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Biomedical subjects

H M Moutsopoulos

Publications and source records attributed to H M Moutsopoulos.

At least 55 records · Page 3Linked to original sources
PubMed2001

Pulmonary capillary endothelial dysfunction in early systemic sclerosis.

OBJECTIVE: Pulmonary capillary endothelium-bound angiotensin-converting enzyme (PCEB-ACE) activity is a sensitive and quantifiable index of endothelial function in vivo. Systemic sclerosis (SSc) is characterized by endothelial damage and excess collagen formation, causing mainly pulmonary hypertension (PH) in the limited cutaneous SSc (lcSSc) subset and interstitial lung disease with pulmonary interstitial fibrosis (PIF) in the diffuse cutaneous SSc (dcSSc) subset. This study was undertaken to investigate the hypothesis that PCEB-ACE activity is reduced early in SSc, in the absence of PH or PIF. METHODS: Applying indicator-dilution techniques, we measured single-pass transpulmonary hydrolysis and percent metabolism (%M) of a synthetic ACE substrate and calculated functional capillary surface area (FCSA) in 25 SSc patients and 11 controls. Substrate hydrolysis and %M reflect ACE activity per capillary; FCSA reflects ACE activity per vascular bed. RESULTS: PCEB-ACE activity was decreased in both SSc subsets. Among patients without PH, substrate hydrolysis and %M were decreased in patients with lcSSc and more profoundly in those with dcSSc; loss of FCSA normalized to body surface area (FCSA/BSA) was observed in dcSSc, but not in lcSSc. High-resolution computed tomography of the lung, performed in all SSc patients, revealed no correlation between substrate %M, hydrolysis, or FCSA/BSA and the degree of PIF; 5 dcSSc and 5 lcSSc patients with no detectable PIF exhibited decreases in hydrolysis and %M, while FCSA/BSA was decreased only in dcSSc. CONCLUSION: Depression of PCEB-ACE activity, indicating pulmonary endothelial dysfunction, occurs early in SSc, in the absence of PH or PIF, and is more pronounced, at this early pulmonary disease stage, in dcSSc than in lcSSc.

Adult↗
PubMed2001

A diepitopic sequential oligopeptide carrier (SOCn) as mimic of the sm autoantigen: synthesis, conformation and biological assays.

Anti-Sm (Sm: U1-U6 RNA-protein complex) antibodies are usually considered highly specific for systemic lupus erythematosus (SLE), while anti-U1RNP (U1RNP: U1RNA-protein complex) are thought of as diagnostic criteria for the mixed connective tissue disease (MCTD). However, both antibody specificities coexist in SLE and MCTD, in varying percentages. Although the anti-Sm/anti-U1RNP immunological cross-reactivity has been initially attributed to a common motif, PPXY(Z)PP (where X, Y, Z are various amino acids), found in the Sm, U1-A and U1-C autoantigens, it appears that the conformational features of the Sm epitopes also play an important role in the immunoreactivity. The PPGMRPP and PPGIRGP main epitopes of the Sm antigen were coupled in duplicate to the tetrameric Ac-(Lys-Aib-Gly)4-OH, SOC4, carrier to form the [(PPGMRPP)2, (PPGIRGP)2]-SOC4 construct as a mimic of the native Sm. It was found that: (i) the 3(10) helical structure of SOC4 allows the epitopes to adopt an exposed orientation, similar to their free forms, that facilitates their recognition from the anti-Sm antibodies, and (ii) the U1-RNP cross-reactivity is minimized.

Amino Acids↗
PubMed2001

Induction of salivary gland epithelial cell injury in Sjogren's syndrome: in vitro assessment of T cell-derived cytokines and Fas protein expression.

Sjogren's syndrome (SS) is an exocrinopathy characterized by T cell infiltrates, salivary gland epithelial cell (SGEC) apoptosis and high Fas and FasL expression. To address the participation of T cell-derived cytokines and of Fas apoptotic pathway in SS glandular lesions, we utilized non-neoplastic SGEC lines established from SS patients and controls. Possibly attesting to their intrinsic activation, cell lines derived from SS patients displayed significantly higher constitutive Fas and FasL than controls. Surface co-expression of Fas and FasL was not associated with spontaneous fratricide apoptosis. SGEC were resistant to anti-Fas-mediated apoptosis (possibly owing to the constitutive expression of anti-apoptotic proteins cFLIP and Bcl-2), but became sensitive after protein or RNA synthesis inhibition. IFN-gamma and TNF-alpha were able to upregulate surface Fas and FasL, whereas IL-1beta downregulated surface FasL. IFN-gamma (but not several other cytokines) reduced the survival of SGEC in a dose- and time-dependent manner and induced Fas/FasL-mediated apoptosis, directly and via anoikia. Dexamethasone inhibited the upregulation of Fas and FasL by IFN-gamma and the induction of SGEC apoptosis and detachment by anti-Fas mAb or IFN-gamma. Our findings indicate the injurious role of IFN-gamma for the salivary epithelia of SS patients through the induction of Fas-mediated apoptosis and anoikia.

Antibodies, Monoclonal↗
PubMed2001

Activation of epithelial and myoepithelial cells in the salivary glands of patients with Sjögren's syndrome: high expression of intercellular adhesion molecule-1 (ICAM.1) in biopsy specimens and cultured cells.

ICAM.1 (CD54) is a surface protein expressed on epithelial and other nonhematopoietic cells upon activation and is known to play an important role in the stimulation of T cells by the provision of cellular adhesion and costimulatory support. Sjogren's syndrome (SS) is an autoimmune exocrinopathy, which is characterized by chronic lymphocytic infiltration of exocrine glands and aberrant activation of epithelial tissues. To address the contribution of ICAM.1 in the pathogenesis of SS, the expression of this protein was studied by immunohistochemistry and flow cytometry in minor salivary gland (SG) biopsies as well as in cultured SG epithelial cell (SGEC) lines obtained from 18 SS patients and 16 controls. In biopsies from SS patients (but not controls), strong ICAM.1 was expressed by infiltrating mononuclear cells (52%) and by a significant proportion of periacinar myoepithelial cells (18%). In addition, a patchy pattern of moderate ICAM.1 expression was detected in 31% of ductal epithelia of SS patients. These ICAM.1-expressing epithelial and myoepithelial cells were observed throughout glandular tissues and were not confined in areas proximal to lymphoid infiltrates. In support to an intrinsic activation profile of SGEC in SS, long-term cultured non-neoplastic SGEC lines derived from SS patients displayed significantly upregulated spontaneous expression of ICAM.1, compared to controls (P < 0.05). The high expression of ICAM.1 protein by the salivary epithelium of SS patients is likely suggestive of its important role in the pathogenesis of the disorder. Further, our results support a model of intrinsic activation of salivary epithelial and myoepithelial cells in SS, whereby these cells actively participate in the induction and maintenance of lymphocytic infiltrates of patients.

Autoimmune Diseases↗
PubMed2001

Molecular analysis of estrogen receptor alpha and beta in lupus patients.

BACKGROUND: In female patients with systemic lupus erythematosus (SLE), we identified estrogen receptor ERa, ERb and ERa variant transcripts in peripheral blood mononuclear cells (PBMC). Exon 1 and 2 of ERa gene was subjected to mutation analysis to assess whether possible nucleotide alterations are linked to the disease. METHODS: The whole coding sequence of ERa was analysed by reverse transcription polymerase chain reaction (RT-PCR) and cDNA sequencing in PBMC prepared from 19 SLE patients and 12 healthy females. ERa exon 1 and exon 2 were subjected to mutation analysis using DNA isolated from whole blood of 21 SLE patients and 29 healthy females. The aminoterminal coding sequence of ERb was also analysed by RT-PCR. RESULTS: Wild type ERa and ERa splicing variants with deletions in exons 2, 5 and 7 were detected both in healthy individuals and in SLE patients, with no qualitative difference in their expression among the two populations. In ERa exon 1, the polymorphisms identified codon 10 and codon 87, both in patients and in healthy individuals who were not associated with the disease. No other mutations were present in ERa exon 1 or ERa exon 2 in all subjects studied. ERb was expressed in both populations. CONCLUSION: PBMC of SLE patients express wild type ERa, ERb and the same ERa variants as do healthy individuals. Genetic alterations in exon 1 and exon 2 of the ERa gene are not linked with SLE disease.

Adult↗
PubMed2001

Mixed cryoglobulinemia is associated with increased risk for death, or neoplasia in HIV-1 infection.

BACKGROUND: Cryoglobulinemia has been reported in several chronic infectious and autoimmune diseases, and in patients with HIV-1 infection. Cryoglobulinemia associated with hepatitis C virus infection is considered a risk factor for the development of neoplasia, especially B-cell non-Hodgkin lymphoma. This study was undertaken to investigate whether the presence of circulating cryoglobulins is associated with survival or development of neoplastic disease in HIV-1 infection. DESIGN: We evaluated 87 unselected consecutive HIV-1 infected patients for the presence of cryoglobulinemia and they were prospectively followed up for a median of 34 months, with clinic visits at 4-month intervals. None of the patients had neoplasia at study entry. Time-to-event analysis for death, neoplasm and B-cell lymphoproliferative disorder were performed with Cox proportional hazards models. RESULTS: Mixed cryoglobulinemia (types II and III) was detected in 24 (28%) of the 87 patients. During the follow up, 12 patients died and 8 developed neoplastic disease. Multivariate analysis showed that circulating cryoglobulins were an independent predictor of death [relative risk (RR), 4.97; 95% confidence intervals (CI), 1.26-19.63] and development of neoplasia (RR, 5.18; 95% CI, 1.23-21.83). In addition, cryoglobulinemia reached borderline significance as a predictor of lymphoproliferative disorder of B-cell origin (P = 0.08; RR, 4.53; 95% CI, 0.83-24.75). CONCLUSIONS: Our results suggest that cryoglobulinemia is associated with an increased risk for death, neoplasia or development of lymphoproliferative disorder of B-cell origin, in HIV-1 infected patients.

Adult↗
PubMed2001

Incomplete lupus erythematosus: results of a multicentre study under the supervision of the EULAR Standing Committee on International Clinical Studies Including Therapeutic Trials (ESCISIT).

OBJECTIVE: Patients characterized with antinuclear antibodies (ANA) and disease symptoms related to one organ system can be described as having incomplete systemic lupus erythematosus (SLE). The aim of this multicentre study was to describe the outcome of these so-called incomplete SLE patients. Two aspects of the outcome were studied: (i) the disease course, defined by the presence or absence of clinical symptoms; and (ii) the number of patients that eventually developed full SLE. METHODS: Outcome parameters were the ACR criteria, the SLE disease Activity Index (SLEDAI), the European Consensus Lupus Activity Measure (ECLAM) and the requirement for treatment. In 10 European rheumatology centres, patients who had been evaluated in the last 3 months of 1994 and had been diagnosed as having incomplete SLE on clinical grounds for at least 1 yr were included in the study. All 122 patients who were included in the study were evaluated annually during 3 yr of follow-up. RESULTS: Our results are confined to a patient cohort defined by disease duration of at least 1 yr, being under clinical care at the different centres in Europe. These patients showed disease activity that was related mostly to symptoms of the skin and the musculoskeletal system, and leucocytopenia. During the follow-up, low doses of prednisolone were still being prescribed in 43% of the patients. On recruitment to the study, 22 of the 122 incomplete SLE patients already fulfilled the ACR criteria for the diagnosis of SLE. In the 3 yr of follow-up only three patients developed SLE. CONCLUSIONS: A high proportion of patients in our cohort defined on clinical grounds as having incomplete SLE eventually showed disease activity defined by the SLEDAI as well as ECLAM. However, only three cases developed to SLE during the follow-up. This suggests that incomplete SLE forms a subgroup of SLE that has a good prognosis.

Adolescent↗
PubMed2001

Right ventricular diastolic dysfunction in patients with anticardiolipin antibodies and antiphospholipid syndrome.

OBJECTIVE: To evaluate the prevalence of diastolic dysfunction in patients with anticardiolipin antibodies (aCL) and to examine whether the antiphospholipid syndrome (APS) is associated with diastolic dysfunction independently of valvular abnormalities and systolic dysfunction. METHODS: Pulsed, continuous, colour Doppler echocardiography was performed in 179 subjects, of whom 15 were excluded from the analysis because of systolic dysfunction or severe valvular disease. The remaining 164 subjects included 29 patients with primary APS, 26 patients with secondary APS (APS in the presence of systemic lupus erythematosus (SLE)), and 30 patients with SLE and aCL but without APS; 43 patients with SLE without aCL and 36 normal volunteers served as control groups. RESULTS: The groups compared differed significantly in all measures of right ventricular function. There was a gradation of increasing diastolic function impairment as manifested by prolonged deceleration time (DT) and isovolumic relaxation time (IVRT) across the groups of patients with SLE without aCL, SLE with aCL, secondary APS, and primary APS. Differences in left ventricular diastolic function measures were less prominent. In regression analysis, DT increased by 19.6 ms (p=0.002) in the presence of primary APS and by 20.1 ms (p=0.038) in the presence of pulmonary hypertension. The titre of IgG aCL was the strongest predictor of a prolonged IVRT. CONCLUSION: Diastolic dysfunction, in particular of the right ventricle-that is, independent of valvular disease and systolic dysfunction, is a prominent feature of APS and may be related to the pathogenesis of the syndrome.

Adult↗
PubMed2001

Systemic lupus erythematosus. Disease outcome in patients with a disease duration of at least 10 years: second evaluation.

Data related to the disease course of patients with systemic lupus erythematosus (SLE) with special attention to the persistence of disease activity in the long term are scarce. At this moment reliable figures are only known about the survival rate as a measure of outcome. The aim of this multicenter study was to describe the outcome of SLE patients with a disease duration of greater than 10 y. Outcome parameters were two disease activity-scoring systems (SLEDAI and ECLAM), the end organ damage (SLICC/ACR damage index) and treatment. Our results are derived from 187 SLE patients followed at 10 different centres in Europe over a period of 1 y. Serious clinical signs or exacerbations, defined by the occurrence or detoriation of already existing symptoms of renal and cerebral nervous systems were observed in 2-11% of the patients, seizures and psychosis in 3%, proteinuria in 11% and an increase in serum creatinine in 5% of the patients. No change took place in the overall damage index. Yet, the disease course in most patients was characterized by periods of tiredness (42-60%), arthritis (20-25%), skin involvement such as malar rash (32-40%), migraine (15-20%), anaemia (15%) and leucopenia (17-19%). Summarizing these results it is shown that patients, still under care after such a long time of having this disease, do have a disease that is far from extinguished.

Adult↗
PubMed2001

How significant is sensorineural hearing loss in primary Sjögren's syndrome? An individually matched case-control study.

OBJECTIVE: We evaluated whether sensorineural loss and vestibular abnormalities are common in patients with primary Sjögren's syndrome (pSS) and whether such abnormalities are clinically significant. METHODS: In an individually matched case-control design, 48 patients with pSS underwent complete audiovestibular evaluation along with 48 age and sex matched individuals without otologic problems. Differences of > 20 dB between patient and control ears at any frequency tested were considered to be significant. RESULTS: Significant differences in hearing loss were seen at 4,000 Hz (6 vs 0 ears; p = 0.03) and at 8,000 Hz (9 vs 0 ears; p = 0.003). Small differences in hearing acuity were also observed in the lower frequencies, but the absolute mean difference was < 3 dB. A decrease of at least 60 dB in hearing acuity at any frequency up to 4,000 Hz was seen only in 3 elderly pSS patients. Abnormal brainstem auditory evoked responses were recorded in 7 patients and 5 controls, but no patient had retrocochlear lesions identified on magnetic resonance imaging. Four patients in each group had abnormalities on electronystagmography. CONCLUSION: pSS is associated with sensorineural hearing loss affecting preferentially the high frequencies, but clinically significant defects are not common. There is no evidence of retrocochlear disease or increased vestibular involvement in pSS.

Aged↗
PubMed2001

Malignant lymphoma in primary Sjogren's syndrome.

Sjogren's syndrome is a chronic inflammatory process involving primarily the exocrine glands. Its association with lymphoma is well documented. A low grade marginal-zone lymphoma related to mucosa-associated lymphoid tissue is the commonest lymphoid neoplasia in Sjogren's syndrome. We review the literature and comment on the molecular, clinical, histopathologic and therapeutic aspects of these tumors in Sjogren's syndrome.

Humans↗
PubMed2000

Predictors of clinical outcome and radiologic progression in patients with neuropsychiatric manifestations of systemic lupus erythematosus.

PURPOSE: We sought to identify the predictors of clinical outcome and of the evolution of cerebral abnormalities in patients with neuropsychiatric systemic lupus erythematosus (SLE). SUBJECTS AND METHODS: Thirty-two patients with SLE (including 14 with the antiphospholipid syndrome) who had been hospitalized with primary neuropsychiatric disease were observed prospectively for at least 2 years. Laboratory and clinical characteristics and data from magnetic resonance imaging (MRI) studies obtained during the hospitalization and 2 years later were evaluated. We ascertained nonreversible or new MRI changes and clinical outcomes, including neuropsychiatric events, during follow-up. RESULTS: Cranial MRI scans on admission were abnormal in 26 (81%) of the 32 patients. Patients with the antiphospholipid syndrome were more likely to have focal cerebral white matter lesions (odds ratio [OR] = 12, 95% confidence interval [CI]: 2.0 to 72). After 2 years, neuropsychiatric deficits substantially improved in 22 (69%) of the patients, stabilized in 6 (19%), and deteriorated in 4 (12%). The number of prior neuropsychiatric events was associated with persistent MRI lesions (OR = 4.8 per each event, 95% CI: 1.1 to 21) and unfavorable clinical outcome (OR = 4.3 per each event, 95% CI: 1.4 to 13) at 2 years. The antiphospholipid syndrome also predicted an unfavorable clinical outcome at 2 years (OR = 11, 95% CI: 1.7 to 65). CONCLUSIONS: Among patients with SLE who have neuropsychiatric disease, prior neuropsychiatric events and the antiphospholipid syndrome increase the risk of adverse outcomes.

Adult↗
PubMed2000

Autoimmune hemolytic anemia in patients with systemic lupus erythematosus.

PURPOSE: We sought to evaluate the clinical and serologic associations with, and outcomes of, autoimmune hemolytic anemia, as compared with other types of anemia, in patients with systemic lupus erythematosus (SLE). SUBJECTS AND METHODS: We studied 41 consecutive patients with SLE with clinically manifest autoimmune hemolytic anemia, including 27 (66%) in whom hemolysis was the initial disease manifestation. We matched each patient for age and disease duration with a patient with SLE with anemia resulting from a different cause. RESULTS: The 41 patients had a total of 50 episodes of autoimmune hemolytic anemia. The recurrence rate was 4 per 100 person-years. Cases and controls had similar mean (+/- SD) lupus activity indexes (2.1 +/- 1.5 vs 2.4 +/- 1.3, P = 0.5). Patients with autoimmune hemolytic anemia at any time could be distinguished from patients with other causes of anemia, because they were more likely to have elevated titers of IgG anticardiolipin antibodies [odds ratio (OR) = 5.8; 95% confidence interval (CI), 1.4 to 24] and thrombosis (OR = 4.6; 95% CI, 1.0 to 21). Autoimmune hemolytic anemia at the onset of SLE was independently associated with renal involvement (OR = 5.4; 95% CI, 1.0 to 28), thrombocytopenia (OR = 7.3; 95% CI, 1.1 to 48), and possibly thrombotic episodes during follow-up (OR = 11; 95% CI, 0.8 to 160) when compared with controls with other types of anemia at the onset of SLE. CONCLUSIONS: Autoimmune hemolytic anemia usually occurs at the onset of SLE, and its recurrence rate is low among treated patients. The association with IgG anticardiolipin antibodies and thrombosis suggests that the occurrence of autoimmune hemolytic anemia may define a subgroup of patients with SLE who have characteristic serologic and clinical manifestations.

Adult↗
PubMed2000

The position of the LysN epsilon H2-grafted antigens along the sequential oligopeptide carrier, Ac-(Aib-Lys-Aib-Gly)n (SOCn-II), influences the antibody recognition: application to the Sm main autoimmune epitope.

A sequential oligopeptide carrier of antigenic peptides is presented, incorporating two Aib residues in each repetitive moiety: Ac-(Aib-Lys-Aib-Gly)(n) (SOC(n) -II; n = 2-4). The conformational study, by (1)H-nmr, CD, and Fourier transform ir spectroscopy, indicated that the SOC(n) -II carrier displays a pronounced 3(10)-helix, compared to the Ac-(Lys-Aib-Gly)(n) (SOC(n) -I) carrier of the same approximately backbone length, previously reported. One of the dominant autoimmune epitopes of the Sm and U1RNP cellular components, the PPGMRPP sequence, was coupled to the Lys-N(epsilon)H(2) groups of the SOC(n) -II carrier and used as antigenic substrate for detecting anti-Sm/U1RNP autoantibodies in ELISA assays. Anti-Sm antibodies are highly specific for systemic lupus erythematosus, while anti-U1RNP are specific for mixed connective tissue disease. The anti-(PPGMRPP)(5)-SOC(n) -II ELISA was compared with the anti-(PPGMRPP)(n) -SOC(n) -I ELISA, provided that both antigenic substrates possess the same amount of the epitope replicates. The significance of the lysine positions along the oligopeptide backbone of the carrier for a favorable antibody recognition of the anchored antigens is also examined.

Amino Acid Sequence↗