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ID PMID Title PublicationDate abstract
10813282 KL-6 as a novel serum marker for interstitial pneumonia associated with collagen diseases. 2000 May OBJECTIVE: To investigate the diagnostic value of the serum concentrations of KL-6, a mucinous glycoprotein expressed on type II pneumocytes, for interstitial pneumonia (IP) in various collagen diseases. METHODS: Serum KL-6 levels were measured by ELISA. RESULTS: The mean values and the positive rates of serum KL-6 levels for patients with rheumatoid arthritis, systemic sclerosis, or polymyositis/dermatomyositis with IP were significantly higher than those without IP. Sensitivity, specificity, positive and negative predictive values of serum KL-6 level for IP associated with collagen diseases were 60.7, 98.9, 97.4, and 77.1%, respectively. The mean serum KL-6 level of patients with active IP was significantly (p = 0.0001) higher than that of patients with inactive IP. Serum KL-6 levels increased with the deterioration of IP, while the successful treatment of IP resulted in a significant decrease of these levels. CONCLUSION: Serum KL-6 concentration levels are a useful marker for diagnosis and evaluation of the disease activity of IP associated with collagen diseases.
10700340 Cerebral responses to pain in patients suffering acute post-dental extraction pain measure 1999 Jun Previous studies with normal volunteers have demonstrated distributed cortical responses to experimental heat pain within a network of structures. The network includes the insula, anterior cingulate, prefrontal, inferior parietal and somatosensory cortices. Patients suffering from chronic nociceptive pain following rheumatoid arthritis (RA) have shown damped central responses to experimental heat pain applied to the back of the right hand. In this study of patients with acute, left-sided, post-molar-extraction (surgical) pain, we assessed the cortical responses to experimental heat pain, applied to the back of the right hand, using positron emission tomography (PET), and compared the responses with a previously reported control group and the RA group. In response to the experimental heat pain, the surgical group indicated significantly increased regional cerebral blood flow in the prefrontal cortex [Brodman's area (BA) 44] ipsilateral to the heat stimulus. Contralateral increases were detected in the putamen and transverse temporal gyrus (BA 40/41/42) with bilateral increases in the insular cortex. Compared to the control and RA group, there were significantly reduced responses in the anterior cingulate (BA 24), pre-frontal medial, and orbito-frontal (BA 9/10/32/47) cortices. These results suggest that relatively discrete regions of the cerebral cortex are responsible for acute nociceptive processing during an acute inflammatory episode. The reduced frontal and anterior cingulate responses to the experimental heat pain (applied to the right hand) during acute inflammatory pain (left jaw) illustrates cortical modulation of nociceptive processing that may be related to non-somatotopic, bilateral, nociceptive inputs to these areas. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.
10662872 Quantification of the cell infiltrate in synovial tissue by digital image analysis. 2000 Jan OBJECTIVE: The experience with digital image analysis (DIA) in the assessment of synovial inflammation is limited. In this study we compared DIA with two currently applied methods for the evaluation of the synovium. METHODS: Synovial tissue (ST) specimens were obtained by arthroscopy from knee joints of rheumatoid arthritis (RA) patients with variable disease expression and in control subjects. CD68+ macrophages and CD3+ T-cells were detected by immunohistochemical staining using two different labelling techniques. The labelled ST sections were quantified using three different analysis techniques: manual cell counting (MC), semi-quantitative analysis (SQA) and DIA. RESULTS: We observed strongly positive correlations between the three methods when examining T-cell infiltration: between MC and SQA: sigma=0.91 (P<0. 0001), between MC and DIA: sigma=0.95 (P<0.0001), and between SQA and DIA: sigma=0.83 (P<0.0001). Similarly, for the analysis of synovial intimal macrophages, positive correlations were noted between MC and SQA (sigma=0.62; P=0.002), MC and DIA (sigma=0.56; P<0.01), and SQA and DIA (sigma=0.79; P<0.0001). Finally, the analysis of synovial sublining macrophages revealed positive correlations between MC and SQA (sigma=0.95; P<0.0001), MC and DIA (sigma=0.64; P=0.001) and SQA and DIA (sigma=0.69; P<0.0001). CONCLUSION: These three different methods generated similar results. DIA offers the opportunity of a reliable and time-efficient analysis of the synovial infiltrate.
10648013 A citrus flavonoid, nobiletin, suppresses production and gene expression of matrix metallo 2000 Jan OBJECTIVE: Flavonoids including nobiletin are known to exert many biological actions in vitro. We investigated the chondroprotective effect of citrus flavonoids, especially nobiletin, using cultured rabbit synovial fibroblasts and articular chondrocytes. METHODS: We examined the effects of citrus flavonoids on the production and gene expression of matrix metalloproteinases (MMP) and prostaglandin E2 (PGE2)production in rabbit synovial fibroblasts. RESULTS: Six flavonoids isolated from Citrus depressa Rutaceae including tangeretin, 6-demethoxytangeretin, nobiletin, 5-demethylnobiletin, 6-demethoxynobiletin, and sinensetin suppressed the interleukin 1 (IL-1) induced production of proMMP-9/progelatinase B in rabbit synovial cells in a dose dependent manner (<64 microM); nobiletin most effectively suppressed proMMP-9 production along with the decrease in its mRNA. Nobiletin also reduced IL-1 induced production of PGE2 in the synovial cells, but did not modify the synthesis of total protein. These suppressive effects of nobiletin were also observed in rabbit articular chondrocytes. Nobiletin inhibited proliferation of rabbit synovial fibroblasts in the growth phase. CONCLUSION: These results suggest nobiletin is a novel antiinflammatory candidate that has the potential to inhibit PGE2 production, matrix degradation of the articular cartilage, and pannus formation in osteoarthritis and rheumatoid arthritis.
10586159 Pathophysiology of surgical site infection in total hip arthroplasty. 1999 Dec This article is a case report of a 69-year-old man who underwent a right total hip replacement procedure and developed a surgical site infection. Areas of concern in prevention and treatment of hip arthroplasty infection are presented, focusing on the pathophysiologic process involved. A review of the patient risk factors and the pathophysiologic action potentiating risk for infection include host immunity, nutritional status, diabetes, age, use of steroids or immunosuppressive drugs, rheumatoid arthritis, and urinary tract or other infections. The case report identifies the patient's age, multiple instrumentation of the bladder resulting in bacteriuria and the reinfusion of 400 cc of autologous shed blood via cell saver, a controversial risk subject, as the primary risk factors for surgical site infection in this patient. Readmission to the hospital on day 16 after the operation was completed on identification of 2 pathogenic organisms, methicillin-resistant Staphylococcus aureus and Acinetobacter calcoaceticus bio anitratus. The infection was successfully treated with oral ciprofloxacin and intravenous administration of tobramycin, preventing progression from superficial to deep infection and preserving the prosthesis.
10559228 CD45-induced tumor necrosis factor alpha production in monocytes is phosphatidylinositol 3 1999 Nov 19 The pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha plays a pivotal role in the pathogenesis of rheumatoid arthritis. The mechanisms involved in regulating monocyte/macrophage TNFalpha production are not yet fully understood but are thought to involve both soluble factors and cell/cell contact with other cell types. Ligation of certain cell surface receptors, namely CD45, CD44, and CD58, can induce the production of TNFalpha in monocytes. In this paper, we investigate further the signaling pathways utilized by cell surface receptors (specifically CD45) to induce monocyte TNFalpha and compare the common/unique pathways involved with that of lipopolysaccharide. The results indicate that monocyte TNFalpha induced upon CD45 ligation or lipopolysaccharide stimulation is differentially modulated by phosphatidylinositol 3-kinase and nuclear factor-kappaB but similarly regulated by p38 mitogen-activated protein kinase. These results demonstrate that both common and unique signaling pathways are utilized by different stimuli for the induction of TNFalpha. These observations may have a major bearing on approaches to inhibiting TNFalpha production in disease where the cytokine has a pathogenic role.
10502542 Metals and kidney autoimmunity. 1999 Oct The causes of autoimmune responses leading to human kidney pathology remain unknown. However, environmental agents such as microorganisms and/or xenobiotics are good candidates for that role. Metals, either present in the environment or administered for therapeutic reasons, are prototypical xenobiotics that cause decreases or enhancements of immune responses. In particular, exposure to gold and mercury may result in autoimmune responses to various self-antigens as well as autoimmune disease of the kidney and other tissues. Gold compounds, currently used in the treatment of patients with progressive polyarticular rheumatoid arthritis, can cause a nephrotic syndrome. Similarly, an immune-mediated membranous nephropathy frequently occurred when drugs containing mercury were commonly used. Recent epidemiologic studies have shown that occupational exposure to mercury does not usually result in autoimmunity. However, mercury induces antinuclear antibodies, sclerodermalike disease, lichen planus, or membranous nephropathy in some individuals. Laboratory investigations have confirmed that the administration of gold or mercury to experimental animals leads to autoimmune disease quite similar to that observed in human subjects exposed to these metals. In addition, studies of inbred mice and rats have revealed that a few strains are susceptible to the autoimmune effects of gold and mercury, whereas the majority of inbred strains are resistant. These findings have emphasized the importance of genetic (immunogenetic and pharmacogenetic) factors in the induction of metal-associated autoimmunity. (italic)In vitro(/italic) and (italic)in vivo(/italic) research of autoimmune disease caused by mercury and gold has already yielded valuable information and answered a number of important questions. At the same time it has raised new issues about possible immunostimulatory or immunosuppressive mechanisms of xenobiotic activity. Thus it is evident that investigations of metal-induced renal autoimmunity have the potential to produce new knowledge with relevance to autoimmune disease caused by xenobiotics in general as well as to idiopathic autoimmunity.
10502533 The role of genetic factors in autoimmune disease: implications for environmental research 1999 Oct Studies in both humans and in animal models of specific disorders suggest that polymorphisms of multiple genes are involved in conferring either a predisposition to or protection from autoimmune diseases. Genes encoding polymorphic proteins that regulate immune responses or the rates and extent of metabolism of certain chemical structures have been the focus of much of the research regarding genetic susceptibility. We examine the type and strength of evidence concerning genetic factors and disease etiology, drawing examples from a number of autoimmune diseases. Twin studies of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type I diabetes, and multiple sclerosis (MS) indicate that disease concordance in monozygotic twins is 4 or more times higher than in dizygotic twins. Strong familial associations (odds ratio ranging from 5-10) are seen in studies of MS, type I diabetes, Graves disease, discoid lupus, and SLE. Familial association studies have also reported an increased risk of several systemic autoimmune diseases among relatives of patients with a systemic autoimmune disease. This association may reflect a common etiologic pathway with shared genetic or environmental influences among these diseases. Recent genomewide searches in RA, SLE, and MS provide evidence for multiple susceptibility genes involving major histocompatibility complex (MHC) and non-MHC loci; there is also evidence that many autoimmune diseases share a common set of susceptibility genes. The multifactorial nature of the genetic risk factors and the low penetrance of disease underscore the potential influence of environmental factors and gene-environment interactions on the etiology of autoimmune diseases.
10501627 Antiinflammatory properties of mycophenolate mofetil in murine endotoxemia: inhibition of 1999 Sep Mycophenolate mofetil (MMF) is a new immunosuppressive agent currently used in organ transplantation and under evaluation in immune-mediated inflammatory disorders such as rheumatoid arthritis. Although MMF was shown to inhibit purine nucleotide synthesis in lymphocytes, it is still unclear whether it might also exert direct antiinflammatory actions in vivo. To address this question, we evaluated the effects of MMF administration on the responses of mice to a single challenge with bacterial lipopolysaccharide (LPS). We observed that MMF treatment inhibits the release of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) upon LPS injection whereas it promotes IL-10 production. In parallel, MMF was found to protect mice from LPS-induced lethality. Inhibition of TNF-alpha release was also observed in IL-10-deficient mice indicating that it does not exclusively depend on the upregulation of IL-10 endogenous synthesis. In view of the differential effects of MMF on the LPS-induced production of TNF-alpha and NO on one hand and that of IL-10 on the other hand, we conclude that beside its immunosuppressive action at the lymphocyte level, MMF is also endowed with antiinflammatory properties.
10413121 One-stage posterior decompression and reconstruction of the cervical spine by using pedicl 1999 Jan OBJECT: This retrospective study was conducted to analyze the results of one-stage posterior decompression and reconstruction of the cervical spine by using pedicle screw fixation systems in 46 patients. METHODS: Causes of cervical myelopathy in these 46 patients included spondylosis or ossification of the posterior longitudinal ligament, rheumatoid arthritis, metastatic or primary vertebral tumors, cervical spinal injuries, and spinal cord tumor. Thirty-three patients underwent this one-stage procedure as primary surgery. In the remaining 13 patients who had previously undergone laminectomies, the one-stage procedure was performed as salvage surgery. Cervical pedicle screws were inserted into the pedicles after probing and tapping. Graft bone was placed on the bilateral lateral masses, and pedicle screws were interconnected longitudinally by either plates or rods. Postoperatively, 26 patients showed improved neurological status (at least one grade improvement on Frankel's functional classification). There were no cases of neurological deterioration postoperatively. Solid bony fusion was obtained in all patients, except in seven patients with metastatic tumor who did not receive bone grafts. Correction of kyphosis was satisfactory. Postoperative radiological evaluation revealed that 10 (5.3%) of 190 screws inserted into the cervical vertebrae had perforated the cortex of the pedicles; however, no neurovascular complications were caused by the perforations. CONCLUSIONS: The pedicle screw fixation procedure, which does not require the lamina to be used as a stabilizing anchor, has proven to be valuable when performing one-stage posterior decompressive and reconstructive surgery in the cervical spine. The risk to neurovascular structures in this procedure, however, cannot be completely eliminated. Thorough knowledge of local anatomy and application of established surgical techniques are essential for this procedure.
10390126 Role and regulation of cyclooxygenase-2 during inflammation. 1999 May 31 Prostaglandins are formed from arachidonic acid by the action of cyclooxygenase (COX) and subsequent downstream synthetases. Recently, it has been found that there are two closely related forms of COX, which are now known as COX-1 and COX-2. Although both isoforms of this enzyme convert arachidonate to prostaglandins, there are significant differences in their distribution in the body and their roles in health and disease. The basis for these important differences lies in the genes for COX-1 and COX-2 and the regulation of these genes. COX-1, the predominantly constitutive form of the enzyme, is expressed throughout the body and provides certain homeostatic functions, such as maintaining normal gastric mucosa, influencing renal blood flow, and aiding in blood clotting by abetting platelet aggregation. In contrast, COX-2, the inducible form, is expressed in response to inflammatory and other physiologic stimuli and growth factors and is involved in the production of those prostaglandins that mediate pain and support the inflammatory process. All conventional nonsteroidal anti-inflammatory drugs (NSAIDs) nonspecifically inhibit both COX-1 and COX-2 at standard anti-inflammatory doses. The beneficial anti-inflammatory and analgesic effects occur through the inhibition of COX-2, but the gastrointestinal toxicities and the mild bleeding diathesis occur as a result of concurrent inhibition of COX-1. It is important that physicians fully understand the pharmacologic basis for the differential actions of NSAIDs when prescribing them for pain and inflammation. This understanding is also important so that physicians can critically evaluate the basis for, and the emerging data on, COX-2-specific inhibitors and their potential role in clinical medicine. Agents that would inhibit COX-2 while sparing COX-1 represent an attractive therapeutic development and could represent a major advance in the treatment of rheumatoid arthritis and osteoarthritis, as well as a diverse array of other conditions.
10381489 Chondroitin sulphation patterns in synovial fluid in osteoarthritis subsets. 1999 Jul OBJECTIVES: To determine concentrations of chondroitin sulphate (CS) disaccharides in knee synovial fluid (SF) from normal subjects and patients with osteoarthritis (OA) or rheumatoid arthritis (RA), to test whether these variables differ between different diseases and subsets of OA. METHODS: OA was subdivided into large joint OA (LJOA), nodal generalised OA (NGOA), and OA with calcium pyrophosphate crystal deposition (CPA), with 25, 9, and 11 people in each subset respectively. The SF of 13 normal subjects was also volunteered for analysis along with 15 RA patients. Clinical assessment of inflammation (0-6) was undertaken on OA and RA knees. Concentrations of unsaturated CS disaccharides Deltadi6S and Deltadi4S were measured by capillary zone electrophoresis. RESULTS: Concentrations of Deltadi6S were lower in RA (5.90 ng/ml) and OA (13.24 ng/ml) fluids compared with normal (21.0 ng/ml) but no significant differences were seen between disease and normal fluids for Deltadi4S (about 4-6 ng/ml). The ratio of Deltadi6S:Deltadi4S were RA
10233745 T-cell anergy induced by clonotype-specific antibodies: modulation of an autoreactive huma 1999 Apr Monoclonal antibodies (mAb) specific for the clonotype of an autoreactive T cell may be useful reagents in the modulation of autoimmune disease. We have previously reported the generation of a set of mAb specific for the clonotypic structure of a human T-cell clone recognizing an epitope of human cartilage gp-39. This glycoprotein was recently identified as a candidate autoantigen in rheumatoid arthritis. Here, we demonstrate for the first time that small amounts of immobilized anticlonotype mAb can induce anergy in the autoreactive clone. Following the anergic stimulus, T cells failed to proliferate upon restimulation as a result of a lack of interleukin-2 (IL-2) gene transcription. In addition, a diminished interferon-gamma (IFN-gamma) production was found. Our data indicate that anergy was not a result of T-cell receptor (TCR) downmodulation or the absence of free TCR. The anergic state was induced independent of costimulation or the presence of IL-2 and no protein synthesis was required for the induction of anergy. Anticlonotype mAb-induced anergy was prevented by cyclosporin A, suggesting that active signalling via the calcium/calcineurin pathway was required for the induction of anergy. In coculture experiments, anergic T cells were found to suppress the response of reactive cells from the same clone. This bystander suppression led to 90% inhibition of peptide-induced proliferation. Together, these findings suggest that mAb to the clonotypic structure of autoreactive T cells may be suitable reagents for the functional inactivation of these T cells in autoimmune diseases.
10225817 Increased apoptotic peripheral blood neutrophils in systemic lupus erythematosus: relation 1999 May OBJECTIVE: To quantify the percentage of apoptotic peripheral blood neutrophils in systemic lupus erythematosus (SLE) and to determine the relations with disease activity and neutropenia. METHODS: Neutrophil apoptosis in SLE patients (n =50) was assessed by flow cytometry using annexin V binding and fluorescent labelled anti-fas. Rheumatoid arthritis (RA, n =20) and inflammatory bowel disease patients (IBD, n =20) were studied as disease controls. RESULTS: The percentage of apoptotic neutrophils, determined by annexin V binding, was increased in peripheral blood of SLE patients (median = 3.25%) compared with normal healthy donors (n =20, median = 1.20%) and disease controls (RA: median = 1.15%) (IBD: median = 1.15%). SLE neutrophil apoptosis correlated positively with lupus disease activity measured by SLAM score. SLE patients with increased antibodies to dsDNA (>10 mg/ml) had increased apoptotic neutrophils. Eight of 14 neutropenic SLE patients had increased apoptotic neutrophils. Increased neutrophil fas expression compared with normal controls was observed in SLE, RA, and IBD. CONCLUSION: Neutrophil fas expression is increased non-specifically in inflammatory disease. Increased circulating apoptotic neutrophils in SLE correlate positively with disease activity (SLAM) and may contribute to autoantigen excess including dsDNA.
10222222 Beyond disability: measuring the social and personal consequences of osteoarthritis. 1999 Mar OBJECTIVE: Measuring the impact of osteoarthritis has traditionally focused on the disease (measures of impairment), functional disability and latterly, general health status or quality of life. This paper highlights the importance of measuring the wider personal and social consequences of OA both at a population and an individual patient level. DESIGN: The World Health Organisation definition of handicap is used to describe this wider impact of disease and measures of handicap, both generic and disease-specific are reviewed. The measurement of handicap in OA is illustrated by the use of the Disease Repercussion Profile in a clinical trial of orthopaedic out-patients with OA and low back pain. These data are compared to routine clinical handicap data collected on consecutive patients with rheumatoid arthritis attending a different outpatient clinic. RESULTS: OA patients reported handicap in six areas of their lives: functional and social activities, relationships, socio-economic status, emotional well-being and body image. The prevalence was similar to that reported by RA patients. OA patients reported more severe handicap than RA patients in each of the 6 areas (F ratios 4. 97-55.67) and the differences were statistically significant (P values 0.03-0.0001) for all dimensions except functional and social handicap. The LBP patients scored slightly more severe handicap on all dimensions than the OA patients but these differences did not reach statistical significance. However, they scored significantly more severe handicap than the RA patients (F ratios 8.49-174.72, P< 0.0001). CONCLUSIONS: These data suggest that the psychosocial impact of OA may have been underestimated and highlight the importance of going beyond disability in assessing the impact of OA. Measurement of the wider impact of OA can be achieved using disease-specific and generic measures of handicap. The choice of tool will depend upon the setting (research or clinical practice) and the purpose of measurement.
9787119 Gender differences in autoimmune diseases: estrogen increases calcineurin expression in sy 1998 Nov Systemic lupus erythematosus (SLE) predominantly affects women (9:1 compared to men) of childbearing age and often decreases its intensity in postmenopausal women, suggesting that sex hormones play a role in its pathogenesis. Comparison of steady-state levels of calcineurin mRNA using RNase protection assays revealed increased calcineurin expression in response to estradiol in cultured T cells from nine female lupus patients. Calcineurin mRNA levels did not increase significantly in T cells from eight age-matched normal control female volunteers. Estrogen-dependent calcineurin mRNA increased in a dose-dependent fashion, while progesterone and dexamethasone did not increase calcineurin mRNA in patient cells. Lupus T cell calcineurin mRNA increased in response to estradiol at 6 h but not at 3 h. Calcineurin phosphatase activity increased in lupus T cell extracts after incubation of cells with estradiol, while phosphatase activity in normal T cells was unaffected by estrogen. Calcineurin expression in T cells from patients with vasculitis and rheumatoid arthritis taking medications similar to those taken by the lupus patients was unaffected by estradiol. This study provides the first evidence for a molecular marker of estrogen action in lupus patients and suggests that estrogen-dependent changes in lupus T cell calcineurin could alter proinflammatory cytokine gene regulation and T-B cell interactions.
9106935 Characterization of SV40T antigen immortalized human synovial fibroblasts: maintained expr 1997 In rheumatoid arthritis (RA) synovial fibroblasts are activated by growth factors and cytokines to proliferate and to express matrix-degrading proteases and pro-inflammatory cytokines. This contributes to cartilage degradation and joint destruction. To analyse the parameters that lead to activation of synovial fibroblasts, we established a stable human synoviocyte line (K4IM) from a healthy donor by immortalization with SV40 T antigen (TAg). Characterizing the phenotype of the immortalized K4IM cells, we found that they maintained CD44, CD54 (intercellular adhesion molecule; ICAM-1) and CD95 (Fas) expression, but lost the expression of CD106 (vascular cell adhesion molecule 1; VCAM-1) and the receptors for interleukin 1 (IL-1) and platelet-derived growth factor (PDGF). We also monitored normal expression kinetics of transcription factor Egr-1 upon activation with tumor necrosis factor alpha (TNF-alpha) or synovial fluid from RA patients. In addition, we showed that HLA-DR expression could still be upregulated by recombinant interferon gamma (rINF-gamma). The immortalized K4IM cell line therefore represents a valuable and unique tool to study mechanisms that induce or maintain synoviocyte activation.
10813204 Constrictive (obliterative) bronchiolitis. 1998 Sep Constrictive bronchiolitis (CB), also termed in lung transplant patients obliterative bronchiolitis, is inflammation and fibrosis occurring predominantly in the walls and contiguous tissues of membranous and respiratory bronchioles with resultant narrowing of their lumens. CB is found in a variety of settings, most often as a complication of lung and heart-lung transplantation (affecting 34% to 39% of patients, usually in the first 2 years after transplantation) and bone marrow transplantation, but also in rheumatoid arthritis, after inhalation of toxic agents such as nitrogen dioxide, after ingestion of certain drugs such as penicillamine and ingestion of the East Asian vegetable Sauropus androgynous, and as a rare complication of adenovirus, influenza type A, measles, and Mycoplasma pneumoniae infections in children. In lung transplants, CB is the single most important factor leading to death thereafter. In one study, the overall mortality rate was 25%. However, at the same time, 87% of patients who were asymptomatic and diagnosed solely by transbronchial biopsy had resolution or stabilization of disease. Decreases in FEV1 from baseline can be used to clinically support CB in transplant patients; the term bronchiolitis obliterans syndrome is used to denote this clinical dysfunction, and a grading system has been established for it that is now widely used in the literature. Significant risk factors for the development of CB in lung transplants include alloantigen-dependent and -independent mechanisms. In the former group are late acute rejection and HLA mismatches at the A loci; in the latter are ischemia/reperfusion injuries to airways that result from the transplantation surgery and cytomegalovirus infection.
15016238 Type 1 diabetes in offspring of parents with type 1 diabetes: the tip of an autoimmune ice 2000 Mar The objective of the present study was to examine the prevalence of self-reported autoimmune diseases among offspring of type 1 fathers, type 1 diabetic mothers, and non-diabetic parents. Type 1 diabetic probands (n=265; mean age=42 yr), who were ascertained from the Children's Hospital of Pittsburgh Registry for 1950-1964, recently participated in the Familial Autoimmune and Diabetes Study. Non-diabetic probands (n=96), identified from voter registration lists and matched by age, race, median income, and duration of residence in the Pittsburgh area, were also enrolled. Offspring of type 1 diabetic probands were more likely to have a reported autoimmune disease (5.8% vs. 2.4%; p=0.067) than offspring of non-diabetic probands. Half the cases in the diabetic families were disorders other than type 1 diabetes, (e.g., rheumatoid arthritis, Crohn's disease, etc.). Stratification by parental gender revealed a marginally higher risk for type 1 diabetes among offspring of type 1 diabetic fathers compared to mothers (4.9% vs. 3.4%; p=0.38, respectively, through age 20 yr). However, the risk for other autoimmune disorders was statistically significantly increased among offspring of type 1 diabetic mothers (0% vs. 6.2%; p=0.02, respectively, through age 20 yr). These data suggest that offspring of type 1 diabetic parents may be at high risk of developing other autoimmune disorders during childhood, with pediatric diabetes representing the 'tip of an autoimmune iceberg'. The observed risk differences by parental gender, which have also been reported for other autoimmune disorders, warrant further investigation.
12687182 Influence of Immune Complexes on Expression of CD54 and CD95 on the Surface of Endothelial 2000 Oct The etiology of rheumatoid arthritis (RA) remains unknown; however, recent studies have suggested a central role of the vascular endothelium in RA pathogenesis. The immune complex (IC)-mediated vasculitis is typical for RA. The studies reported herein were undertaken to determine 1) whether IC isolated from plasma of patients with RA are capable of inducing expression of ICAM-1/CD54 and Fas antigen/CD95 on the endothelial cell (EC) in vitro, 2) whether the capacity to induce expression of this phenotypic markers of EC activation is determined by the size or by the composition of the IC. The concentrations of IC were chosen to be within the range for IC levels in plasma. We have shown that all IC-containing samples (n = 8) significantly and in a dose-dependent manner increased level of ICAM-1 expression on the EC. In selected experiments EC were incubated with IC in the presence of complement. The presence of serum containing active complement components resulted in further up-regulation of ICAM-1 expression only in 4 of 8 cases, independently on the ability of IC to fix complement. Additionally, we have found that all IC samples significantly and in a dose-dependent manner induced the marked increase in CD95 expression on the EC. Furthermore, the levels of augmented expression of CD95 correlated with the levels of CD54 expression stimulated by the same IC-containing samples. We have demonstrated that these levels of stimulated expression of ICAM-1 as well as levels of Fas antigen expression negatively correlated with percentage amounts of IgM in total protein concentration of IC and directly correlated with IgG content in comparison to IgM in the structure of this IC. Our results show that IC stimulate ECs to express ICAM-1 and CD95, all of which have been implicated in the pathogenesis of rheumatic disease. The studies reported herein provide further information regarding to inflammatory potential of IC in RA.