifestations. After sacrifice, the colon was examined for pathological changes. TNFα receptors (TNF‐R1, TNF‐R2), Fas/Fas‐L expression and apoptosis were evaluated. IgG2a,k‐treated and untreated B27TR presented signs of IBD at 11 weeks, whereas in anti‐TNFα‐treated B27TR no IBD signs were detected. In the late treatment, IBD signs improved after 1 week. Histopathological analysis of IgG2a,k‐treated B27TR colon showed inflammatory signs that were widely prevented by early anti‐TNFα treatment. Late treatment did not significantly reduce inflammation. TNF‐R1 was weakly expressed in intestinal epithelial cells of IgG2a,k‐treated B27TR, while it was comparable to controls in anti‐TNFα‐treated animals. TNF‐R2 immunopositivity was strongly evident in IgG2a,k‐treated B27TR, whereas was absent in anti‐TNFα‐treated rats. RT‐PCR confirmed these results. IgG2a,k‐treated B27TR showed, at 18 weeks, few Fas‐positive cells and an increase of Fas‐L‐positive cells. At 27 weeks, Fas‐/Fas‐L‐positive cell number was significantly low. Anti‐TNFα treatment increased Fas‐L expression, whereas Fas increased only with the early treatment. TNFα blockade is effective in preventing inflammation in early phase of IBD, maintaining the homeostatic balance of apoptosis.
Temporal PTEN inactivation causes proliferation of saphenous vein smooth muscle cells of human CABG conduits
Authors: Mitra Amit K. , Jia Guanghong , Gangahar Deepak M. , Agrawal Devendra K. 
Published: March 2008

AbstractInternal mammary artery (IMA) coronary artery bypass grafts (CABG) are remarkably resistant to intimal hyperplasia (IH) as compared to saphenous vein (SV) grafts following aorto‐coronary anastomosis. The reason behind this puzzling difference still remains an enigma. In this study, we examined the effects of IGF‐1 stimulation on the PI3K‐AKT/PKB pathway mediating proliferation of smooth muscle cells (SMCs) of IMA and SV origin and the specific contribution of phosphatase and tensin homologue (PTEN) in regulating the IGF‐1‐PI3K‐AKT/PKB axis under these conditions. Mitogenic activation with IGF‐1, time‐dependently stimulated the phosphorylation of PI3K and AKT/PKB in the SV SMCs to a much greater extent than the IMA. Conversely, PTEN was found to be significantly more active in IMA SMCs. Transient overexpression of PTEN in SMCs of SV and IMA inhibited AKT/PKB activity and upstream of AKT/PKB, caused a reduction of IGF‐1 receptors. Downstream, PTEN overexpression in SV SMCs induced the transactivation of tumour suppressor protein p53 by down‐regulating the expression of its inhibitor MDM2. However, PTEN overexpression had no significant effect on MDM2 and p53 expression in IMA SMCs. PTEN overexpression inhibited IGF‐1‐induced SMC proliferation in both SV and IMA. PTEN suppression, induced by siRNA transfection of IMA SMCs diminished the negative regulation of PI3K‐PKB signalling leading to greater proliferative response induced by IGF‐1 stimulation. Thus, we show for the first time that early inactivation of PTEN in SV SMCs leads to temporally increased activity of the pro‐hyperplasia PI3K‐AKT/PKB pathway leading to IH‐induced vein graft occlusion. Therefore, modulation of the PI3K‐AKT/PKB pathway via PTEN might be a novel and effective strategy in combating SV graft failure following CABG.
The induction of bone formation by smart biphasic hydroxyapatite tricalcium phosphate biomimetic matrices in the non‐human primate Papio ursinus
Authors: Ripamonti U. , Richter P. W. , Nilen R. W. N. , Renton L. 
Published: March 2008

AbstractLong‐term studies in the non‐human primate Chacma baboon Papio ursinus were set to investigate the induction of bone formation by biphasic hydroxyapatite/p‐tricalcium phosphate (HA/β‐TCP) biomimetic matrices. HA/β‐TCP biomimetic matrices in a pre‐sinter ratio (wt%) of 40/60 and 20/80, respectively, were sintered and implanted in the rectus abdominis and in calvarial defects of four adult baboons. The post‐sinter phase content ratios were 19/81 and 4/96, respectively. Morphological analyses on day 90 and 365 showed significant induction of bone formation within concavities of the biomimetic matrices with substantial bone formation by induction and resorption/dissolution of the implanted matrices. One year after implantation in calvarial defects, 4/96 biphasic biomimetic constructs showed prominent induction of bone formation with significant dissolution of the implanted scaffolds. The implanted smart biomimetic matrices induce de novo bone formation even in the absence of exogenously applied osteogenic proteins of the transforming growth factor‐β(TGF‐β) superfamily. The induction of bone formation biomimetizes the remodelling cycle of the cortico‐cancellous bone of primates whereby resorption lacunae, pits and concavities cut by osteoclastogenesis are regulators of bone formation by induction. The concavities assembled in HA/β‐TCP biomimetic bioceramics are endowed with multifunctional pleiotropic self‐assembly capacities initiating and promoting angiogenesis and bone formation by induction. Resident mesenchymal cells differentiate into osteoblastic cell lines expressing, secreting and embedding osteogenic soluble molecular signals of the TGF‐β superfamily within the concavities of the biomimetic matrices initiating bone formation as a secondary response.
Can the reporting of adverse skin reactions to cosmetics be improved? A prospective clinical study using a structured protocol
Authors: Berne Berit , Tammela Monica , Färm Gunilla , Inerot Annica , Lindberg Magnus 
Published: March 2008

Background:  The use of cosmetics is rising, and adverse reactions to these products are increasing. In Sweden, the Medical Products Agency (MPA) keeps a voluntary reporting system for such adverse reactions. However, the reporting is sparse, consisting almost only of cases with test‐proven allergic contact dermatitis, thus under‐reporting the more common irritant reactions.Objective:  The aim of the study was to try to improve the reporting system.Patients and Methods:  Dermatologists at 3 dermatology departments used a structured protocol during the clinical investigation of 151 consecutive patients reporting skin reactions to cosmetics. The protocol included symptoms, signs, affected body site, suspected products, and final diagnosis after patch testing. Based on clinical data and patch test results, a causality assessment for each product was made according to a protocol used at the MPA.Results:  Allergic contact dermatitis was found in 28% of the patients, and irritant reactions were equally common at 27%.Conclusions:  Using this structured protocol, the cases of irritant dermatitis were also reported, and it is recommended that such a protocol is used as a standard to improve the reporting of adverse reactions to skin care products.
Skin conditions in instrumental musicians: a self‐reported survey
Authors: Gambichler Thilo , Uzun Akin , Boms Stefanie , Altmeyer Peter , Altenmüller Eckart 
Published: March 2008

Background:  Instrumental musicians are a risk group for a variety of skin conditions.Objectives:  To determine the frequency and risk factors of instrument‐related skin disorders in musicians.Method:  We mailed an 11‐item survey to 19 German universities of music and performing arts.Results:  412 musicians returned the completed questionnaire, of whom 21.6% (89/412) had an instrument‐related skin disorder including callosities (52/89; 58.4%), contact dermatitis (CD; 17/89; 19.1%), fiddler’s neck (17/89; 19.1%), and erosion (3/89; 3.4%). Allergic CD (13/17; 76.5%) was most frequently reported in violinists and violists. Of 116 violinists and violists, 17 (14.7%) suffered from fiddler’s neck. String and plucking instrumentalists most frequently reported callosities (61/89; 68.5%) and skin problems (32/37; 86.5%). Instrument‐related skin disorders were significantly associated with high practice frequencies (P = 0.022) and a professional status (P = 0.001).Conclusions:  Callosities and CD were the most commonly reported skin changes in the respondents. Both callosities and skin problems such as CD and fiddler’s neck are significantly associated with high practice frequencies and professional status. Our data indicate that among those returning the questionnaires, string players and plucking instrumentalists seem to be at highest risk of developing skin problems when compared with players of other musical instruments.
Reduced frequency of atopic dermatitis in quinoline‐allergic patients: the ‘hapten‐atopy hypothesis’
Authors: McFadden John P. , White Jonathan M. L. 
Published: March 2008

Background:  While allergy to food proteins is almost exclusively found in association with atopy, it has been our experience that contact allergy to some contact allergens/haptens with both cutaneous and gastrointestinal exposures is reduced in atopic dermatitis (AD) patients as a group.Objective:  To assess the contact allergy rates of two classes of antimicrobial haptens, one with both cutaneous and gastrointestinal exposures (quinolines) and one with only significant cutaneous exposure (aminoglycosides), with respect to the presence or absence of AD.Methods:  Contact allergy rates to neomycin (aminoglycoside) and quinoline mix/clioquinol in patients attending the St John’s Institute of Dermatology for diagnostic patch testing were retrospectively analysed; current AD and history of AD were noted.Results:  In comparison to neomycin‐allergic subjects, there was a highly significant negative association between quinoline contact allergy and current presence of AD (P = 0.0028); negative association between quinoline contact allergy and a history of AD did not reach significance (P = 0.07).Conclusions:  In comparison to an antimicrobial with no significant gastrointestinal exposure (neomycin), contact allergy to quinolines is negatively associated with the presence of AD. This is in contrast to food protein allergy, which is strongly associated with atopy. Possible explanations could include (i) confounding factors or (ii) AD patients are efficient at orally tolerising haptens and inefficient at orally tolerising proteins, secondary to their atopic status or (iii) oral tolerance of haptens antagonizes tolerance of food proteins and also leads to an immunological shift towards atopy (hapten‐atopy hypothesis).
Patients with vulval pruritus: patch test results
Authors: Utaş Serap , Ferahbaş Ayten , Yıldız Sinem 
Published: March 2008

Background:  Persistent vulval pruritus is a frequent problem and patients may not show signs of a primary vulval dermatosis. Allergic contact sensitivity is an important factor in such patients but may also occur as a secondary event in women with vulval dermatoses.Objectives:  We aim to describe women with vulval pruritus who were evaluated for vulval dermatoses. We patch tested to help define or exclude allergens.Methods:  In a 3‐year period, 50 women with vulval pruritus were examined for existence of vulval dermatosis. All the patients were patch tested to the European Baseline Series, medicaments, preservatives, vehicles, cosmetics and products they routinely used.Results:  Ages of the patients ranged from 22 to 62 years (mean 39.9 ± 9 years) and duration of the diseases ranged from 0.5–360 months (mean 56.1 ± 65.6 months). 52% of the women had at least 1 positive patch test. 8 patients (16%) had 1 or more relevant allergic positive reactions. The relevant allergens were usually cosmetics, preservatives and medicaments.Conclusions:  Women with vulval pruritus were patch tested to help define or rule our allergens. Contact allergy incidence in these patients is high. The relevant allergens were usually cosmetics, preservatives and medicaments.
In vitro characterization of a monoclonal IgGκ from a patient with planar xanthomatosis*
Authors: Horne McDonald K. , Merryman Paula , Cullinane Ann , Remaley Alan T. 
Published: March 2008

AbstractObjective:  To characterize a monoclonal IgGκ (MAb) from a patient with planar xanthoma that precipitated with serum lipids at reduced temperature.Methods:  The molecular weight (Mr), sensitivity to proteases, and glycosylation of the purified MAb were analyzed. The specificity of the MAb was tested by measuring cryoprecipitation with pure high‐ (HDL) and low‐density (LDL) lipoproteins. The effect of choline, phosphocholine, and glycerol 3‐phosphate on the precipitation temperature of LDL by the MAb was studied.Results:  The MAb was larger than normal IgG due to hyperglycosylation of the MAb light chain. It formed cryoprecipitates with pure HDL and LDL as well as the lipids extracted from these lipoproteins. Fab fragments of the MAb lowered the temperature of its precipitation with LDL. Choline, phosphocholine, and glycerol 3‐phosphate also lower the precipitation temperature.Conclusion:  This is the first human IgG reported with apparent specificity for phosphocholine antigens. Its precipitation with lipids at reduced temperature suggests that it recognizes conformations of phospholipid head groups that develop below core body temperature.
Identification of HLA‐A2 restricted T‐cell epitopes within the conserved region of the immunoglobulin G heavy‐chain in patients with multiple myeloma
Authors: Belle Sebastian , Han Fang , Condomines Maud , Christensen Olaf , Witzens‐Harig Mathias , Kasper Bernd , Kleist Christian , Terness Peter , Moos Marion , Cremer Friedrich , Hose Dirk , Ho Anthony D. , Goldschmidt Hartmut , Klein Bernard , Hundemer Michael 
Published: March 2008

AbstractObjective:  The aim of this study is the identification of HLA‐A2 restricted T‐cell epitopes in the conserved region of the immunoglobulin‐G‐heavy‐chain (IgGH) that can be used for immunotherapy in multiple myeloma (MM) patients.Methods:  After the IgGH gene sequence was scanned for HLA‐A2 restricted T‐cell epitopes with a high binding affinity to the MHC‐I‐complex, promising nona‐peptides were synthesized. Peptide specific CD8 +  T‐cells were generated from peripheral blood mononuclear cells (PBMC) of healthy donors (HD) and patients with MM using peptide pulsed dendritic cells (DC) in vitro. The activation and cytotoxicity of CD8 +  T‐cells was analyzed by IFN‐α ELISpot‐assay and 51Chromium release‐assay. HLA‐A2 restriction was proven by blocking T‐cell activation with anti‐HLA‐A2 antibodies.Results:  Two HLA‐A2 restricted T‐cell epitopes–TLVTVSSAS derived from the IgGH‐framework‐region 4 (FR4) and LMISRTPEV from the constant region (CR)‐induced expansion of specific CD8 +  T‐cells from PBMC in two of three (TLVTVSSAS) and one of three (LMISRTPEV) HD respectively. Specific T‐cells were induced from PBMC in two of six (TLVTVSSAS) and eight of 19 (LMISRTPEV) patients with MM. Specific CD8 +  T‐cells also lysed peptide‐pulsed target cells in 51Chromium release‐assay. LMISRTPEV specific CD8 + T‐cells from MM patients lysed specifically the HLA‐A2 +  IgG myeloma cell line XG‐6.Conclusion:  We identified two HLA‐A2 restricted T‐cell epitopes–TLVTVSSAS and LMISRTPEV–which can yield an expansion of CD8 +  T‐cells with the ability to kill peptide‐loaded target cells and HLA‐A2 +  IgG+ myeloma cells. We conclude that TLVTVSSAS and LMISRTPEV could be T‐cell epitopes for immunotherapy in MM patients.
Topically applied growth factors change skin cytoplasmic creatine kinase activity and distribution and produce abnormal keratinocyte differentiation in murine skin
Authors: Zemtsov Alexander , Montalvo‐Lugo Victor 
Published: March 2008

Background/purpose: The skin has a functional and active phosphocreatine (PCR)/creatine kinase (CPK) system that regenerates adenosine triphosphate energy reserves during periods of ischemia. The objective of this study was to evaluate how topically applied growth factors affect CPK activity and distribution, and what histological changes growth factors induce in murine skin.Methods: Epidermal growth factor (EGF), transforming growth factor α (TGF‐α) and suramin (growth factor inhibitor) were applied to murine skin for nine days before mice were sacrificed and CPK level and distributions were measured.Results: TGF‐α considerably increased CPK activity. Both EGF and TGF‐α induced a CPK MM to CPK BB transition and histologically induced abnormal differentiation of keratinocytes.Conclusion: The skin PCR/CPK system is affected by growth factors. Furthermore, this system appears to play an important role, both in the normal physiology of skin and pathophysiological conditions such as psoriasis and carcinogenesis.
Point‐spread imaging for measurement of skin translucency and scattering
Authors: Jiang Zhi‐xing , Kaplan Peter D. 
Published: March 2008

Background/purpose: The translucency of skin has long been identified as an important cue for healthy and youthful looking skin. There is currently no universal definition for skin translucency let alone a measurement method. We propose that skin translucency is the light scattering beneath skin surface. We demonstrate the use of polarization gated point spreading imaging for non‐invasive, in vivo measurement of the translucency and the reduced scattering coefficient of skin.Methods: We developed a polarization‐gated point‐spread imaging system to measure the spread of the incident pencil‐thin laser beam on the skin. Skin translucency was calculated as the spread of the laser beam. From the measurement of the shift of the light diffuse center from the light injection point, the reduced scattering coefficient of the skin was calculated. We validated the measurement technique with milk as an in vitro model for skin.Results and conclusion: The measured of milk solution was found to be linearly proportional to the milk concentration, in agreement with Beer's law. The calculated translucency decreased as the milk concentration increased or as the reduced scattering coefficient increased. It was also found that the translucency decreased as the absorption coefficient of the milk solution increased. The measured translucency of a set of custom made clay tiles correlated well with the consumer perception of the incremental ranking of the translucency. In vivo measurement of skin translucency and the reduced scattering coefficient were carried out on several volunteers. The measured reduced scattering coefficient was in agreement with those in the literature. The measured skin translucency for different skin ethnicities of Caucasian, North Asian, South Asian and African American were in line with the expectation that skin translucency decreases as the skin color gets darker.
Visualizing nuclei in skin cryosections: viable options to 4′6‐diamidino‐2‐phenylindol for confocal laser microscopy
Authors: Gläser K. , Wilke K. , Wepf R. , Biel S. S. 
Published: March 2008

Background: Visualization of nuclei in skin (cryo‐) sections is essential for both, rapid overview and reliable orientation within skin samples. Therefore, nuclear staining is a very common counterstain for immunohistochemical studies of human skin as this nuclear staining precisely depicts the cellular distribution within the epidermis. Moreover, it clearly shows the epidermal–dermal border as well as the transition zone between the living and the cornified layers of the epidermis. For standard epifluorescence microscopy, 4′6‐diamidino‐2‐phenylindol (DAPI) is commonly used. For confocal laser scanning microscopy (CLSM), however, DAPI is often not suitable because its excitation maximum is in the ultraviolet (UV) range (Exmax 359 nm) when bound to DNA, and UV lasers and the corresponding optics are not part of CLSM standard configuration.Methods: In order to find an adequate DAPI substitute that is excitable with standard visible light lasers, the following nuclear stains were tested: LOLO™‐1 iodide (Exmax 565 nm), TOTO®‐3 iodide (Exmax 642 nm), LO‐PRO™‐1 iodide (Exmax 567 nm), SYTO® 84 (Exmax 567 nm), SYTO® 85 (Exmax 567 nm), SYTOX® Green (Exmax 488 nm) and SYTOX® Orange (Exmax 547 nm), Propidium iodide (Exmax 535 nm). Besides optimal concentration and incubation time, following criteria were also evaluated: photobleaching, background, e.g. cytoplasmic staining of RNA, and sensitivity to different fixation conditions (unfixed, IEM fixation, PLP fixation and PFA fixation).Results: According to these criteria Sytox® Green showed the best overall staining score and can be used for variously fixed skin samples and shows a distinct and stable green nuclear fluorescence.
Border detection in dermoscopy images using statistical region merging
Authors: Emre Celebi M. , Kingravi Hassan A. , Iyatomi Hitoshi , Alp Aslandogan Y. , Stoecker William V. , Moss Randy H. , Malters Joseph M. , Grichnik James M. , Marghoob Ashfaq A. , Rabinovitz Harold S. , Menzies Scott W. 
Published: March 2008

Background: As a result of advances in skin imaging technology and the development of suitable image processing techniques, during the last decade, there has been a significant increase of interest in the computer‐aided diagnosis of melanoma. Automated border detection is one of the most important steps in this procedure, because the accuracy of the subsequent steps crucially depends on it.Methods: In this article, we present a fast and unsupervised approach to border detection in dermoscopy images of pigmented skin lesions based on the statistical region merging algorithm.Results: The method is tested on a set of 90 dermoscopy images. The border detection error is quantified by a metric in which three sets of dermatologist‐determined borders are used as the ground‐truth. The proposed method is compared with four state‐of‐the‐art automated methods (orientation‐sensitive fuzzy c‐means, dermatologist‐like tumor extraction algorithm, meanshift clustering, and the modified JSEG method).Conclusion: The results demonstrate that the method presented here achieves both fast and accurate border detection in dermoscopy images.
Diagnostic image analysis of malignant melanoma in in vivo confocal laser‐scanning microscopy: a preliminary study
Authors: Gerger Armin , Wiltgen Marco , Langsenlehner Uwe , Richtig Erika , Horn Michael , Weger Wolfgang , Ahlgrimm‐Siess Verena , Hofmann‐Wellenhof Rainer , Samonigg Hellmut , Smolle Josef 
Published: March 2008

Background/purpose: In this study we assessed the applicability of image analysis and a machine learning algorithm on diagnostic discrimination of benign and malignant melanocytic skin tumours in in vivo confocal laser‐scanning microscopy (CLSM).Methods: A total of 857 CLSM tumour images including 408 benign nevi and 449 melanoma images was evaluated. Image analysis was based on features of the wavelet transform. For classification purposes we used a classification tree software (CART). Moreover, automated image analysis results were compared with the prediction success of an independent human observer.Results: CART analysis of the whole set of CLSM tumour images correctly classified 97.55% and 96.32% of melanoma and nevi images. In contrast, sensitivity and specificity of 85.52% and 80.15% could be reached by the human observer. When the image set was randomly divided into a learning (67% of the images) and a test set (33% of the images), overall 97.31% and 81.03% of the tumour images in the learning and test set could be classified correctly by the CART procedure.Conclusion: Provided automated decisions can be used as a second opinion. This can be valuable in assisting diagnostic decisions in this new and exciting imaging technique.