HLA distribution in Italian patients with fibromyalgia.
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Biomedical subjects
Publications and source records attributed to G Biasi.
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We observed that peripheral T cells activated in vivo or in vitro by superantigens are susceptible to cell death when their antigen receptor is cross-linked with the appropriate anti-alpha beta TCR mAb. TCR ligation by mAbs specifically drove the T cell clonal deletion in both CD4+ and CD8+ cell subsets. An IL-2/IL-2R interaction seems to be a critical step in predisposing superantigen activated cells to death; in fact, in vivo IL-2R blockade reversed T cell deletion in superantigen plus anti-alpha beta TCR mAb treated mice. TCR ligation by mAbs also produced cell death of the relevant targets in in vitro IL-2 activated T cells. Surprisingly, no T cell deletion was demonstrable in IL-2 activated cells following staphylococcal enterotoxin B--TCR interaction, ruling out the possibility that superantigen in itself can induce cell death. Thus, while superantigen activation opens the cell death program, a subsequent TCR--antigen (self) interaction appears necessary to produce clonal deletion in mature T lymphocytes.
Fibromyalgia syndrome is a form of extraarticular rheumatism of unknown origin; its diagnosis is fundamentally based on clinical and anamnestic findings, on characteristics of pain and on number and sites of tender points, very painful areas to palpation. At present there is no laboratory or instrumental test available for a more objective diagnosis. The Authors verified the utility of telethermography for fibromyalgia syndrome diagnosis to point out a possible specific pattern; in particular the tender points were studied, even to find some analogy to myofascial syndromes trigger points, which appear as hot spot to telethermography. The telethermographic patterns of 156 patients with fibromyalgia syndrome have been compared with tender point maps obtained from same subjects and with telethermographic data of patients affected by spine osteoarthritis and normal controls. The patients with fibromyalgia syndrome showed a non specific hyperthermic pattern, corresponding to painful muscular areas, comparable with pattern of osteoarthritic patients. This phenomenon can be interpreted as a greater thermic emission by hypertonic muscles. Therefore, telethermography in fibromyalgia syndrome cannot represent a basic diagnostic tool but can support the clinical diagnosis and play an important role in the follow-up of patients.
The possibility of increasing the resistance of a synthetic vascular graft to intraoperative or immediate postoperative bacterial contamination justifies the interest in methods such as antibiotic bonding or antibiotic soaking. On the basis of this experience and with the aim of testing the efficacy of such a graft, a multicentre experimental study on sheep to compare the susceptibility to infection of Dacron Gelseal grafts (control) versus rifampicin-bonded Dacron Gelseal grafts (treated) following the intravenous infusion of 10(7)-10(8) cells Staphylococcus aureus was conducted. The grafts were implanted in both common carotid arteries of sheep. In a group of 11 animals (group A), a treated and a control graft were implanted in the same animal. In a group of four sheep (group B), only treated or control grafts were implanted in each animal. In group A, 36% of (four of 11) the treated grafts became infected versus 54% (six of 11) of the control prostheses. In group B, none of the treated grafts was infected by the inoculated pathogen, which, by contrast, infected 75% (three of four) of the controls. These observations confirm the recent interest aroused by the possibility of pretreating gelatin-coated Dacron grafts with rifampicin in the prevention of early graft infection.
The most suitable treatment for intraluminal carotid thrombi remains still a much debated question. Some authors have reported a lower morbidity in patients treated with anticoagulant or antiplatelet therapy; on the other side, urgent or delayed surgery is burdened with a high risk of perioperative stroke. Over 11 years (october 1981-november 1992) 602 surgical revascularizations on epi-aortic vessels have been performed at Vascular Surgery Unit of Udine Regional Hospital. Only 2 cases of intraluminal carotid thrombi were observed: both fulfilled the angiographic requirements for endovasal filling defect, surrounded by contrast medium, adherent to posterior wall and extending to distal internal carotid artery. First patient suffered a TIA 20 days before surgery, the second one a previous major stroke contralateral to the thrombus. The former was given preoperatively a medical anticoagulant treatment (warfarin). At operation we discovered a nearly complete resolution of the thrombus: only its adherent base was still present. Therefore we performed a routine endarterectomy and a PTFE patch angioplasty. The latter case reported had no preliminary medical treatment; a thrombus extending from carotid bulbus to external and internal carotid was detected and then removed without any distal embolization. Arteriotomy was closed by Dacron Velour patch angioplasty. No perioperative stroke occurred in both cases: our second patient showed a partial resolution of his motility deficit. According to our limited experience, delayed surgical treatment of intraluminal carotid thrombi seems not to be affected with higher risk of perioperative stroke than prophylactic carotid endarterectomy.(ABSTRACT TRUNCATED AT 250 WORDS)
To help fibromyalgia syndrome's diagnosis, the authors propose the use of Back Pain Classification Scale (BPCS), verbal test for pain analysis, able to distinguish between organic and functional disease. Two-hundred patients suspected for fibromyalgia and forty controls completed the questionnaire and so it was possible correctly to distinguish patients with organic disease from those affected by fibromyalgia. The authors conclude that BPCS can represent a useful tool for fibromyalgia diagnosis.
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To investigate whether a clonal deletion mechanism is responsible for the mature T cell tolerance that may be induced in vivo by TCR signal to anti-CD4 (H129.19 mAb) coated cells, we analyzed the T cell repertoire in anti-CD4 mAb treated BALB/c mice by flow cytometry following TCR signals through anti-alpha beta TCR mAb or SEB superantigen. Lymph nodes showed a strong reduction in the CD4+/CD8+ cell ratio, and a selective clonal loss of CD4+ V beta 8+ cells 4d following anti-alpha beta TCR or SEB injection, respectively. Following lymph node cell activation in a short-term in vitro assay with SEB or anti-V beta 8 mAb, a selective elimination of CD4+ V beta 8+ cells was again detected, and DNA fragmentation analysis disclosed a cell death by apoptosis. These findings suggest that TCR triggering transduces an apoptotic signal into CD4+ mAb saturated cells that in turn leads to specific holes in the mature T cell repertoire.
We have investigated the in vivo role of 2 different adhesion molecules, LFA-1 and LECAM-1, in the immune reaction to Moloney-murine-sarcoma-virus(M-MSV)-induced tumors, which undergo a peculiar spontaneous regression due to generation of a strong virus-specific cytotoxic-T-lymphocyte(CTL) response. Repeated administration of anti-LFA-1 monoclonal antibody (FD441.8 MAb), i.p. or at the site of virus inoculation, enhanced tumor growth and delayed regression, while i.p. administration of anti-LECAM-1 MEL-14 MAb gave rise to tumors that grew progressively and caused host death. Evaluation of the immunological response in MAb-treated mice showed reduced generation of virus-specific CTL precursors (p) in the spleen of animals given FD441.8 MAb i.p.; CTLp frequency in locally treated mice overlapped with that of control mice injected with virus only. FD441.8 MAb treatment did not interfere with CTL homing in the tumor, since the frequency of M-MSV-specific CTLps in sarcomas was similar in treated and control mice. Cytofluorimetric analysis indicated that the majority of tumor-infiltrating lymphocytes (TIL) from MAb-treated mice were covered by anti-LFA-1 MAb, and lacked cytotoxic activity when assayed against target cells bearing relevant tumor antigens. Instead, in mice injected i.p. with MEL-14 MAb, a very low frequency of CTLps was detected in lymph nodes draining the tumor area, and within the tumor. Our results indicate that enhanced tumor growth, depending on the MAb used, is the resultant of an inhibitory effect on different T-lymphocyte functions. Tumor progression in anti-LFA-1 MAb-injected mice is explained mostly by blockage of CTL lytic activity at the tumor site; in mice receiving i.p. MEL-14 MAb treatment, by the failure of naive T lymphocytes to enter peripheral lymph nodes and subsequently by the lack of generation of tumor-specific CTLs.
Adult mice injected with Moloney murine leukemia virus (M-MuLV) 1 day after a short term treatment with anti-CD4 mAb developed T cell lymphomas, or sarcomas when rechallenged with Moloney murine sarcoma virus (M-MSV). Neoplastic development was correlated with virus spread, as thymic and peripheral T and B lymphocytes promptly expressed M-MuLV-induced Ag after virus introduction; no virus-specific CTL generation was detected in MLTC. This failure, which was selective for M-MuLV-induced Ag, persisted throughout the life span of the mice, and was not sustained by suppressor cell activity. The frequencies of splenic virus-specific CTL precursor varied in relation to time after virus injection; in the first postinjection month, frequencies were similar to those in nonimmune control mice, while at 4 mo post-virus exposure, they showed a striking reduction. These findings indicate that a transient functional impairment of CD4+ cells at the time of retrovirus injection provided the appropriate milieu for tolerance induction in both the peripheral mature and intrathymic T cell compartments.
Although the exact etiology of progressive systemic sclerosis (SSP) is still unknown, it is felt that immunologic disorders may be implicated in its pathogenesis. On the basis of these considerations, an open study with an immunomodulating drug, thymopentin, was performed in 20 SSP outpatients. These subjects were initially treated with thymopentin three times a week for three consecutive months (phase I); during a second study phase lasting three months, 10 patients continued to receive thymopentin and the remaining 10 placebo (phase II). A significant improvement in various clinical, laboratory and instrumental findings was seen following thymopentin treatment. During phase II, those on placebo regressed to basal conditions, while an added improvement was noted in those who continued with thymopentin.
An application of the Southern blot technique is described which permits the detection of DNA fragmentation due to cell death by apoptosis. DNA fragments were isolated from cell suspensions and tissues, separated on agarose gel, transferred by Southern blot and hybridized with a radiolabeled total cellular DNA probe. The application of this procedure to thymus cell samples, revealed the distinct ladder pattern of DNA fragments in multiples of about 180-200 base pairs, a characteristic feature of DNA fragmentation. In comparison to conventional DNA visualization with ethidium bromide staining, the radiolabeled probe improved the detection of DNA fragments at least eight-fold. This method detects low levels of DNA fragments, as well as physiological tissue DNA fragmentation, while avoiding cell damage due to DNA radiolabeling.
The role of CD4+ cells in the immune response to Moloney murine sarcoma/leukemia virus complex was studied in adult mice undergoing long-term CD4+ cell functional depletion by treatment with anti-CD4 H129.19 monoclonal antibody (immunoglobulin G2a, kappa). Adult mice given injections of Moloney murine sarcoma/leukemia virus complex 1 day or 2 wk after monoclonal antibody treatment died with progressing sarcomas at the inoculation site; mice challenged 4 wk after such treatment, when CD4+ cells recovered their functional activity, behaved like conventional mice; i.e., they spontaneously regressed the virus-induced sarcomas. Mice with progressing tumors did not generate virus-specific cytotoxic T-lymphocytes, despite a normal cytotoxic T-lymphocyte response to unrelated antigens, and they became virus carriers as demonstrated by Moloney murine leukemia virus antigen expression on their lymphoid cells a few days after virus injection. Moreover, the observed T-lymphocyte unresponsiveness was not due to the activity of specific suppressor T-cells. The findings indicate that the transient functional depletion of CD4+ cells at the time of virus administration provides appropriate environmental conditions for the spread of virus and facilitates tolerance induction.
Spirals of human saphenous veins (HSV), mounted in a 5 ml organ bath containing Krebs-Henseleit solution (37 degrees C), when kept in contact with defibrotide (100-200 ug/ml) for 15 min, enhance (2 and 3 fold) their own basal release of 6-keto-PGF 1 alpha (61 +/- 1.3 pg/mg w.t. n = 12). The phenomenon was long lasting upon repeated washing and sensitive to indomethacin (1 ug/ml). Endothelin-1 (ET-1, 20-40 ng) induced a sustained contraction of HSV and concomitantly released from the venous tissue a proportional amount of 6-keto-PGF 1 alpha. Indomethacin (1 ug/ml), by inhibiting cyclo-oxygenase enzyme, potentiated the contractile activity of ET-1 in HSV whereas exogenous PGE2 (20 ng/ml) considerably reduced the tension developed by the peptide on this venous tissue. Defibrotide (200 ug/ml), by releasing 6-keto-PGF 1 alpha, and other vasoactive prostaglandins, antagonized the contractile effect ET-1 (20 ng) in HSV. This data indicates that the eicosanoid metabolism is involved in the modulation of the potent vasoconstrictor effect of ET-1 in HSV and that PGI2-releaser, such as defibrotide, may have therapeutical value against immoderate changes of venous tone.
The antalgic activity of a newly characterized NSAID (cinnoxicam) was evaluated by cutaneous sensimetry. A precocious and significant increase in pain threshold was demonstrated by the algometric data observed after oral administration of one tablet of the drug under examination in both healthy volunteers and in rheumatic patients.
In 20 patients suffering from osteoarthritis and treated with non steroidal anti-inflammatory drugs (NSAIDs) for one month sucralfate has been added for further two months. Endoscopic examination before/after this treatment confirmed the cytoprotective property of sucralfate, with normalization of the gastric mucosa and subsidence of subjective symptomatology.
CTL activation by specific targets leads to a rapid rise of inositol phosphates (InsPs) and of cytoplasmic-free Ca2+ concentration ([Ca2+]i). While these events are considered necessary to trigger granule secretion, Ca2+-independent cytolytic mechanisms have been recently proposed in addition or as an alternative to the classical Ca2+-dependent exocytosis model. We observed that lymphokine-activated killer (LAK) cells, obtained after stimulation with supraoptimal concentrations of IL-2 in short- or long-term cultures, kill susceptible targets in the absence of a [Ca2+]i rise and InsP3 formation. Moreover, LAK cell-mediated lysis was not associated with an increase in cytotoxic granule exocytosis, as evaluated by BLT-esterase release into the culture supernatant. Furthermore, using an antigen-specific CTL clone, which acquires LAK-like activity when cultured in medium containing high IL-2 doses, second messenger generation and cytolytic granule content secretion were not detected during lysis of unrelated target cells, while killing of specific targets triggered both these processes. These findings suggest that two lytic pathways may coexist in the same effector cells: a second messenger-dependent pathway involving degranulation, which is activated after TCR interaction with specific targets, and another pathway, independent of any known second messenger generation, responsible for unrelated target cell lysis.
The authors investigated the possible correlation between blood concentrations and clinical outcome in 38 auranofin-treated patients with rheumatoid arthritis, diagnosed according to ARA criteria. The results showed that the whole blood gold concentrations did not correlate with the clinical parameters investigated and some laboratory findings. The authors discuss this lack of correlation, suggesting that a clear genetic disposition can interfere with the clinical response, affecting the metabolism and kinetics of the drug.