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ID PMID Title PublicationDate abstract
10693872 Evidence for the expression of a second CD6 ligand by synovial fibroblasts. 2000 Feb OBJECTIVE: CD6, a cell surface glycoprotein expressed primarily on T cells, may function as a costimulatory molecule and may play a role in autoreactive immune responses. Recently, a CD6 ligand termed CD166 (previously known as activated leukocyte cell adhesion molecule [ALCAM]) has been identified and shown to be expressed on activated T cells, B cells, thymic epithelium, keratinocytes, and in rheumatoid arthritis synovial tissue. However, the results of functional studies have suggested the existence of a second CD6 ligand. The present study was undertaken to seek evidence for a second CD6 ligand on cultured synovial fibroblasts. METHODS: Flow cytometric and biochemical techniques were applied, using anti-CD166 monoclonal antibody (mAb) and a recombinant CD6 fusion protein, to determine whether cultured synovial fibroblasts and other cell types expressed a non-ALCAM CD6 ligand. RESULTS: CD14- fibroblastic synoviocytes showed greater binding of a recombinant CD6 fusion protein than of anti-ALCAM mAb. With interferon-gamma treatment of synovial fibroblasts, binding of both reagents increased, but this was more marked for binding of CD6 fusion protein. Exposure of synovial fibroblasts to other cytokines or to the superantigen staphylococcal enterotoxin A also regulated binding of CD6 fusion protein and anti-ALCAM mAb in a discordant manner. Immunoprecipitation of proteins from membrane extracts of synovial fibroblasts with a CD6-Ig fusion protein revealed a novel 130-kd band distinct from CD166; an identical molecule was also precipitated from membranes of HBL-100 tumor cells. CONCLUSION: Taken together with previous data regarding CD6 and CD166 function, the present findings strongly suggest the existence of a second CD6 ligand distinct from CD166, which can be expressed by synovial fibroblasts as well as other cells.
10648110 Vaccination and autoimmunity-'vaccinosis': a dangerous liaison? 2000 Feb The question of a connection between vaccination and autoimmune illness (or phenomena) is surrounded by controversy. A heated debate is going on regarding the causality between vaccines, such as measles and anti-hepatitis B virus (HBV), and multiple sclerosis (MS). Brain antibodies as well as clinical symptoms have been found in patients vaccinated against those diseases. Other autoimmune illnesses have been associated with vaccinations. Tetanus toxoid, influenza vaccines, polio vaccine, and others, have been related to phenomena ranging from autoantibodies production to full-blown illness (such as rheumatoid arthritis (RA)). Conflicting data exists regarding also the connection between autism and vaccination with measles vaccine. So far only one controlled study of an experimental animal model has been published, in which the possible causal relation between vaccines and autoimmune findings has been examined: in healthy puppies immunized with a variety of commonly given vaccines, a variety of autoantibodies have been documented but no frank autoimmune illness was recorded. The findings could also represent a polyclonal activation (adjuvant reaction). The mechanism (or mechanisms) of autoimmune reactions following immunization has not yet been elucidated. One of the possibilities is molecular mimicry; when a structural similarity exists between some viral antigen (or other component of the vaccine) and a self-antigen. This similarity may be the trigger to the autoimmune reaction. Other possible mechanisms are discussed. Even though the data regarding the relation between vaccination and autoimmune disease is conflicting, it seems that some autoimmune phenomena are clearly related to immunization (e.g. Guillain-Barre syndrome). The issue of the risk of vaccination remains a philosophical one, since to date the advantages of this policy have not been refuted, while the risk for autoimmune disease has not been irrevocably proved. We discuss the pros and cons of this issue (although the temporal relationship (i.e. always 2-3 months following immunization) is impressive).
9933631 Activation of Sp1 and its functional co-operation with serum amyloid A-activating sequence 1999 Feb 12 The serum amyloid A (SAA) protein has been implicated in the progression and pathogenesis of rheumatoid arthritis through induction of collagenase activity in synovial fibroblast cells that line the joint tissues. We demonstrate that SAA is synergistically induced in synovial cells by interleukin (IL)-1 and IL-6 that are present at significantly high level in the synovial fluid of arthritis patients. These cytokines induced phenotypic changes in synovial cells, promoting protrusion and increased cellular contact. Induction of SAA under this condition is mediated by promoter elements located between -254 and -226, which contains binding sites for transcription factors Sp1 and SAA activating sequence binding factor (SAF). Mutation of these sequences abolishes SAA promoter response to IL-1 and IL-6. The role of Sp1 in SAA induction was demonstrated by increased DNA binding activity, phosphorylation, and increased protein content of Sp1 during cytokine treatment. Sp1 interacts with the SAA promoter in association with SAF as an SAF. Sp1 heteromeric complex. Furthermore, using a phosphatase inhibitor, we demonstrated increased transactivation potential of both Sp1 and SAF as a consequence of a phosphorylation event. These results provide first evidence for cytokine-mediated activation of Sp1 in synovial fibroblast cells and its participation in regulating SAA expression by acting in conjunction with SAF.
9113538 Integral porous femoral stem. 5-to 8-Year follow-up study. 1997 Apr The outcome of total hip arthroplasty without cement was prospectively followed in patients who received a titanium taper wedge femoral component with a circumferential titanium plasma spray coating on the proximal surface (Integral femoral stem, Biomet, Warsaw, IN). One hundred ninety femoral components were implanted in 179 patients. Nine patients (9 hips) died prior to their 5-year examination, leaving 170 patients available for follow-up evaluation. Thirty-one of the 170 patients (33 hips) were lost at an intermediate follow-up period of 5 years. (mean, 5.8 years, range; 5-8 years), giving a follow-up rate of 82% for patients and hips. The preoperative diagnoses included osteoarthritis (91 hips), avascular necrosis (38), post-traumatic arthritis (10), rheumatoid arthritis (4), congenital dislocation of the hip (3), and fractures (2). The 78 men and 61 women had a mean age of 55 years (range, 18-81 years) and a mean weight of 81 kg (range, 50-136 kg). Pre-operative Harris pain and function scores for the hip were 19.9 (range, 0-40) and 55.6 (range, 12-84), respectively. At the most recent follow-up visit, the mean pain score increased to 41.2 (range, 10-44) and the mean function score increased to 93.5 (range, 6-100). Thigh pain was present in 4% of the hips at the most recent follow-up visit. Radiographically, 99% of the femoral components demonstrated spot welds in the porous-coated zone. Two hips had demarcation of the femoral component in the porous-coated zone consistent with fibrous fixation. None of the femoral stems had been revised and there were no signs of aseptic loosening. Additionally, there were no cases of pain that could be directly attributed to the stem and there was no evidence of distal femoral osteolysis. It is concluded that the integral femoral stem provides excellent clinical and radiographic results at intermediate follow-up periods.
11303305 Clinical, radiologic, demographic, and occupational aspects of hand osteoarthritis in the 2001 Apr OBJECTIVE: Osteoarthritis (OA) of the hand is common in elderly patients. The aim of this study was to characterize OA frequency, severity, and distribution and to trace interrelationships between these findings and the demographic, occupational, and medical data from elderly Jewish nonrheumatologic patients. METHODS: Study participants were 253 consecutive patients admitted to a geriatric center for a variety of nonrheumatic medical conditions. Excluded patients were those with rheumatoid arthritis; neurologic, orthopedic, or other conditions that would interfere with symmetric hand function; and mental or medical states that would interfere with history taking and radiographic studies. Patient occupations were graded as workload degree (on a scale of 1 to 3) and as the total occupational score (workload degree multiplied by the duration of each job). Clinical findings of Heberden nodes, Bouchard nodes, and malignment, graded on a scale of 0 to 3, were summed as the clinical OA score. Hand radiographs were independently read (modified Altman method), grading 5 parameters in each joint on a scale of 0 to 3, summed as a radiologic OA score. Statistical analyses included the Student t test, chi(2) test, ANOVA, Pearson correlation, and partial correlation coefficients. RESULTS: Among 253 elderly patients (171 women, 82 men; mean age, 79 years) OA was frequent (occurring in about 80% of patients), involving most severely the second and third distal interphalangeal, right first interphalangeal, and both first carpometacarpal joints. The prevalence of OA was similar in women and men, with higher scores in women, and reached significance only in the distal interphalangeal joints. Metacarpophalangeal joints were more involved in men. Age had a clear influence on OA scores. Ethnicity affected OA severity, with Ashkenazi Jews having significantly higher scores than Sepharadi Jews. Dominant hands had significantly higher global OA scores as well as isolated joint scores (except for the first carpometacarpal joint). Occupational load, housekeeping tasks, and the number of children did not influence the total or specific joint OA scores. Associated conditions such as obesity, diabetes, hypothyroidism, and chondro calcinosis were not associated with more pronounced OA. CONCLUSIONS: Hand OA was prevalent in our elderly cohort, and its severity was influenced by inherent traits such as age, female gender, ethnicity, and handedness. In contrast, acquired factors such as workload, number of children, and associated diseases did not appear to influence OA expression.
11077990 Antibodies against mycobacterial antigens in the synovial fluid of patients with temporoma 2000 Oct In the absence of active pulmonary disease, mycobacterial infection frequently causes arthritis and can be considered to initiate autoimmune diseases such as rheumatoid arthritis. Temporomandibular disorder (TMD) is a disease in which pain and impaired mandibular movement appear to arise directly from degenerative or inflammatory changes within the temporomandibular joint, but its precise pathogeny has not been elucidated. Here we examined whether mycobacterial infection is related to the pathology of TMD. The antibody levels against mycobacterial antigen in the synovial fluid (SF) of patients with TMD were assessed by enzyme-linked immunosorbent assay (ELISA). Six of 17 TMD patients (35%) were found to possess mycobacterial antigen-specific immunoglobulin (Ig) G but not IgM, while the six healthy volunteers possessed neither. Western-blot analysis was used to isolate the reacted antigen, and the IgG reacted strongly to 44-kDa antigen. The first 14 N-terminal amino acid sequences were determined, and computer analysis revealed that it was homologous to translational elongation factor Tu (EF-Tu) of Mycobacterium tuberculosis, which was a major target antigen for these antibodies. The 44-kDa protein of Mycobacterium bovis BCG (BCG) was identical with the EF-Tu of M. tuberculosis. We cloned the gene encoding the EF-Tu of BCG by using the synthesized oligonucleotide primers by means of polymerase chain-reaction. The gene was expressed in Escherichia coli. The protein was purified, and the antibody levels against this recombinant protein in the SF of TMD patients were assessed by ELISA. Our findings suggest that some cases of TMD are concerned with the synovial IgG against the EF-Tu of M. tuberculosis, and that the existence of the antibody is a clinical indication of TMD.
10990231 The spectrum of conditions mimicking polymyalgia rheumatica in Northwestern Spain. 2000 Sep OBJECTIVE: To examine the spectrum and the main clinical data of patients presenting with polymyalgia symptoms who have conditions other than polymyalgia rheumatica (PMR) or PMR associated with giant cell arteritis (GCA) during a 10 year period in Northwestern Spain. METHODS: Clinical records of patients presenting with polymyalgia symptoms diagnosed at the Hospital Xeral-Calde Lugo from 1987 to 1996 were reviewed by rheumatology staff members. Patients were considered as having a condition suggestive of PMR if they met the following criteria: (1) Age > or =50 years at the onset of symptoms; (2) severe bilateral pain associated with morning stiffness for > 1 mo in at least 2 of 3 areas: neck, shoulder, and/or pelvic girdle; (3) erythrocyte sedimentation rate at the time of diagnosis > or =40 mm/h. Patients with pure PMR or with PMR associated with GCA were excluded from study. RESULTS: Twenty-three of the 208 patients (age 67.8 +/- 9.0 yrs) presenting with PMR symptoms were finally diagnosed as having conditions different from PMR and GCA. Men outnumbered women (61%). Malignancies and rheumatic diseases, especially seronegative symmetrical polyarthritis (SSP), were the most common entities. Elderly patients with solid malignancies had a poor response to low doses of prednisone. In patients with hematologic malignancies atypical symptoms of PMR such as lack of accentuation of symptoms with movement and a more diffuse continuous aching were observed. During followup 5 patients developed episodes of SSP (median duration 13 months, range 5 to 24), particularly in both hands, satisfying the American College of Rheumatology 1987 criteria for rheumatoid arthritis. However, arthritis responded promptly to corticosteroids with no disease progression. No cortical erosions or new episodes of PMR were seen in these patients after a followup of 6.8 +/- 2.6 years. With the exception of these 5 patients, duration of polymyalgia symptoms was not longer than 3 months from the onset of polymyalgia symptoms until a specific diagnosis was made. CONCLUSION: Polymyalgia symptoms are not uncommon as presenting manifestations of a wide spectrum of conditions. Special concern about the presence of diseases different from PMR or GCA must be considered in patients presenting with atypical symptoms of PMR. Also, the possibility of developing a SSP has to be considered during the followup of these patients.
10090163 Clinical and serological associations of anti-Ku antibody. 1999 Mar OBJECTIVE: To ascertain the clinical and serological associations of anti-Ku antibody. METHODS: Twenty-seven patients over a 7 year period (1987-1996) had anti-Ku antibody detected by counterimmunoelectrophoresis (CIEP). Nineteen patients were available for clinical review. Five patients were assessed by chart review. Serum was taken at review for repeat antibody analysis. Patients were assigned to diagnostic groups based on the American College of Rheumatology criteria. RESULTS: There were 22 women and 5 men. The duration of symptoms ranged from one year to 28 years. Nine patients fulfilled criteria for systemic lupus erythematosus (SLE), 4 scleroderma, 3 rheumatoid arthritis (RA), one discoid lupus, and 7 had an undifferentiated connective tissue disease. There was a low incidence of renal (2/24) and central nervous system involvement (1/24); 19/24 had Raynaud's phenomenon, 15/24 had inflammatory arthritis but only one had erosions on radiograph; 11/24 reported esophageal reflux symptoms. Three of 24 patients had myositis. All patients had anti-nuclear antibody using indirect immunofluorescence of > 640 titer with a speckled and nucleolar pattern. Anti-Ku antibody was detected on CIEP in 15/19 sera available for repeat testing. Three patients had anti-Ro antibody, 2 had anti-U1RNP antibody, one patient had anti-topoisomerase-1 and anti-Ro. CONCLUSION: Anti-Ku antibody is found in a wide variety of connective tissue syndromes. While several patients fulfilled diagnostic criteria for SLE, scleroderma, and RA, their clinical features were usually mild and did not form a distinctive clinical pattern. Common features associated with anti-Ku were Raynaud's phenomenon, arthralgia, skin thickening, and esophageal reflux. Few patients had associated autoantibody specificities found in SLE or scleroderma.
9693968 Mimotopes identified by phage display for the monoclonal antibody CII-C1 to type II collag 1998 Jun The characterization of B cell epitopes has been advanced by the use of random peptide libraries displayed within the coat protein of bacteriophage. This technique was applied to the monoclonal antibody (mAb) C1 to type II collagen (CII-C1). CII-C1 is known to react with a conformational epitope on type II collagen that includes residues 359-363. Three rounds of selection were used to screen two random nonameric phage libraries and 18 phagotopes were isolated. CII-C1 reacted by ELISA with 17 of the 18 phagotopes: one phagotope contained a stop codon. Of the eight most reactive phage, seven inhibited the reactivity by ELISA of CII-C1 with type II collagen. Of the 18 phage isolated, 11 encoded the motif F-G-x-Q with the sequence F-G-S-Q in 6, 2 encoded F-G-Q, and one the reverse motif Q-x-y-F. Most phagotopes that inhibited the reactivity of CII-C1 encoded two particular motifs consisting of two basic amino acid residues and a hydrophobic residue in the first part of the insert and the F-G-x-Q or F-G-Q motif in the second part; phagotopes which contained only one basic residue in the first part of the sequence were less reactive. These motifs are not represented in the linear sequence of type II collagen and thus represent mimotopes of the epitope for CII-C1 on type II collagen. There were five phagotopes with peptide inserts containing the sequence RLPFG occurring in the Epstein-Barr virus nuclear antigen, EBNA-1. This is of interest because EBV has been implicated in the initiation of rheumatoid arthritis (RA) by reason of increased reactivity to EBNA-1 in RA sera. In conclusion, the phage display technique disclosed mimotopes for a conformational epitope of type II collagen, and revealed an interesting homology with a sequence of the EBNA-1 antigen from Epstein Barr virus.
9620515 Experimental pain in healthy human subjects: gender differences in nociception and in resp 1998 Jun We used electrically induced pain in healthy young subjects to study gender differences in nociception and the analgesic efficacy of ibuprofen. Cutaneous stimulation of the earlobe allowed measurement of pain detection thresholds and maximal pain tolerance. Drug and placebo were each administered twice using a double-blind, randomized, multiple cross-over design. Male subjects had greater stimulus thresholds (lower nociception) compared with female subjects (18 +/- 0.3 vs 15 +/- 0.3 volts, mean +/- SEM; n = 10 in each group) and a greater pain tolerance (24 +/- 0.4 vs 21 +/- 0.4 volts). Response variability was also greater in the male subjects, yet only the men exhibited a statistically significant analgesic response to ibuprofen (deltavolts; ibuprofen versus placebo: 2.80 +/- 0.33 vs -0.18 +/- 0.34; P < 0.05, n = 10). None of these results could be attributed to pharmacokinetic differences. The finding that ibuprofen was less effective in women than in men has potential clinical significance, especially as a factor in the response variability to nonsteroidal antiinflammatory drugs. IMPLICATIONS: In this study, we examined ibuprofen, a widely used nonsteroidal antiinflammatory drug, for its ability to reduce experimental pain. We found that it had such properties in healthy young male subjects but not in young female subjects. This is a paradox because many of the painful conditions for which nonsteroidal antiinflammatory drugs are used (e.g., rheumatoid arthritis) occur more often in women.
10606365 A computer based intervention to reduce unnecessary serologic testing. 1999 Dec OBJECTIVE: Laboratory testing is important in the evaluation of patients with possible systemic rheumatic disease, but uncritical use of any test may result in misleading information and unnecessary costs. We attempted to reduce the number of unnecessary antinuclear antibody, rheumatoid factor, and complement level tests ordered by house officers at a large teaching hospital, where inpatient orders are written through a computer based order entry system. METHODS: We conducted a prospective cohort study of an interactive test ordering program. The intervention consisted of displaying post-test probability estimates during the usual physician order entry session. These estimates were based on pretest probabilities entered by the ordering physician and sensitivities and specificities derived from a literature review. Another group of test orders did not prompt the intervention and were considered controls. The outcome of interest was the percentage of tests canceled in the intervention group versus the control group. RESULTS: Eleven percent (11/99) of intervention orders were canceled, versus only one order among 236 controls (p = 0.001). However, there was no association between the physicians' pretest probability estimates and whether test orders were canceled (p = 0.59). Additionally, 43 of the 335 orders (13%) yielded positive tests, but only 4 patients (1%) were given new diagnoses of rheumatic disease. CONCLUSION: The computer based intervention significantly reduced orders for antinuclear antibody and rheumatoid factor levels by 10%. Further reductions without clinical harm are probably possible, since the yield of testing for new rheumatic diseases was low.
9597123 Interleukin-1 receptor antagonist: role in biology. 1998 The interleukin-1 receptor antagonist (IL-1Ra) is a member of the IL-1 family that binds to IL-1 receptors but does not induce any intracellular response. Two structural variants of IL-1Ra have previously been described: a 17-kDa form that is secreted from monocytes, macrophages, neutrophils, and other cells (sIL-1Ra) and an 18-kDa form that remains in the cytoplasm of keratinocytes and other epithelial cells, monocytes, and fibroblasts (icIL-1Ra). An additional 16-kDa intracellular isoform of IL-1Ra has recently been described in neutrophils, monocytes, and hepatic cells. Both of the major isoforms of IL-1Ra are transcribed from the same gene through the use of alternative first exons. The two promoters regulating transcription of the secreted and intracellular forms have been cloned, and some of the functional cis-acting DNA regions have been characterized. The production of IL-1Ra is stimulated by many substances including adherent IgG, other cytokines, and bacterial or viral components. The tissue distribution of IL-1Ra in mice indicates that sIL-1Ra is found predominantly in peripheral blood cells, lungs, spleen, and liver, while icIL-1Ra is found in large amounts in skin. Studies in transgenic and knockout mice indicate that IL-1Ra is important in host defense against endotoxin-induced injury. IL-1Ra is produced by hepatic cells with the characteristics of an acute phase protein. Endogenous IL-1Ra is produced in numerous experimental animal models of disease as well as in human autoimmune and chronic inflammatory diseases. The use of neutralizing anti-IL-1Ra antibodies has demonstrated that endogenous IL-1Ra is an important natural antiinflammatory protein in arthritis, colitis, and granulomatous pulmonary disease. Treatment of human diseases with recombinant human IL-1Ra showed an absence of benefit in sepsis syndrome. However, patients with rheumatoid arthritis treated with IL-1Ra for six months exhibited improvements in clinical parameters and in radiographic evidence of joint damage.
11592384 Inhibition of bone resorption in vitro and prevention of ovariectomy-induced bone loss in 2001 Sep OBJECTIVE: Inhibitors of prostaglandin production, such as nonsteroidal antiinflammatory drugs (NSAIDs), and pharmacologic nitric oxide (NO) donors, such as organic nitrates, have been suggested to protect against bone loss in both humans and experimental animals. Recently, a new class of nitrosylated NSAID (known as NO-NSAIDs) has been developed, which combines the properties of a NO donor with those of a cyclooxygenase (COX) inhibitor. This study investigated the effects of one of these compounds, flurbiprofen nitroxybutylester (HCT1026), on bone metabolism in vitro and in vivo. METHODS: The effects of HCT1026 on osteoclast formation and resorption were determined in vitro using cocultures of primary mouse osteoblasts and osteoclasts. The effect of HCT1026 in vivo was assessed using a mouse model of ovariectomy-induced bone loss. RESULTS: HCT1026 was significantly more efficacious than the parent compound, flurbiprofen, at inhibiting osteoclast formation and bone resorption in vitro, and these effects could not be reproduced by combinations of flurbiprofen with a variety of NO donors. Studies in vivo showed that HCT1026 protected against ovariectomy-induced bone loss by inhibiting osteoclastic bone resorption, whereas flurbiprofen at similar concentrations was ineffective. CONCLUSION: These data indicate that HCT1026 is a potent inhibitor of bone resorption in vitro and protects against ovariectomy-induced bone loss in vivo by a novel mechanism that appears to be distinct from its NO donor properties and from its inhibitory effects on COX activity. We conclude that HCT1026 may be of clinical value in the prevention and treatment of inflammatory diseases such as rheumatoid arthritis, which are characterized by joint inflammation as well as periarticular and systemic bone loss.
11032098 Antiinflammatory and analgesic efficacy of COX-2 specific inhibition: from investigational 2000 Oct Research strongly indicates that increased expression of the isoenzyme cyclooxygenase-2 (COX-2) is responsible for elevated production of prostaglandins in inflamed joint tissues and is involved in the mediation of pain. In contrast, COX-1 is a constitutively produced isoenzyme that is involved in the synthesis of eicosanoids that have important homeostatic functions, for example, in the gastric mucosa and platelets. This new knowledge led to the development of drugs that are highly specific inhibitors of COX-2 while not inhibiting COX-1 at maximally efficacious dosages. The first COX-2 specific agent approved for clinical use in the United States was celecoxib. Large multicenter trials have shown that celecoxib at dosages of 100 mg BID and 200 mg BID is as effective as naproxen 500 mg BID in patients with osteoarthritis of the knee or hip. Another large multicenter trial also demonstrated that celecoxib 200 mg BTD and 400 mg BID is as effective as naproxen 500 mg BID in patients with rheumatoid arthritis (RA). A comparative trial showed that celecoxib 200 mg BID is as effective as diclofenac SR 75 mg BID in patients with RA. The potential of COX-2 specific inhibitors to provide antiinflammatory and analgesic efficacy equivalent to that of conventional nonsteroidal antiinflammatory drugs without the adverse gastrointestinal mucosal and platelet effects associated with nonspecific COX inhibitors promises to revolutionize the clinical care of arthritis patients.
9795440 [Dorsal occipitocervical fusion--indications and results]. 1998 Jul STUDY DESIGN: This report will relate to our experience with the occipitocervical fusion with the y-plate, which we used in the treatment of 53 patients. METHODS: 39 of the patients had rheumatoid arthritis. Other indications demanding surgery were posttraumatic conditions, degenerative and congenital lesions, osteomyelitis, tumor and psoriasis arthritis. Before surgery, all patients suffered from pain in the neck and/or in the back of the head. On a linear scale from 0 to 10, the pain was rated as 8.0 in average (range 4 to 10). 33 patients had an instability of the atlantoaxial region and 26 patients a basilar invagination of the odontoid. A cervical myelopathy was found in 23 cases. One surgeon fused the occiput to C2 in 30 cases, to C3-C5 in 14 cases and to C7-T2 in 9 cases. In 17 patients a resection of the odontoid had to be performed before fusion to adequately decompress the spinal cord. RESULTS: 31 of the patients could be controlled with a follow-up of at average 45.9 months. 16 patients had died. At the time of follow-up, the pain was rated as 2.1 in average (range 0 to 8). The myelopathy cleared up in all cases but 3.9 patients required further operations on the cervical spine. 5 patients developed an instability at the level(s) below the fusion and an enlargement of the fusion to these levels had been performed. The fusion rate was 98.1%. The results were satisfying in 25 (80.6%) and not satisfying in 5 patients (19.4%). CONCLUSIONS: These results show the effectiveness of the occipitocervical fusion with the y-plate in a wide range of applications. It offers advantages above other techniques.
9566861 Application of a bioassay with CHO cells for the routine detection of stimulating and bloc 1998 Mar The importance of bioassays measuring stimulating and blocking autoantibodies to the TSH-receptor (TSH-R) by their effect on cAMP production in CHO cells transfected with the recombinant TSH-R is increasingly recognized. The standard technique for this bioassay is cumbersome, as it involves purification of serum IgG with polyethylene glycol (PEG) and resuspension in hypotonic buffer. We have therefore established a simpler approach for the detection of stimulating and blocking autoantibodies using JP09 CHO cells and unfractionated human serum. The cAMP concentration was measured by a highly sensitive commercial radioimmuno assay. Thyroid stimulating autoantibodies (TSAb) were present in 107 out of 126 patients with Graves' disease (85%) and in 4 out of 40 patients with Hashimoto's thyroiditis (10%). Specificity was confirmed by the fact that only 1 patient with insulin dependent diabetes mellitus (IDDM) out of 64 patients with different non-thyroid autoimmune disorders (46 with IDDM, 10 with stiff man syndrome and 8 with rheumatoid arthritis) and 2 out of 100 healthy controls (2%) were positive in this assay. In the subgroup of hyperthyroid Graves' disease patients 76 out of 83 (92%) had TSAb and the same number had TSH binding inhibiting immunoglobulin (TBII), as assessed by the commercial TRAK assay. Although both antibody types showed only a weak correlation (r = 0.30), a combination of TSAb and TBII detected 98% of all Graves' patients and 99% of the hyperthyroid subgroup. Thyroid blocking autoantibodies (TBAb) were measured in 4 out of 24 TSAb negative patients with Graves' disease (17%), who were hypothyroid and positive for TBII. A comparison of our bioassay with the standard bioassay using PEG precipitation showed a good correlation (r = 0.76,p < 0.001), demonstrating the feasibility of the simplified assay for the routine detection of TSAb and TBAb in Graves' disease.
9249646 COX-1 and COX-2 tissue expression: implications and predictions. 1997 Jul It has been proposed that cyclooxygenase (COX)-1 and COX-2 subserve different physiologic functions largely because of the striking differences in their tissue expression and regulation. COX-1 displays the characteristics of a "housekeeping" gene and is constitutively expressed in almost all tissues. COX-1 appears to be responsible for the production of prostaglandins (PG) that are important for homeostatic functions, such as maintaining the integrity of the gastric mucosa, mediating normal platelet function, and regulating renal blood flow. In sharp contrast, COX-2 is the product of an "immediate-early" gene that is rapidly inducible and tightly regulated. Under basal conditions, COX-2 expression is highly restricted; however, COX-2 is dramatically upregulated during inflammation. For example, synovial tissues in patients with rheumatoid arthritis (RA) express increased levels of COX-2. In animal models of inflammatory arthritis, COX-2 increases in parallel with PG production and clinical inflammation. In vitro experiments have revealed increased COX-2 expression after stimulation with proinflammatory cytokines, such as interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), in many cell types, including synoviocytes, endothelial cells, chondrocytes, osteoblasts, and monocytes/macrophages. Another distinguishing characteristic of COX-2 is decreased expression in response to glucocorticoids. COX-2 is also increased in some types of human cancers, particularly colon cancer. Mechanisms underlying the association between COX-2 overexpression and tumorigenic potential may include resistance to apoptosis, or programmed cell death. Upregulated COX-2 expression undoubtedly plays a role in pathologic processes characterized by increased local PG production. One would predict, based on current information regarding the differential tissue expression of COX-1 and COX-2, that highly selective inhibitors of COX-2 will provide effective antiinflammatory activity with marked reduction in toxicity.
9771210 Ultrasound and operative evaluation of arthritic shoulder joints. 1998 Jun OBJECTIVE: To assess the diagnostic value of ultrasonography (US) in the evaluation of arthritic shoulder joints. METHODS: Twenty shoulders of 20 inpatients with arthritis were evaluated by US one day before the shoulder operation. Changes in the subacromial-subdeltoid bursa, biceps tendon and tendon sheath, rotatof cuff, and glenohumeral joint were recorded and compared with findings at operation. RESULTS: In the detection of effusion/hypertrophy in the subacromial-subdeltoid bursa, US had a sensitivity of 93% and a specificity of 83%. For a biceps tendon rupture US had a sensitivity of 70% and a specificity of 100%. US missed three intraarticular biceps tendon ruptures. For effusion/hypertrophy in the biceps tendon sheath US had a sensitivity of 100% and a specificity of 83%. For a rotator cuff tear US had a sensitivity of 83% and a specificity of 57%. US missed two small longitudinal rotator cuff tears. Three thin membranous, but intact, rotator cuff tendons were classified as full thickness tears by US. Synovial effusion/hypertrophy was detected by US and at operation in all of the 12 glenohumeral joints that were evaluable at surgery. CONCLUSION: US is a reliable method in experienced hands for the evaluation of inflammatory changes of an arthritic shoulder. In advanced stages of rheumatoid shoulder joints, however, US is not useful, because destructive bone changes and tendon ruptures change the normal anatomy and restrict shoulder motions, limiting the visibility of US.
10498595 Simultaneous phenotypically distinct but clonally identical mucosa-associated lymphoid tis 1999 Oct 1 A 44-year-old woman with a 12-year history of Sjögren's syndrome (SS) developed a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma in the parotid gland. Two years later, she presented with generalized lymphadenopathy and hepatosplenomegaly and a follicular lymphoma was diagnosed. To investigate the relationship of the two histologically distinct lymphomas, we re-examined their histology and immunophenotype and studied the lymphomatous tissue from the parotid, cervical lymph node, and spleen using molecular genetic methods. Histologic and immunophenotypic studies confirmed the previous diagnoses and also identified a previously unnoticed focus of follicular lymphoma in the second parotid gland biopsy. Polymerase chain reaction (PCR) amplification of the rearranged Ig heavy-chain gene showed the same sized dominant product in the MALT lymphoma and the follicular lymphoma. Similarly, PCR analysis of the t(14:18) translocation yielded an identical sized band from both MALT and follicular lymphoma. Cloning and sequencing of the Ig PCR products showed an identical CDR3 sequence from each lesion, indicating a common clonal lineage. The follicular lymphoma of the parotid gland lymph node and the follicular lymphoma of the spleen showed an identical mutation signature to that of the salivary gland MALT lymphoma. We propose that follicular lymphoma in the parotid gland lymph node may have resulted from colonization of lymphoid follicles by MALT lymphoma cells, following which the tumor cells were induced to express a follicular lymphoma phenotype, due to Bcl-2 overexpression caused by t(14;18), leading to a change in clinical behavior resulting in rapid widespread dissemination of disease. These observations suggest that the distinct phenotypes of low-grade B-cell lymphomas may be the consequence of interplay between genetic and local microenvironmental factors.
10925313 Autoantigen-specific CD4+CD28low T cell subset prevents autoimmune exocrinopathy in murine 2000 Aug 15 Organ-specific autoimmune exocrinopathy resembling Sjögren's syndrome (SS) that spontaneously develops in NFS/sld mutant mice thymectomized 3 day after birth is dependent on Th1-type CD4+ T cells. We previously reported that a cleavage product of 120-kDa alpha-fodrin may be an important autoantigen in the pathogenesis of SS in both an animal model and the patients. We demonstrate that in an animal model of SS with overt exocrinopathy, a unique CD4+ T cell subset expressing CD28low is dramatically increased in spleen cells before the disease onset, but that the CD4+ T cells of diseased mice were virtually all CD28high. We found that the spleen cells in these mice before the disease onset showed a significant increase in autoantigen-specific T cell proliferation. Analysis of in vitro cytokine production by spleen cells indicated, before the disease onset, severely impaired production of IL-2 and IFN-gamma in the animal model, whereas high levels of IL-4 were observed. Expression of cytokine genes, including IL-4, IL-10, and TGF-beta, was detected in FACS-sorted CD4+CD28low T cells by RT-PCR analysis. Transfer of CD4+CD28low T cells into the animal model actually prevented the development of autoimmune lesions including autoantibody production. These results suggest that a CD4+CD28low T cell subset that is continuously activated by an organ-specific autoantigen may play a regulatory role in the development of organ-specific autoimmune disease in an animal model of SS.