Search PubMedSearch

Biomedical subjects

L Bonomo

Publications and source records attributed to L Bonomo.

At least 19 recordsLinked to original sources

Nonrheumatoid IgM in human hepatitis C virus-associated type II cryoglobulinemia recognize mimotopes of the CD4-like LAG-3 protein.

Type II mixed cryoglobulinemia (CryoII) is an autoimmune disorder frequently associated to human hepatitis C virus (HCV) infection and characterized by the presence of cold-insoluble immunocomplexes containing IgM with rheumatoid activity. To identify disease-related epitopes, we screened a phage-displayed random peptide library using purified IgM from patients with HCV-associated CryoII(CryoII/HCV). A dominant population of phage isolates bearing the HPLAP pentapeptide consensus motif was identified and shown to be recognized by a nonrheumatoid IgM species strongly associated to CryoII/HCV. The phage-borne mimotopes (phagotopes) displayed a strong homology with an exposed extra-loop region of human lymphocyte activation 3 gene (LAG-3) product. Consistently, rabbit sera raised against a synthetic LAG-3 peptide efficiently recognized the selected phagotopes. Furthermore, one such phagotope was revealed to be a good immunogenic mimic of LAG-3 when injected into rabbits. IgM purified from CryoII/HCV patients' sera specifically reacted with the LAG-3 peptide in ELISA, and this binding was inhibited by the selected phagotopes. These results provide experimental support for a general strategy to identify novel autoantigens.

Amino Acid Sequence

Long echo time STIR sequence MRI of optic nerves in optic neuritis.

MRI of the optic nerves was obtained in 13 patients with acute optic neuritis and 13 with a previous optic neuritis (ON), assessed by clinical features, visual fields and visual evoked potentials. Results of the conventional short tau inversion recovery (STIR) sequence obtained with a short echo time (STE-STIR; 22 ms) were compared with those of a long echo time (LTE-STIR: 80 ms) sequence. The conventional STE-STIR sequence revealed lesions in the optic nerves in 78.5% of acute and 58.8% of previous ON. The LTE-STIR sequence showed abnormalities in 92.8% of acutely symptomatic nerves and 94.1% of nerves with previous ON. The optic nerve lesions appeared significantly longer with the LTE-STIR sequence than with the conventional STE-STIR sequences, in both acute and previous ON.

Adult

Long time echo STIR sequence magnetic resonance imaging of optic nerves in optic neuritis.

Magnetic resonance images of optic nerves were obtained in 20 patients with acute optic neuritis (ON), and assessed by means of clinical, visual field and visual evoked potential evaluations; the imaging was repeated 1 year later. The results of the conventional Short Tau Inversion Recovery (STIR) sequence obtained using short time echo (STE-STIR: 22 msec) were compared with those of the long time echo sequence (LTE-STIR: 80 msec). The conventional STE-STIR sequence revealed lesions in 57.2% cases of acute ON and in 42.9% of the optic nerves affected by previous ON; the LTE-STIR sequence was diagnostic in 95.2% of acute ON cases and in 85% of patients with previous ON. The calculated length of the optic nerve lesions was significantly longer in the images obtained using the LTE-STIR sequence than in those obtained using conventional STE-STIR sequences.

Adult

Lung cancer staging: the role of computed tomography and magnetic resonance imaging.

Because complete resection remains the only reliable method of cure of lung cancer, one important aim of preoperative staging is to select patients with localised disease who may benefit from surgery, while avoiding unnecessary thoracotomies in patients with unresectable neoplasm. Computed tomography (CT) of the chest is a valuable method for staging local and regional spread of lung neoplasms, although limitations in its accuracy are well-known. While gross invasion of the mediastinum and major structures as well as the presence of metastatic disease can be easily demonstrated with CT, differentiation between tumour contiguity and subtle invasion of mediastinum or chest wall often remains a problem. Although magnetic resonance imaging (MRI) may have the same limitations as CT, in specific situations it may be superior in diagnosing minimal chest wall or mediastinal invasion. Moreover, MRI is useful in the assessment of patients with superior sulcus tumours as well as in patients with contraindication to intravenous administration of ionic contrast material. Since nodal size is the only useful criterion for evaluating lymph node metastases, CT and MRI show similar, poor accuracies in lymph node staging resulting from both low sensitivity (normal-sized nodes may contain microscopic metastases) and low specificity (enlarged lymph nodes may be reactive). For this reason, if enlarged lymph nodes are detected, further evaluation is recommended before excluding the patient from a potentially curative resection. Advantages and limitations of CT and MRI in the preoperative staging of non-small-cell carcinoma are reviewed in this article. The imaging of small-cell carcinoma is not included because most patients with this cell type do not benefit from surgical resection. Similarly we do not discuss imaging of distant metastases.

Humans

Two spatially distant epitopes of human lactoferrin.

Lactoferrin (LF) is an iron binding protein, which may represent a target for antineutrophil cytoplasmic antibodies (ANCA) in patients affected by rheumatoid arthritis, ulcerative colitis, and primary sclerosing cholangitis. Here we describe the production and characterization of two new monoclonal antibodies (MAbs) against human LF. These MAbs (AGM 10.14, an IgG1, and AGM 2.29, an IgG2b) recognize spatially distant epitopes of LF as assessed by cross-blocking experiments. We also demonstrated by indirect immunofluorescence that both MAbs react with ethanol-fixed neutrophil granulocytes showing a perinuclear staining pattern. AGM 2.29 and AGM 10.14 have been utilized as capture and labeled tracer antibody, respectively, in a double determinant immunoassay (DDIA) to measure soluble LF. The results obtained show that this DDIA allows us to quantify even low concentrations of LF, the maximal range of the assay sensitivity being between 12 and 780 ng/ml. Therefore, AGM 10.14 and AGM 2.29 may represent useful reagents for studying the role of autoantibodies to LF as well as for measuring soluble LF, which is a reliable secretory marker of neutrophil activation.

Animals

Tissue plasminogen activator, tissue plasminogen activator inhibitor and lipoprotein(a) in patients with coronary, epiaortic and peripheral occlusive artery disease.

In order to evaluate the relationship between the presence of atherosclerotic disease, documented by angiography, and the fibrinolytic profile, 262 consecutive patients affected by coronary (n = 90), epiaortic (n = 60) and peripheral (n = 104) artery disease have been included in the study. Twenty-two healthy subjects were used as controls for laboratory parameters determination. All patients were classified on the basis of the presence (S+) or absence (S-) of clinically significant stenosis, according to specific scoring systems. Lipoprotein(a), plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA) and the PAI-1/t-PA ratio were significantly lower in controls than in coronary, epiaortic and peripheral artery disease patients. However, the levels of these parameters were not statistically different between S+ and S- subjects. These results confirm the association between lipoprotein(a), PAI-1 and t-PA levels and the presence of atherosclerotic disease independently of the arterial districts considered, while they do not appear to be directly linked to the severity of the morphological disease.

Adult

Heart rate variability and cardiac autonomic function in systemic lupus erythematosus.

The cardiac autonomic function was evaluated in 23 patients with Systemic Lupus Erythematosus (SLE) without clinical expression of dysautonomia and in 14 healthy volunteer subjects as a control group, by analysis of Heart Rate Variability (HRV) from 24h ambulatory electrocardiography. All the patients were taking corticosteroids and 10 of them also Ciclosporin A (CsA). The following parameters of HRV were performed: Time domain: standard deviation of the RR intervals average (SDNN) and percentage of RR adjacent intervals differing from each other more than 50 msec (pNN50). Frequency domain: low frequencies (LF) and high frequencies (HF). Significant lower values were detected in SLE patients vs controls: SDNN = 69.40 vs 127.72; pNN50 = 16.44 vs 25.95; LF = 8.34 vs 34.97; HF = 3.21 vs 12.18. The incidence of autonomic dysfunction in our SLE population evaluated by considering intervals of normality is approximately 78% for SDNN; 17% for pNN50; 91% for LF and, finally, 56% for HF. The analysis of HRV may be a valuable technique in the study of the incidence of dysautonomia for these patients.

Adolescent

[Induratio penis plastica: the diagnostic possibilities of gradient-echo sequences (magnetic resonance angiography)].

The authors investigated the diagnostic capabilities of gradient echo sequences (magnetic resonance angiography) in the study of induratio penis plastica. Twenty patients (mean age: 39 years) were examined. MRA was performed with a superconductive magnet (1.5 T) and a Helmoutz coil; the dynamic test with PGE (20-40 mg) was also carried out. The images acquired on the axial and sagittal planes were processed according to the MIP. The FLASH 2D sequence was used with the following parameters: FA 18 degrees, TR 40 ms, TE ms, MA 256 x 256, slice thickness 5 mm. A multiple choice card was filled in by a reader with the following diagnostic information: identification and localization of the plaques and involvement by the plaques of the albuginea, corpora cavernosa, septum and dorsal vein; surgery was the gold standard. MRA showed 10/11 plaques ranging 8-30 mm in diameter and missed a 5-mm plaque. Moreover, MRA depicted the infiltration of the albuginea in 10/10 cases, of the septum in 3/3 cases, of the dorsal vein in 4/4 cases and of the corpora cavernosa in 9/9 cases. Our preliminary experience shows that in the study of induratio penis plastica, the gradient echo sequence (MRA) permits better depiction of the plaques and of the infiltration of the corpora cavernosa, septum and albuginea.

Adult

[Spiral computerized tomography and videothoracoscopy in the assessment of contralateral nodular lesions in patients with bronchogenic carcinoma].

Recent improvements in endoscopic technology and surgical techniques have widened the application field of video-assisted thoracoscopy (VAT). We report our personal experience in 14 male patients (mean age: 67 years, range: 55-73 years) in whom one or multiple indeterminate contralateral lung nodules were found during bronchogenic carcinoma staging and then surgically resected with VAT. All patients underwent volumetric CT of the chest. Sixteen lung nodules were detected contralateral to the neoplasm; their mean diameter was 5 mm (range: 2-10 mm). The mean distance between pleural surface and lung nodule was 8 mm. All patients had primary lung cancer (3 central and 11 peripheral lesions), histologically confirmed by bronchoscopic or percutaneous CT-guided biopsy. None of them had any contraindication to surgery because of extrathoracic pathologic conditions. VAT was performed as normal, under general anesthesia, with assisted ventilation with a double-lumen endotracheal tube and using a percutaneous mechanical stapler. The nodules were easier to identify using a skin reference point corresponding to the parietal projection of the nodule, positioned with CT before surgery. Surgery lasted 58 minutes on the average (range: 30-120 minutes). In all patients VAT was successful in resecting the nodule. In 9 patients a metastasis from a contralateral lung cancer was found: 4 adenocarcinomas, 4 epidermoid carcinomas and 1 small cell carcinoma. In the remaining 5 patients, VAT-resected lung nodules were of chronic inflammatory nature. The latter patients underwent definitive surgery of the primary tumor (2 adenocarcinomas, 2 epidermoid and 1 large cell carcinomas) ten days later (range: 9-30 days). There were no major complications but a prolonged air leak in one patient, which needed drainage to be maintained for 5 days. Presently, VAT permits an atypical resection, avoiding the morbility of thoracoscopy and thus represents a mandatory technique in selected patients amenable to definitive surgery.

Aged

[Pulmonary artery: angiographic technique optimization with magnetic resonance].

The authors optimized the Magnetic Resonance Angiography (MRA) technique for the study of the different portions of the pulmonary artery-i.e., the common trunk, right and left main arteries and the lobar, segmental and subsegmental branches. Twenty volunteers were examined with MRA of the pulmonary arteries with a 1-T superconductive magnet (Impact) and the time-of-flight (TOF) technique. The volunteers were divided into two groups by age (ranges: 20-40 and 41-70 years). The trunk and main branches were studied with the 2D TOF technique, while 2D TOF images were compared with 3D TOF images in the study of peripheral (lobar, segmental and subsegmental) branches. The images were processed with the maximum intensity projection (MIP). In the statistical comparison between 2D and 3D TOF images, the t-test was used (p < 0.05). The 2D TOF images acquired on the sagittal oblique and coronal planes, with presaturation pulses, permitted optimal depiction of the trunk and of the right and left branches in all the volunteers. Both 2D and 3D TOF images yielded excellent images in the study of the lobar branches. In the volunteers under 40 years of age, 3D TOF sequences visualized the peripheral (segmental and subsegmental) vessels better than 2D TOF sequences (451 vs. 361); the difference was statistically significant. In the volunteers over 41 years of age, the ratio was reversed: 467 for 2D TOF vs. 362 for 3D TOF sequences; again, the difference was statistically significant. The correct integration of 2D and 3D TOF sequences, according to the different segments of the pulmonary artery and to patients' age, permitted the complete and accurate visualization of the pulmonary arteries with MRA.

Adult

[Magnetic resonance angiography of the origin of the supraaortic trunks: the tridimensional time-of-flight with single volume technique].

This work was aimed at studying the origin of the epiaortic vessels with Magnetic Resonance Angiography (MRA). Twenty normal volunteers (mean age: 21.5 years) were examined with MRA with a superconductive magnet at 1 T (Impact). All volunteers were examined with a body coil and the time of flight (TOF) technique. The FISP 3D TONE sequence was used, with the following parameters: TR 46 ms, TE 10 ms, FA 20 degrees, ST 2.2 mm, matrix 192 x 256. The images, acquired on the axial plane with three presaturation pulses, were rotated according to the maximum intensity projection on the Z axis. To classify the images, a multiple choice card was used by a reader, with three diagnostic judgements for the different segments of the vessels (i.e., good, poor and not visualized). 3D TOF MRA permitted good visualization of the right and left common carotid in 80% and 77% of cases, of the right and left vertebral arteries in 55% and 50% of cases, of the left and right subclavian arteries in 47% and 62% of cases, and of the anonymous artery in 100% of cases. To conclude, our preliminary results indicate FISP 3D TOF MRA as the best noninvasive technique to study the origin of the epiaortic vessels.

Adult

Antineutrophil cytoplasmic antibodies in synovial fluid and in serum of patients with rheumatoid arthritis and other types of synovitis.

OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCA) are present in several vasculitides and in other immunomediated diseases. The reported prevalence of ANCA in rheumatoid arthritis (RA) is variable. In addition, the presence of such autoantibodies has been poorly investigated in synovial fluid (SF). The objectives of this study were (1) to investigate the presence of ANCA both in the serum and in SF from patients with RA and other forms of synovitis (OS); (2) to analyze the reactivity of ANCA against isolated antigens proteinase 3 (PR3), myeloperoxidase (MPO) and lactoferrin (LF); and (3) to evaluate the clinical relevance of these autoantibodies. METHODS: Twenty-eight patients with RA, 13 with OS, and 17 with osteoarthritis (OA) of the knee joint were studied. No patient had clinical manifestations of vasculitis. SF and serum samples were investigated for the presence of ANCA by indirect immunofluorescence (IIF); the reactivity against PR3, MPO and LF was assessed by ELISA. RESULTS: ANCA were detected by IIF in SF of 39.3% patients with RA, 38.5% with OS, and 5.9% with OA. With 2 exceptions, patients who had ANCA in SF showed positivity also in serum. The presence of both anti-MPO and anti-LF antibodies was found in 3 patients with RA and 1 with OA; a patient with RA showed antibodies only against LF and another one with RA only against MPO. No reactivity was found against PR3. In patients with RA ANCA were not associated with disease activity. CONCLUSION: We found an increased incidence of ANCA both in SF and serum from patients with RA and OS. The pathogenic role and the clinical relevance of such autoantibodies in these diseases remain to be established.

Adult

Long time echo stir sequence magnetic resonance imaging of optic nerves in optic neuritis.

Magnetic resonance imaging of optic nerves was obtained in 13 patients with acute optic neuritis and in 13 patients with a previous history of optic neuritis (ON), assessed by clinical, visual fields and visual evoked potentials evaluations. Results of the conventional short tau inversion recovery (STIR) sequence obtained with short time echo (STE-STIR: 22 ms) were compared with long time echo (LTE-STIR: 80 ms) sequence. The conventional STE-STIR sequence revealed lesions in 78.5% of acute ON and in 58.8% of optic nerves affected by previous ON. The LTE-STIR sequence was diagnostic in 92.8% of acutely symptomatic nerves, in 94.1% of nerves with previous ON. The calculated length of optic nerve lesions was significantly longer in imaging obtained with the LTE-STIR sequence than with the conventional STE-STIR sequences, both in acute and previous ON.

Adult

Granulocytopenia after combined therapy with interferon and angiotensin-converting enzyme inhibitors: evidence for a synergistic hematologic toxicity.

PURPOSE: The purpose of this study was to assess whether granulocytopenia observed in 3 of 38 patients with essential mixed cryoglobulinemia who were treated with low-dose interferon was due to the underlying disease or to synergistic toxicity of interferon with other drugs. PATIENTS AND METHODS: Adverse effects of interferon therapy were monitored in 38 patients affected with type II essential mixed cryoglobulinemia. Patients were treated with 3 million units (MU), daily or on alternate days, of recombinant interferon-alpha 2a (35 patients) or with natural interferon-beta (3 patients). The duration of treatment ranged between 6 and 15 months; the total duration of follow-up, including after therapy, ranged between 8 and 93 months. RESULTS: None of 35 patients treated with interferon alone developed significant hematologic alterations. In addition, none of 7 patients treated with angiotensin-converting enzyme (ACE) inhibitors alone showed hematologic toxicity. Three patients who were treated with a combination of interferon and ACE inhibitors developed severe granulocytopenia a few days after starting treatment. Granulocytopenia subsided within 1 to 2 weeks after suspending therapy. Resumption of treatment with this drug combination produced a granulocytopenia relapse in 1 patient. In these 3 patients, interferon treatment alone, or ACE inhibitor monotherapy, was not followed by granulocytopenia. CONCLUSION: Although severe hematologic toxicity rarely develops in patients treated with low-dose interferon, granulocytopenia occurred in all 3 of our patients with mixed cryoglobulinemia who were treated with a combination of low-dose interferon-alpha 2a and ACE inhibitors. Neither drug alone was toxic in any of our cryoglobulinemic patients, indicating a high risk of severe hematologic toxicity for this drug combination, at least in patients with this disease. Physicians should be aware of this danger when using interferon treatment in patients with this, or possibly other, disorder(s) that also require antihypertensive therapy.

Adult