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ID PMID Title PublicationDate abstract
14676339 Small stem Exeter total hip replacement: clinical and radiological follow-up over a minimu 2003 Dec PURPOSE: To evaluate the clinical and radiological outcome in patients undergoing small stem Exeter total hip replacement. METHODS: A total of 46 small stem Exeter total hip replacements were performed on 44 consecutive patients (18 men and 26 women) attending the University of Malaya Medical Centre. The mean age at the time of operation was 58 years (range, 24-81 years). Of the 46 procedures performed, 35 were primary total hip replacements and 11 were revision operations, with aseptic loosening of the original implant being the main indication for revision. The main indications for surgery in primary cases were avascular necrosis and rheumatoid arthritis. Clinical and radiographic outcomes were assessed at 6 weeks', 12 weeks', 6 months' follow-up, and annually thereafter. Postoperative cementing technique was also assessed. RESULTS: The mean follow-up period was 4 years. The mean Oxford Hip Score improved from 46 points preoperatively to 17 points at the final follow-up examination. There were no revision operations, no implant breakages, and no excessive migration of the implants. The potential complications of implant failure due to smaller implant size and increased patient activity were not observed. CONCLUSION: Due to the smaller size of Asian femora, the small stem Exeter implant is a very useful development. This study suggests that it will perform as well as its larger counterparts.
14672890 Interferon beta stimulates interleukin 1 receptor antagonist production in human articular 2004 Jan BACKGROUND: Interferon (IFN) beta displays anti-inflammatory and immunosuppressive activity and has been considered for the treatment of rheumatoid arthritis (RA). Information about the effects of this molecule on joint cells is scarce, however. OBJECTIVE: To investigate the effects of IFNbeta on the production of interleukin-1 receptor antagonist (IL1Ra) in human articular chondrocytes and synovial fibroblasts. METHODS: Chondrocytes and synovial fibroblasts were stimulated with IFNbeta alone or in combination with interleukin (IL) 1beta. IL1Ra concentrations in culture supernatants and cell lysates were determined by ELISA. Expression of mRNA encoding the secreted sIL1Ra or the intracellular icIL1Ra1 isoforms was quantified by real time reverse transcriptase-polymerase chain reaction. RESULTS: In chondrocytes, IFNbeta alone had no effect, but dose dependently enhanced the secretion of IL1Ra induced by IL1beta. Chondrocyte cell lysates contained undetectable or low levels of IL1Ra, even after stimulation with IL1beta and IFNbeta. Consistently, IL1beta and IFNbeta induced sIL1Ra mRNA expression in chondrocytes, while expression of icIL1Ra1 was not detectable. Human articular chondrocytes thus mainly produce secreted IL1Ra. In synovial fibroblasts, IFNbeta alone dose dependently increased IL1Ra secretion. In addition, IFNbeta enhanced the stimulatory effect of IL1beta on IL1Ra production. In synovial cell lysates, IFNbeta and IL1beta also increased IL1Ra levels. Consistently, IFNbeta and IL1beta induced the expression of both sIL1Ra and icIL1Ra1 mRNA in synovial fibroblasts. CONCLUSION: IFNbeta increases IL1Ra production in joint cells, which may be beneficial in cartilage damaging diseases such as RA or osteoarthritis.
14622751 The role of rofecoxib, a cyclooxygenase-2-specific inhibitor, for the treatment of non-can 2002 Aug Rofecoxib was the first specific inhibitor of cyclooxygenase-2 (COX-2) approved for the treatment of acute pain. It has been shown to provide analgesia that is significantly better than placebo and has an onset of action and efficacy similar to that of traditional nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), such as naproxen and ibuprofen. In addition, the analgesic efficacy of rofecoxib has been demonstrated to be superior to that of the opioid combination of codeine 60 mg/acetaminophen 600 mg in an acute dental pain model. For the treatment of acute pain, the efficacy of rofecoxib was further demonstrated in a study of patients who had undergone orthopedic surgery. Rofecoxib has been found to be as effective as naproxen sodium and more effective than placebo in studies evaluating its use for the treatment of primary dysmenorrhea. In patients with osteoarthritis (OA) of the knee or hip, rofecoxib is superior to placebo and similar to diclofenac and ibuprofen in relieving OA pain and improving physical function. Rofecoxib has also been shown to be superior to acetaminophen and celecoxib after 6 weeks of treatment for OA. The efficacy of rofecoxib has also been demonstrated in patients with rheumatoid arthritis and low back pain. The advantages of using COX-2-specific NSAIDs include convenient once-daily dosing schedule and improved safety compared with traditional NSAIDs. Two large outcomes studies, VIGOR and CLASS, have shown that gastric mucosal ulceration occurs significantly less often in patients taking COX-2-specific inhibitors than in those treated with ibuprofen, diclofenac, or naproxen and occurs with a similar incidence to that of placebo. Absence of any effect on platelet aggregation and bleeding time further distinguishes these agents from traditional NSAIDs. Because COX-2-specific inhibitors do not have an antiplatelet effect, they cannot be used as a substitute for low-dose aspirin for cardiovascular prophylaxis. Rofecoxib is a safe and highly effective alternative to previously available NSAIDs and should be considered for the treatment of acute pain conditions in adult patients, especially those at risk for developing gastrointestinal complications. It is preferred in the perioperative setting because of its analgesic efficacy and lack of platelet effects. Because of its more favorable gastrointestinal toxicity profile compared with nonselective NSAIDs, rofecoxib is safer in patients, especially older patients, for whom chronic anti-inflammatory or analgesic therapy is indicated.
14533499 [Thrombosis prevention in orthopaedic surgery: clinical practice in the Netherlands in 200 2003 Sep 20 OBJECTIVE: Establish the use of thromboprophylaxis in orthopaedic surgery both during and after the hospital admission. DESIGN: Cross-sectional study. METHOD: In April 2002, a letter was sent to all orthopaedic surgeons in the Netherlands announcing that at every hospital with a Department of Orthopaedic Surgery, an orthopaedic surgeon would be approached for a telephone survey. They were phoned in the months April-June 2002. This study included hospitals where major orthopaedic surgery (e.g. the insertion of hip or knee prostheses and hip fracture surgery) took place (n = 124) as well as clinics that only performed day treatments (n = 5). RESULTS: For major orthopaedic operations, 91% of the hospitals used low molecular weight heparin (LMWH) during the admission period: 36% as monotherapy and 55% in combination with coumarin derivates. In 85% of cases the use of LMWH was started preoperatively. Coumarin derivates were used as a monotherapy in 9% of the hospitals. In 37% of the hospitals the use of NSAIDs was continued, particularly in patients with rheumatoid arthritis. In 94% of the hospitals, the use of acetylsalicylic acid was always stopped. In 97% of the hospitals prophylaxis was given after discharge in the form of LMWH (37% of the cases) or coumarin derivates (63% of the cases). The use of thromboprophylaxis with respect to arthroscopies and plaster immobilisation was variable.
12962568 [Effect of nitric oxide on iron metabolism in rats with anemia of chronic disease]. 2003 Aug To explore the role of nitric oxide (NO) in the pathogenesis and effect on regulation of iron metabolism in anemia of chronic disease (ACD) and provide experimental evidence for prevention and treatment of ACD. On the basis of traditional animal model of rheumatoid arthritis, an ACD rat model was established by repeated injection of Freund's complete adjuvant. The relationship between NO concentration and iron metabolism was observed in ACD rats with and without NO synthase inhibitor, L-NAME, (N omega-nitro-L-arginine methyl ester L-NAME). The results showed that anemia was induced in the rat model. In the ACD group, NO concentration and NO synthase activity in serum increased; iron, total iron binding capacity (TIBC) and transferrin saturation (TS) in serum and ferritin in erythrocytes (rFn) decreased; transferrin receptor (TfR) and iron in bone marrow cells decreased; ferritin in serum and iron in liver increased and meanwhile the acotinase activity in liver decreased. After administration of L-NAME, anemia was improved, when NO, NO-synthase activity, liver iron and serum ferritin decreased, but serum iron, TS, TIBC, rFn, TfR, iron in marrow cells and liver acotinase activity elevated. The levels of parameters for iron metabolism in ACD + L-NAME group were situated between ACD and control groups. It is concluded that NO plays an important role in pathogenesis of ACD and influences the regulation of iron in ACD. Decrease of NO level as early as possible will benefit to block the development of anemia, that will provide a new strategy of therapy for ACD.
12820650 Characterization of the anti-DnaJ monoclonal antibodies and their use to compare immunolog 2003 Spring Escherichia coli DnaJ (Hsp40) is suspected to participate in rheumatoid arthritis (RA) pathogenesis in humans by an autoimmune process. In this work a set of 6 anti-DnaJ monoclonal antibodies (mAbs) was raised and localization of the epitopes recognized by the mAbs was investigated. Western blotting and enzyme-linked immunosorbent assay (ELISA) experiments showed that the mAbs efficiently bound only native antigen. Using DnaJ mutant proteins with deletions of specified domains and ELISA, we found that AC11 mAb reacted with the best conserved in evolution N-terminal J domain, whereas BB3, EE11, CC5, CC8, and DC7 bound to the C-terminal part after residue 200. Mapping performed with the use of a random peptide library displayed by filamentous phage indicated that (1) AC11 mAb bound to a region between residues 33-48, including D-34 which belongs to the HPD triad, present in all DnaJ homologues, (2) BB3 recognized residues localized in the 204-224 region, (3) EE11 recognized the 291-309 region, (4) CC5--the region 326-359, and (5) CC8--the 346-366 region. All these mAbs, as well as the polyclonal antibodies against the N- or C-terminal domain, bound efficiently to HDJ-1, human Hsp40. These results show the presence of a significant immunological similarity between bacterial DnaJ and human HDJ-1, which is not restricted to the evolutionarily conserved parts of the proteins, and suggest that HDJ-1 could be a possible target of immune response triggered by DnaJ.
12748886 Craniocervical junction instability: instrumentation and fusion with titanium rods and sub 2003 Apr BACKGROUND: The aim of the study was to evaluate the effectiveness, pitfalls and failures of instrumentation and fusion with titanium wires and rods in 12 h patients with craniovertebral junction instability. METHODS: Among nine adult patients (mean age 48.11 years) with craniovertebral junction instability, four had basilar impression, three metastatic disease, one rheumatoid arthritis and one Down's syndrome. Three children (mean age 7.33 years) with genetic (Down's syndrome, 2 cases) and metabolic (mucopolisaccarydoses type IV, i.e. Morquio Syndrome, 1 case) disease were studied as well. Each patient underwent preoperative radiological evaluation by means of X-Ray, CT scan and MRI of the craniocervical region. Occipitocervical instrumentation with a titanium U-shaped wired rod was performed in each patient. Autologous bone fusion was performed in all but the two cancer patients, in whom polymethylmetacrylate was used. Postoperatively, all the patients used an external orthosis for 3-6 months. Post-operative X-Ray, CT and MRI were performed on each patient. The Frankel clinical scale was used to asses the outcome at follow-up which ranged from 1 to 10 years. At maximum follow up, there was either clinical improvement or stabilization recorded in all but one patient. This patient with basilar impression transiently worsened from grade D to C and a spinal cord lesion was already evident before the operation on MRI examination. INTERPRETATION: The effectiveness of surgical management of craniovertebral junction instability by instrumentation and fusion was demonstratedly in our experience. Nevertheless, the choice of the surgical technique should be made with caution when a spinal cord lesion is revealed by preoperative neuroimaging studies.
12701851 Proxy reporting in after-death interviews: the use of proxy respondents in retrospective a 2003 Mar This study evaluates the quality of data obtained from after-death interviews with significant others of deceased older persons regarding the prevalence of chronic diseases and symptoms in the terminal phase of life. These data are compared with reports from physicians and earlier self-reports from the deceased person. There were significant increases in nonresponse and nonavailability of significant others for decedents who had been divorced or had never been married, thus introducing some selection bias. At the level of the total sample, significant others seem to give accurate information about the prevalence of chronic diseases when compared with self-reports and reports from physicians. At the level of the individual sample member, after-death interviews with significant others provide valid information for the assessment of the prevalence of malignant neoplasms, diabetes mellitus, chronic obstructive pulmonary disease and cerebrovascular disease, but not for osteo- and rheumatoid arthritis and artherosclerotic disease. At the level of the total sample, the prevalence of symptoms assessed by significant others did not differ greatly from the assessment made by physicians. However, at the level of the individual sample member, the validity of symptom assessment by significant others could not be supported by data obtained from the physicians. With regard to the type of significant others interviewed, children reported more symptoms than partners. The use of significant others in after-death interviews can be a valid method with regard to the assessment of chronic diseases and symptoms on a group level. On an individual level this can be concluded only for chronic diseases with clearly observable consequences.
12675521 Cystatins C, E/M and F in human pleural fluids of patients with neoplastic and inflammator 2003 Feb Secretory type 2 cystatins, like cystatins C, E/M and F, are thought to be involved in many pathobiological processes, including vascular amyloidosis, rheumatoid arthritis, Alzheimer's disease, osteoporosis, viral and bacterial infections, inflammatory disorders and tumour invasion and metastasis. In order to define the levels of cystatins C, E/M, and F in pleural effusions and to investigate whether these cystatins correlate with diagnostic parameters of pleural and lung diseases, we determined their concentrations in 160 pleural effusions. The median concentration of cystatin C in pleural effusions was 1437 microg/l (95.8 nM), ranging between 18-3967 microg/l. Cystatin C did neither correlate with malignant nor with benign diseases. The concentration of cystatin E/M was significantly higher in effusions of primary pleural tumours (mesotheliomas) compared to secondary pleural tumours and benign diseases. Furthermore, there was a significant correlation between the concentration of cystatin E/M of mesotheliomas and the pleural fluid tumour cell count and of cystatin C. The median values of cystatin F were significantly increased in parapneumonic/empyema thoracis pleural effusions and tuberculous pleurisy compared to malignant pleural effusions, respectively. The concentration of cystatin F in benign effusions correlated significantly with diagnostic parameters and inflammation (total protein; lactate dehydrogenase; C-reactive protein). Finally, only in the group of parapneumonic/empyema thotatin F and the neutrophil count. In conclusion, pleural effusions of different origin contain high levels of cystatin C, perhaps constituting the major part of an inhibitor reservoir. The level of cystatin E/M appears to be significantly associated with primary pleural tumours and cystatin F correlates with inflammatory processes of lung disorders.
12590015 Hypoglycemia due to nateglinide administration in diabetic patient with chronic renal fail 2003 Mar A 56-year-old woman with diabetic triopathy, rheumatoid arthritis and chronic renal failure was admitted for severe hypoglycemic coma. Arthralgia had been deteriorating for 6 months. Therefore, 5 mg of prednisolone was administered. Postprandial blood glucose (PPG), however, elevated from 260 to 290 mg/dl, although fasting blood glucose (FBG) levels ranged from 80 to 110 mg/dl. Three months after, 270 mg of nateglinide was given in addition to acarbose. After 2 days, hypoglycemia occurred at 02:00 h. Nateglinide was then decreased to 180 mg (before breakfast and lunch). After 5 days, hypoglycemia re-occurred at 01:00 h. Nateglinide was subsequently decreased to 90 mg before breakfast. The PPG levels ranged from 130 to 150 mg/dl. Hypoglycemia did not occur during the next 2 months. On admission, FBG; 59 mg/dl, fasting immunoreactive insulin; 34 microU/ml, indicated hyperinsulinemic hypoglycemia. We administered 20 g of glucose intravenously, however, hypoglycemia recurred 4 times and 20 g of glucose was then administered. Although the plasma nateglinide level decreased, the nateglinide metabolite, N-[trans-4-(1-hydroxy-1methylethyl)-cyclohexanecarbonyl]-D-phenylalanine levels still had not decreased 29 h after nateglinide administration. Therefore, chronic renal failure appeared to alter the pharmacokinetic parameters of the nateglinide metabolite, which had accumulated by chronic renal failure. The nateglinide metabolite caused severe hypoglycemia in this case.
12576215 Daeganghwal-tang inhibits the stem cell factor-induced migration and inflammatory cytokine 2003 Mar Traditional Oriental medicinal prescription, Daeganghwal-tang (DGHT) has been used for the treatment of rheumatoid arthritis (RA) in Korea. However, its effect in experimental models remains unknown. Recent reports suggest that in patients with RA, synovial mast cells increase in number and show signs of activation and inflammatory cytokines secretion. Our results show that stem cell factor (SCF) is a potent chemotactic factor for the mast cells in vitro. The chemotactic response to SCF was blocked by DGHT. When DGHT (1mg/ml) was added, the secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 was inhibited by 60.1, 81.8, 72.5%, respectively in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated HMC-1 cells. In addition, the expression of TNF-alpha mRNA in HMC-1 cells was inhibited by DGHT (1mg/ml). These findings indicate that DGHT inhibits SCF-induced migration and PMA plus calcium ionophore-stimulated inflammatory cytokines secretion in mast cells.
12557024 [Pars plana vitrectomy in cystoid macular edema of different forms of chronic uveitis]. 2003 Jan BACKGROUND: Cystoid macular edema (CME) is a common complication in different forms of chronic uveitis. In spite of immunosuppressive and anti-inflammatory therapy, chronic or relapsing courses can occur which may have a negative impact on visual prognosis. Pars plana vitrectomy (PPV) is known to positively influence chronic uveitis. This retrospective study was performed to investigate the role of PPV in the therapy refractive uveitic CME. PATIENTS AND METHODS: PPV for CME was performed in eyes with CME in intermediate uveitis (IMU, n=42), chronic iridocyclitis in juvenile rheumatoid arthritis (CIC, n=14) and multifocal chorioretinitis (MFC, n=12). In none of the eyes had immunosuppressive and/or anti-inflammatory therapy or anti-edema treatment (e.g.acetazolamide) led to regression of the CME. After a postoperative follow-up period of 7 and 106 months all patients were re-examined. RESULTS: Postoperative complete or partial regression of CME was observed as follows: IMU: 25/42 (59.5%), CIC: 8/14 (57.1%),MFC: 5/12 (41.7%). A significant increase in visual acuity of 2 lines and more was observed in 50%,71.4% and 41.7% of eyes, respectively. In the long-term follow-up best functional results were achieved in eyes with IMU. CONCLUSIONS: Response to PPV was variable according to the type of underlying form of uveitis. The lowest success rate could be observed in eyes with MFC. Although the postoperative regression rate of CME was satisfactory in eyes with CIC, long-term visual acuity results were disappointing due to secondary complications of CIC in this young age group. Best results were achieved in patients with IMU (statistically not significant). A multicenter study in a larger series of patients is needed to investigate the exact role of PPV in different forms of chronic uveitis.
12393854 Amiloride-blockable acid-sensing ion channels are leading acid sensors expressed in human 2002 Oct Many painful inflammatory and ischemic conditions such as rheumatoid arthritis, cardiac ischemia, and exhausted skeletal muscles are accompanied by local tissue acidosis. In such acidotic states, extracellular protons provoke the pain by opening cation channels in nociceptors. It is generally believed that a vanilloid receptor subtype-1 (VR1) and an acid-sensing ion channel (ASIC) mediate the greater part of acid-induced nociception in mammals. Here we provide evidence for the involvement of both channels in acid-evoked pain in humans and show their relative contributions to the nociception. In our psychophysical experiments, direct infusion of acidic solutions (pH > or = 6.0) into human skin caused localized pain, which was blocked by amiloride, an inhibitor of ASICs, but not by capsazepine, an inhibitor of VR1. Under more severe acidification (pH 5.0) amiloride was less effective in reducing acid-evoked pain. In addition, capsazepine had a partial blocking effect under these conditions. Amiloride itself neither blocked capsaicin-evoked localized pain in human skin nor inhibited proton-induced currents in VR1-expressing Xenopus oocytes. Our results suggest that ASICs are leading acid sensors in human nociceptors and that VR1 participates in the nociception mainly under extremely acidic conditions.
12379312 The CD23b promoter is a target for NF-AT transcription factors in B-CLL cells. 2002 Oct 9 CD23 is atypically highly expressed in various chronic diseases, including B-CLL, lupus erythematodes and rheumatoid arthritis. Its expression can be further enhanced by interleukin 4 (IL-4). We have shown before that in B-CLL cells nuclear factor(s) of activated T cells (NF-ATs) show permanent nuclear localization and therefore constitutive transcriptional activity. Here we identify CD23b promoter as a novel target for NF-AT factors in B-CLL cells. The CD23b promoter contains two NF-AT binding sites to which NF-ATp and NF-ATc factors bind with high affinity. Mutations introduced into these sites abolished NF-AT binding and impaired the promoter activity, as did cyclosporin A (CsA), an inhibitor of nuclear transport of NF-ATs. Furthermore, we show that IL-4-induced transcription factor STAT6 cooperates with NF-ATs in the induction of the CD23b promoter activity. These results show that the CD23b promoter is a target for NF-AT factors and suggest that the cooperation between NF-AT and STAT factors might be one of the molecular mechanisms responsible for high-level expression of CD23 on the surface of B-CLL cells.
11961039 Binding and functional comparisons of two types of tumor necrosis factor antagonists. 2002 May Two tumor necrosis factor (TNF) antagonists infliximab (a chimeric monoclonal antibody) and etanercept (a p75 TNF receptor/Fc fusion protein) have been approved for treatment of rheumatoid arthritis. However, these agents have shown different degrees of clinical benefit in controlled clinical trials in other TNF-mediated diseases such as Crohn's disease (CD) and psoriasis. We investigated whether structural differences between these two antagonists translate into different binding and functional characteristics. To study the binding of infliximab and etanercept to both the soluble and cell-surface transmembrane forms of TNF, a variety of in vitro binding and cell-based assays were performed. Binding assays using (125)I-labeled TNF showed that infliximab binds to both monomer and trimer forms of soluble TNF (sTNF), whereas etanercept binding is restricted to the trimer form. Infliximab formed stable complexes with sTNF, whereas etanercept formed relatively unstable complexes, resulting in release of dissociated TNF. KYM-1D4 cell killing assays and human umbilical vein endothelial cell activation assays demonstrated that TNF that had dissociated from etanercept was bioactive. Infliximab also formed more stable complexes with the transmembrane form of TNF expressed on transfected cells relative to analogous complexes formed with etanercept. Additionally, more infliximab molecules bound to the transmembrane TNF with higher avidity than etanercept. Although both infliximab and etanercept inhibited transmembrane TNF-mediated activation of human endothelial cells, infliximab was significantly more effective. The differences between infliximab and etanercept in their TNF binding characteristics may help explain their differential efficacy in CD and psoriasis clinical trials.
11950004 Immunosuppressant effect of IDS 30, a stinging nettle leaf extract, on myeloid dendritic c 2002 Apr OBJECTIVE: Dendritic cells are important antigen presenting cells that play a role in the initiation of rheumatoid arthritis (RA). The stinging nettle leaf extract IDS 30 (Hox alpha) has been recommended for adjuvant therapy of rheumatic diseases. We investigated the immunomodulating effect of IDS 30 extract on the maturation of hematopoietic dendritic cells. METHODS: Human dendritic cells were generated from peripheral blood mononuclear cells cultured in granulocyte macrophage-colony stimulating factor and interleukin 4 (IL-4). Dendritic cell maturation was induced by keyhole limped hemocyanin (KLH). Dendritic cell phenotype was characterized by flow cytometric analysis; dendritic cell cytokine production was measured by ELISA. The ability of dendritic cells to activate naive autologous T cells was evaluated by mixed leukocyte reaction. RESULTS: IDS 30 prevented the maturation of dendritic cells, but did not affect their viability. IDS 30 reduced the expression of CD83 and CD86. It increased the expression of chemokine receptor 5 and CD36 in a dose dependent manner. The secretion of tumor necrosis factor-alpha was reduced. Application of IDS 30 to dendritic cells in culture caused a high endocytosis of dextran and a low capacity to stimulate T cell proliferation. CONCLUSION: Our in vitro results showed the suppressive effect of IDS 30 on the maturation of human myeloid dendritic cells, leading to reduced induction of primary T cell responses. This may contribute to the therapeutic effect of IDS 30 on T cell mediated inflammatory diseases like RA.
11861076 Combination of MHC-peptide multimer-based T cell sorting with the Immunoscope permits sens 2002 Mar 1 Identification of MHC-restricted antigens and progress in the induction and control of adaptive cytotoxic immune responses have led to renewed interest in immunotherapy as a treatment for severe pathologies such as cancer and autoimmune diseases. Reliable procedures for detecting and monitoring T cell responses induced by the treatment throughout a clinical trial are needed in order to design rational protocols with increased efficiency. We have attempted to develop such a procedure by combining T cell sorting using HLA-peptide complexes multimerized on magnetic beads together with the quantitative Immunoscope approach. Once a recruited patient has been typed for HLA and target antigens, relevant HLA--peptide multimers can be selected and used for sorting specific peripheral T cells prior to any treatment and at the peak of the expected response to treatment. Clonotypic primers specific for the TCR rearrangements of the specific T cell clones can then be designed and used for measuring the frequency of their TCR transcripts by quantitative PCR on blood samples or T cell subsets throughout the trial. In reconstruction experiments as well as in samples from one rheumatoid arthritis patient, we were readily able to detect and follow several T cell clones with a frequency as low as 10(-5) among CD8+ T cells. The main advantages of this procedure over other currently available assays are that it does not require any assumptions on the functional status of the specific T cells and it permits the monitoring of individual T cell clones whose phenotypic shift can thus be evaluated.
11840100 A comparative study of localization of heat shock protein 27 and heat shock protein 72 in 2002 Feb 15 STUDY DESIGN: The lumbar intervertebral discs of 135 subjects after autopsy were immunostained with antihuman heat shock protein 27 (HSP27) monoclonal antibody and antihuman heat shock protein 72 (HSP72) polyclonal antibody. OBJECTIVES: To present the data on metabolic changes that occurred in the chondrocytes of intervertebral discs during development and aging. SUMMARY OF BACKGROUND DATA: Heat shock proteins have been implicated in the progressive degeneration of articular cartilage in joint disease, such as rheumatoid arthritis and osteoarthritis. However, the role and expression of heat shock proteins in human intervertebral discs have received little study. METHODS: One hundred thirty-five specimens of human intervertebral discs were stained with hematoxylin and eosin, alcian blue, and Masson's trichrome and were immunostained with HSP27 and HSP72 by an indirect immunoperoxidase method. The relative amounts of HSP27 and HSP72 deposition were graded according to a semiquantitative scoring system. RESULTS: Heat shock protein 72 accumulated in the cytoplasm of the chondrocytes of both endplate cartilage and nucleus pulposus during gestation and thereafter decreased with aging (age,
11772527 Alpha-lipoic acid modulates NF-kappaB activity in human monocytic cells by direct interact 2002 Jan The constitutive activity of the redox-sensitive transcription factor, NF-kappaB, which regulates the production of many inflammatory cytokines and adhesion molecules, appears to be up-regulated in an age-associated manner and it is thought this might contribute to the increased incidence of chronic inflammatory conditions observed with increasing age. As some antioxidants have demonstrated protective effects against rheumatoid arthritis, we are investigating the effects of vitamin E, vitamin C and alpha-lipoic acid (ALA) on NF-kappaB activity and on the expression of intracellular adhesion molecule (ICAM)-1. MonoMac6 cells (a human monocytic cell line) stimulated with tumour necrosis factor-alpha (TNF-alpha) were treated with antioxidants at physiological achievable levels and ICAM-1 mRNA levels investigated. Both vitamin E and vitamin C had no effect on ICAM-1 expression at the doses used, but ALA reduced the TNF-alpha-stimulated ICAM-1 expression in a dose-dependent manner, to levels observed in unstimulated cells. Alpha-lipoic acid also reduced NF-kappaB activity in these cells in a dose-dependent manner. Addition of ALA to the binding reaction of nuclear extract with DNA prior to gel-shift analysis showed that it caused inhibition at this level. These initial results suggest that antioxidant modulation of monocyte activity might have potential benefits in inhibiting the dysregulated activity of redox-sensitive transcription factors that occurs with increasing age.
15022338 Family study of fibromyalgia. 2004 Mar OBJECTIVE: To assess for familial aggregation of fibromyalgia (FM) and measures of tenderness and pain, and for familial coaggregation of FM and major mood disorder (major depressive disorder or bipolar disorder). METHODS: Probands meeting the American College of Rheumatology criteria for FM and control probands with rheumatoid arthritis (RA) and no lifetime diagnosis of FM were recruited from consecutive referrals to 2 community-based rheumatology practices. Probands were ages 40-55 years and had at least 1 first-degree relative age 18 years or older who was available for interview and examination. All probands and interviewed relatives underwent a dolorimeter tender point examination and a structured clinical interview. Interviewed relatives were asked about first-degree relatives who were not available for interview, using a structured family interview. Logistic and linear regression models, adjusting for the correlation of observation within families, were applied to study the aggregation and coaggregation effects. RESULTS: Information was collected for 533 relatives of 78 probands with FM and 272 relatives of 40 probands with RA. FM aggregated strongly in families: the odds ratio (OR) measuring the odds of FM in a relative of a proband with FM versus the odds of FM in a relative of a proband with RA was 8.5 (95% confidence interval [95% CI] 2.8-26, P = 0.0002). The number of tender points was significantly higher, and the total myalgic score was significantly lower in the relatives of probands with FM compared with the relatives of probands with RA. FM coaggregated significantly with major mood disorder: the OR measuring the odds of major mood disorder in a relative of a proband with FM versus the odds of major mood disorder in a relative of a proband with RA was 1.8 (95% CI 1.1-2.9, P = 0.013). CONCLUSION: FM and reduced pressure pain thresholds aggregate in families, and FM coaggregates with major mood disorder in families. These findings have important clinical and theoretical implications, including the possibility that genetic factors are involved in the etiology of FM and in pain sensitivity. In addition, mood disorders and FM may share some of these inherited factors.