bluuebunny/crossref_metadata_2025_split huggingface dataset:
The formation and functions of the 21‐ and 23‐kDa tyrosine‐phosphorylated TCR ζ subunits
Authors: Pitcher Lisa A. , Young Jennifer A. , Mathis Meredith A. , Wrage Philip C. , Bartók Beatrix , Van Oers Nicolai S. C. 
Published: March 2003

Summary:The interaction between the T cell receptor (TCR) and its cognate antigen/major histocompatibility complex (MHC) complex activates a cascade of intracellular protein phosphorylations within the T cell. The signals are initiated by the specific phosphorylation of two tyrosine residues located in a conserved sequence motif termed an ITAM (immune receptor‐based tyrosine activation motif). There are 10 ITAMs in the TCR complex, and 6 of these ITAMs are present in the TCR ζ homodimer. Following TCR stimulation, the TCR ζ subunit forms two tyrosine‐phosphorylated intermediates of 21‐ and 23‐kDa, respectively. The dramatic and diverse biological responses of T cells are proposed to be partly regulated by the relative ratios of the 21‐ vs. 23‐kDa phosphorylated forms of TCR ζ that are induced following TCR ligation. In this review, we describe a stepwise model of ζ phosphorylation required for the formation of these two phosphorylated derivatives. We describe the kinases and phosphatases controlling these phosphorylation processes. In addition, we present some preliminary findings from ongoing studies that discuss the contributions of each phosphorylated form of ζ on T cell development, TCR signaling, T cell anergy induction, and T cell survival.
Initiation of TCR signaling: regulation within CD3 dimers
Authors: Alarcón Balbino , Gil Diana , Delgado Pilar , Schamel Wolfgang W. A. 
Published: March 2003

Summary:The number of possible T cell activation outcomes resulting from T cell receptor (TCR) engagement suggests that the TCR is able to differentially activate a myriad of signaling pathways depending on the nature of the stimulus. The complex structural organization of the TCR itself could underlie this diversity of responses. Assembly and stoichiometric studies have helped us to shed some light on the initiation of TCR signaling. The TCR is composed of TCR and CD3 dimers. Changes in the interaction between CD3 subunits within the CD3 dimers and in the interaction of these dimers with the TCR heterodimer could be the triggering mechanism that initiates the first activation events. One of the hallmarks of these early changes in TCR conformation is the induced recruitment of the adapter protein Nck to a proline‐rich sequence of the cytoplasmic tail of CD3ε, but there may be others. According to our most recent observations, the TCR is organized in pre‐existing clusters within plasma membrane microdomains, exhibiting a complexity above and beyond that of dimer composition complexity. How the presence of TCR in clusters influences TCR avidity and propagation of TCR signals is something that has yet to be investigated.
Record review of baboons with histologically confirmed endometriosis in a large established colony
Authors: Jr Dick E.J. , Hubbard G.B. , Martin L.J. , Leland M.M. 
Published: March 2003

Abstract: Spontaneous endometriosis was diagnosed in 43 baboons over a 14‐year period. Thirty‐seven have died; five remain alive; one was sold and lost to follow‐up. The average age at diagnosis was 17.2 years; 29 (67%) were between 12 and 21 years of age. Fifteen (35%) were diagnosed by biopsy and received surgical excision of the endometriotic tissue; four of these were identified during caesarian section, confirming one prior report of endometriosis in pregnant animals. Twenty‐eight (65%) were diagnosed at or shortly preceding necropsy. When diagnosed by a palpable abdominal mass, there was a significantly greater likelihood the animal died or was killed as a result of complications of endometriosis. When diagnosis was at necropsy, there was a significantly greater likelihood that the animal died from causes unrelated to endometriosis. Early identification with surgical removal appears to provide a benefit for both survival and delivering offspring after diagnosis. In twenty‐one baboons (49%), endometriosis affected multiple sites within the peritoneal cavity. In the remaining baboons, lesions were more localized. Ovarian involvement was seen in sixteen (37%) of these baboons. This paper is the first to describe significant ovarian involvement in baboons, previously considered a limitation of the usefulness of this species as an animal model. We also describe the first reported endometriosis seeding of an abdominal surgery scar in a baboon. Many of these baboons were middle aged, had few or no offspring, or had evidence of a long duration of uninterrupted menstrual cycles, consistent with risk factors for women. Endometriosis was an incidental finding in 17 (40%) of these baboons, consistent with previous reports of minimal endometriosis as a common asymptomatic finding in baboons and in women. Overall, endometriosis in baboons presents a spontaneously occurring animal model that shares important features with the disease in women and the rhesus macaque.
Altered cytokeratin expression during chemoprevention of experimental hamster buccal pouch carcinogenesis by garlic
Authors: Balasenthil S. , Rao K. S. , Nagini S. 
Published: March 2003

AbstractBackground: Cytokeratins (also known as keratins (K)) are members of the family of intermediate filaments and form major components of the mammalian epithelial cell cytoskeleton. Cytokeratins have emerged as reliable cellular markers of oral cancer development and chemoprevention because of their abundance, stability and high antigenicity.Methods: We investigated the effect of aqueous garlic extract on cytokeratin expression during 7,12‐dimethylbenz[a]anthracene (DMBA)‐induced hamster buccal pouch (HBP) carcinogenesis. Hamsters were divided into four groups of six animals. Animals in group 1 were painted with a 0.5% solution of DMBA in liquid paraffin, on the right buccal pouches, three times a week for 14 weeks. Group 2 animals were painted with DMBA as in group 1 and also received 250 mg/kg body weight aqueous garlic extract orally on alternate days to the DMBA application. Group 3 animals received garlic extract only, as in group 2. Group 4 animals received neither DMBA nor garlic extract and served as the control. The hamsters were killed after an experimental period of 14 weeks.Results: Cytokeratin expression was studied using human monoclonal antibodies AE1 and AE3, which react with type I and II keratins. In DMBA‐induced squamous cell carcinomas, decreased expression of high molecular weight keratins was observed. Administration of garlic extract to animals painted with DMBA suppressed HBP carcinomas and restored normal cytokeratin expression.Conclusion: The results of the present study suggest that inhibition of HBP carcinogenesis by garlic may be due to its regulatory effects on differentiation, tumour invasiveness, migratory and metastatic potential. We suggest that one of the mechanisms of tumour inhibition by garlic is an influence on cellular differentiation.
Burning mouth syndrome (BMS): double blind controlled study of alpha‐lipoic acid (thioctic acid) therapy
Authors: Femiano F. , Scully C. 
Published: March 2003

Abstract Background: Burning mouth syndrome (BMS) has features of a neuropathy and could be related to the production of the toxic free radicals that are released in stress situations. Alpha‐lipoic acid is an antioxidant able to increase the levels of intracellular glutathione and eliminate free radicals. This study aimed to examine the effectiveness of alpha‐lipoic acid in the therapy of BMS. Method: This was a double blind, controlled study conducted for two months on 60 patients with constant BMS. Comparing alpha‐lipoic acid (test) with cellulose starch (placebo), there was no laboratory evidence of deficiencies in iron, vitamins or thyroid function and no hyperglycaemia. Results and Conclusion: Following treatment with alpha‐lipoic acid, there was a significant symptomatic improvement, compared with placebo, with the majority showing at least some improvement after 2 months, thus supporting the hypothesis that burning mouth syndrome is a neuropathy. This improvement was maintained in over 70% of patients at the 1 year follow‐up.
The relationship between MMPs and pH in whole saliva of radiated head and neck cancer patients
Authors: Vuotila T. , Ylikontiola L. , Sorsa T. , Luoto H. , Hanemaaijer R. , Salo T. , Tjäderhane L. 
Published: March 2003

AbstractBackground: Radiation therapy for head and neck tumour patients may lead to decreased salivary flow, oral mucosal lesions and increased caries experience. Salivary matrix metalloproteinases (MMPs) may participate in the pathogenesis of mucosal lesions and dentinal caries. The aims of this study were: (i) to assay the presence, molecular forms and proteolytic activity of MMP‐8 (collagenase‐2) and MMP‐9 (gelatinase B) in the whole saliva of head and neck cancer patients having radiation therapy; (ii) to see whether salivary pH affects the activity of MMP‐8 and MMP‐9; and (iii) to find out the possible connection between MMP‐8 and MMP‐9 with the eruption of oral mucosal lesions during radiation therapy.Methods: The whole saliva samples of 39 head and neck cancer patients having radiation therapy were collected before, during and after radiation therapy, and saliva flow rate, pH, buffer capacity, Streptococcus mutans, Lactobacillus and Candida albicans were measured. Any oral mucosal lesions were examined during each visit. The levels of MMP‐8 were measured by immunofluorometric assay (IFMA) and the presence of different MMP‐8 forms was analysed using Western immunoblotting. The presence and molecular forms of MMP‐9 were analyzed by gelatin zymography. MMP‐9 capture activity assay was used to determine the APMA‐activated MMP‐9 activity (total) and the endogenously active MMP‐9 (free activity).Results: Salivary flow rate, buffer capacity and pH decreased, and the levels of Lactobacilli increased significantly, during the first half of the radiation therapy. The endogenously activated salivary MMP‐9 correlated with low salivary pH (P = 0.013). No connection was found between the oral mucosal lesions and salivary MMP‐8 or MMP‐9.Conclusions: In this study, salivary MMP‐8 or MMP‐9 did not correlate with the presence of radiation induced oral mucosal lesions, but the activation of MMP‐9 may be dependent on pH.
Interleukin‐1β induces interleukin‐6 mRNA expression and protein production in synovial cells from human temporomandibular joint
Authors: Ogura Naomi , Tobe Makiko , Sakamaki Hiroyuki , Kujiraoka Hiroaki , Akiba Masakazu , Abiko Yoshimitsu , Nagura Hideaki 
Published: March 2003

AbstractBackground:  Interleukin (IL)‐1β and IL‐6 were found to be elevated in fluid from the temporomandibular joint (TMJ), although the source of these cytokines was not elucidated. There is little known about the function and response of synovial cells in the TMJ. The purpose of this study was to prepare cultured human synovial cells (HTS cells) from the TMJ and to investigate IL‐6 production in HTS cells incubated with IL‐1β.Methods:  HTS cells were isolated from temporomandibular joint synovial tissue using an outgrowth method and then cultured in Ham's F12 medium containing 10% fetal bovine serum. The HTS cells were treated with or without IL‐1β for 3, 6, 9 and 24 h. IL‐6 and soluble IL‐6 receptor (sIL‐6R) levels in cultured supernatant were measured by ELISA. IL‐6 mRNA expression was investigated using immunocytochemistry and RT‐PCR.Results:  HTS cells were morphologically heterogeneous. IL‐1β increased IL‐6 production in HTS cells. In those treated with IL‐1β, several cells were strongly stained in the cytoplasm around the nucleus, while several cells were weakly stained in this area. IL‐1β also stimulated IL‐6 mRNA expression. In contrast, sIL‐6R could not be detected in cells treated with or without IL‐1β.Conclusions:  IL‐1β increased IL‐6 production in synovial cells resulting from an increase in IL‐6 mRNA expression. Enhanced production of IL‐6, which is associated with bone resorption and inflammatory response, seems to be related to the progression of TMJ disorders.
Calcifying odontogenic cyst: clinicopathological features and immunohistochemical profile of 10 cases
Authors: Fregnani Eduardo Rodrigues , Pires Fábio Ramôa , Quezada Rivera Daniel , Shih Ie Ming , Vargas Pablo Agustin , De Almeida Oslei Paes 
Published: March 2003

AbstractBackground:  Calcifying odontogenic cyst (COC) is an uncommon odontogenic lesion with few studies describing its immunohistochemical profile and proliferative activity reported in the literature.Methods:  Clinical and histological features and immunohistochemical expression of cytokeratins, Mel‐CAM (CD146), bcl‐2, PCNA and ki‐67, in 10 cases of COC were studied.Results:  All 10 cases affected the maxilla, eight intraosseous and two peripheral. Five central cases were cystic and three were cystic associated with odontoma, and the two extraosseous showed solid histological pattern; immunohistochemistry was positive for cytokeratins 8, 14, 19, AE1/AE3 and 34βE12 and bcl‐2 in all cases, and Mel‐CAM in six cases. Proliferative activity was greater in the epithelium of central cystic COC in relation to COC associated with odontoma and peripheral lesions.Conclusion:  Calcifying odontogenic cysts showed odontogenic cytokeratin profile and bcl‐2 and Mel‐CAM expression indicate that these proteins may be involved in the development of COC. There were no recurrences after surgery, irrespective of their proliferative activity.
Also sprach Confusius: Ein vergessenes Kapitel aus Nietzsches Wiener Frührezeption
Authors: Benne Christian 
Published: March 2003

Blick in die Zukunft. – Was für ein Bein wird der Uebermensch haben? Ein Tanzbein? Tschandalagedanke! Ein Ueberbein! (Also sprach Confusius, 49)Der Artikel beschreibt ein wiederentdecktes Dokument aus der Frühzeit der Nietzsche‐Rezeption. Es handelt sich um die anonym erschienene Nietzsche‐Parodie zweier Wiener Journalisten, die durch ihre satirische Technik eindrucksvoll die Verbreitung Nietzsches schon zu Beginn der 1890er Jahre erkennen lässt. Neben Darstellung und Bewertung von Also sprach Confusius wird den verschlungenen Wegen der frühen Nietzsche‐Rezeption nachgegangen, die nicht zuletzt über Dänemark führten. Nicht die Intensität der Rezeption unterschied die Aufnahme Nietzsches in Österreich und Deutschland, sondern die Art und Weise.
Combined TUNEL and TRAP methods suggest that apoptotic bone cells are inside vacuoles of alveolar bone osteoclasts in young rats
Authors: Cerri P. S. , Boabaid F. , Katchburian E. 
Published: March 2003

Although it is generally accepted that osteoclasts breakdown and resorb bone matrix, the possibility that they may also be able to engulf apoptotic osteoblasts/lining cells and/or osteocytes remains controversial. Apoptosis of osteoblasts/ lining cells and/or osteocytes and interactions between these cells and osteoclasts are extremely rapid events that are difficult to observe in vivo. A suitable in vivo model for studying these events is the alveolar bone of young rats because it is continuously undergoing intense resorption/remodeling. Thus, sections of aldehyde fixed alveolar bone of young rats were stained by the combined terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling (TUNEL) method and the tartrate‐resistant acid phosphatase (TRAP) method for the simultaneous visualization of apoptotic cells and osteoclasts in the same section.The combined TUNEL and TRAP reactions, in the same section, greatly facilitated visualization of relationship between osteoclasts and apoptotic bone cells during alveolar bone remodeling. Our results showed that several TRAP‐positive osteoclasts exhibited large vacuoles containing TUNEL positive apoptotic structures, probably derived from osteoblasts/lining cells and/or osteocytes. These results support the idea that alveolar bone osteoclasts are able to internalize dying apoptotic bone cells.
Efficacy of ultraviolet A1 phototherapy on the expression of bcl‐2 in atopic dermatitis and cutaneous T‐cell lymphoma in vivo: a comparison study
Authors: Breuckmann F. , Von Kobyletzki G. , Avermaete A. , Kreuter A. , Altmeyer P. 
Published: March 2003

Background/Purpose: Atopic dermatitis (AD) is characterized immunohistochemically by a high number of skin infiltrating T‐helper cells (CD4 + ). In most cases cutaneous T‐cell lymphoma (CTCL) is characterized by a malignant proliferation of CD4 +  T‐helper lymphocytes. The purpose of our study was to evaluate the extent of anti‐apoptotic effects in patients suffering from AD or CTCL, respectively, which may contribute to the prolonged inflammation. Furthermore, we investigated whether medium‐dose ultraviolet A1 (UVA1) phototherapy is able to modulate the expression of bcl‐2 within the dermal inflammatory infiltrate.Methods: In order to enumerate bcl‐2+ cells pre‐ and post‐therapeutic punch skin biopsies of ten patients with AD and five patients with CTCL were stained immunohistochemically for features of apoptosis using a monoclonal antibody detecting bcl‐2.Results: Both AD and CTCL sections revealed a high percentage of bcl‐2+ cells within the dermal perivascular infiltrate before therapy. After the successful treatment using medium‐dose UVA1 phototherapy this percentage could be decreased significantly.Conclusion: Both T‐cell‐derived skin diseases exhibit an increased pre‐therapeutic number of bcl‐2+ cells. After medium‐dose UVA1 phototherapy the substantial improvement of the skin condition was linked to a significant decrease of the dermal bcl‐2+ cell count. Moreover, we could demonstrate a remarkable correlation referring to the decrease and staining pattern of bcl‐2 between these two groups as well as within each group. Because the bcl‐2 protein is known to act as an apoptosis inhibitor, its pre‐therapeutic increase may provide the persistent cutaneous inflammatory reaction in T‐cell‐derived skin diseases. Additionally, the post‐therapeutic reduction of bcl‐2+ cells might represent a key mechanism of medium‐dose UVA1 phototherapy.
Analytic quantification of phototype‐related regional skin complexion
Authors: Hermanns Jean François , Petit Ludivine , Hermanns‐Lê Trinh , Piérard Gérald E. 
Published: March 2003

Background/aims: Narrow‐band spectrophotometry that yields melanin (M) and erythema (E) indexes is a convenient method for assessing skin colour. The objective of the study was to assess the phenotype‐associated body site differences in skin complexion.Method: The Mexameter MX16 was used to record the skin colour in 137 subjects. Evaluations were made on the inner arm, volar forearm, dorsal forearm and forehead.Results: The inner arm and volar forearm had similar values for each of the colorimetric values. The dorsal forearm exhibited the highest M values, and the forehead had the highest E values. Significant positive linear correlations were found between M values from the distinct body sites. The E values showed a correlation only between the inner arm and the volar forearm.Conclusion: Regional skin colour differences are obvious. Sun‐exposed skin does not react in the same way on the forearm and forehead. Regional variations in M can be predicted from the innate M value. In contrast, the regional variability in E is highly variable among subjects.
Effects of ageing on dermal echogenicity
Authors: Gniadecka M. 
Published: March 2003

Background/aims: Changes in the dermis associated with ageing can be detected by high‐frequency skin ultrasonography. In photoaged skin, this technique shows a subepidermal low echogenic band (SLEB) that is probably an ultrasound manifestation of elastosis and oedema in the papillary dermis. Since some authors found an association between age and SLEB thickness or its echogenicity on exposed sites, it has been proposed to use these parameters to quantify skin photoageing.Methods: To determine whether SLEB can be used as a quantitative marker of ageing, its prevalence was determined on forearm skin in a group of 55 individuals (age 18–57 years). The size of SLEB has been measured by quantifying the number of low echogenic pixels in the subepidermal area, which is an accurate method for assessing SLEB severity.Results: The prevalence of SLEB increased with age, but SLEB was also present in young subjects. The echogenicity of the subepidermal area did not show any age dependence. However, when a ratio of echogenicity between upper and lower dermis was calculated, a linear dependence on age was found.Conclusions: This study indicates that skin echogenicity measured as a ratio between the upper and lower dermis may be used to objectively estimate photoageing.
A noninvasive method to assess skin irritation and compromised skin conditions using simple tape adsorption of molecular markers of inflammation
Authors: Perkins Mary A. , Osterhues Marcia A. , Farage Miranda A. , Robinson Michael K. 
Published: March 2003

Background/aims: We have developed a simple noninvasive method to assess inflammatory changes in human skin, even in the absence of visible clinical irritation. Our approach is based on a simple tape (Sebutape®) adsorption method to recover molecular mediators of skin inflammation (e.g., cytokines). This procedure has been used to investigate baseline cytokine levels on skin, to assess normal skin condition and to evaluate changes due to chemical insult, existing dermatitis, or sun exposure.Methods: In clinical studies, Sebutape was applied to normal appearing uncompromised skin, as well as to compromised (diaper or heat rash), chemically treated (sodium laurel sulfate), or sun‐exposed skin. Sebutape was applied to the skin for a 1 min collection interval. Tapes were extracted in saline using a 10 min sonication, and the extracts were analyzed for human interleukin‐1α (IL‐1α), IL‐1 receptor antagonist (IL‐1RA) and IL‐8 using commercial immunoassay test kits. The cytokine levels recovered from each tape extract were normalized to total protein (TP) levels. In infant product use tests, the severity of skin irritation (diaper and heat rash or erythema) was also assessed using a visual grading scale.Results: The method itself caused minimal, if any, skin damage. Additionally, Sebutape was shown to quantitatively adsorb detectable levels of cytokine from normal‐appearing (control) or compromised (e.g., rashed or chemically treated) skin. In infant studies, significant increases in IL‐1α levels were found in skin exhibiting diaper rash, heat rash and erythema compared with normal appearing control skin sites. When these results were normalized to total protein levels recovered from each tape, the significance was maintained. A positive correlation (r2=0.82) existed between IL‐1RA levels and diaper rash severity. Significant increases in IL‐8 levels were recovered from diaper rash versus control skin sites. There were differences in baseline cytokine levels in normal skin related to body site and sun exposure. The IL‐1RA/IL‐1α ratios for sun‐exposed skin of the face and lower leg were significantly (P<0.05) higher (3–6‐fold) than those for skin sites that typically receive minimal sun exposure (i.e., underarm, upper leg and upper back). There was a significant increase in IL‐1α and a directional increase in IL‐8 levels in adult skin sites treated with the irritant, sodium lauryl sulfate, even in the absence of visible skin irritation (erythema).Conclusion: Our results demonstrate that this method is a useful noninvasive technique for assessing skin inflammatory events. In addition, the method is simple and easily applied in a clinical setting, whether on infants or adults.