bluuebunny/crossref_metadata_2025_split huggingface dataset:
The importance of gd T cells in the resolution of pathogen‐induced inflammatory immune responses
Authors: Carding Simon R. , Egan Paul J. 
Published: March 2003

Summary: The aim of our research is to determine the biological function of gd T lymphocytes and in particular the role they play in microbial immunity. Although evidence of gd T‐cell activation and expansion has been obtained from numerous infectious diseases, how they contribute to pathogen‐induced immune responses is still not clear. Based upon extensive studies of gd T‐cell involvement in the immune response to viral and bacterial pathogens in both mice and humans, we have uncovered evidence of their direct involvement in terminating host immune responses to infection and preventing chronic disease. We have identified an interaction between peripheral gd T cells and a population of activated, pro‐inflammatory macrophages elicited by infection that occurs late in the course of infection during or after pathogen clearance. As a result of this interaction, activated gd T cells acquire cytotoxic activity and kill the stimulatory macrophages, leading us to propose a model for gd T‐cell–macrophage interactions that contributes to macrophage homeostasis, the resolution of inflammatory immune responses, and prevention of chronic inflammatory disease.
Structure and biology of complement protein C3, a connecting link between innate and acquired immunity
Authors: Sahu Arvind , Lambris John D. 
Published: March 2003

Summary:Complement protein C3 is a central molecule in the complement system whose activation is essential for all the important functions performed by this system. After four decades of research it is now well established that C3 functions like a double‐edged sword: on the one hand it promotes phagocytosis, supports local inflammatory responses against pathogens, and instructs the adaptive immune response to select the appropriate antigens for a humoral response; on the other hand its unregulated activation leads to host cell damage. In addition, its interactions with the proteins of foreign pathogens may provide a mechanism by which these microorganisms evade complement attack. Therefore, a clear knowledge of the molecule and its interactions at the molecular level not only may allow the rational design of molecular adjuvants but may also lead to the development of complement inhibitors and new therapeutic agents against infectious diseases.A.S. is a Wellcome Trust Overseas Senior Research Fellow in Biomedical Science in India. This research was supported by National Institutes of Health grants AI 30040, GM 56698, HL28220, and AI 48487.
Strategies for target cell recognition by natural killer cells
Authors: Diefenbach Andreas , Raulet David H. 
Published: March 2003

Summary: Stimulation of natural killer (NK) cells is regulated by a complex balance of inhibitory and stimulatory receptors expressed by NK cells. However, the interaction of stimulatory receptors and their ligands is poorly understood. One stimulatory receptor, NKG2D, is expressed by all NK cells, stimulated CD8+ T cells, γδ T cells and macrophages. Recently, progress has been made in defining cellular ligands for NKG2D. Four different families of ligands have been identified in mice and humans, all of which are distantly related to MHC class I molecules. Some of the ligands are upregulated in transformed and infected cells, provoking an attack by the innate and adaptive immune systems. It appears that these “induced‐self” ligands recognized by the NKG2D receptor may be a precedent for a new strategy of target cell recognition by the immune system.The authors wish to thank Dennis Wolan for preprints and discussions on the manuscript. AD is a Physician Postdoctoral Fellow of the Howard Hughes Medical Institute.
Recombinant allergen molecules: tools to study effector cell activation
Authors: Valenta Rudolf , Kraft Dietrich 
Published: March 2003

Summary: The IgE antibody‐mediated activation of allergic effector cells is the key pathomechanism underlying the immediate symptoms of Type I allergy, a genetically determined hypersensitivity disease affecting 25% of the population. In recent years important environmental allergens and their epitopes have become available as structurally defined recombinant molecules. In addition, corresponding human monoclonal IgE and IgG antibodies have been isolated. This review summarizes data obtained regarding the three‐dimensional structure of allergens, their IgE epitopes and the recognition of allergens by IgE and IgG antibodies. In particular, we discuss results of recent in vitro and in vivo studies with defined allergen molecules, their epitopes and the corresponding antibodies which support the hypothesis that the density and geometrical arrangement of IgE epitopes on a particular allergen molecule may profoundly affect effector cell activation. If the structural requirements for effector cell activation can be delineated, it may be envisaged that, based on this knowledge, allergens can be converted into hypoallergenic immunogens by reorientation of IgE epitopes. Such allergen derivatives may be used for allergen‐specific immunotherapy with reduced risk of inducing anaphylactic side effects.The authors would like to thank Dr. Peter Valent, Department of Hematology, Vienna General Hospital, Austria, and Dr. Steven C. Almo, Department of Biochemistry, Albert Einstein College of Medicine, New York, USA, for fruitful collaboration regarding effector cell activation and structural biology, respectively. The skilful editorial assistance of Irmgard Lubelik is acknowledged. This work was supported by grant Y078 GEN of the Austrian Science Fund and by the ICP Program of the Austrian Federal Ministry for Education, Science and Culture.
Elemental signals regulating eosinophil accumulation in the lung
Authors: Foster Paul S. , Mould Arne W. , Yang Ming , Mackenzie Jason , Mattes Joerg , Hogan Simon P. , Mahalingam Surendran , Mckenzie Andrew N. J. , Rothenberg Marc E. , Young Ian G. , Matthaei Klaus I. , Webb Dianne C. 
Published: March 2003

Summary: In this review we identify the elemental signals that regulate eosinophil accumulation in the allergic lung. We show that there are two interwoven mechanisms for the accumulation of eosinophils in pulmonary tissues and that these mechanisms are linked to the development of airways hyperreactivity (AHR). Interleukin‐(IL)‐5 plays a critical role in the expansion of eosinophil pools in both the bone marrow and blood in response to allergen provocation of the airways. Secondly, IL‐4 and IL‐13 operate within the allergic lung to control the transmigration of eosinophils across the vascular bed into pulmonary tissues. This process exclusively promotes tissue accumulation of eosinophils. IL‐13 and IL‐4 probably act by activating eosinophil‐specific adhesion pathways and by regulating the production of IL‐5 and eotaxin in the lung compartment. IL‐5 and eotaxin co‐operate locally in pulmonary tissues to selectively and synergistically promote eosinophilia. Thus, IL‐5 acts systemically to induce eosinophilia and within tissues to promote local chemotactic signals. Regulation of IL‐5 and eotaxin levels within the lung by IL‐4 and IL‐13 allows Th2 cells to elegantly co‐ordinate tissue and peripheral eosinophilia. Whilst the inhibition of either the IL‐4/IL‐13 or IL‐5/ eotaxin pathways resulted in the abolition of tissue eosinophils and AHR, only depletion of IL‐5 and eotaxin concurrently results in marked attenuation of pulmonary inflammation. These data highlight the importance of targeting both IL‐5 and CCR3 signalling systems for the resolution of inflammation and AHR associated with asthma.S.M. is a Postdoctoral Fellow funded by a grant from the Human Frontiers Foundation to P.S.F. and M.E.R. J.M. is supported by the German Research Association (grant MA 2241/1‐1) and S.P.H by a NH&MRC CJ Martin Postdoctoral Fellowship.
The influence of the src‐family kinases, Lck and Fyn, on T cell differentiation, survival and activation
Authors: Zamoyska Rose , Basson Albert , Filby Andrew , Legname Giuseppe , Lovatt Matthew , Seddon Benedict 
Published: March 2003

Summary:The src‐family kinases p56lck (Lck) and p59fyn (Fyn) are expressed in T cells and are among the first signaling molecules to be activated downstream of the T cell receptor (TCR). Evidence is emerging that although closely related, these signaling molecules have discrete functions during development, maintenance and activation of peripheral T cells. For example, during thymopoiesis Lck is uniquely able to provide all the signals required for pre‐TCRβ selection, although Fyn can substitute for a subset of these. Positive selection of CD4 single‐positive (SP) cells is also critically dependent on the expression of Lck but not Fyn, while differentiation of CD8 SP cells proceeds relatively efficiently in the absence of Lck. In naïve peripheral T cells either Lck or Fyn can transmit TCR‐mediated survival signals, and yet only Lck is able to trigger TCR‐mediated expansion signals under conditions of lymphopenia. Stimulation of naïve T cells by antigenic stimuli is also severely compromised in the absence of Lck, but more subtly impaired by the absence of Fyn. We discuss recent experiments addressing how these two src‐kinase family members interface with downstream signaling pathways to regulate these diverse aspects of T cell behavior.
Five‐year survival predictive factors in patients with excessive alcohol intake and cirrhosis. Effect of alcoholic hepatitis, smoking and abstinence
Authors: Pessione F. , Ramond M‐J. , Peters L. , Pham B‐N. , Batel P. , Rueff B. , Valla D‐C. 
Published: March 2003

Abstract:  Aim: To evaluate 5‐year survival predictive factors in hospitalised patients with excessive alcohol intake and cirrhosis, including in a multivariate analysis the severity of the liver disease, gastrointestinal bleeding, concomitant viral B or C infection, smoking status, presence of alcoholic hepatitis at inclusion and abstinence from alcohol during follow‐up.Methods: In a non‐concurrent cohort study, 122 patients with excessive alcohol intake and cirrhosis were followed up at least five years or till death. Two patients were lost to follow‐up. Results: The 5‐year survival rates were 43% in the 122 patients and 66%, 50% and 25% in Child–Pugh class A, B and C patients, respectively. In multivariate analysis, age (P = 0.01), Child–Pugh score (P = 0.0001), gastrointestinal bleeding (P = 0.01), presence of HBs Ag and/or anti‐HCV (P = 0.03), smoking (P = 0.01), absence of histologically proven alcoholic hepatitis (P = 0.05) and persistent alcohol intake (P = 0.002) were associated with significantly increased risk ratios of death.Conclusions: In hospitalised patients with excessive alcohol intake and cirrhosis: (1) age, liver failure, gastrointestinal bleeding, concomitant viral B or C infection and persistent alcohol intake are independent poor prognostic markers, (2) smoking may contribute to the aggravation of cirrhosis, and (3) alcoholic hepatitis, being a potentially reversible cause of liver failure, has a favourable prognostic significance.
The unexplained survival of cells in oral cancer: what is the role of p53?
Authors: Whyte Donna A. , Broton Claire E. , Shillitoe Edward J. 
Published: March 2003

AbstractIn normal oral epithelium the cells divide, mature, differentiate, and die. This sequence is not normally followed in oral cancer. Instead, the death of the cells is somehow prevented, although the pathways toward cell death in normal oral epithelium and the defects in oral cancer are not well defined. However, several components in the system have been identified, and information on their interactions is becoming available. This review summarizes the evidence for cell death being due to apoptosis and the central role of thep53gene product in its regulation. Areas for future research are also identified.
Hepatocyte growth factor and c‐Met (HGF/c‐Met) in adenoid cystic carcinoma of the human salivary gland
Authors: Suzuki K. , Cheng J. , Watanabe Y. 
Published: March 2003

AbstractBackground:  Hepatocyte growth factor (HGF) enhances cell growth, morphogenesis, and scattering of various epithelial cells. The aim of this study was to evaluate the hypothesis that HGF/c‐Met plays a biological role in the invasive growth of adenoid cystic carcinoma (ACC).Methods:  Immunohistochemically, expression of HGF and its receptor c‐Met was examined in 15 cases of ACC. To examine the direct effects of HGF on ACC, cell line derived from of ACC (ACC3) was used. The expression of HGF and c‐met in ACC3 was investigated by RT‐PCR. Analysis of mechanisms of invasion was done by performing scattering assay and matrigel invasion chamber assay.Results:  Positive staining of HGF was found in all cases, and that of c‐Met was 67%. In ACC3, c‐met was expressed, but not HGF. Stimulation of ACC3 by rhHGF induced scattering and promoted invasion.Conclusion:  The present results suggest that HGF/c‐Met increases tumor cell scattering and may play a part in invasiveness of ACC.
Selection of antimicrobial agents in periodontal therapy
Authors: Slots Jørgen 
Published: March 2003

Background: The recognition over the past 3 decades of microbial specificity in periodontitis has afforded dental practitioners the ability to prevent and treat the disease with a variety of antimicrobial drugs. These include systemic antibiotics, topical antibiotics and topical antiseptics.Results: Systemic antibiotic therapy can be essential in eliminating pathogenic bacteria that invade gingival tissue and in helping control periodontal pathogens residing in various domains of the mouth from where they may translocate to periodontal sites. Frequently used periodontal combination antibiotic therapies are metronidazole‐amoxicillin (250–375 mg of each 3 × daily for 8 days) and metronidazole‐ciprofloxacin (500 mg of each 2 × daily for 8 days). Microbiological analysis helps determine the optimal antibiotic therapy and effectiveness of treatment. Topical antibiotics that are commercially available as controlled release devices suffer from several potential problems, including insufficient spectrum of antimicrobial activity in some periodontal polymicrobial infections, risks of producing an antibiotic resistant microbiota, and high acquisition costs. Topical antiseptics of relevance in periodontal treatment include 10% povidone‐iodine placed subgingivally by a syringe for 5 min, and 0.1% sodium hypochlorite solution applied subgingivally by patients using an irrigation device.Clinical implications: The present paper recommends periodontal treatment that includes a battery of professionally and patient‐administered antimicrobial agents (properly prescribed systemic antibiotics, povidone‐iodine and sodium hypochlorite subgingival irrigants, and chlorhexidine mouthrinse). Available chemotherapeutics can provide effective, safe, practical and affordable means of controlling subgingival colonization of periodontal pathogens and various types of periodontal disease.
Effects of a 2‐week treatment with pulsed monochromatic light in healthy pigs: a clinical and morphological study
Authors: Jensen‐Waern M. , Ekman S. 
Published: March 2003

Background: Pulsed monochromatic light (PML) is now used clinically for pain relief and wound healing in both human and veterinary practice. The purpose of this study was to evaluated the clinical and pathological effects of PML irradiation in an animal model, using healthy specific pathogen‐free pigs.Methods: After 2 weeks of habituation, one group of animals (n=9) underwent treatment with pulsating monochromatic infrared and red light while the control group (n=9) was left untreated. PML was given five times a week during a 2‐week period, and at each treatment the total radiant exposure was 6.3 J/cm2. At the completion of the study, all pigs were subjected to complete necropsy.Results: None of the animals showed any clinical signs of disease during the study period. The measured hematological and clinico‐chemical variables all showed values within the reference range and the daily weight gain was high in both the treatment and control groups (825 and 923 g/day, respectively). The pathological examination revealed no morphological differences between treated and non‐treated animals.Conclusion: In healthy pigs, no adverse effects of low‐energy photon therapy on the clinical state of health or on the morphology of different tissues were observed.
The effects of EGb 761 on lipid peroxide levels and superoxide dismutase activity in sunburn
Authors: Ozkur Mehtap Kilinc , Bozkurt Meral Sasoglu , Balabanli Barbaros , Aricioglu Aysel , Ilter Nilsel , Gürer Mehmet Ali , Inalöz H. Serhat 
Published: March 2003

Background/Purpose: Free oxygen radicals are involved in inflammatory skin reactions induced by ultraviolet B (UVB). In this study, the effect of a herbal antioxidant Ginkgo biloba extract (EGb 761) was investigated in UVB irradiated mice skin.Methods: The study was carried out on four groups of mice (n = 6 in each group). The first group was a control group (G1). The second group (G2) was only exposed to acute UVB irradiation. The third group (G3) received 100 mg/kg/day of EGb 761 orally for 5 days before UVB irradiation and the fourth group (G4) was given only a single dose of EGb 761 immediately after UVB irradiation. Eighteen hours after exposing to UVB, lipid peroxide levels, and superoxide dismutase (SOD) activities were studied and UVB damage was evaluated histopathologically according to ‘sun‐burn cell count’.Results: The SOD activities and Malondialdehyde (MDA) levels in G2, G3 and G4 were found to be decreased significantly when compared with G1 (P < 0.05). The SOD activities of G3 and G4 were higher when compared with G2 (P < 0.05). The number of sunburn cells (SBCs) was the highest in G2.Conclusions: Our results suggest that EGb 761 may have an important effect, both as a protective and therapeutic agent, in sunburn after UVB irradiation.
Skin cancer and ultraviolet‐B radiation under the Antarctic ozone hole: southern Chile, 1987–2000
Authors: Abarca Jaime F. , Casiccia Claudio C. 
Published: March 2003

Background:  Punta Arenas, Chile, the southernmost city in the world (53°S), with a population of 154 000, is located near the Antarctic ozone hole (AOH) and has been regularly affected by high levels of ultraviolet‐B (UV‐B) radiation each spring for the last 20 years. Large increases in UV‐B associated with the AOH have been measured with increases in UV‐B at 297 nm of up to 38 times those of similar days with normal ozone. Recently we reported significant increases in sunburns during the spring of 1999 on days with low ozone because of the AOH. Methods:
A surveillance of skin cancers occurring from 1987 to 2000 was performed. Age, sex, location, type of skin cancer and skin phototype were recorded. A Brewer Spectrophotometer was used in order to obtain in situ measurements of ozone and UV‐B. Total Ozone Mapping Spectrometer (TOMS) data from National Aeronautics and Space Administration (NASA) was used in order to establish pre‐ozone hole climatology. Results:
Ozone levels as low as 145 DU (Dobson Units) were recorded, a 56% decrease in ozone, and UV‐B levels up to 4.947 J/m2. These levels are close to summertime levels at mid latitudes. For the 14‐year period – from 1987 to 2000 – 173 cases of skin cancer were diagnosed, 65 during the first 7 years, 108 during the second, an increase of 66%. Cutaneous malignant melanoma (CMM), 19% of the cases, increased by 56%, raising the rate from 1.22 to 1.91 per 100 000. Non‐melanoma skin cancer (NMSC), 81% of the total, increased the rate from 5.43 to 7.94 per 100 000 (P < 0.05), a 46% increase. Patients with CMM and NMSC had skin phototypes I–II in 59% and 54% of cases, respectively. Days with more than 25% ozone loss occurred in 143 days during the last 20 springs. Significant increases of UV‐B were observed under ozone hole conditions, especially around 300 nm, the most carcinogenic wavelengths. Conclusions:  Highly unusual ozone loss and UV‐B increases have occurred in the Punta Arenas area over the past two decades resulting in the non‐photoadapted population being repeatedly exposed to an altered solar UV spectrum with a greater effectiveness for erythema and photocarcinogenesis. This phenomenon has not previously been reported over other populated areas and an additional increase in the skin cancer rate attributable to the AOH may be occurring. Research on the clinical and subclinical impact of these abnormalities is urgently needed.
Extracorporeal photochemotherapy for secondary chronic progressive multiple sclerosis: a pilot study
Authors: Besnier D. P. , Chabannes D. , Mussini J.‐M. G. , Dupas B. , Esnault V. L. M. 
Published: March 2003

Background/purpose:  Extracorporeal photochemotherapy (ECP) has been proposed for the treatment of various auto‐ and allo‐immune reactions. However, a standard ECP regimen did not significantly alter the course of chronic progressive multiple sclerosis (MS). We tested whether an intensive ECP treatment can affect the course of secondary chronic progressive form of MS.
Methods:
Five patients free of immunosuppression were included. Soluble 8‐MOP was added ex vivo to a mononuclear cell suspension obtained in a cell separator. This cellular suspension was then irradiated using an UVA irradiator and re‐infused into the patient. ECP was performed once a week for 6 weeks and then, depending on clinical evaluation, for a maximum of 6 months, with 2‐year follow‐up after treatment discontinuation. Scoring was performed with the Kurzke scale and EDSS by a single independent neurologist.Results: One patient was excluded because of recurrent attacks at the very beginning of treatment. Four patients completed the study: one exhibited clinical improvement and three remained stable during the first 6 months of treatment. However, all experienced relapse or worsening of the disease after discontinuation of ECP treatment.Conclusion:  Our intensive ECP treatment only transiently alters the course of the severe secondary chronic progressive form of MS, with rebound after treatment discontinuation.