bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular pathogenesis of human cytomegalovirus infection
Authors: Rasmussen L. 
Published: March 2003

Abstract:Despite progress in diagnosis and treatment of human cytomegalovirus (CMV) infection, we do not understand why, in hosts with comparable levels of immunosuppression, some CMV infections result in symptomatic CMV disease while others are limited to asymptomatic virus shedding with no discernible clinical consequences. CMV viral detection and quantification are useful for identifying those at highest risk, but do not consistently predict clinical outcome. Factors such as host genotype and immune response are active areas of research. However, the importance of CMV strain variability, recognized since 1976, is now receiving attention. Advances in technology that allow the rapid sequencing of viral DNA for purposes of strain characterization have fueled the renewed interest. The focus of this review will be to summarize our evolving knowledge of CMV strain variability and to document where possible a potential relationship to strain virulence. Studies with the UL55 (gB) envelope glycoprotein will be emphasized because of the ability to clearly identify naturally occurring variants, as well as the increasing number of reports that there are differences in biological activities that may contribute to virulence 1.
Mechanisms of human cytomegalovirus (HCMV) (re)activation and its impact on organ transplant patients
Authors: Reinke P. , Prösch S. , Kern F. , Volk H.‐D. 
Published: March 2003

Abstract:Human cytomegalovirus (HCMV) infection plays an important role in transplant patients. Its impact is both direct and indirect. This review focuses on new aspects of HCMV (re)activation and HCMV related pathology, particularly HCMV‐associated renal allograft injury. During the last two years we have learned that HCMV is more frequently (re)activated, even in healthy people, than previously expected. Inflammatory as well as stress mediators and some drugs may (re)activate the virus by using distinct intracellular pathways. Commonly, HCMV (re)activation is accompanied by HCMV antigenemia/DNAemia, suggesting that precursor cells in the bone marrow play an important role as a reservoir of latent virus. However, local HCMV (re)activation (colon, lung) without detection of active HCMV infection in the peripheral blood is possible. In healthy people a sufficient type 1 T‐cell response controls the active HCMV infection, while in patients with severe immune deficiency (AIDS, high‐dose immunosuppression) the virus can spread in an uncontrolled fashion and induce ‘classic’ HCMV disease. In patients with moderate immune deficiency (e.g. long‐term transplant patients on low‐dose immunosuppression) virus spreading is controlled but the elimination of cells harboring the active virus may be insufficient. The resulting persistent HCMV antigenemia may induce chronic inflammatory processes leading to tissue injury, particularly in the allograft. Therefore, antiviral therapy may be useful in patients suffering from graft deterioration with otherwise clinically symptomless HCMV infection. HCMV‐related immune deficiency with an increased risk of developing bacterial/fungal superinfections is frequently seen in patients with symptomatic HCMV disease but not in asymptomatic CMV antigenemia. The risk of developing superinfections can be predicted by flow‐cytometric monitoring of peripheral blood monocytes.
Toxoplasma gondii pneumonia in liver transplantation: survival after a severe case of reactivation
Authors: Barcán L.A. , Dallurzo M.L. , Clara L.O. , Valledor A. , Macías S. , Zorkin E. , Gerona S. , Livellara B. , Barcán L.A. , Dallurzo M.L. , Clara L.O. , Valledor A. , Macías S. , Zorkin E. , Gerona S. , Livellara B. 
Published: March 2003

Abstract: Toxoplasmosis is an infrequent infection in solid organ transplantation, except in heart transplantation, where the grafting of a positive organ in a negative recipient transmits the infection in a high percentage of cases, in the absence of prophylaxis.We report a case of pneumonia by Toxoplasma gondii in a woman who received a liver transplant and had pre‐transplant positive serology. Diagnosis was made by cytologic examination of bronchoalveolar lavage fluid, where the parasite was observed with hematoxylin–eosin and Giemsa staining. That finding was confirmed by direct immunofluorescence and positive polymerase chain reaction. The patient had a favorable outcome, although she had not initially received first‐choice drugs. This was a case of severe illness secondary to reactivation of Toxoplasma infection, diagnosed pre‐mortem and with a favorable outcome. Duration of treatment and need for secondary prophylaxis in these patients are discussed in the literature. Although infrequent, toxoplasmosis must be considered among the differential diagnoses of pulmonary infiltrates in solid organ transplantation.
Compstatin, a peptide inhibitor of C3, prolongs survival of ex vivo perfused pig xenografts
Authors: Fiane Arnt E. , Mollnes Tom E. , Videm VIBEKE , Hovig TORSTEIN , Høgåsen Kolbjørn , Mellbye Ove J. , Spruce LYNN , Moore William T. , Sahu ARVIND , Lambris John D. 
Published: March 2003

Fiane AE, Mollnes TE, Videm V, Hovig T, Høgåsen K, Mellbye OJ, Spruce L, Moore WT, Sahu A, Lambris JD. Compstatin, a peptide inhibitor of C3, prolongs survival of ex vivo perfused xenografts. Xenotransplantation 1999; 6: 000‐000 ©Munksgaard, CopenhagenCompstatin, a newly described C3‐binding peptide, inhibits complement activation by blocking C3 convertase‐mediated cleavage of C3. As the complement activation is an essential part of the rejection reaction, we evaluated the ability of Compstatin to delay or prevent hyperacute rejection in an ex vivo xenograft model. Porcine kidneys were perfused with fresh human blood containing either Compstatin (n=6) or a control agent (n=6). Graft survival and activation of complement, leukocytes and platelets both in the fluid phase and in the tissue were examined. The survival of the Compstatin‐perfused kidneys (median, 380 min) was significantly (P=0.0036) longer than that of the controls (median, 90 min). The classical complement pathway (C1rs‐C1inhibitor and C4bc) was significantly and equally activated in both groups during the first 60 min. C3 activation products increased fivefold and terminal complement complex eightfold in the control group, but no increase occurred in the Compstatin group during this period. Immunohistochemistry showed less C3 and fibrin deposition and immuno‐electron microscopy showed less terminal SC5b‐9 complement complex deposition in the Compstatin group. A significant change in total white cells, neutrophils, myeloperoxidase, and expression of the surface activation markers CD11b (CR3) and CD35 (CR1) and CD62 L (
l‐selectin) was observed in both groups. Leukocyte activation was lower in the Compstatin group but the difference was not statistically significant. There were no differences in platelet counts, thrombospondin, soluble P‐selectin or β‐thromboglobulin between the groups. We conclude that Compstatin prolongs graft survival and suggest that it may be a useful agent for attenuating hyperacute rejection by inhibiting C3 and thus terminal complement pathway activation.
Pre‐transplant analysis of accommodation in donor pigs
Authors: Beschorner William E. , Shearon C. Carson , Yang Tianyu , Langnas Alan N. , Thompson Scott C. , Zhao Yong , Franco Kenneth L. , Radio Stanley J. , Sudan Debra L. 
Published: March 2003

Beschorner WE, Shearon CC, Yang T, Langnas AN, Thompson SC, Zhao Y, Franco KL, Radio SJ, Sudan DL. Pre‐transplant analysis of accommodation in donor pigs. Xenotransplantation 2003; 10: 66–71. © Blackwell Munksgaard, 2003Accommodation could lead to xenograft acceptance without the need for severe immune suppression. Generally graft accommodation is appreciated in the sensitized recipient, after transplantation. By inducing accommodation in chimeric donors, however, the risk and cost of inducing accommodation in the recipient would be reduced. An indirect assay of accommodation in the donor pig is needed for screening donors prior to procurement of the xenograft. The resistance of peripheral blood lymphocytes to cytolysis by antibody and complement was assessed in chimeric pigs and compared with control pigs. Peripheral blood lymphocytes (PBL) from chimeric pigs demonstrated a wide range of cytolysis (0 to 85%, median 13%) whereas PBL from control pigs were consistently lysed with these conditions (86 to 99%, median 96.5%, P < 0.0001). Accommodation or reduction in cytolysis did not correlate with the amount of chimerism. A longitudinal study demonstrated persistent accommodation of the PBL for as long as 15 weeks, when the donors averaged 68 kg in weight. Accommodation has been induced by low levels of antibodies interacting with the target tissue. An ELISA for sheep IgG was developed and the serum from newborn pigs assessed. Sheep IgG (up to 4.6 μg/ml) was detected in four of seven piglets with chimerism detectable by flow cytometry and in one of four piglets with minimal chimerism, detectable only by PCR. Lymphocyte accommodation was observed in all pigs with detectable sheep IgG. Of four pigs without accommodation, none had sheep IgG. Three pigs without detectable sheep IgG also had accommodation, suggesting that factors other than sheep IgG may induce accommodation. Acute vascular rejection was not observed in the heterotopic heart transplants from six donors with PBL accommodation. Only one incident of moderate diffuse cellular rejection (grade 3) was observed.
The ancestral complement system in sea urchins
Authors: Smith L. Courtney , Clow Lori A. , Terwilliger David P. 
Published: March 2003

Summary:The origin of adaptive immunity in the vertebrates can be traced to the appearance of the ancestral RAG genes in the ancestral jawed vertebrate; however, the innate immune system is more ancient. A central subsystem within innate immunity is the complement system, which has been identified throughout and seems to be restricted to the deuterostomes. The evolutionary history of complement can be traced from the sea urchins (members of the echinoderm phylum), which have a simplified system homologous to the alternative pathway, through the agnathans (hagfish and lamprey) and the elasmobranchs (sharks and rays) to the teleosts (bony fish) and tetrapods, with increases in the numbers of complement components and duplications in complement pathways. Increasing complexity in the complement system parallels increasing complexity in the deuterostome animals. This review focuses on the simplest of the complement systems that is present in the sea urchin. Two components have been identified that show significant homology to vertebrate C3 and factor B (Bf), called SpC3 and SpBf, respectively. Sequence analysis from both molecules reveals their ancestral characteristics. Immune challenge of sea urchins indicates that SpC3 is inducible and is present in coelomic fluid (the body fluids) in relatively high concentrations, while SpBf expression is constitutive and is present in much lower concentrations. Opsonization of foreign cells and particles followed by augmented uptake by phagocytic coelomocytes appears to be a central function for this simpler complement system and important for host defense in the sea urchin. These activities are similar to some of the functions of the homologous proteins in the vertebrate complement system. The selective advantage for the ancestral deuterostome may have been the amplification feedback loop that is still of central importance in the alternative pathway of complement in higher vertebrates. Feedback loop functions would quickly coat pathogens with complement leading to phagocytosis and removal of foreign cells, a system that would be significantly more effective than an opsonin that binds upon contact as a result of simple diffusion. An understanding of the immune response of the sea urchin, an animal that is a good estimator of what the ancestral deuterostome immune system was like, will aid us in understanding how adaptive immunity might have been selected for during the early evolution of the vertebrates and how it might have been integrated into the pre‐existing innate immune system that was already in place in those animals.The authors are grateful to Drs Sham Nair and Paul Gross for their critique of the manuscript and helpful suggestions. This work was supported by the National Science Foundation (MCB 9603086).
Genesis of the ILT/LIR/MIR clusters within the human leukocyte receptor complex
Authors: Volz Armin , Wende Hagen , Laun Katja , Ziegler Andreas 
Published: March 2003

Summary: The human leukocyte receptor complex (LRC) contains at least 26 genes which belong to the immunoglobulin superfamily. The genes include two clusters of immunoglobulin‐like transcript (ILT)/leukocyte immunoglobulin‐like receptor (LIR)/monocyte‐macrophage inhibitory receptor (MIR) loci, a cluster of killer cell inhibitory receptor (KIR) genes, two leukocyte‐associated immunoglobulin‐like receptor genes, as well as the Fc receptor for IgA and the natural cytotoxicity receptor 1 loci. It has already been postulated that these genes have evolved by multiple duplications, while the two ILT clusters are likely to have been generated by the inverse duplication of an ancient ILT cluster. To shed more light on the possible origin of the loci within the LRC, we have now investigated the presence of KIR and ILT loci in a variety of vertebrates by hybridizations and compared the genomic sequences of all ILT genes. Our results lead to the following conclusions: 1) the origin of KIR genes dates back to about 100 million years, but only primate and human KIRs are closely related; 2) in contrast, genes which are detectable with human ILT cDNAs are already found in birds, suggesting their presence already about 300 million years ago. Using the sequence data produced by the human genome project, we have developed a hypothesis that reconstructs the genesis of the two human ILT clusters in detail which will help to understand the function of the LRC.This work was supported by the European Union through grant BMH4‐CT96–1105 (to A.Z.). We also thank the Sonnenfeld‐Stiftung (Berlin) and the Berliner Krebsgesellschaft for financial support.
Role of Shc in T‐cell development and function
Authors: Zhang Li , Lorenz Ulrike , Ravichandran Kodi S. 
Published: March 2003

Summary:Shc is a prototype adapter protein that is expressed from the earliest stages of T‐cell development. Shc becomes rapidly tyrosine phosphorylated after T‐cell receptor (TCR) engagement. Expression of dominant negative forms of Shc in T‐cell lines had also suggested a role for this adapter downstream of the TCR. However, until recently, the relative significance of Shc compared to several other adapters in T cells was unclear. Mice lacking Shc expression specifically in the T‐cell lineage together with inducible expression of dominant negative Shc in transgenic mice have revealed an essential and nonredundant role for Shc in thymic T‐cell development. Functional defects in a Jurkat T‐cell line lacking Shc expression also suggest a role for Shc in mature T‐cell functions. While the requirement of Shc in T‐cell signaling is now established, precisely what signaling pathways downstream of Shc make this adapter unique are less clear. Although the Shc‐mediated activation of the extracellular signal regulated kinase (Erk)/mitogen‐activated protein kinase (MAPK) pathway could be one component, Shc likely signals to other pathways in T cells that are not yet discovered. A better molecular understanding of Shc function in the future could provide insights into how multiple adapters coordinate the various outcomes downstream of the TCR.
Co‐expression of interleukin‐1β and tumor necrosis factor α in synovial tissues and synovial fluids of temporomandibular joint with internal derangement: comparision with histological grading of synovial inflammation
Authors: Suzuki Toshikazu , Segami Natsuki , Nishimura Masaaki , Nojima Takayuki 
Published: March 2003

AbstractBackground:  It has been clarified that interleukin‐1 (IL‐1)β and tumor necrosis factor (TNF)α play an important role in pathogenesis of various joint disease. The purpose of this study was to investigate the cellular source of IL‐1β and TNFα in temporomandibular joint (TMJ), and to analyze the relation between the expression of these cytokines and the intensity of TMJ synovial inflammation.Methods:   We examined 33 synovial biopsy specimens from patients with internal derangement of the TMJ by an immunohistochemical technique using specific antibodies to IL‐1β and TNFα. We also studied 20 synovial fluids from the patients by enzyme‐linked immunosorbent assay method. These data are compared with histological grading of synovial inflammation by Gynther's system.Results:   Both IL‐1β and TNFα were predominantly localized in the synovial lining cell layer and the blood vessels of synovial biopsy specimens obtained from patients with TMJ internal derangement. A statistically significant correlation was found between the intensity of IL‐1β expression and that of TNFα. Additionally, the intensity of TNFα expression was statistically correlated with histological grading by Gynther's system.Conclusion:   These results supported that IL‐1β and TNFα may be involved in the occurrence of TMJ internal derangement and that they coordinately play an role in pathogenesis of TMJ internal derangement.
Ameloblastomatoid, central odontogenic fibroma: an epithelium‐rich variant
Authors: Ide Fumio , Sakashita Hideaki , Kusama Kaoru 
Published: March 2003

AbstractTwo cases are presented of a central odontogenic fibroma (OF) in the mandible of a middle‐aged female, which posed considerable difficulty in microscopic diagnosis. These well‐demarcated but non‐encapsulated intraosseous tumors had hybrid features of both OF and ameloblastoma. Their clinical findings are more in keeping with the putative OF rather than ameloblastoma. The present lesions alert pathologists to this unusual type of central OF in order to avoid misdiagnosis.
Effect of home bleaching and smoking on marginal gingival epithelium proliferation: a histologic study in women
Authors: Da Costa Filho Luiz Cesar , Da Costa Carolina Covolo , Sória Marina Lara , Taga Rumio 
Published: March 2003

AbstractBackground:  Animal studies have suggested that home bleaching agents can cause morphological alterations and changes in the proliferative rate of oral epithelium.Methods:  A bleaching agent containing 10% carbamide peroxide with carbopol was used in 11 women (five smokers and six non‐smokers) during a 5‐week period. Two biopsies were performed, one of them 15 days before the beginning of the home bleaching treatment and the other immediately after the 5‐week bleaching treatment. Two analyses were performed in the histological sections obtained from the biopsies: epithelium morphometry and assessment of the epithelium's proliferative activity by proliferating cell nuclear antigen (PCNA) immunohistochemistry.Results:  The home bleaching agent increases epithelium thickness and the PCNA index in both smoker and non‐smoker patients.Conclusion:  Carbamide peroxide (10%) caused an augmentation in the proliferative activity within the basal and parabasal layers of the gingival epithelium, resulting in a change in this tissue's morphometry.
Rising trends in oral cancer mortality in Spain, 1975–94
Authors: Nieto Adoración , Ramos Miguel Ruiz 
Published: March 2003

AbstractBackground: Epidemiological studies have shown that the worldwide incidence and mortality rates for oral cancer have increased considerably over the last decade. This study investigates the Spanish trend in mortality of oral cancer from 1975–94.Methods: Age‐standardized, truncated, cumulative, age‐specific and potential years of life lost (PYLL) rates were calculated by gender. Poisson regression models allowed the measurement of age and period effects.Results: Age‐standardized and cumulative mortality rates increased in males, while truncated and PYLL rates doubled. Changes were less marked in females. There were annual increases in oral cancer mortality from 1975–94, of 25% and 9% in males and females, respectively. In males there was an interaction between age and period. There was also an increase in age‐specific mortality rates in males.Conclusions: Mortality from oral cancer rose substantially in males, with concomitant changes in the age‐distribution pattern of mortality. Increases were less marked in females, with some minor modifications to the age‐distribution pattern of mortality.
Infrequent genetic alterations of the tumor suppressor gene PTEN/MMAC1 in squamous cell carcinoma of the oral cavity
Authors: Mavros A. , Hahn M. , Wieland I. , Koy S. , Koufaki O. N. , Strelocke K. , Koch R. , Haroske G. , Schackert H. K. , Eckelt U. 
Published: March 2003

AbstractBackground: Fifty tumor specimens from primarily untreated patients were analyzed to elucidate the involvement of the tumor suppressor gene PTEN/MMAC1 in the development of oral squamous cell cancer.Methods: Eight microsatellite markers, spanning 10 cM of genomic DNA located centromeric, telomeric or intragenic of PTEN/MMAC1 were used for loss of heterozygosity (LOH) and breakpoint analysis. The microsatellite panel within or in close proximity (1 cM) to the 10q23.3 locus showed a LOH rate of 12%. Complete sequence analysis of the genes coding region was performed in all 10 cases that exhibited LOH in one of the eight microsatellite markers within or around the PTEN/MMAC1 gene. Comparative multiplex PCR reactions served to screen for homozygous deletions.Results: There was no association between allelic loss of the gene, overall patient survival and recurrence‐free survival. Sequencing did not reveal any mutation in the coding region of PTEN/MMAC1. Differential PCR analysis failed to detect any homozygous deletion.Conclusions: We conclude that PTEN/MMAC1 gene alterations do not play a key role in tumorigenesis of oral squamous cell cancers.
Progressive bulbar palsy: a case report diagnosed by lingual symptoms
Authors: Cerero Lapiedra R. , Moreno López L. A. , Esparza Gómez G. C. 
Published: March 2003

AbstractThe aim of this report is to show a case of Progressive Bulbar Palsy (PBP), diagnosed by oral medicine specialists, from oral symptoms of the disease. We have found no more than two published cases of PBP diagnosed by lingual alterations. We have followed the patient for almost four years, which is remarkable considering that the normal survival period for these patients is up to three years. We would like to emphasize the role of general dentists in the diagnosis of systemic conditions based on an oral examination that should include the oro‐facial muscles.
Thermal sensation and pain in oral lichen planus and lichenoid reaction
Authors: Niissalo Sirkku , Hampf Göran , Hietanen Jarkko , Malmström Maria , Solovieva Svetlana , Pertovaara Antti , Konttinen Yrjö T. 
Published: March 2003

AbstractBackground:  Our previous findings in oral lichen planus (OLP) and lichenoid reactions (LR) raised the question whether the histopathological changes observed in sensory and autonomic innervation produce oral sensory disorders.Methods:  Spontaneous pain was assessed using the Visual Analogue Scale (VAS). Thermal pain thresholds were measured with a contact thermostimulator and mechanical pain thresholds with an electronic algometer.Results:  Patients with OLP reported a higher intensity of spontaneous pain than LR patients (P = 0.001). Even erosive LRs were relatively painless. No thermal or mechanical hyperalgesia was detected in oral lesions. Highest separate cold pain threshold was measured in lesions affected by intense Candida growth.Conclusion:  Together with previous histological findings, the present data suggest that increased somatic innervation and sympathetic denervation do not promote clinical pain sensitivity or hyperalgesia in oral mucosa and that these sensory functions are not affected by OLP and LR. Candida growth may function as secondary irritant modulating the pain responses.