bluuebunny/crossref_metadata_2025_split huggingface dataset:
The early pattern of joint involvement predicts disease progression in children with oligoarticular (pauciarticular) juvenile rheumatoid arthritis
Authors: Al‐Matar Mohammad J. , Petty Ross E. , Tucker Lori B. , Malleson Peter N. , Schroeder Maria‐Louise , Cabral David A. 
Published: October 2002

AbstractObjectiveTo evaluate features during the first 6 months of disease that may be associated with a poor outcome as measured principally by extension to a polyarticular disease course in patients with oligoarticular‐onset juvenile rheumatoid arthritis (oligo‐JRA).MethodsThis study was a retrospective review of patients who fulfilled the American College of Rheumatology criteria for oligo‐JRA, were followed up for at least 5 years, and did not have juvenile psoriatic arthritis, spondylarthropathy‐like disease, or rheumatoid factor positivity. Data from the first 6 months of disease were collected. Continuous variables were dichotomized and then screened by univariate analysis for association with poor outcome at the last followup visit, as measured by extension of involvement (>4 accumulated involved joints) and by “clinically meaningful” extension (≥10 accumulated joints). Variables significantly associated with this latter outcome, with the addition of disease duration as a confounding independent variable, were included in a multiple logistic regression analysis. The same variables were then examined in separate multiple logistic regression models to look at other measures of outcome, including use of disease‐modifying antirheumatic drugs (DMARDs) at any time, erosive disease on radiographs, any remission of disease ever occurring, physician's global assessment of disease activity at the last visit, and disability as measured by the Childhood Health Assessment Questionnaire (C‐HAQ)/HAQ.ResultsOf the 205 patients (160 of whom were female) studied for a median of 10.8 years (range 5–26.6 years), 39.5% developed extension to >4 joints and 17.6% developed arthritis in ≥10 joints. Using the logistic regression model, symmetric disease was predictive of all measures of poor outcome: extension to ≥10 joints (odds ratio [OR] 19.2), the need to use DMARDs (OR 11.5), radiographic demonstration of erosive disease (OR 4.73), inflammatory activity at last followup visit (OR 3.23), no remission of disease (OR 4.73), and disability as measured by a C‐HAQ score >0.12 (OR 2.95). Ankle and/or wrist disease was predictive of extension (OR 6.61) and erosions (OR 3.59). Wrist disease alone was predictive of the need to use DMARDs (OR 5.87) and of inflammatory disease activity at the last followup visit (OR 4.01). An elevated erythrocyte sedimentation rate (ESR) was predictive of extension (OR 3.76), the need to use DMARDs (OR 6.47), and no remission of disease (OR 2.30). Disease duration was a confounding variable for extension (OR 1.18) and erosive disease (OR 1.19).ConclusionThe early presence of ankle and/or wrist disease, symmetric joint involvement, and an elevated ESR in a child with oligo‐JRA indicates the likelihood of disease progression.
Lack of isoprenoid products raises ex vivo interleukin‐1β secretion in hyperimmunoglobulinemia D and periodic fever syndrome
Authors: Frenkel Joost , Rijkers Ger T. , Mandey Saskia H. L. , Buurman Sandra W. M. , Houten Sander M. , Wanders Ronald J. A. , Waterham Hans R. , Kuis Wietse 
Published: October 2002

AbstractObjectiveTo investigate whether the increased interleukin‐1β (IL‐1β) secretion in hyperimmunoglobulinemia D and periodic fever syndrome is due to the accumulation of mevalonate kinase (MK), the substrate of the deficient enzyme, or the lack of its products, the isoprenoid compounds.MethodsThe effects of lovastatin and farnesol (FOH), geranylgeraniol (GGOH), and mevalonate on peripheral blood mononuclear cells (PBMCs) from 8 patients with MK deficiency and from 13 controls were studied. Lovastatin inhibits isoprenoid biosynthesis by reducing the production of mevalonate. FOH and GGOH restore isoprenoid biosynthesis downstream from MK. Culture supernatants were collected for cytokine analysis 48 hours after stimulation with monoclonal antibodies against CD2 + CD28.ResultsLovastatin induced a 15‐fold rise in IL‐1β secretion by normal anti–CD2 + CD28–stimulated cells (P < 0.001). This effect could be countered by mevalonate and, to a lesser extent, by FOH and GGOH. In the absence of lovastatin, mevalonate did not change IL‐1β secretion. Stimulated MK‐deficient cells secreted 9‐fold more IL‐1β than control PBMCs (P < 0.005), rising 2.4‐fold in the presence of lovastatin. The effect of lovastatin on IL‐1β secretion was reduced by mevalonate, FOH, and GGOH. Isoprenoid biosynthesis in PBMCs from patients was impaired due to the endogenous MK deficiency. Bypassing this defect with FOH, in the absence of lovastatin, led to a 62% reduction (P < 0.02) in IL‐1β secretion by these cells.ConclusionIn this model, shortage of isoprenoid end products contributes to increased IL‐1β secretion by MK‐deficient PBMCs, whereas excess mevalonate does not.
Association of global brain damage and clinical functioning in neuropsychiatric systemic lupus erythematosus
Authors: Bosma G. P. Th. , Middelkoop H. A. M. , Rood M. J. , Bollen E. L. E. M. , Huizinga T. W. J. , Van Buchem M. A. 
Published: October 2002

AbstractObjectiveTo investigate the relationship between quantitative estimates of global brain damage based on magnetization transfer imaging (MTI) and cerebral functioning, as measured by neurologic, psychiatric, and cognitive assessments, as well as disease duration in patients with a history of neuropsychiatric systemic lupus erythematosus (NPSLE).MethodsIn a clinically heterogeneous group of 24 female patients (age range 19–65 years, mean age 35 years) with a history of NPSLE, the correlation values of several volumetric MTI measures and an estimate of cerebral atrophy, neurologic functioning (Kurtzke's Expanded Disability Status Scale [EDSS]), psychiatric functioning (the Hospital Anxiety and Depression Scale [HADS]), and cognitive functioning (cognitive impairment score [CIS] derived from the revised Wechsler Adult Intelligence Scale), as well as several measures of disease duration were assessed using Pearson's correlation coefficient.ResultsQuantitative volumetric estimates of global brain damage based on MTI and a measure of global brain atrophy correlated significantly with the EDSS, HADS, and CIS scores. No significant correlation was found between the quantitative estimates of global brain damage and the measures of disease duration.ConclusionThe results of this study demonstrate that volumetric MTI parameters and cerebral atrophy reflect functionally relevant brain damage in patients with NPSLE. Furthermore, the absence of a linear relationship between disease duration and results of volumetric MTI measures and atrophy suggests a complicated pattern of accumulating brain damage in patients with NPSLE.
Human intervertebral disc aggrecan inhibits nerve growth in vitro
Authors: Johnson William E. B. , Caterson Bruce , Eisenstein Stephen M. , Hynds Dianna L. , Snow Diane M. , Roberts Sally 
Published: October 2002

AbstractObjectiveTo assess the effects of human intervertebral disc aggrecan on nerve growth and guidance, using in vitro techniques.MethodsAggrecan extracted from human lumbar intervertebral discs was incorporated into tissue culture substrata for the culture of the human neuronal cell line, SH‐SY5Y, or explants of chick dorsal root ganglia. The effects on nerve growth of different concentrations of aggrecan extracted from the anulus fibrosus and nucleus pulposus, and of these aggrecan preparations following enzymic deglycosylation, were compared.ResultsDisc aggrecan inhibited the growth of neurites from SH‐SY5Y cells and induced growth cone turning of chick sensory neurites in a concentration‐dependent manner. Aggrecan isolated from the anulus fibrosus was more inhibitory than that isolated from the nucleus pulposus, but enzymic pretreatments to reduce the glycosylation of both types of disc aggrecan partially abrogated their inhibitory effects.ConclusionNerve growth into degenerate intervertebral discs has been linked with the development of low back pain, but little is known about factors affecting disc innervation. The finding that disc aggrecan inhibits nerve growth in vitro, and that this inhibitory activity depends on aggrecan glycosylation, has important implications for our understanding of mechanisms that may regulate disc innervation in health and disease.
Cachexia in rheumatoid arthritis is not explained by decreased growth hormone secretion
Authors: Rall Laura C. , Walsmith Joseph M. , Snydman Laura , Reichlin Seymour , Veldhuis Johannes D. , Kehayias Joseph J. , Abad Leslie W. , Lundgren Nancy T. , Roubenoff Ronenn 
Published: October 2002

AbstractObjectivePatients with rheumatoid arthritis (RA) lose body cell mass (BCM) by unknown mechanisms. Since the loss of BCM in normal aging individuals parallels the characteristic age‐related decline in growth hormone (GH) secretion, this study was carried out to determine whether further decreased GH secretion plays a role in the pathogenesis of this loss of BCM in RA patients, termed “rheumatoid cachexia.”MethodsGH secretory kinetics were determined by deconvolution analysis in 16 patients with RA and 17 healthy controls matched for age (mean ± SD 45.4 ± 13.2 years and 47.1 ± 14.6 years, respectively), sex, race, and body mass index. Blood samples were obtained every 20 minutes for 24 hours. Body composition was ascertained using total‐body potassium (TBK) as a measure of BCM and dual x‐ray absorptiometry to determine fat mass.ResultsBCM was reduced in patients with RA compared with healthy controls (mean ± SD gm TBK 79.5 ± 9.5 versus 94.9 ± 11.9; P < 0.0005), but there was no difference in fat mass. GH kinetic parameters in patients with RA did not differ from those in controls.ConclusionThese findings suggest that GH kinetics are unaltered in RA patients compared with healthy subjects; thus, GH deficiency does not account for rheumatoid cachexia.
Evaporation heat transfer of steady thin film in micro capillary tubes of micron scale
Authors: Qu Wei , Ma Tongze 
Published: October 2002

AbstractThis paper reports that the heat transfer mechanism of phase change in a capillary tube belongs to liquid film conduction and surface evaporation. The surface evaporation is influenced by vapor temperature, vapor‐liquid interfacial temperature, and vapor‐liquid pressure difference. In the vapor‐liquid flow mechanism, flow is effected by both the gradient of disjoining pressure, and the gradient of capillary pressure. The mechanism of vapor‐liquid interaction consists of the shear stress caused by momentum transfer owing to evaporation, and frictional shear stress due to the velocity difference between vapor and liquid. In the model presented for a capillary tube, the heat transfer, vapor‐liquid flow, and their interaction are more comprehensively considered. The thin film profile and heat transfer characteristics have close relations with a capillary radius and heat transfer power. The results of calculation indicate that the length of the evaporating interfacial region decreases to some extent with decreasing capillary radius and increasing heat transfer power. © 2002 Wiley Periodicals, Inc. Heat Trans Asian Res, 31(7): 513–523, 2002; Published online in Wiley InterScience (www.interscience.wiley.com).DOI 10.1002/htj.10050
Hyaluronidase reduces human breast cancer xenografts in SCID mice
Authors: Shuster Svetlana , Frost Gregory I. , Csoka Antonei B. , Formby Bent , Stern Robert 
Published: October 2002

AbstractA hyaluronan‐rich environment often correlate with tumor progression. and may be one mechanism for the invasive behavior of malignancies. Eradication of hyaluronan by hyaluronidase administration could reduce tumor aggressiveness and would provide, therefore, a new anti‐cancer strategy. Hyaluronan interaction with its CD44 receptor and the resulting signal transduction events may be among the mechanisms for hyaluronan‐associated cancer progression. We have shown previously that hyaluronidase treatment of breast cancer cells in vitro not only eradicates hyaluronan but also modifies expression of CD44 variant exons of tumor cells. We now determine if such effects occur in vivo and if it is accompanied by tumor regression. SCID mice bearing xenografts of human breast carcinomas were given intravenous hyaluronidase. Tumor volumes decreased 50% in 4 days. Tumor sections showed decreased hyaluronan. Intensity of staining for CD44s was not affected, whereas staining for specific CD44 variant exon isoforms was greatly reduced in residual tumors. Necrosis was not evident. Hyaluronidase, used previously as an adjunct in cancer treatment, presumably to enhance penetration of chemotherapeutic drugs, may itself have intrinsic anti‐cancer activity. Removing peritumor hyaluronan appears to cause an irreversible change in tumor metabolism. Continuous hyaluronan binding to CD44 variant exon isoforms may also be required to stabilize inherently unstable isoforms that participate perhaps in tumor progression. Further investigation is required to confirm a cause and effect relationship between loss of hyaluronan, changes in CD44 variant exon expression and tumor reduction. If confirmed, hyaluronidase may provide a new class of anti‐cancer therapeutics and one without toxic side effects. © 2002 Wiley‐Liss, Inc.
After hMSH2 and hMLH1—what next? Analysis of three‐generational, population‐based, early‐onset colorectal cancer families
Authors: Jenkins Mark A. , Baglietto Laura , Dite Gillian S. , Jolley Damien J. , Southey Melissa C. , Whitty Jonathan , Mead Leeanne J. , St. John D. James B. , Macrae Finlay A. , Bishop D. Timothy , Venter Deon J. , Giles Graham G. , Hopper John L. 
Published: October 2002

AbstractThe aim of our study was to examine the role of genetic factors on early‐onset colorectal cancer after excluding the impact of germline mutations in the two major mismatch repair genes. A total of 131 incident probands, under 45 years at diagnosis of a first primary colorectal cancer selected from the Victorian Cancer Registry, and their first‐and second‐degree relatives, were interviewed. Germline DNA from all 12 probands with a family history meeting the modified Amsterdam Criteria for Hereditary Non‐Polyposis Colorectal Cancer (HNPCC) and a random sample of 31 of the remaining probands was screened for mutations in hMSH2 and hMLH1 via manual sequencing. Germline mutations were identified in 6 of the 131 probands (5%), all from the “HNPCC” families. Of the remaining 125 probands, 51 (41%) reported at least one first‐or second‐degree relative with colorectal cancer with an excess of colorectal cancer in first‐degree relatives (SMR = 2.7, 95% CI = 1.7–4.1, p < 0.001). The lifetime risk to age 70 for first‐degree relatives was 8.0% (5.0–12.8%), compared to the Victorian population risk of 3.2% (p = 0.01). The best fitting major gene model was a recessively‐inherited risk of 98% to age 70 (95% CI = 24–100%) carried by 0.17% of the population and would explain 15% of all colorectal cancer in cases with a diagnosis before age 45. Early‐onset colorectal cancer is strongly familial even after excluding families found to be segregating a mutation in either of the 2 major mismatch repair genes. There is evidence for a role of yet to be identified genes associated with a high recessively‐inherited risk of colorectal cancer. © 2002 Wiley‐Liss, Inc.
Tumor‐targeting properties of antibody–vascular endothelial growth factor fusion proteins
Authors: Halin Cornelia , Niesner Uwe , Villani Maria Elena , Zardi Luciano , Neri Dario 
Published: October 2002

AbstractA major problem of antibody‐based targeting of solid tumors is the poor penetration of antibodies into tumor tissue. Vasoactive immunoconjugates have been proposed as a means of increasing antibody uptake in tumors. In principle, VEGF (also known as vascular permeability factor) could selectively alter vascular permeability, leading to improved tumor targeting. A possible role for VEGF in the targeting of tumor neovasculature has been postulated, based on the overexpression of VEGF receptors in tumor endothelial cells. However, quantitative biodistribution studies on this topic are not available. In this report, we describe the cloning, expression, characterization and biodistribution in tumor‐bearing mice of antibodies fused to either VEGF120 or VEGF164 The MAb fragments chosen for analysis were scFv(L19), specific for the ED‐B domain of fibronectin, a marker of angiogenesis, and scFv(HyHEL‐10), a negative control antibody of irrelevant specificity in mice. Neither unconjugated VEGF nor scFv(HyHEL‐10)–VEGF fusion proteins showed accumulation in the tumor (tumor:blood ratios approx. 1 at 4 hr and 24 hr postinjection). By contrast, scFv(L19)–VEGF120 but not scFv(L19)–VEGF164 showed significant accumulation in tumors (tumor:blood ratio = 9.3 at 24 hr) but was not superior to unconjugated scFv(L19). Preinjection of unlabeled scFv(L19)–VEGF120 prior to administration of radiolabeled fusion protein led to increased accumulation of radiolabeled scFv(L19)–VEGF120 in the tumor but only at very high concentrations (20 μg/mouse). © 2002 Wiley‐Liss, Inc.
Mutation analysis of EP300 in colon, breast and ovarian carcinomas
Authors: Bryan Emma J. , Jokubaitis Venta J. , Chamberlain Narelle L. , Baxter Simon W. , Dawson Elisabeth , Choong David Y.H. , Campbell Ian G. 
Published: October 2002

AbstractThe putative tumour suppressor gene EP300 is located on chromosome 22q13 which is a region showing frequent loss of heterozygosity (LOH) in colon, breast and ovarian cancers. We analysed 203 human breast, colon and ovarian primary tumours and cell lines for somatic mutations in EP300. LOH across the EP300 locus was detected in 38% of colon, 36% of breast, and 49% of ovarian primary tumours but no somatic mutations in EP300 were identified in any primary tumour. Analysis of 17 colon, 11 breast, and 11 ovarian cancer cell lines identified truncating mutations in 4 colon cancer cell lines (HCT116, HT29, LIM2405 and LIM2412). We confirmed the presence of a previously reported frameshift mutation in HCT116 at codon 1699 and identified a second frameshift mutation at codon 1468. Bi‐allelic inactivation of EP300 was also detected in LIM2405 that harbours an insC mutation at codon 927 as well an insA mutation at codon 1468. An insA mutation at codon 1468 was identified in HT29 and a CGA>TGA mutation at codon 86 was identified in LIM2412. Both these lines were heterozygous across the EP300 locus and western blot analysis confirmed the presence of an apparently wild‐type protein. Our study has established that genetic inactivation of EP300 is rare in primary colorectal, breast and ovarian cancers. In contrast, mutations are common among colorectal cancer cell lines with 4/17 harbouring homozygous or heterozygous mutations. The rarity of EP300 mutations among these tumour types that show a high frequency of LOH across 22q13 may indicate that another gene is the target of the loss. It is possible that bi‐allelic inactivation of EP300 is not necessary and that haploinsufficiency is sufficient to promote tumorigenesis. Alternatively, silencing of EP300 may be achieved by epigenetic mechanisms such as promoter methylation. © 2002 Wiley‐Liss, Inc.
BRCA2 mutations in a population‐based series of patients with ocular melanoma
Authors: Scott Rodney J. , Vajdic Claire M. , Armstrong Bruce K. , Ainsworth Christopher J. , Meldrum Cliff J. , Aitken Joanne F. , Kricker Anne 
Published: October 2002

AbstractWe studied the BRCA2 gene for germline mutations in 71 of 99 patients (72%) with ocular melanoma who were diagnosed consecutively in Australia in 1997 and 1998. Patients considered for our study fulfilled one of the following critiera: (i) were 50 years of age or less at diagnosis; (ii) had bilateral disease (2 patients); (iii) reported a family history of ocular melanoma (4 patients). Mutation detection was performed using the protein truncation test and denaturing high‐performance liquid chromatography with primers designed to include intron‐exon boundaries. Six DNA changes were found of which 2 were exonic, in exons 14 (A>C in nucleotide 7244 leading to His>Arg) and 27 (base pair substitution in nucleotide 9976 leading to a stop codon). One exonic change has been reported previously. None of the intronic mutations were deemed to affect splicing efficiency. Neither exonic mutation was in a person with bilateral ocular melanoma or a family history of cutaneous melanoma. We estimated the prevalence of possible loss of function changes in BRCA2 in patients with ocular melanoma at 3% (95% CI 0–10%). This figure was similar to previous estimates of 2.8% and 2% in nonrepresentative samples of patients with ocular melanoma and 2.1% in a representative sample of young women with breast cancer. © 2002 Wiley‐Liss, Inc.
Targets of transcriptional regulation by two distinct type I receptors for transforming growth factor‐β in human umbilical vein endothelial cells
Authors: Ota Tatsuru , Fujii Makiko , Sugizaki Takashi , Ishii Masami , Miyazawa Keiji , Aburatani Hiroyuki , Miyazono Kohei 
Published: October 2002

AbstractTransforming growth factor‐β (TGF‐β) plays a crucial role in vascular development and homeostasis by regulating many transcriptional targets. Activin receptor‐like kinase 5 (ALK‐5) is a TGF‐β type I receptor expressed in various TGF‐β‐responsive cells. In contrast, ALK‐1 functions as a TGF‐β type I receptor in endothelial cells, and is responsible for human hereditary hemorrhagic telangiectasia (HHT) type II. ALK‐5 and ALK‐1 mediate TGF‐β signals through distinct Smad proteins, i.e., Smad2/Smad3 and Smad1/Smad5, respectively. To identify target genes of ALK‐1 and ALK‐5 in endothelial cells, we conducted oligonucleotide microarray analysis. Human umbilical vein endothelial cells (HUVEC) were infected with recombinant adenoviruses carrying a constitutively active form of ALK‐1 or ALK‐5. ALK‐5 inhibited the proliferation, network formation, and tube formation of HUVEC and induced their apoptosis, whereas ALK‐1 did not exhibit significant effects on HUVEC in vitro. mRNAs were extracted from HUVEC and used for hybridization of oligonucleotide arrays representing approximately 7,000 human genes. Northern blot and quantitative real‐time polymerase chain reaction (PCR) analyses were also performed for some of these genes, confirming the validity of this microarray analysis. We found that ALK‐1 specifically upregulated Smad6, Smad7, Id1, Id2, endoglin, STAT1, and interleukin 1 receptor‐like 1. ALK‐5, in contrast, upregulated PlGF, SM22α, connexin 37, βIG‐H3, and LTBP1. ALK‐1 downregulated Smad1, CXCR4, Ephrin‐A1, and plakoglobin, whereas ALK‐5 downregulated claudin 5 and integrin β5. These results revealed some new targets of TGF‐β in endothelial cells, and differences in transcriptional regulation patterns between ALK‐1 and ALK‐5. J. Cell. Physiol. 193: 299–318, 2002. © 2002 Wiley‐Liss, Inc.