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Biomedical subjects

C Montecucco

Publications and source records attributed to C Montecucco.

At least 271 records · Page 15Linked to original sources
PubMed1978

Interaction of cytochrome c with cytochrome c oxidase. Photoaffinity labeling of beef heart cytochrome c oxidase with arylazido-cytochrome c.

Cytochrome c derivatives labeled with a 3-nitrophenylazido group at lysine 13, at lysine 22, or at both residues have been prepared. The interaction of the cytochrome c derivatives with beef heart cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) in the presence of ultrviolet light results in formation of a covalent complex between cytochrome c and the oxidase. Using the lysine 22 derivative, the polypeptide composition of the oxidase is not modified, nor is its catalytic activity, whereas with the lysine 13 derivative, the gel electrophoretic pattern is altered and the catalytic activity of the complex diminished. The data are consisten with a specfic covalent interaction of the lysine 13 derivative of cytochrome c with the polypeptide of molecular weight 23,700 (Subunit II) of cytochrome c oxidase.

Affinity Labels↗
PubMed1975

Molecular interactions of adenosine triphosphatase with the mitochondrial membrane as revealed by a spin label study.

Mitochondrial ATPase complex has been spin-labeled in the membrane using the inhibitor N-(2,2,6,6-tetramethylpeperidyl-1-OXYL)-N(cyclohexyl)carbodiimide (nccd). the amount of NCCD bound to mitochondrial fragments is 0.5 nmol/mg and cannot be dialyzed or extracted with ether, chloroform, or methanol. The electron paramagnetic resonance spectrum of NCCD bound to fragments is pH-sensitive, a greater label immobilization occurring at pH values lower or higher than 7. Ether extraction removes the ATPase inhibition by NCCD without detaching the label. This effect appears to be the consequence of the dislocation of some components of the ATPase complex. Removal of F1 natural inhibitor or of F1 does not affect the spectrum of NCCD bound to fragments, while the removal of oligomycin sensitivity-conferring protein produces an increase in the extreme splitting. Oligomycin sensitivity-conferring protein may thus interact with the NCCD binding component of the membrane. The isolation of the NCCD-binding proteolipid results in a large increase in the mobility of the label, but addition of dipalmitoyllecithin decreases the mobility of the label to the original level. Phospholipids are thus necessary to keep the NCCD-binding proteolipid in the native conformation.

Adenosine Triphosphatases↗
PubMedDate not supplied

Helical packing in the hydrophobic sector of cytochrome c oxidase.

An arrangement for the membrane-spanning segments of the three larger subunits of cytochrome c oxidase is proposed on the basis of sequence comparison and polarity distribution estimated from the data available for 11 different organisms.

Amino Acid Sequence↗
PubMedDate not supplied

Severe retinopathy in systemic lupus erythematosus associated with IgG anticardiolipin antibodies.

A six-year-old boy with systemic lupus erythematosus developed insidiously a monolateral serous retinal detachment leading to severe visual loss. Serial determinations of anticardiolipin antibodies showed the presence of IgG anticardiolipin antibodies only at the time of ocular involvement. This case underlines the need for regular ophthalmologic evaluation in children with active systemic lupus erythematosus and supports the previous hypothesis of a relationship between antiphospholipid antibodies and retinal involvement in systemic lupus erythematosus.

Antibodies, Anticardiolipin↗
PubMedDate not supplied

Anticardiolipin antibodies in first-degree relatives of type 1, insulin-dependent, diabetic patients.

First-degree relatives (FDRs) of diabetic patients are at risk of IDDM, and frequently present several autoantibodies. We detected anticardiolipin antibodies (aCL) in 42 FDRs, aged 12.4 +/- 4.2 years and in 52 controls. aCL (IgG and IgM) were measured by ELISA and their results expressed in arbitrary units. All FDRs underwent islet cell antibodies (ICA) measurement, intravenous glucose tolerance test and HbA1c levels. HLA typing and HLA-DQ molecular analysis were performed in all FDRs. Positive levels of aCL-IgG were observed in 8/42 FDRs and no control subject (p = 0.04); aCL-IgM values were similar in FDRs and controls. No correlation was found between aCL levels and chronologic age or HbA1c levels. No association was observed between aCL frequency and immunologic (ICA), metabolic or genetic (HLA) parameters. No FDR showed any feature of antiphospholipid syndrome. aCL-IgG presence in FDRs is suggestive of a need to carry out a follow-up study to establish the significance of these antibodies.

Adolescent↗
PubMedDate not supplied

A new monoclonal antibody against DNA ligase I is a suitable marker of cell proliferation in cultured cell and tissue section samples.

The extensive characterization of the replicative human DNA ligase I (LigI) undertaken in the last decade demonstrated that the level of this protein strongly correlates with the rate of cell proliferation. This may allow to expand the repertoire of clinical biomarkers for the analysis of cell proliferation. We have produced a new monoclonal antibody (5H5) against LigI and exploited it as cell proliferation marker in Western blotting and immunofluorescence as well as in immunohistochemistry on paraffin tissue sections. The Western blot analysis showed that the LigI level detected by 5H5 antibody is high in all proliferating cells. On the contrary the protein is down regulated in resting human fibroblast and peripheral blood lymphocytes. Immunofluorescence analysis on cultured HeLa cells showed that 5H5 antibody labels all proliferating cells and displays the same staining pattern of BrdU in S-phase nuclei. Finally the analysis of serial sections of inflamed tonsils and NHL lymph nodes (either frozen or paraffin embedded) demonstrated that 5H5 marks the same population of cells as the Ki-67 antibody. Our results demonstrate that 5H5 antibody is a valuable tool for labeling proliferating cells that can be conveniently used in Western blotting, immunocytochemistry and immunohistochemistry.

Antibodies, Monoclonal↗
PubMedDate not supplied

[Early electroretinografic changes in elderly RA patients treated with hydroxychloroquine].

OBJECTIVE: To evaluate the effectiveness of fundoscopy, electrooculography, electroretinogram and visually evoked potentials in early detection of hydroxychloroquine retinal toxicity in RA patients and to evaluate the influence of patients' age, drug dosage, concomitant therapy (prednisone and methotrexate) and serum creatinine levels in the development of this side effect. METHODS: From september to december 1999, we have enrolled 32 RA patients (13 males, 19 females) starting hydroxychloroquine treatment. The patients underwent regular ophthalmological examination (fundoscopy, electro-oculography, electroretinogram and visually evoked potentials) every 4 months. Disease activity was evaluated every two months by clinical and routine serological examination. RESULTS: No patients developed retinopathy during 1 year's follow-up; fundoscopy, electrooculography, and visually evoked potentials did not vary from the baseline. On the other hand, electroretinogram showed early alterations of scotopic and photopic response; moreover a significant statistical correlation between patients' age (more than 65 years) and b1 photopic wave increase (p < 0,05) was observed. No correlation was found between the development of electro-retinographic alterations and hydroxychloroquine dosage, concomitant therapy and serum creatinine levels CONCLUSION: Our data show the inefficacy of fundoscopy, electrooculography and visually evoked potentials in early detection of hydroxychloroquine retinopathy. On the other hand electroretinogram allows early detection of retinal alterations during hydroxychloroquine treatment, in patients older than 65 years.

Adult↗
PubMedDate not supplied

[Outcome predictors in rheumatoid arthritis].

Predicting which patients will develop severe rheumatoid arthritis is essential for selection of the most appropriate treatment regimen in early arthritis. The key outcomes in rheumatoid arthritis are persistence of the disease, joint damage (evaluated by X-ray progression), functional disability, and mortality rate. Rheumatoid factor positivity and number of swollen joints appear to be related to all of these outcomes, while radiologic scores are mostly related to joint damage and health assessment questionnaire (HAQ) to functional disability. Other relevant prognostic parameters are erythrocyte sedimentation rate or serum C-reactive protein levels, and antibodies to citrullinated peptides.

Arthritis, Rheumatoid↗
PubMedDate not supplied

[Milwaukee shoulder syndrome (apatite associated destructive arthritis): therapeutic aspects].

Milwaukee shoulder is a well defined clinical entity that can be observed in particular in older women. It is a destructive arthropathy associated with the deposition of calcium pyrophosphate dihydrate crystals, characterized by the presence of large amount of synovial fluid and a complete tear of the rotator cuff. Clinical features include pain, swelling and progressive functional impairment. The first-line treatment include the use of analgesic drugs and repeated arthrocentesis followed by intra-articular steroid administration; closed-needle tidal irrigation has been reported to be useful. In late phase we can observe narrowing of the acromion-humeral and of the gleno-humeral joint and progressive degenerative changes at the humeral head, leading to almost complete functional impairment. In these cases a surgical approach with total shoulder arthroplasty may be considered.

Editorial↗
PubMedDate not supplied

[TNF-alpha inhibition in anti-Ro/SSA positive patients with rheumatoid arthritis: clinical and immunologic effects].

OBJECTIVE: To analyse efficacy and safety of anti-TNFalpha treatment in 17 patients with rheumatoid arthritis (AR) and anti-Ro antibodies, in order to detect difference in clinical and immunological response. METHODS: 322 patients, affected by RA and treated with anti-TNFalpha drugs, were considered, searching every 6-12 months ANA, anti-dsDNA and anti-ENA antibodies. Seventeen were anti-Ro positive and 305 anti-Ro negative before starting treatment. RESULTS: Anti-Ro positive subjects showed active arthritis at baseline (mean DAS: 5), with frequent extra-articular features, such as ocular and oral sicca symptoms. They showed rapid and stable improvement during the treatment, with-out significant difference compared to anti-Ro negative group. A good clinical Eular response was shown in 46% of anti-Ro negative subjects, steady stable during time. On the contrary, fewer anti-Ro positive patients seem to be "good" responders. RA remission (DAS <1,6) was achieved in 9-25% of anti-Ro positive and 21-29% of anti-Ro negative, without significant difference. Antinuclear antibodies tend to increase in both groups, during the time. Anti-DNA increased to 40% of anti-Ro positive sera since 6th month, while they slightly increased in first 12 months in anti-Ro negative ones, then decreased to baseline value. No differences were shown about the frequency and reasons of anti-TNFalpha withdrawal, except for cutaneous lupus-like disease, more detected in anti-Ro positive group. CONCLUSIONS: Anti-TNFalpha drugs are effective in anti-Ro positive RA as well as other RA patients. Anti-DNA positivity and lupus-like disease were more frequently observed in anti-Ro positive group.

Antibodies, Antinuclear↗
PubMedDate not supplied

Impaired diastolic function in active rheumatoid arthritis. Relationship with disease duration.

OBJECTIVE: Using digitized M-mode and Doppler echocardiography, we evaluated left ventricular (LV) function in 54 patients (43 women and 11 men; mean age 50 years) suffering from active rheumatoid arthritis (RA) without obvious cardiovascular disease, and compared them with 54 age- and sex-matched normal subjects. RESULTS: No differences were found in LV end-diastolic diameter, systolic function and parietal thickness between the patients and controls. However, a significant reduction in various indexes of LV diastolic function was found, including E/A (ratio of early to late filling waves of mitral inflow Doppler) and the peak lengthening rate of the LV diameter (an index of LV relaxation evaluated by M-mode echocardiography). The former was correlated with patient age and was independent of disease duration, while the latter was more markedly correlated with disease duration than with patient age. CONCLUSION: The relationship between diastolic impairment and disease duration in active RA may open new perspectives in the study of RA-associated cardiovascular disease.

Adult↗
PubMedDate not supplied

Infliximab in the treatment of adult Still's disease refractory to conventional therapy.

In this study we evaluated the efficacy of Infliximab in the treatment of adult Still's disease (ASD) refractory to conventional therapy. Three patients with chronic and active ASD unresponsive to corticosteroids and methotrexate were given intravenous Infliximab infusions at a dosage of 3 mg/kg at weeks 0, 2, 6 and then once every 8 weeks. Methotrexate was maintained in all cases at a dosage of 15 mg/week, whereas the prednisone dose was modified according to disease activity. The follow-up lasted 50 weeks and disease activity improved in all cases during Infliximab therapy. Two patients presented arthralgias and sore throat at 20 and 28 weeks, that was rapidly controlled by Infliximab reinfusion every 4 weeks. One patient relapsed at 18 weeks and dropped out at 22 weeks due to an urticarioid rash after the beginning of the fifth infusion. Infliximab may be effective in the treatment of relapse of ASD refractory to conventional therapy and requiring continuous high dose corticosteroid medication. Further studies are needed to evaluate the long-term safety, efficacy and the optimal schedule of infusion.

Adult↗
PubMedDate not supplied

Undifferentiated connective tissue disease with antibodies to Ro/SSa: clinical features and follow-up of 148 patients.

OBJECTIVE: To evaluate the clinical and serologic profile, the rate of progression to well defined CTD and the possible predictors of disease evolution in patients affected by UCTD with antibodies anti-RoISSA. METHODS: 148 patients diagnosed as UCTD were retrospectively evaluated. Antibodies to SSA/Ro were determined by counter-immunoelectrophoresis and ELISA. RESULTS: Thirty-six patients (24.3%) developed a well-defined CTD after a mean follow-up of 4.5 years. Most patients developed primary Sjögren's syndrome (SS) (50%) or systemic lupus erythematosus (SLE) (30.5%). Leukopenia and xerophthalmia developed more frequently in the group of patients evolving to defined CTDs (p < 0.0032 and p < 0.0063). Leukopenia independently predicted the evolution in CTD by multivariate regression analysis (p < 0.019). Anti-dsDNA predicted the evolution in SLE (p < 0.0207), while the presence of additional anti-ENA specificity to anti-Ro/SSA was not associated with the outcome. CONCLUSION: 24.3% of patients with UCTD and antibodies to Ro/SSA can progress in a relatively short period of time to well-defined CTDs. The development of primary SS could be predicted by xerophthalmia and SLE by the appearance of anti-dsDNA antibodies.

Adolescent↗