bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity among patients with tumor necrosis factor receptor–associated periodic syndrome phenotypes
Authors: Aganna Ebun , Hammond Linda , Hawkins Philip N. , Aldea Anna , McKee Shane A. , van Amstel Hans Kristian Ploos , Mischung Claudia , Kusuhara Koichi , Saulsbury Frank T. , Lachmann Helen J. , Bybee Alison , McDermott Elizabeth M. , La Regina Micaela , Arostegui Juan I. , Campistol Josep M. , Worthington Sharron , High Kevin P. , Molloy Michael G. , Baker Nicholas , Bidwell Jeff L. , Castañer José L. , Whiteford Margo L. , Janssens‐Korpola P. L. , Manna Raffaele , Powell Richard J. , Woo Patricia , Solis Pilar , Minden Kirsten , Frenkel Joost , Yagüe Jordi , Mirakian Rita M. , Hitman Graham A. , McDermott Michael F. 
Published: September 2003

AbstractObjectiveTo investigate the prevalence of tumor necrosis factor receptor–associated periodic syndrome (TRAPS) among outpatients presenting with recurrent fevers and clinical features consistent with TRAPS.MethodsMutational screening was performed in affected members of 18 families in which multiple members had symptoms compatible with TRAPS and in 176 consecutive subjects with sporadic (nonfamilial) “TRAPS‐like” symptoms. Plasma concentrations of soluble tumor necrosis factor receptor superfamily 1A (sTNFRSF1A) were measured, and fluorescence‐activated cell sorter analysis was used to measure TNFRSF1A shedding from monocytes.ResultsEight novel and 3 previously reported TNFRSF1A missense mutations were identified, including an amino acid deletion (ΔD42) in a Northern Irish family and a C70S mutation in a Japanese family, both reported for the first time. Only 3 TNFRSF1A variants were found in patients with sporadic TRAPS (4 of 176 patients). Evidence for nonallelic heterogeneity in TRAPS‐like conditions was found: 3 members of the “prototype familial Hibernian fever” family did not possess C33Y, present in 9 other affected members. Plasma sTNFRSF1A levels were low in TRAPS patients in whom renal amyloidosis had not developed, but also in mutation‐negative symptomatic subjects in 4 families, and in 14 patients (8%) with sporadic TRAPS. Reduced shedding of TNFRSF1A from monocytes was demonstrated in vitro in patients with the T50M and T50K variants, but not in those with other variants.ConclusionThe presence of TNFRSF1A shedding defects and low sTNFRSF1A levels in 3 families without a TNFRSF1A mutation indicates that the genetic basis among patients with “TRAPS‐like” features is heterogeneous. TNFRSF1A mutations are not commonly associated with nonfamilial recurrent fevers of unknown etiology.
Expression of the markers BDCA‐2 and BDCA‐4 and production of interferon‐α by plasmacytoid dendritic cells in systemic lupus erythematosus
Authors: Blomberg Stina , Eloranta Maija‐Leena , Magnusson Mattias , Alm Gunnar V. , Rönnblom Lars 
Published: September 2003

AbstractObjectiveTo study the expression of blood dendritic cell antigen 2 (BDCA‐2) and BDCA‐4 molecules by plasmacytoid dendritic cells (PDCs) in the blood of patients with systemic lupus erythematosus (SLE), and to study PDC production of interferon‐α (IFNα) and its inhibition by anti–BDCA‐2 and anti–BDCA‐4 antibodies.MethodsPeripheral blood mononuclear cells (PBMCs) from SLE patients (SLE PBMCs) and from healthy controls were induced to produce IFNα in vitro by SLE serum containing an endogenous IFNα‐inducing factor (SLE‐IIF) or by herpes simplex virus type 1 (HSV‐1). The frequencies and numbers of BDCA‐2–, BDCA‐3–, and BDCA‐4–expressing cells were analyzed by flow cytometry, and the effects of anti–BDCA‐2 and anti–BDCA‐4 monoclonal antibodies (mAb) on IFNα production were investigated.ResultsIFNα production by SLE PBMCs induced by SLE‐IIF or HSV‐1 was decreased compared with that of healthy control PBMCs (P = 0.002 and P = 0.0007, respectively). The proportions of BDCA‐2– and BDCA‐3–expressing cells in SLE PBMCs were reduced compared with those in PBMCs from healthy controls (P = 0.01 and P = 0.004, respectively). IFNα producers in culture, especially among SLE PBMCs, displayed reduced BDCA‐2 expression and constituted only a minority of the BDCA‐2–positive cells, at least in healthy control PBMCs (median 18%). IFNα production by both SLE and healthy control PBMCs stimulated by SLE‐IIF or HSV‐1 was markedly reduced by anti–BDCA‐2 mAb (median 81–98% inhibition). Anti–BDCA‐4 mAb only partially inhibited SLE‐IIF–induced IFNα production.ConclusionSLE patients had a reduced number of BDCA‐2–expressing PDCs, also termed natural IFNα‐producing cells, and their IFNα production could be inhibited by anti–BDCA‐2/4 mAb. Such mAb may be a therapeutic option for inhibiting the ongoing IFNα production in SLE patients.
Prevention of the onset and progression of collagen‐induced arthritis in rats by the potent p38 mitogen‐activated protein kinase inhibitor FR167653
Authors: Nishikawa Masataka , Myoui Akira , Tomita Tetsuya , Takahi Koichiro , Nampei Akihide , Yoshikawa Hideki 
Published: September 2003

AbstractObjectiveFR167653 is a potent inhibitor of p38 mitogen‐activated protein kinase (MAPK) and inhibits tumor necrosis factor α (TNFα) and interleukin‐1β (IL‐1β) production in inflammatory cells. In this study we investigated the effect of FR167653 on collagen‐induced arthritis (CIA).MethodsRats with CIA were subcutaneously injected with FR167653 (32 mg/kg/day) starting on the day of the booster injection (day 7) in the prophylactic treatment group and after the onset of arthritis (day 21) in the therapeutic treatment group. Hind‐paw swelling, body weight, radiographic and histologic scores, and osteoclast number were evaluated. Cytokine levels in the serum and tissue were assessed by enzyme‐linked immunosorbent assays. Flow cytometric analysis of T lymphocytes from bone marrow was performed. The effect of FR167653 on in vitro osteoclast formation induced by soluble receptor activator of nuclear factor κB ligand (sRANKL) and TNFα was examined.ResultsSwelling of hind paws and loss of weight occurred in the CIA rats, but this was not evident in the prophylactic treatment group. Therapeutic treatment also significantly reduced paw swelling. The mean radiographic and histologic scores as well as the osteoclast numbers were significantly lower in the treatment group than in the CIA rats without treatment. FR167653 treatment reduced the serum levels of TNFα and IL‐1β, lowered the IL‐1β concentration in the ankle joints, and decreased the CD4−,CD8a+ T cell population in bone marrow. Furthermore, FR167653 inhibited the osteoclast‐like cell differentiation induced by both sRANKL and TNFα in vitro.ConclusionFR167653 prevents the onset of arthritis in a prophylactic treatment model and suppresses the progression of joint destruction in a therapeutic treatment model, suggesting that p38 MAPK is a potential therapeutic target for rheumatoid arthritis.
Expression of the MAPK kinases MKK‐4 and MKK‐7 in rheumatoid arthritis and their role as key regulators of JNK
Authors: Sundarrajan Monisha , Boyle David L. , Chabaud‐Riou Martine , Hammaker Deepa , Firestein Gary S. 
Published: September 2003

AbstractObjectiveThe mitogen‐activated protein (MAP) kinase JNK is a key regulator of interleukin‐1 (IL‐1)–induced collagenase gene expression and joint destruction in arthritis. Two upstream kinases, MKK‐4 and MKK‐7, have been identified as potential activators of JNK. However, the role of MAP kinase kinases (MAPKKs) and their functional organization within fibroblast‐like synoviocytes (FLS) have not been defined. We therefore evaluated the interactions between the various MAP kinase components and determined their subcellular localization.MethodsMKKs were identified by immunohistochemistry of rheumatoid arthritis (RA) and osteoarthritis (OA) synovium. Western blotting was used to determine the expression of FLS. Immunoprecipitation experiments using antibodies specific for MKK‐4, MKK‐7, and JNK were performed. Phosphospecific antibodies and immunohistochemistry were used to evaluate the activation state of synovial MKK‐4 and MKK‐7. Confocal microscopy was used to determine the subcellular location of the kinases.ResultsImmunohistochemistry studies demonstrated abundant MKK‐4 and MKK‐7 in RA and OA synovium, but the levels of phosphorylated kinases were significantly higher in RA synovium. MKK‐4 and MKK‐7 were constitutively expressed by cultured RA and OA FLS, and IL‐1 stimulation resulted in rapid phosphorylation of both kinases. JNK was detected in MKK‐4 and MKK‐7 immunoprecipitates. Furthermore, MKK‐4 coprecipitated with MKK‐7 and vice versa, indicating that the 3 kinases form a stable complex in FLS. Confocal microscopy confirmed that JNK, MKK‐4, and MKK‐7 colocalized in the cytoplasm, with JNK migrating to the nucleus after IL‐1 stimulation. The signal complex containing MKK‐4, MKK‐7, and JNK was functionally active and able to phosphorylate c‐Jun after IL‐1 stimulation of FLS.ConclusionThese studies demonstrate that JNK, MKK‐4, and MKK‐7 form an active signaling complex in FLS. This novel JNK signalsome is activated in response to IL‐1 and migrates to the nucleus. The JNK signalsome represents a new target for therapeutic interventions designed to prevent joint destruction.
Citrullination of synovial proteins in murine models of rheumatoid arthritis
Authors: Vossenaar Erik R. , Nijenhuis Suzanne , Helsen Monique M. A. , van der Heijden Annemarie , Senshu Tatsuo , van den Berg Wim B. , van Venrooij Walther J. , Joosten Leo A. B. 
Published: September 2003

AbstractObjectiveAntibodies directed to citrulline‐containing proteins are highly specific for rheumatoid arthritis (RA) and can be detected in up to 80% of patients with RA. Citrulline is a nonstandard amino acid that can be incorporated into proteins only by posttranslational modification of arginine by peptidylarginine deiminase (PAD) enzymes. The objective of this study was to investigate the presence of anticitrulline antibodies, PAD enzymes, and citrullinated antigens in mouse models of both acute and chronic destructive arthritis: streptococcal cell wall (SCW)–induced arthritis and collagen‐induced arthritis (CIA), respectively.MethodsSynovial tissue biopsy specimens were obtained from naive mice, mice with CIA, and mice with SCW‐induced arthritis. The expression of messenger RNA (mRNA) for PAD enzymes was analyzed by reverse transcriptase–polymerase chain reaction; the presence of PAD proteins and their products (citrullinated proteins) was analyzed by Western blotting and by immunolocalization. The presence of anticitrullinated protein antibodies was investigated by an anti–cyclic citrullinated peptide (anti‐CCP) enzyme‐linked immunosorbent assay (ELISA) and an ELISA using in vitro citrullinated fibrinogen.ResultsIn both mouse models, PAD type 2 (PAD2) mRNA was present in the synovium but was not translated into PAD2 protein. In contrast, PAD4 mRNA, although absent from healthy synovium, was readily transcribed and translated by polymorphonuclear neutrophils infiltrating the synovial tissue during inflammation. As a consequence, several synovial proteins were subjected to citrullination. One of these proteins was identified as fibrin, which has been reported to be citrullinated also in synovium of patients with RA. Although generation of citrullinated antigens during synovial inflammation in the mice was eminent, no anti‐CCP antibodies could be detected.ConclusionCitrullination of synovial antigens is an active process during joint inflammation in both mice and humans, but the induction of autoantibodies directed to these proteins is a more specific phenomenon, detectable only in human RA patients.
Osteoarthritis‐like changes and decreased mechanical function of articular cartilage in the joints of mice with the chondrodysplasia gene (cho)
Authors: Xu L. , Flahiff C. M. , Waldman B. A. , Wu D. , Olsen B. R. , Setton L. A. , Li Y. 
Published: September 2003

AbstractObjectiveTo investigate whether heterozygosity for a loss‐of‐function mutation in the gene encoding the α1 chain of type XI collagen (Col11a1) in mice (chondrodysplasia, cho) causes osteoarthritis (OA), and to understand the biochemical and biomechanical effects of this mutation on articular cartilage in knee and temporomandibular (TM) joints.MethodsArticular cartilage from the knee and TM joints of mice heterozygous for cho (cho/+) and their wild‐type littermates (+/+) was examined. The morphologic properties of cartilage were evaluated, and collagen fibrils were examined by transmission electron microscopy. Immunohistochemical staining was performed to examine the protein expression levels of matrix metalloproteinase 3 (MMP‐3) and MMP‐13 in knee joints. In 6‐month‐old animals, fixed‐charge density was determined using a semiquantitative histochemical method, and tensile stiffness was determined using an osmotic loading technique.ResultsThe diameter of collagen fibrils in articular cartilage of knee joints from heterozygous cho/+ mice was increased relative to that in control cartilage, and histologic analysis showed OA‐like degenerative changes in knee and TM joints, starting at age 3 months. The changes became more severe with aging. At 3 months, protein expression for MMP‐3 was increased in knee joints from cho/+ mice. At 6 months, protein expression for MMP‐13 was higher in knee joints from cho/+ mice than in joints from their wild‐type littermates, and negative fixed‐charge density was significantly decreased. Moreover, tensile stiffness in articular cartilage of knee joints from cho/+ mice was moderately reduced and was inversely correlated with the increase in articular cartilage degeneration.ConclusionHeterozygosity for a loss‐of‐function mutation in Col11a1 results in the development of OA in the knee and TM joints of cho/+ mice. Morphologic and biochemical evidence of OA appears to precede significant mechanical changes, suggesting that the cho mutation leads to OA through a mechanism that does not initially involve mechanical factors.
A mind to blame: new views on involuntary acts
Authors: Denno Deborah W. 
Published: September 2003

AbstractThis article examines the legal implications linked to recent scientific research on human consciousness. The article contends that groundbreaking revelations about consciousness expose the frailties of the criminal law's traditional dual dichotomies of conscious versus unconscious thought processes and voluntary versus involuntary acts. These binary doctrines have no valid scientific foundation and clash with other key criminal law defenses, primarily insanity. As a result, courts may adjudicate like individuals very differently based upon their (often unclear) understanding of these doctrines and the science that underlies them. This article proposes a compromise approach by recommending that the criminal law's concept of voluntariness consist of three parts: (i) voluntary acts, (ii) involuntary acts, and (iii) semi‐voluntary acts. The semi‐voluntary acts category, which is new, incorporates modern ideas of consciousness and also advances the law. Using some actual criminal cases, this article applies this new three‐part grouping and demonstrates how it enhances a more just outcome for defendants, victims, and society. Copyright © 2003 John Wiley & Sons, Ltd.
Impulsive versus premeditated aggression: implications formens readecisions
Authors: Barratt Ernest S. , Felthous Alan R. 
Published: September 2003

AbstractScience can provide more information about the nature of aggressive acts, and therefore themens reaof criminal offenses, than is commonly assumed. For example, progress has been made in classifying aggression as impulsive or premeditated within the context of the role of conscious experience in controlling behavior. This review of the status of the scientific ability to distinguish conscious from unconscious acts and more specifically impulsive from premeditated aggressive acts is organized around four themes: (i) How is aggression defined and measured in general? (ii) How does the distinction between impulsive and premeditated aggression relate to the legal concept ofmens rea? (iii) How do various scientific disciplines contribute to the mind/body discourse? (iv) What risk factors are associated with impulsive and premeditated aggression respectively? The authors conclude that the most promising approach to researching the nature of behavioral intention and motivation is to apply a discipline neutral model that integrates the data from multiple disciplines, collectively designated the cognitive neurosciences. Copyright © 2003 John Wiley & Sons, Ltd.
Fine‐needle aspiration biopsy and intraoperative cytologic smear findings in a case of benign mesothelial‐cell inclusions involving a lymph node: Case report and review of the literature
Authors: Paull Gerson , Mosunjac Marina 
Published: September 2003

AbstractAlthough first described over a decade ago, the rare entity of mesothelial lymph node inclusions (nonneoplastic mesothelial cells involving lymph node sinuses) is not well‐known among pathologists. Unlike most lymph node inclusions such as Müllerian inclusions or nevus cells, which usually occur in the capsule of the lymph node, mesothelial cells involve the lymph node sinus, mimicking metastatic carcinoma or metastatic mesothelioma. The spectrum of histologic findings ranges from a few mesothelial cells, perhaps only detectable by immunohistochemical stains, to a massive distention of the lymph node sinus with abundant mesothelial cells. Mesothelial‐cell inclusions in lymph nodes are usually found in mediastinal lymph nodes of patients with pleural and/or pericardial effusions. It is hypothesized that the effusion, due to whatever cause, allows for mesothelial‐cell migration into the submesothelial lymphatics and regional lymph nodes. To our knowledge, cytologic findings on aspiration biopsy and intraoperative smear preparations of a lymph node with mesothelial‐cell inclusions have never been described. Familiarity with this entity is important in preventing misdiagnosis of malignancy. Diagn. Cytopathol. 2003;29:163–166. © 2003 Wiley‐Liss, Inc.
Fine‐needle aspiration cytology in lymphadenopathy of HIV‐positive patients
Authors: Nayak Sujata , Mani Reeta , Kavatkar Anita N. , Puranik Shaila C. , Holla Vasudev V. 
Published: September 2003

AbstractFine‐needle aspiration cytology (FNAC) of 32 HIV‐positive cases presenting with lymphadenopathy was performed to evaluate its role in this group of patients. For each case air‐dried smears were stained with Leishman, hematoxylin and eosin, and Zeihl‐Neelsen stains for acid fast bacilli (AFB). The results were tuberculous (TB) lymphadenopathy (15), reactive lymphadenopathy (10), acute lymphadenitis/abscess (5), and suspected malignancy (2). In seven cases of TB lymphadenitis findings were suggestive of TB since no AFB was demonstrable on the cytology smears. In TB lymphadenitis, two additional patterns besides necrotising granulomatous (4) and granulomatous (2) were observed. These were necrotising (6) and necrotising suppurative (3) patterns. FNAC is a simple, inexpensive, rapid investigative procedure which can reduce surgical excisions and provide definite guidelines about further management. Diagn. Cytopathol. 2003;29:146–148. © 2003 Wiley‐Liss, Inc.
Review of cytologic criteria of bacterial vaginosis: Examination of 2,841 Papanicolaou‐stained vaginal smears
Authors: Demirezen Şayeste 
Published: September 2003

AbstractTo review the cytologic criteria used in the diagnosis of bacterial vaginosis cases [Bv (+)], 2,841 Papanicolaou‐stained vaginal smears were examined cytologically. Clue cells and other cytologic findings were observed in 94 of 2,841 (3.30%) vaginal smears. To detect Bv(+) cases, 94 vaginal smears were screened again. Clue cells, profuse free cocci among cornified type epithelial cells, absence of PMNLs, and vaginal Lactobacilli were detected in 43 of 94 (45.74%). The observation of free cocci which resembled a nebulous appearance was detected first in this study. These four cytologic criteria strongly suggested Bv(+) cases (n = 43). Although clue cells were seen in 51 of 94 (54.25%) vaginal smears, due to the presence of abundant PMNLs, metaplastic cells, vaginal Lactobacilli, and some infectious agents, mainly Trichomonas vaginalis and yeasts, they were considered bacterial vaginosis negative [Bv(–)]. It was postulated that 51 vaginal smears might be aerobic vaginitis. In conclusion, if vaginal smears contain profuse PMNLs, some infectious agents, and metaplastic cells, and even clue cells have been observed they are not accepted as Bv(+) cases. Diagn. Cytopathol. 2003;29:156–159. © 2003 Wiley‐Liss, Inc.
Extraction of Juniperus oxycedrus ssp. oxycedrus essential oil by supercritical carbon dioxide: inﬂuence of some process parameters and biological activity
Authors: Marongiu Bruno , Porcedda Silvia , Caredda Alessandra , De Gioannis Barbara , Vargiu Laura , Paolo  
Published: September 2003

AbstractSupercritical carbon dioxide extraction of the leaves and berries of Juniperus oxycedrus L. ssp. oxycedrus, coupled with a two‐stage separation, allowed the entrapment of cuticular waxes in the ﬁrst separator (90 bar, −10 °C), thereby allowing pure essential oils to be collected in the second separator (15 bar, 10 °C). An extraction carried out on a charge of leaves, at 90 bar and 50 °C, gave a yield of 0.8% (w/w) with respect to the charged material, of an oil whose major constituents were germacrene D (15.9%), manoyl oxide (10.2%) and 1‐epi‐cubenol (5.4%). The berry oil obtained, at the same pressure and temperature as those for the leaves, gave a yield of 0.45% (w/w) and was composed chieﬂy of germacrene D (13.8%), α‐pinene (10.5%) and β‐myrcene (8.1%). At a constant temperature of 50 °C, different extraction pressures (80, 90 and 100 bar) were tested in order to obtain the juniper wood essential oil. The extraction yield depended strongly on the extraction pressure, reaching a maximum of 14.7% (w/w) at 100 bar. The main constituents in the extract were δ‐cadinene, calamenene, cubenol and 1‐epi‐cubenol. Hydrodistillation of the wood of J. oxycedrus gave a yield of 11.0% (w/w) of essential oil, with a reduced level of sesquiterpene hydrocarbons and an enhanced amount of oxygenated sesquiterpenes, with respect to the oil obtained by supercritical carbon dioxide extraction. The extracts obtained at different pressures were tested for cytotoxicity, antiviral and antimicrobial activities. The results showed that the extracts of leaves and berries obtained at 200 bar were cytotoxic against different cell lines used to support virus growth. As far as antiviral activiy is concerned, some of the extracts were active against a single‐stranded RNA+ virus (Poliovirus‐1). When tested for antimicrobial activity, none of the samples were shown to be active. Copyright © 2003 John Wiley & Sons, Ltd.
Supercritical carbon dioxide separation of bergamot essential oil by a countercurrent process
Authors: Poiana Marco , Mincione Antonio , Gionfriddo Francesco , Castaldo Domenico 
Published: September 2003

AbstractThe efﬁciency of separation of bergamot essential oil, performed by a countercurrent column ﬁlled with Raschig rings and using supercritical carbon dioxide as partition solvent, is affected by various parameters. In the experiments explained in this work, the direct effect of CO2 density was shown and the ratio between the amount of oil loaded to on the column and the amount of CO2 used were discussed. The conditions that produced extracts with a similar volatile fraction composition of starting material and with a high yield (more than 80% of recovery) were those with a low feed:solvent ratio; the lowest bergaptene content was obtained at low CO2 density or at high feed:solvent ratio. A good result was observed at a CO2 density of 206 g/dm3 (8 MPa of pressure and a temperature gradient of 46–50–54 °C) and a feed:solvent ratio of 9.4–9.6; in this separation, a yield of 74–77% and a bergaptene content lower than 0.01% was measured. Copyright © 2003 John Wiley & Sons, Ltd.