bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adult human mylohyoid muscle fibers express slow‐tonic, α‐cardiac, and developmental myosin heavy‐chain isoforms
Authors: Mu Liancai , Su Hungxi , Wang Jun , Han Yingshi , Sanders Ira 
Published: July 2004

AbstractSome adult cranial muscles have been reported to contain unusual myosin heavy‐chain (MHC) isoforms (i.e., slow‐tonic, α‐cardiac, embryonic, and neonatal), which exhibit distinct contractile properties. In this study, adult human mylohyoid (MH) muscles obtained from autopsies were investigated to detect the unusual MHC isoforms. For comparison, the biceps brachii and masseter muscles of the same subjects were also examined. Serial cross‐sections from the muscles studied were incubated with a panel of isoform‐specific anti‐MHC monoclonal antibodies that distinguish major and unusual MHC isoforms. On average, the slow type I and fast type II MHC‐containing fibers in the MH muscle accounted for 54% and 46% of the fibers, respectively. In contrast to limb and trunk muscles, the adult human MH muscle was characterized by a large proportion of hybrid fibers (85%) and a small percentage of pure fibers (15%; P < 0.01). Of the fast fiber types, the proportion of the type IIa MHC‐containing fibers (92%) was much greater than that of the type IIx MHC‐containing fibers (8%; P < 0.01). Our data demonstrated that the adult human MH fibers expressed the unusual MHC isoforms that were also identified in the masseter, but not in the biceps brachii. These isoforms were demonstrated by immunocytochemistry and confirmed by electrophoretic immunoblotting. Fiber‐to‐fiber comparisons showed that the unusual MHC isoforms were coexpressed with the major MHC isoforms (i.e., MHCI, IIa, and IIx), thus forming various major/unusual (or m/u) MHC hybrid fiber types. Interestingly, the unusual MHC isoforms were expressed in a fiber type‐specific manner. The slow‐tonic and α‐cardiac MHC isoforms were coexpressed predominantly with slow type I MHC isoform, whereas the developmental MHC isoforms (i.e., embryonic and neonatal) coexisted primarily with fast type IIa MHC isoform. There were no MH fibers that expressed exclusively unusual MHC isoforms. Approximately 81% of the slow type I MHC‐containing fibers expressed slow‐tonic and α‐cardiac MHC isoforms, whereas 80% of the fast type IIa MHC‐containing fibers expressed neonatal MHC isoform. The m/u hybrid fibers (82% of the total fiber population) were found to constitute the predominant fiber types in the adult human MH muscle. At least seven m/u MHC hybrid fiber types were identified in the adult human MH muscle. The most common m/u hybrid fiber types were found to be the MHCI/slow‐tonic/α‐cardiac and MHCIIa/neonatal, which accounted for 39% and 33% of the total fiber population, respectively. The multiplicity of MHC isoforms in the adult MH fibers is believed to be related to embryonic origin, innervation pattern, and unique functional requirements. © 2004 Wiley‐Liss, Inc.
Remodeling capacity of calcified fibrocartilage of the hip
Authors: Bloebaum Roy D. , Kopp Derinna V. 
Published: July 2004

AbstractIt is well known that the incidence of hip fractures increases exponentially with age and that hip fractures can be a major cause of morbidity and morality among elderly humans; this has prompted substantial research on hip fractures. The majority of research on hip fractures has focused on morphological changes of the proximal femur with age. Recently calcified fibrocartilage in the proximal femur has been shown to increase in fractional area with age and can ultimately make up to 60% of the fractional area of the cortex. However, the capacity of the tissue to remodel and heal is currently unknown. The purpose of the present study was to determine the remodeling capacity of calcified fibrocartilage on the proximal femur compared to the underlying cortical bone. The remodeling capacity of calcified fibrocartilage and cortical bone was assessed in adult female sheep by means of tetracycline labeling. The number of double and single labels within each tissue type was quantified and analyzed with a paired t‐test. The data showed very few labels in the calcified fibrocartilage compared to the cortical bone. This indicated that calcified fibrocartilage lacked a capacity to remodel in a manner similar to bone. The results of this investigation demonstrate that while the underlying cortical bone was actively remodeling, the calcified fibrocartilage appeared to have no remodeling capacity similar to that of cortical bone. © 2004 Wiley‐Liss, Inc.
Alveolar bone Sharpey fibers of the rat incisor in normal and altered functional conditions examined by scanning electron microscopy
Authors: Silva Miralva A.J. , Merzel José 
Published: July 2004

AbstractThe morphology and the area density of Sharpey fibers in the socket of the rat incisor under normo‐, hyper‐, and hypofunctional conditions were evaluated using scanning electron microscopy. Sharpey fibers appeared either as dome‐shaped projections, when highly mineralized, or as depressions when less mineralized. Near the alveolar crest, most of the fibers were fully mineralized and arranged in compact longitudinal rows. Toward the basal end of the socket, the rows became interrupted, forming islets of gradually smaller size and number. The density of the Sharpey fibers was higher (P < 0.01) in the mesial and distal faces than in the lingual face in most of the socket length. In normofunctional conditions, in all faces the density decreased 70 to 90 times from the crestal toward the basal region of the socket (P < 0.01). The degree of mineralization of the Sharpey fibers also decreased steadily in the same direction, indicating that, for support, the periodontal ligament matures from basal to incisal and is fully developed only in the crestal region. In hyper‐ and hypofunctional conditions, the same distribution was observed. The area density of the Sharpey fibers in the hyperfunctional condition showed a slight increase at the basal levels of the socket mesial and distal faces (P < 0.01 or P < 0.05). In hypofunctional incisors, the density decreased significantly (P < 0.01) at the mesial and distal faces in all regions of the socket, and at the lingual face, the decrease (P < 0.05) was restricted to the incisal regions. This may be one of the factors for the weakening of the periodontal ligament in hypofunctional incisors. © 2004 Wiley‐Liss, Inc.
Human T cell clones specific for heterogeneous nuclear ribonucleoprotein A2 autoantigen from connective tissue disease patients assist in autoantibody production
Authors: Greidinger Eric L. , Gazitt Tal , Jaimes Kimberly F. , Hoffman Robert W. 
Published: July 2004

AbstractObjectiveTo identify and characterize human T cells reactive with heterogeneous nuclear RNP A2 (hnRNP A2) antigen, and to determine the ability of hnRNP‐reactive T cells to assist in the production of human autoantibodies.MethodsT cells from patients with high serum levels of anti‐hnRNP IgG autoantibody were stimulated with an hnRNP recombinant fusion protein, and the cells were cloned by limiting dilution. The surface phenotype and cytokine profiles of the T cells were examined by flow cytometry and enzyme‐linked immunosorbent assay (ELISA), respectively. T cell clones were cultured with highly purified autologous B cells, and the ability of T cells to enhance autoantibody production under a variety of conditions was measured by ELISA.ResultsHuman T cells reactive with hnRNP antigen were cloned from 2 patients with systemic lupus erythematosus (SLE) and 1 patient with mixed connective tissue disease (MCTD). The T cells were CD4+ and had a Th1‐like functional phenotype. In coculture in vitro with autologous B cells, T cell clones augmented anti‐hnRNP autoantibody production and did so without the need for direct T cell–B cell contact.ConclusionThis study provides direct evidence for a role of anti‐hnRNP–reactive T cells in autoantibody production in SLE and MCTD. These findings support the notion that hnRNP‐reactive T cells play a role in the pathogenesis of these diseases.
A randomized trial of parenteral methotrexate comparing an intermediate dose with a higher dose in children with juvenile idiopathic arthritis who failed to respond to standard doses of methotrexate
Authors: Ruperto Nicolino , Murray Kevin J. , Gerloni Valeria , Wulffraat Nico , Feitosa De Oliveira Sheila Knupp , Falcini Fernanda , Dolezalova Pavla , Alessio Maria , Burgos‐Vargas Ruben , Corona Fabrizia , Vesely Richard , Foster Helen , Davidson Joyce , Zulian Francesco , Asplin Line , Baildam Eileen , Consuegra Julia Garcia , Ozdogan Huri , Saurenmann Rotraud , Joos Rik , Pistorio Angela , Woo Pat , Martini Alberto 
Published: July 2004

AbstractObjectiveTo compare the safety and efficacy of parenteral methotrexate (MTX) at an intermediate dosage (15 mg/m2/week) versus a higher dosage (30 mg/m2/week) in patients with polyarticular‐course juvenile idiopathic arthritis (JIA) who failed to improve while receiving standard dosages of MTX (8–12.5 mg/m2/week).MethodsIn the screening phase, 595 patients who were newly started on a standard dose of MTX were followed up for 6 months. Subsequently, the nonresponders, defined according to the American College of Rheumatology (ACR) pediatric 30% improvement criteria (pediatric 30), were randomized to receive an intermediate dose or higher dose of parenteral MTX for an additional 6 months. Improvement in the screening and randomization phase was defined by the ACR pediatric 30 response, as well as by the 50% and 70% response levels (ACR pediatric 50 and ACR pediatric 70, respectively).ResultsIn the screening phase, after receiving standard doses of MTX, 430 patients (72%) improved according to the ACR pediatric 30, while 360 (61%) met the ACR pediatric 50 and 225 (38%) met the ACR pediatric 70; among these patients, 69 (12%) also met the definition of complete disease control. Of the 133 nonresponders, 80 were randomized to receive an intermediate dose or higher dose of MTX. In the randomization phase, the ACR pediatric 30 response rate was 25 of 40 children (62.5%) in the intermediate‐dose group versus 23 of 40 children (57.5%) in the higher‐dose group. An ACR pediatric 50 response rate was attained by 23 patients (57.5%) receiving an intermediate dose versus 22 (55%) in the higher‐dose group. An ACR pediatric 70 response rate was seen in 18 children (45%) receiving an intermediate dose versus 19 (47.5%) receiving a higher dose. Five children (12.5%) in the intermediate‐dose group versus 4 (10%) receiving the higher dose of MTX also met the definition of complete disease control. None of the intergroup differences in response rate were significant. There were no significant differences in the frequency of adverse events or laboratory abnormalities between the 2 randomized groups.ConclusionThis study shows that the plateau of efficacy of MTX in JIA is reached with parenteral administration of 15 mg/m2/week and that a further increase in dosage is not associated with any additional therapeutic benefit. MTX should be administered for up to 9–12 months to appreciate its full therapeutic effect.
Medical care expenditures and earnings losses of persons with arthritis and other rheumatic conditions in the United States in 1997: Total and incremental estimates
Authors: Yelin Edward , Cisternas Miriam G. , Pasta David J. , Trupin Laura , Murphy Louise , Helmick Charles G. 
Published: July 2004

AbstractObjectiveTo provide estimates of the total medical care expenditures and earnings losses associated with arthritis and other rheumatic conditions (AORC), as well as the increment in such costs specifically attributable to these conditions, in the US in 1997.MethodsThe estimates were derived from the 1997 Medical Expenditures Panel Survey (MEPS), a national probability sample of 14,147 households including 34,551 persons, of whom 4,776 self‐reported arthritis. After weighting, those who self‐reported AORC represent 38.4 million persons. We tabulated all medical care expenditures of the adult MEPS respondents, stratified by arthritis and comorbidity status, and then used regression techniques to estimate the increment in health care expenditures attributable to AORC, after taking comorbidity, demographic characteristics, and insurance status into account. Using the same methods, we also estimated the magnitude of the earnings losses sustained by persons of working ages (18–64 years) who had AORC.ResultsPersons with AORC incurred mean total medical care expenditures of $4,865 (total $186.9 billion). The largest components of these expenditures were inpatient care (39%), ambulatory care (29%), and prescriptions (14%). The mean increment in medical care expenditures specifically attributable to AORC among those ages 18 years and older was $1,391 (total ∼$51.1 billion). Persons with AORC ages 18–64 years earned $3,812 less on average than did other persons of these ages (total $82.4 billion). Of this average, $1,579 was attributable to the AORC (total $35.1 billion).ConclusionIn 1997, persons with AORC incurred direct and indirect costs of $269.3 billion, of which $86.2 billion was attributable to these conditions.
Anti–tumor necrosis factor therapy in patients with difficult to treat Takayasu arteritis
Authors: Hoffman Gary S. , Merkel Peter A. , Brasington Richard D. , Lenschow Deborah J. , Liang Patrick 
Published: July 2004

AbstractObjectiveGranulomatous inflammation is a typical feature of Takayasu arteritis (TA), and tumor necrosis factor (TNF) is important in the formation of granulomas. In this study, we assessed therapy with anti‐TNF agents in patients with TA that was not controlled by glucocorticoid therapy or other immunosuppressants.MethodsWe conducted an open‐label trial of anti‐TNF therapy at 3 academic medical centers over a period of 4.25 years. Fifteen patients with active, relapsing TA (median 6 years) were selected. Seven received etanercept (later changed to infliximab in 3 patients), and 8 received infliximab. Relapses had occurred in all patients while they were receiving glucocorticoids and, in 13 patients, additional immunosuppressive drugs. No other agents were added to the treatment regimen concurrently with anti‐TNF. If patients were receiving cytotoxic agents, the dosage was not increased. Clinical symptoms were recorded, and physical examinations, laboratory studies, and serial magnetic resonance imaging were performed.ResultsThe median daily dose of prednisone required to maintain remission prior to anti‐TNF therapy was 20 mg. Ten of the 15 patients achieved complete remission that was sustained for 1–3.3 years without glucocorticoid therapy. Four patients achieved partial remission, with a >50% reduction in the glucocorticoid requirement. At a median of 12 months of followup, the median dose of prednisone was 0. Therapy failed in 1 patient. In 9 of the 14 responders, an increase in the anti‐TNF dosage was required to sustain remission. Two relapses occurred during periods when anti‐TNF therapy (etanercept) was interrupted, but remission was reestablished upon reinstitution of therapy.ConclusionIn this pilot study of relapsing TA, addition of anti‐TNF therapy resulted in improvement in 14 of 15 patients and sustained remission in 10 of 15 patients, who were able to discontinue glucocorticoid therapy. Anti‐TNF may be a useful adjunct to glucocorticoids in the treatment of TA. Our results justify a randomized, controlled clinical trial of anti‐TNF therapy for TA.
Elevation of activated protein C in synovial joints in rheumatoid arthritis and its correlation with matrix metalloproteinase 2
Authors: Buisson‐Legendre Nathalie , Smith Sue , March Lyn , Jackson Christopher 
Published: July 2004

AbstractObjectiveTo investigate the involvement of the anticoagulant serine protease activated protein C (APC) in tissue remodeling in rheumatoid arthritis (RA).MethodsPC/APC, matrix metalloproteinase 2 (MMP‐2), and MMP‐9 were detected in synovial fluid by Western blotting, and their antigen levels were quantified by enzyme‐linked immunosorbent assay in patients with osteoarthritis (OA) or RA. Enzymatic activity of MMP‐2 was assayed using a specific fluorogenic substrate. We developed an improved assay to measure APC activity in synovial fluid utilizing a chromogenic substrate following immunoprecipitation with a specific PC/APC antibody. PC/APC and MMP‐2 were localized by immunohistochemistry in RA, OA, and normal synovial tissues.ResultsSynovial fluid analysis demonstrated that APC is present in both RA and OA synovial fluid, with APC activity being markedly higher in RA (mean ± SEM 462 ± 112 ng/ml versus 136 ± 42 ng/ml; P < 0.02). A correlation (r2 = 0.61) was found between APC and MMP‐2 activity levels in RA patients, but not in OA patients. Immunohistochemical studies of synovial sections showed colocalization of APC and MMP‐2 in endothelial and synovial lining cells. Additionally, APC and MMP‐2 coimmunoprecipitated with an anti‐PC/APC antibody.ConclusionOur results show, for the first time, that APC and MMP‐2 are coordinately up‐regulated and tightly bound in RA synovial fluid and colocalized in synovia. Their association suggests that APC may modulate MMP‐2 activity in RA.
Macrophage release of transforming growth factor β1 during resolution of monosodium urate monohydrate crystal–induced inflammation
Authors: Yagnik Darshna R. , Evans Betsy J. , Florey Oliver , Mason Justin C. , Landis R. Clive , Haskard Dorian O. 
Published: July 2004

AbstractObjectiveIt has previously been shown that as monocytes differentiate into macrophages, they lose the ability to secrete proinflammatory cytokines in response to monosodium urate monohydrate (MSU) crystals. The purpose of this study was to investigate whether MSU crystals induce macrophages to secrete antiinflammatory factor instead.MethodsHuman monocyte or macrophage isolates were prepared from samples obtained from healthy volunteer donors either by differentiation of blood monocytes in vitro or by collecting cells from skin blisters during the early or late phase of the dermal inflammatory response to cantharidin. Monocyte or macrophage isolates were then incubated with MSU crystals for 24 hours, and culture supernatants were assayed for candidate antiinflammatory mediators (by enzyme‐linked immunosorbent assay) and for the capacity to activate or suppress endothelial cell E‐selectin expression and secondary neutrophil recruitment under shear flow.ResultsAnalysis of supernatants from in vitro–differentiated macrophages revealed that transforming growth factor β1 (TGFβ1) was induced following MSU crystal stimulation (mean ± SEM 1.50 ± 0.24 ng/ml/106 cells), but there was no evidence of interleukin‐10 (IL‐10), IL‐1 receptor antagonist, or tumor necrosis factor (TNF) receptor p55 release. Macrophage TGFβ1 significantly suppressed endothelial cell E‐selectin expression and secondary neutrophil capture on endothelial monolayers stimulated with supernatants from MSU‐treated monocytes. Leukocytes isolated from resolving (40‐hour) skin blisters similarly elaborated TGFβ1 when challenged with MSU crystals (0.66 ± 1.3 ng/ml/105 CD14+ cells). In contrast, cells isolated from acute (16‐hour) skin blisters secreted TNFα (0.49 ± 0.08 ng/ml/105 CD14+ cells) but no detectable TGFβ1.ConclusionThese data provide further support for the concept that differentiated macrophages play a protective role in the pathophysiology of gout, and they identify macrophage TGFβ1 as a mediator of paracrine suppression during the resolution phase of inflammation.
Enhanced intracellular replication of Salmonella enteritidis in HLA–B27–expressing human monocytic cells: Dependency on glutamic acid at position 45 in the B pocket of HLA–B27
Authors: Penttinen Markus A. , Heiskanen Kaisa M. , Mohapatra Rajashree , DeLay Monica L. , Colbert Robert A. , Sistonen Lea , Granfors Kaisa 
Published: July 2004

AbstractObjectiveTo reveal the cause of the impaired elimination of Salmonella enteritidis in HLA–B27–transfected human monocytic cells and to study whether the B pocket of HLA–B27 contributes to these modulatory effects.MethodsStable U937 cell transfectants expressing HLA–A2, B27, or different forms of B27 with amino acid substitutions in the B pocket were prepared. Mock‐transfected cells were prepared using the antibiotic resistance vector (pSV2neo) alone. Cells were differentiated, infected with S enteritidis, and the number of live intracellular S enteritidis organisms was determined using the colony‐forming unit method. To visualize intracellular S enteritidis, the bacteria were transformed with green fluorescent protein (GFP), and studied by confocal microscopy.ResultsCells expressing wild‐type HLA–B27 were more permissive of intracellular replication of S enteritidis compared with mock‐transfected or A2‐transfected controls. Cells expressing B27 with an altered B pocket composition having either 6 amino acid substitutions (B27.A2B; substitutions H9F, T24A, E45M, I66K, C67V, and K70H) or a single substitution (B27.E45M) were no longer permissive of S enteritidis replication. In contrast, cells expressing B27 with the single substitution of F for H at position 9 (B27.H9F) retained their permissiveness. Studies using GFP‐transformed S enteritidis confirmed that the increase in the amount of intracellular bacteria in B27‐expressing cells was due to replication of the bacteria.ConclusionOur data indicate that HLA–B27 expression modulates the host–microbe interaction that results in an impaired capacity of monocytes to resist intracellular replication of S enteritidis. The phenotype is dependent on glutamic acid at position 45 in the B pocket and, thus, may be due to properties of the B27 heavy chain that are related to this residue. The ability of HLA–B27 to confer susceptibility to Salmonella‐triggered reactive arthritis may occur, at least in part, through these modulatory effects.
Cytochrome P450 pharmacogenetics as a predictor of toxicity and clinical response to pulse cyclophosphamide in lupus nephritis
Authors: Takada Kazuki , Arefayene Million , Desta Zeruesenay , Yarboro Cheryl H. , Boumpas Dimitrios T. , Balow James E. , Flockhart David A. , Illei Gabor G. 
Published: July 2004

AbstractObjectivePulse cyclophosphamide is the treatment of choice for severe lupus nephritis. However, not all patients respond to this therapy, and gonadal toxicity is of particular concern. Cyclophosphamide is a prodrug that requires activation by cytochrome P450 (CYP) enzymes. We conducted a retrospective cohort study to test whether genetic polymorphisms of these enzymes are associated with the toxicity of, and clinical response to, cyclophosphamide in patients with lupus nephritis.MethodsSixty‐two patients with proliferative lupus nephritis treated with cyclophosphamide were genotyped for common variant alleles of CYP2B6, 2C19, 2C9, and 3A5. We examined the association between these genotypes and the following clinical end points: development of premature ovarian failure, end‐stage renal disease (ESRD), doubling of serum creatinine level, and achievement of complete renal response.ResultsThe observed frequencies of the variant alleles CYP2B6*5, CYP2C19*2, CYP2C9*2, and CYP3A5*3 were 12.1%, 25.0%, 4.0%, and 75.8%, respectively. Patients who were either heterozygous or homozygous for CYP2C19*2 had a significantly lower risk of developing premature ovarian failure (relative risk 0.10; 95% confidence interval 0.02–0.52), after adjustment for age and total number of cyclophosphamide pulses received. In a survival analysis, patients homozygous for CYP2B6*5 (n = 3) or CYP2C19*2 (n = 4) had a higher probability of reaching ESRD (P = 0.0005) and of doubling the creatinine level (P = 0.0005) as well as a trend toward a lower probability of achieving a complete renal response (P = 0.051).ConclusionDetermination of selected cytochrome P450 enzyme genotypes may be valuable for predicting the risk of premature ovarian failure in lupus nephritis patients treated with cyclophosphamide. The association of these genotypes with renal response needs further validation.