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ID PMID Title PublicationDate abstract
1550404 Production and modulation of interleukin 6 synthesis by synoviocytes derived from patients 1992 Feb Interleukin 6 (IL-6) is a potent cytokine, the biological activities of which include the stimulation of immunoglobulin secretion, T cell activation, induction of the acute phase response, activation of megakaryocytes, and pyrogenicity. These biological activities make it a plausible contributor to rheumatoid arthritis. The ability of synoviocytes to synthesise this potential mediator of inflammation was tested. Cultures of fibroblast-like cells were established from joint tissue from patients with rheumatoid arthritis, degenerative joint disease, or trauma. Supernatants from synoviocytes from each diagnostic category contained IL-6-like activity as detected in a B9 plasmacytoma cell proliferation assay. Supernatants from IL-1 stimulated synoviocytes from patients with rheumatoid arthritis (n = 5) contained an average of 70,000 U/ml IL-6. Western blot analysis confirmed that these supernatants contained peptides that reacted with a highly specific antibody to IL-6. A cDNA probe specific for IL-6 hybridised with mRNA derived from synoviocytes representative of each disease state. Interleukin 6 mRNA expression increased by culturing synoviocytes in the presence of 10% calf serum, IL-1 (30 U/ml), insulin (166 ng/ml), or basic fibroblast growth factor (16 ng/ml). In contrast, dexamethasone (10(-6) mol/l) suppressed the ability of IL-1 to increase the expression of IL-6 mRNA. Recombinant IL-6 itself did not detectably upregulate its own message. The regulation of production of IL-6 by synoviocytes may be important in the pathogenesis of joint inflammation.
8898963 Comparison of rheumatoid factors of rheumatoid arthritis patients, of individuals with myc 1996 Oct We analyzed the rheumatoid factors (RF) produced by Epstein-Barr virus-transformed monoclonal B cells established from four patients with rheumatoid arthritis (RA), three individuals with a history of Mycobacterium tuberculosis (TB) and four normal controls (NI). Fifty-eight RF were analyzed for specific activity (international units-RF/microgram) for the Fc part of IgG and their interaction with tetanus toxoid (TT) and DNA (polyspecificity). Furthermore, we sequenced the V-D-J heavy chain region of 16 (9TB-/7RA-) RF. Significant differences were observed between the NI-RF and the TB- and RA-RF. While the RF repertoire of normal individuals comprised of low-avidity RF of which the majority (15/17) were polyspecific, more than half of the TB- and RA-RF were monoreactive. Furthermore, the monospecific TB- and RA-RF were of significantly higher avidity than the NI-RF (RA > TB > > NI). With respect to polyspecificity specificity, the RF in the three groups were comparable: the interaction with DNA, TT as well as with Fc was inhibited either by an increase of the ionic strength to 0.3-0.5 M NaCl or by addition of the polyanion dextran sulfate, indicating that the antibodies interacted with similar anionic epitopes shared by the three antigens. Analysis of the V-D-J heavy chain regions showed significant differences between the respective RF. The salt-sensitive binding was highly correlated with the presence of arginine in the complementarity-determining region 3 (CDR3). Furthermore, whereas the polyspecific RF consisted predominantly of germ-line encoded antibodies, the genes of the monospecific RA/TB-RF were somatically mutated (RA > TB). It is therefore likely that maturation of RF can be initiated by chronic infections and that monospecific, somatically mutated RF are not a unique characteristic of autoimmune diseases.
7833994 [Early experience with total shoulder arthroplasty]. 1994 The author gives a report on the indication, on the surgical technique and on the results of shoulder arthroplasty, following 30 porous coated, unconstrained, BIO-MODULAR total endoprothesis were implanted. The pain, which was uncurable with any other methods, was relieved by implanting the total shoulder prosthesis. The functional result is determined by the condition of rotator cuff and by the way of reconstruction, rehabilitation and cooperation of the patients. The experience in soft tissue surgery is absolute necessary to be successful.
8436988 Intramedullary versus extramedullary tibial alignment systems in total knee arthroplasty. 1993 Feb One hundred twenty consecutive total knee arthroplasties were performed to compare the accuracy of intramedullary versus extramedullary tibial resection guides. An intramedullary guide (group 1) was used in 60 cases and an extramedullary guide (group 2) was used in another 60 cases. In group 2, the distal portion of the extramedullary guide was shifted 3 mm medial to the midpoint of the ankle in order to position it over the center of the talus. Postoperative tibial component alignment angles were similar in both groups (group 1, 0.43 degrees varus; group 2, 0.36 degrees valgus). However, 88% of tibial components in group 2 were aligned within 2 degrees of the 90 degrees goal versus only 72% of tibial components in group 1. Satisfactory alignment can be obtained with either intramedullary or extramedullary resection guides, although a wider range of error was encountered with intramedullary guide use. Distal positioning of the extramedullary guide over the center of the talus rather than the midpoint of the ankle is important to avoid varus tibial resection. Extramedullary guides avoid the potential complications of intramedullary guide use, including fat embolization and hypoxia, intraoperative fracture, loss of polymethyl methacrylate pressurization, and inability of intramedullary rod passage due to deformity, retained hardware, or pathologic bone disease.
8189103 [Pathologic findings of mouse air-pouches injected with Escherichia coli O: 14, lipopolysa 1994 Apr Inflammation of the facsimile synovium was induced by injecting 4 mg of heat-killed Escherichia coli (E. coli) O: 14, 1 mg of lipopolysaccharide (LPS), or 100 U of recombinant interleukin-1 beta (IL-1 beta) into a 7-day-old subcutaneous air-pouch in C 57 Black mice. Saline was used for control animals. A total of 150 mice were used. Hyperplasia in the lining cells (lining greater than 5 cells thick) was induced in the inner layer of 18 of 20 air-pouches (in 9 of 10 mice) at 7 days after injection of E. coli or LPS. The results at 7 days after were significantly higher than those at 3 days after injection of E. coli (11/20 mice) or LPS (5/10). The number of lining layers with neutrophil infiltration reached a maximum 3 days after injection of E. coli (3 days: 10/20, 7 days: 2/20, p < 0.01) or LPS (3 days: 7/10, 7 days: 2/10, p < 0.01). There was a greater number of mononuclear cells in the sublining layers 7 days after injection of E. coli (9/20 mice) or LPS (7/10) than at 3 days (2/20, 3/10), (p < 0.01). There was a higher incidence of mononuclear cells around the post-capillary venules (PCV) at 7 days after injection of E. coli (9/20 mice) or LPS (7/10) than at 1 day (0/20, 0/10), (p < 0.01). There were significantly more mast cells around the PCV at 1 day after injection of E. coli (6.0 +/- 2.1) or LPS (5.0 +/- 1.8) than in the saline controls (1.0 +/- 0.4), (p < 0.01). Immunohistochemical stains for IgG showed more positive cells at 7 days after injection of E. coli (4.0 +/- 1.7) or LPS (4.0 +/- 1.4) than in controls (0.5 +/- 0.2), (p < 0.05). Significantly more exudate (0.5 +/- 0.3 mls) was found in the air-pouch at 1 day after injection with IL-1 beta than at 1 day after in the other groups. In conclusion, these results suggest that the air-pouch model may be very useful for investigating possible roles of arthritogenic agents or cytokines on the acute and/or chronic phases of inflammation in connective tissue.
7688934 Investigation of the HLA component involved in rheumatoid arthritis (RA) by using the mark 1993 Sep In order to investigate the HLA component involved in rheumatoid arthritis (RA), we tested genetic models by the marker association-segregation chi 2 (MASC) method, using the HLA genotypic distribution observed in a sample of 97 RA patients. First we tested models assuming the involvement of a susceptibility gene linked to the DR locus. We showed that the present data are compatible with a simple model assuming the effect of a recessive allele of a biallelic locus linked to the DR locus and without any assumption of synergistic effect. Then we considered models assuming the direct involvement of the DR allele products, and we tested the unifying-shared-epitope hypothesis, which has been proposed. Under this hypothesis the DR alleles are assumed to be directly involved in the susceptibility to the disease because of the presence of similar or identical amino acid sequences in position 70-74 of the third hypervariable region of the DRBI molecules, shared by the RA-associated DR alleles DR4Dw4, DR4Dw14, and DR1. This hypothesis was strongly rejected with the present data. In the case of the direct involvement of the DR alleles, hypotheses more complex than the unifying-shared-epitope hypothesis would have to be considered.
8774126 Expression of immunoreactive activin A protein in remodeling lesions associated with inter 1996 Mar The expression of activin A, one of the transforming growth factor-beta supergene family, was studied in various pulmonary conditions associated with interstitial pulmonary fibrosis (3 cases with diffuse alveolar damage, 6 cases with idiopathic pulmonary fibrosis, and 1 case with pulmonary fibrosis associated with rheumatoid arthritis) using immunohistochemical techniques on paraffin-embedded sections. Controls consisted of 10 cases with normal pulmonary parenchyma, and 2 cases with primary pulmonary hypertension and 1 case with secondary pulmonary hypertension were also studied. The lung specimens from normal parenchyma weakly expressed immunoreactive activin A on the bronchiolar epithelium. In marked contrast, all of the specimens from cases with diffuse alveolar damage and interstitial pulmonary fibrosis demonstrated strong expression of activin A on metaplastic epithelium, hyperplastic smooth muscle cells, desquamated cells, and alveolar macrophages. Pulmonary arteries from patients with primary or secondary pulmonary hypertension showed abundant immunoreactive activin A on smooth muscle cells. These findings suggest a potential role for this growth factor, activin A, in the pathogenesis of pulmonary tissue remodeling associated with interstitial pulmonary fibrosis.
8620637 Long term bone remodeling around the Charnley femoral prostheses. 1996 May Femoral bone remodeling after total hip replacement was studied by following patients who received 326 Charnley femoral prostheses for 10 to 20 years (mean, 13.3 years). The radiographic state of the bone remodeling was visually assessed and measured with a digitizer. Demineralization that started proximally and then progressed distally caused cortical thinning, which correlated with widening of the intramedullary canal, not with changes that developed in the periosteal width, and occurred in the medial femoral neck, around the proximal half of the stem, and around the distal half in 87%, 33%, and 10%, respectively. Cortical thinning around the distal half of the stem was always accompanied by proximal thinning, and extensive cortical thinning (both proximal and distal) correlated with both lower clinical scores and radiologic loosening of the femoral prosthesis. A low canal flare index of Noble, a large canal width, and a patient age of 60 years or more were risk factors for extensive cortical thinning. Accelerated polyethylene wear was related to resorption of the medial femoral neck but not to cortical thinning or radiological loosening. Cortical thickening occurred only around the distal half of the stem in 29%. These findings establish a basis for the performance of cemented femoral prostheses, and allow comparison of bone remodeling when evaluating other femoral prostheses.
8151561 Synovial tissue implants from patients with rheumatoid arthritis cause cartilage destructi 1994 Jan OBJECTIVE: To establish in SCID.bg mice a model in which joint destruction is initiated by human inflammatory cells from patients with rheumatoid arthritis (RA). METHODS: Development of a surgical technique and immunohistologic analysis. RESULTS: Initial experiments with single cell suspensions failed because more than 70% of the cells injected intraarticularly left the mouse knee joint within 16 h without causing destruction. This was observed with peripheral blood mononuclear cells, T cell lines reactive to mouse or rat collagen type II, and synovial mononuclear cells. Cell immigration was reduced but not prevented by preactivation with mitogens. In contrast, small tissue implants from human synovial membrane which were transferred by surgical intervention into mouse knee joints remained at the site of injection and could be easily localized within the mouse joint (observation period up to 8 weeks). The human synovial membrane implants induced pannus formation and erosion of cartilage and bone while only a mild and transient synovitis was observed with normal synovial membrane and control tissues like human thymus. The predominant cells at the site of destruction were human (CD68+) and murine (Mac-2+) monocytes/macrophages. CONCLUSION: The human/murine SCID arthritis is a useful model for studying pathogenetic aspects of joint destruction as well as effects of new drugs or novel treatment strategies.
1388840 Heat-shock proteins: immunity and autoimmunity. 1992 Aug Antigens from a wide variety of pathogens have been identified as members of conserved heat-shock protein families, sharing upwards of 50% amino acid identity with corresponding host-cell proteins. Analysis of the responses to these conserved antigens may provide insights into regulation of the immune system during infection and autoimmunity.
8214287 Transoral-transpharyngeal approach to the upper cervical vertebrae. 1993 Oct The classical operative approaches to the cervical spine include the posterior one and the anterior exposure along the sternomastoid muscle. However, neither of these are helpful in exposing the upper cervical vertebrae, especially the odontoid process, atlas, and axis. We have used the transoral-transpharyngeal exposure for lesions of the odontoid process and upper (first to third) cervical vertebrae in six patients. The pathologic processes included rheumatoid disease and fracture of the cervical vertebrae, suspected tumor with compression of the spinal cord, basilar invagination, and compression of the medulla. In all six patients, the exposure was excellent, and postoperative morbidity was minimal. Tracheostomy was performed routinely in all these patients. In five patients, vertebral stabilization was performed as a secondary procedure a few days after the initial anterior decompressive surgery. The transoral-transpharyngeal approach appears to be relatively easy. It is associated with minimal complications and provides excellent exposure of the odontoid and upper cervical vertebrae for a microneurosurgical approach. Modifications of this approach include incision of the soft palate, excision of a portion of the hard palate, and, occasionally, transmandibular median labio-mandibulo-glossotomy (Trotter's) approach. Although the technique was described initially approximately 35 years ago, this neglected anatomic approach will facilitate cooperative efforts between head and neck surgeons and neurosurgeons.
1364935 Enteric coated naproxen; a double blind trial comparing the tolerance of enteric coated an 1992 Enteric coated naproxen (Nycopren) was compared with standard naproxen in a double blind comparative trial of 348 patients with either rheumatoid or osteoarthritis. There were slightly fewer gastric side effects and slightly fewer withdrawals because of side effects in the enteric coated naproxen group but the differences did not reach statistical significance. There was no significant difference in the efficacy of the two formulations. A satisfaction index was used to assess the therapeutic ratio with visual analogue scales assigned to both efficacy and side effects. The scale performed as intended and is worthy of further exploration.
1439030 [Ulnar translocation of the carpus after surgery of the rheumatic wrist. Review of 54 case 1992 Fifty-four rheumatoid wrists, on which synovectomy and caput ulnar resection had been performed, were re-examined 1 to 8 years after the operation (average follow-up: 3.8 years). The clinical results were good, and the wrists pain-free in 91 per cent of cases, with a low rate of synovitis recurrence (4 per cent), and 88 per cent of the mobility in the sagittal plane was preserved. Radiological examination revealed a moderate aggravation of carpite over the years. This evolution was not linked, however, to the fact that no intracarpal synovectomy was performed in our series since a similar evolution has been reported by authors who carry out this synovectomy. Ulnar translocation of the carpus was commonly measured in relation to the ulna axis, but as the latter tends to get into a more medial position after the surgery this analysis was incorrect. Ulnar translocation should be measured in relation to the axis of the radius, which remains in the same position. Studied in this way, the average translocation in this whole series was 2 mm. A comparative study of the operated wrist and the non-operated wrist in 27 patients revealed a significant aggravation (p < 0.2) of ulnar translocation of the carpus at radiological stages 2 and 3. This translocation remained however minimal. A combined transfer of the extensor carpi radialis brevis or longus onto the extensor carpi ulnaris did not slow down ulnar translocation of the carpus, but the other hand it improved the correction of radial deviation of the carpus and ulnar deviation of the fingers.
7504438 Vascular cell adhesion molecule 1 and alpha 4 and beta 1 integrins in lymphocyte aggregate 1993 Nov OBJECTIVES: Interactions between vascular cell adhesion molecule 1 (VCAM-1) and its ligand, the alpha 4/beta 1 integrin, have been shown to be important in a number of cellular events in vitro. To assess the importance of such interactions in the development of lymphocytic infiltration in diseased tissue the distribution of the two ligands has been studied immunohistochemically. METHODS: Cryostat sections of labial tissue from patients with Sjögren's syndrome, normal labial tissues, rheumatoid synovia, and normal tonsils were stained using antibodies to VCAM-1, alpha 4 and beta 1 integrin chains, and markers for T cells, B cells, macrophages, and follicular dendritic reticulum cells (FDRCs), visualised using alkaline phosphatase and fast red. RESULTS: Staining patterns for VCAM-1 and integrin chains in lymphocyte aggregates in synovial and labial tissues were similar. VCAM-1 staining was found on both vascular and ramifying dendritic cells at the centre of large T cell aggregates and in all aggregates where there was a central clustering of B cells. VCAM-1 colocalised with, but also extended beyond, staining for the FDRC marker R4/23. Staining for the alpha 4 and beta 1 integrin chains was more widespread than staining for VCAM-1, with no significant increase in staining at sites of maximum VCAM-1 staining. In tonsils VCAM-1 and R4/23 codistributed in germinal centres, but staining for the alpha 4 and beta 1 integrin chains was chiefly seen in T lymphocyte areas. CONCLUSIONS: VCAM-1 may be more important in determining the distribution of B than T lymphocytes in lymphocytic infiltration of non-lymphoid tissue. Unlike the follicles of lymphoid tissue, ectopic follicle-like structures in non-lymphoid tissues may form by immigration of B cells via VCAM-1+ vessels at the centre of T cell aggregates.
7582719 Altered levels of soluble adhesion molecules in rheumatoid arthritis, vasculitis and syste 1995 Sep We compared the levels of soluble adhesion molecules E-selectin (sE-selectin), intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) alongside von Willebrand factor (vWf), CRP and rheumatoid factor in 40 patients in serum by ELISA, rheumatoid factor by sheep red blood cell agglutination and CRP by immunonephelometry. Compared to controls, increased sE-selectin was found in patients with RA (P = 0.0015), vasculitis (P < 0.0003) and SSc (P = 0.0126), whilst raised sICAM-1 was found in RA (P < 0.0003), vasculitis (P < 0.0003) and SSc (P < 0.0378). sVCAM was lower in RA than in controls (P = 0.0102), but was unchanged in vasculitis or in SSc. vWF was raised in RA (P = 0.0102), vasculitis (P < 0.0003) and SSc (P < 0.0003). In a Spearman's rank analysis of all the data, vWf correlated with sVCAM-1 and sICAM-1 (both P < 0.001), sE-selectin with sICAM-1 (P < 0.001) and sVCAM with sICAM-1 (P < 0.005). Levels of rheumatoid factor correlated with those of sE-selectin (P = 0.003) and sVCAM-1 (P = 0.012), but there were no correlations between any index and CRP. The strongest correlations within the RA group were between sICAM and sVCAM (P = 0.001), in vasculitis it was between sE-selectin and sICAM (P < 0.001), and in SSc it was between sE-selectin and sVCAM (P = 0.019). These data suggest that the differing levels of vWf, sE-selectin and sICAM-1 in the inflammatory vasculitides may be useful in establishing a role for leucocyte/endothelial adhesion in these diseases.
8484695 Protective effect of androgens against inflammation induced cartilage degradation in male 1993 Apr OBJECTIVES: Rheumatoid arthritis (RA) is a disease which predominantly affects women. Interestingly, low serum androgen levels and clinical improvement with androgen replacement have been reported in male patients. The aetiopathogenic role of sex hormones in arthritis and their potential long term effects on joint destruction and disability remains unclear, however. This study was designed to investigate the potential influence of sex hormones on inflammation induced cartilage degradation in male rodents. METHODS: An in vivo model of cotton wrapped cartilage implants was used to assess the effects of androgen, oestradiol, and progesterone on inflammation induced cartilage degradation, and in vitro techniques were used to investigate the direct actions on cartilage metabolism and cytokine production in male animals. RESULTS: Orchidectomy resulted in accelerated cartilage damage which was reversed by replacement of physiological levels of androgens. Granulomatous tissue from castrated male rodents produced higher amounts of interleukin 1. Sex hormones reduced spontaneous proteoglycan loss in vitro but did not interfere with the effects of interleukin 1 on cultured cartilage. CONCLUSIONS: Androgens appear to protect cartilage from inflammation induced breakdown in male animals. These results support a pathogenic role for hypoandrogenism in rheumatoid arthritis and suggest that long term androgen replacement may help prevent joint damage and disability.
8068951 Clinical spectrum of clonal proliferations of T-large granular lymphocytes: a T-cell clono 1994 Sep 1 We identified 68 patients with clonal T-large granular lymphocyte (T-LGL) proliferations who were seen at the Mayo Clinic between 1984 and 1992. Nineteen (28%) were asymptomatic at diagnosis, while the rest experienced fatigue (60%), B-symptoms (12%), and recurrent infections (15%). Associated comorbid conditions included rheumatoid arthritis (RA) in 26%. Severe anemia (hemoglobin [Hb] < 8g/dL) and neutopenia (absolute neutrophil count [ANC] < 500/microL) were seen in 19% and 40% of patients, respectively. Immunophenotypic studies showed CD3+, CD8+ phenotype in the majority (72%). Twenty-one patients (31%) have required no therapy, and remain relatively stable with a median follow-up period of 50 months. Treatment was required at either diagnosis (36 patients) or at subsequent follow-up (11 patients). Initial response rates were similar in patients treated with cyclophosphamide (CTX) with or without prednisone (69%), or prednisone alone (73%). Overall, 61 patients (90%) are alive with a median follow-up of 44 months. Actuarial median survival of this entire cohort is 161 months. The presence of anemia or symptoms does not appear to correlate with the tumor burden. In patients requiring therapy, a lower ANC and the presence of B-symptoms/infection were independently associated with a significantly lower probability of achieving a molecular or hematologic complete remission (H-CR). Intermittent immunosuppressive therapy is effective in achieving durable responses in a number of patients. T-LGL proliferations are associated with a favorable prognosis and response to therapy. However, significant heterogeneity exists in clinical presentation and associated comorbid conditions. These disorders should be included in the differential diagnosis of patients with unexplained cytopenias, particularly in the setting of RA and other autoimmune disorders. Analogous to the situation with monoclonal gammopathies, a term such as T-cell clonopathy of undetermined significance (TCUS) may be more appropriate to describe these patients.
7985402 [Results in patello-femoral joint replacement in various knee endoprostheses (Type GSB and 1994 Sep 105 patients with 137 total knee replacements (105 model GSB, 32 model ES) were reexamined 4.3 years (2 to 9.7 years) postoperatively. 63.9 percent suffered from chronic polyarthritis. The clinical result (Insall 100-point score) averaged 73.6 points (78.2 ES-, 71.7 GSB II-knees). In 28.6 percent of the GSB- and 3.1 percent of the ES-knees osteolyses of the patella were apparent. Subluxation or complete dislocation of the patella was present in 85.7 percent of the GSB- and 25 percent of the ES-knees. The result was dependent on the preoperative knee axis, patellar height and the implant site of the tibial component. Revisions with complete removal of the inlay were most successful.
8761181 Expression of cyclooxygenase-2 in human and an animal model of rheumatoid arthritis. 1996 Aug An inducible form of cyclooxygenase-2 (COX-2) has been shown to be upregulated in vitro by various pro-inflammatory agents, such as lipopolysaccharide, IL-1 and TNF, COX-2 appears to be responsible for the increase in prostaglandin synthesis at the site of inflammation. To examine the involvement of COX-2 in inflammation, we analysed the expression of this gene in human rheumatoid arthritis (RA) and in rat adjuvant-induced arthritis. Immunocytochemical studies of synovial membrane biopsies from human RA, osteoarthritic (OA) and normal joints using a COX-2 specific antibody showed positive staining in RA, but not in normal synovial membranes. Specifically, expression of COX-2 was detected in synovial lining cells, lymphoid aggregates and endothelial cells of blood vessels. Although some positive staining was observed in the OA joints, the number of stained cells was dramatically lower and the staining of the cells was less intense than in the rheumatoid tissue. By reverse transcription and polymerase chain reaction analysis, COX-2 mRNA was detected in the rat adjuvant arthritic limb, whereas no COX-2 mRNA was detectable in the normal limb. These observations indicate that COX-2 expression is upregulated in inflammatory joint disease and that COX-2 is a potential therapeutic target for specific inhibition.
8857959 Soluble L-selectin in the connective tissue diseases. 1996 Oct Plasma levels of the leucocyte adhesion molecule L-selectin were measured by ELISA in 41 patients with rheumatoid arthritis, 18 with ankylosing spondylitis, 18 with systemic sclerosis and 27 with vasculitis together with 42 age- and sex-matched controls. Low levels of soluble L-selectin were found in systemic sclerosis (797 +/- 302 ng/ml, P < 0.05) and vasculitis (941 +/- 329 ng/ml, P < 0.05) relative to controls (1244 +/- 269 ng/ml). The exact reasons for low levels of soluble L-selectin are unclear, but may reflect reduced shedding from leucocytes and/or strong binding to its cell membrane ligand(s). An approximate inverse relationship between soluble L-selectin and disease severity may have clinical relevance.