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Biomedical subjects

M Fabbri

Publications and source records attributed to M Fabbri.

At least 37 records · Page 2Linked to original sources
PubMed1999

Insect glycobiology: a lectin multigene family in Drosophila melanogaster.

Glycodeterminants play an important role in mediating cellular and cell-substrate interactions during development and immune-related reactions enabling an organism to distinguish self determinants from non-self or modified-self determinants. One of the hallmarks of sugar recognition molecules (lectins) is their wide range of binding activities and their organisation in multigene families. Here we describe a group of Drosophila genes that are possible members of the C-type lectin family.

Amino Acid Sequence↗
PubMed1999

Regulation of lymphocyte traffic by adhesion molecules.

Lymphocytes are antigen specific cells whose effector function is acquired through complex differentiation pathways. This implies, firstly, antigen encounter and recognition at specific sites, and, subsequently, the transition from a naive to a memory/effector phenotype. Clonotypically expanded cells must then be capable of recirculating to the tissue where their effector function is needed. To this aim, defined receptor-counter receptor pairs are expressed on lymphocytes versus endothelial cells. Extravasation is therefore a key-process in this scenario. Indeed, different lymphocyte subsets display distinct recirculation patterns and capability to migrate into lymphoid and non-lymphoid tissues. As a general rule, naive lymphocytes preferentially migrate into secondary lymphoid organs, where all the requirements for effective antigen presentation and differentiation are available; in contrast, memory/effector lymphocytes preferentially migrate to peripheral tissues, such as skin and mucosa. We review here the molecular events that regulate leukocyte extravasation and the specific migration properties acquired by both naive and memory/effector lymphocytes under physiological and pathological conditions.

Animals↗
PubMed1999

High impedance low energy pacing leads: long-term results with a very small surface area steroid-eluting lead compared to three conventional electrodes.

We evaluated the handling performance at implant, and the long-term atrial and ventricular electrical performance of a new generation using a very small surface area (1.2 mm2) steroid-eluting electrode (Medtronic CapSure Z). We compared the performance of CapSure Z to that of traditional passive fixation leads, with and without steroid elution. The study was conducted during 2 years of follow-up. We studied 188 patients (105 males and 83 females; mean age 71 +/- 7 years). All of the patients were implanted with a dual chamber pacemaker and the same type of lead in both chambers. Forty-one patients received CapSure Z leads, 25 patients received Target Tip leads (8-mm2 surface area; no steroid elution), 63 patients received CapSure leads (8-mm2 surface area; steroid elution), and 59 patients received CapSure SP leads (5.8-mm2 surface area; steroid elution). The four groups were homogeneous in regards to sex, age, cardiac disease, and reason for implant. At follow-up, the CapSure Z lead showed sensing values comparable to the other leads, with lower pacing thresholds and higher pacing impedance in both chambers. We evaluated the mean current drained from the pacemaker by the different types of leads when using safe, low energy output settings. We found that by using CapSure Z leads, the mean current was significantly lower than that of the other types of leads (0.42 microA for CapSure Z ventricular lead vs 0.85 for CapSure SP, 1.42 for CapSure, and 1.54 for Target Tip). Thus, the use of the CapSure Z lead, combined with low energy output programming, will increase pacemaker longevity compared to the use of traditional leads and standard output programming.

Aged↗
PubMed1998

Tumor-driven matrix invasion by infiltrating lymphocytes: involvement of the alpha1 integrin I-domain.

Here we show that tumor cells (TC) from renal cancers regulate the migratory properties of autologous tumor-infiltrating lymphocytes (TIL), enhancing their ability to invade the extracellular matrix. A similar effect is exerted by human recombinant macrophage chemotactic protein 1 (MCP-1) and IL-8, chemokines known to increase T lymphocyte migration both across vascular endothelium and subendothelial matrix. We found that TC freshly derived from renal cell carcinoma surgical specimens constitutively secrete both IL-8 and MCP-1 and that TIL express both specific receptors. TIL matrix invasion elicited by TC is inhibited by the addition of neutralizing antisera specific for IL-8 and MCP-1, demonstrating the direct relationship between chemokine release by TC and TIL invasion. Of note, TIL invasion of the extracellular matrix requires the alpha1 integrin, which acts through its I-domain that is upregulated upon culture with MCP-1 and IL-8. Collectively, these findings suggest that TC may actively recruit TIL via the release of chemotactic factors that enhance an alpha1 integrin-mediated pathway of matrix invasion.

Antigens, CD↗
PubMed1998

Interictal inhibitory mechanisms in patients with cryptogenic motor cortex epilepsy: a study of the silent period following transcranial magnetic stimulation.

The silent period (SP) following transcranial magnetic stimulation (TMS) of the motor cortex is mainly due to cortical inhibitory mechanisms. The aim of the present study was to investigate these inhibitory phenomena in primary motor cortex epilepsy. We studied the TMS-induced SP in both the first dorsal interosseous (FDI) muscles in 8 patients who suffered from cryptogenic partial epilepsy with seizures starting with clonic movements of the right upper limb. All patients were on chronic medication with antiepileptic drugs. Therefore, besides contrasting the results with 16 age-matched normal controls, we also studied 10 patients receiving similar antiepileptic treatments who suffered from cryptogenic partial epilepsy with seizures characterised by the absence of clonic manifestations. The duration of the SP was bilaterally increased in the patients with clonic seizures when compared with the two other groups of subjects. The SP was longer in the left FDI muscle (contralateral to the side of the clonic manifestation in all the patients). Our findings likely indicate enhanced interictal inhibitory mechanisms in patients with partial epilepsy involving the primary motor cortex. The resulting inhibitory effect could be greater in the intact hemisphere rather than in the affected one, in which the hyperexcitability of the epileptic focus had to be counterbalanced.

Adolescent↗
PubMed1998

Mapping of topoisomerase II alpha epitopes recognized by autoantibodies in idiopathic pulmonary fibrosis.

Autoantibodies against DNA topoisomerase II alpha have been identified in the sera of patients with idiopathic pulmonary fibrosis (IPF). To map topoisomerase II autoepitopes, we tested by ELISA and immunoblotting the IPF anti-topoisomerase II-positive sera against a series of recombinant proteins which covered the full length of topoisomerase II alpha. Specific patterns of reactivity were observed, indicating the existence of multiple epitopes on topoisomerase II, either highly complex or conformational/discontiguous or conformational/contiguous ones. The latter resided in amino acid residues 854-1147 and 1370-1447. A detailed analysis of these regions was undertaken, but we were not able to pinpoint a sequential peptide-sized epitope, or any significant homology with foreign pathogens. Further, we observed a significant correlation between the progression from a contiguous to a quaternary/tertiary structure-dependent autoepitope and the disease duration but not with the disease severity. Therefore, this result supports the hypothesis that anti-topoisomerase II autoreactivity evolves following an antigen-driven process.

Adult↗
PubMed1997

Steroid-eluting electrodes prevent chronic pacing threshold rise in the atrial chamber after oral propafenone administration.

The aim of the study was to evaluate chronic atrial pacing threshold increase after oral propafenone therapy. Fifty patients affected by advanced AV block and sick sinus syndrome were studied at least 6 months after pacemaker implantation, before and after oral propafenone therapy (450-900 mg/day based on body weight). The patients were subdivided into three groups as to the type of electrode implanted, all three unipolar: group I (20 patients) Medtronic CapSure 4003, group II (13 patients) Medtronic Target Tip 4011, group III (17 patients) Medtronic 4057 screw-in leads. In all cases, Medtronic unipolar pacemakers were implanted with the same noninvasive autothreshold measurement method. Propafenone and 5-OH-propafenone blood levels were measured 3-5 hours after drug administration. The packing autothreshold was measured at 0.8, 1.6, and 2.5 V by reducing the pulse width. After propafenone, groups II and III showed a statistically significant threshold rise (P ranging from < 0.01 to 0.05), whereas no significant difference was found in group I. Propafenone and 5-OH-propafenone blood vessels did not show any significant difference among the three groups. Strength-duration curves were drawn for the three groups before and after propafenone: at baseline the curves shifted to the left with the steep part above the knee, clearly favoring CapSure over the other two groups. After propafenone, the curves shifted to the right, with the flat par progressively more evident in groups II and III. In the atrial chamber, steroid-eluting leads prevented threshold increase after propafenone therapy, in contrast with a significant threshold rise with conventional porous and screw-in leads.

Aged↗
PubMed1997

Assessment of the severity of pulmonary emphysema by computed tomography.

Pulmonary emphysema is defined as an abnormal enlargement of alveolar spaces distal to the terminal bronchioles, with alveolar wall disruption and without obvious fibrosis. Clinico-functional evaluation and chest radiographic diagnosis are not highly accurate in detecting emphysema and in establishing the extent of the process of alveolar destruction. Several computed tomography (CT) techniques are now available for detection and quantitative assessment of emphysema. The results appear to correlate significantly better than chest radiography with functional impairment and pathological score. Many options have been proposed by different authors regarding CT technique. The choice, however, is essentially between inspiratory high resolution CT (HRCT) with a visual scoring system, and automated quantitative evaluation by means of a "density mask" (DM) program. This paper presents the state of the art on CT quantification of pulmonary emphysema and briefly discusses the technical options and parameters to be used, together with the problems to be solved.

Humans↗
PubMed1997

[Quantitative assessment of pulmonary emphysema with computerized tomography. Comparison of the visual score and high resolution computerized tomography, expiratory density mask with spiral computerized tomography and respiratory function tests].

CT is the most accurate method to detect pulmonary emphysema in vivo. We compared prospectively two different methods for emphysema quantitation in 5 normal volunteers and 20 consecutive patients with chronic obstructive pulmonary disease (COPD). All subjects were submitted to function tests and HRCT; three scans were acquired at preselected levels during inspiration. The type and extent of pulmonary emphysema were defined, using the time-honored visual score system, by two independent observers under blind conditions. Disagreements were subsequently settled by consent. All subjects were also examined with expiratory spiral CT, using a density mask program, at two different cut-off levels (-850, -900 HU). Visual score and expiratory spiral density mask values (-850 HU) were significantly correlated (r = 0.86), but the visual extent of emphysema was always higher than shown by expiratory spiral CT. The emphysema extent assessed with both CT methods correlated with the function result of expiratory airflow obstruction and gas diffusion impairment (visual score versus forced expiratory volume in one second: r = -0.81, versus single breath carbon monoxide diffusion: r = -0.78. Spiral expiratory density mask -850 HU versus forced expiratory volume in one second: r = -0.85, versus single breath carbon monoxide diffusion: r = -0.77). When -900 HU was used as the cut-off value for the expiratory density mask, the correlation with single breath carbon monoxide diffusion worsened (r = -0.56). Visual score and expiratory density mask -850 HU gave similar results and permitted COPD patients to be clearly distinguished from normal controls (p < 0.01). Residual lung volume, measured with expiratory spiral CT correlated significantly with residual volume measured with the helium dilution technique (r = 0.66), but CT values were always higher than function results. We believe the true residual volume should lie somewhere in between the CT value and the function results with the helium dilution technique and conclude that the extent of pulmonary emphysema can be confidently assessed with CT methods. Finally, the simple visual score may be as reliable as such highly sophisticated new methods as the spiral expiratory density mask. Expiratory studies offer new insights into different normal and abnormal features of COPD and respiratory impairment.

Aged↗
PubMed1996

Regulation of the insect immune response: the effect of hemolin on cellular immune mechanisms.

Hemolin is a bacteria-inducible protein of the immunoglobulin superfamily identified in the silk moth Hyalophora cecropia. The role of this protein, in hemocyte aggregation and phagocytosis, was studied in vitro. Hemocyte aggregation, stimulated by phorbol myristate acetate or lipopolysaccharide (LPS), was prevented by hemolin in a dose-dependent fashion, but hemolin did not disrupt aggregates once they had been formed. Furthermore, hemolin was able to stimulate phagocytic activity in both hemocytes and hemocytic mbn-2 cells and this activity was enhanced by LPS. The enhanced phagocytosis produced by a combination of hemolin and LPS was prevented by the protein kinase C (PKC) inhibitors staurosporine and H-7, and PKC activity in hemocyte crude extracts was enhanced by hemolin and LPS, with the highest activity observed in the presence of both. Hemolin affected tyrosine phosphorylation of hemocyte proteins, enhancing the phosphorylation of two proteins of 20 and 30 kDa and preventing tyrosine phosphorylation of two proteins of 35 and 40 kDa. These results suggest that hemolin is involved in the regulation of the cellular immune responses via a pathway that includes PKC activation and protein tyrosine phosphorylation.

Animals↗
PubMed1996

A functional monoclonal antibody recognizing the human alpha 1-integrin I-domain.

Alpha 1 beta 1 heterodimer is a member of the integrin receptor superfamily that has been described to be involved in cell-matrix binding through its interaction with collagens, fibronectin and laminin. The alpha 1 integrin belongs to a subset of I-domain containing integrins that includes alpha M, alpha L, alpha X and alpha 2. In this study we describe an anti-alpha 1 mAb (FB12) that recognizes an epitope located in the human alpha 1 I-domain, since the mAb can bind to human, but not to rat, recombinant I-domain GST fusion protein. FB12 mAb efficiently and specifically inhibits the binding of activated human lymphocytes to laminin, collagen and fibronectin. These data support the notion that the alpha 1 I-domain itself has an important role in receptor-ligand binding. In particular, we show that alpha 1 integrin-dependent lymphocyte adhesion to fibronectin is I-domain mediated, at variance with the RGD-dependent adhesion which seems to be mediated by the beta 1 rather than the alpha 1 integrin chain. Lastly, the overexpression of the alpha 1-integrin by stromal cells and blood vessels of solid tumors may suggest a role for this integrin in tumor biology.

Animals↗
PubMed1996

Incidence of hepatitis C virus infection in Italian patients with idiopathic pulmonary fibrosis.

BACKGROUND: A viral cause of idiopathic pulmonary fibrosis (IPF) was recently suggested by a Japanese study in which a high prevalence of anti-hepatitis C virus (HCV) antibodies was detected. A subsequent British study failed to confirm these results. METHODS: Antibodies to HCV were evaluated in 60 patients with IPF, 130 patients with non-interstitial lung disease, and in 4614 blood donors. HCV-RNA and HCV genotypes were evaluated in the anti-HCV positive patients with IPF. Anti-HCV antibodies were evaluated by ELISA and confirmed by recombinant immunoblotting assay (RIBA). HCV-RNA and genotypes were detected by reverse transcriptase polymerase chain reaction (PCR). RESULTS: Eight patients with IPF had anti-HCV antibodies detected by ELISA (13.3%). In the blood donor control group the prevalence of HCV antibodies was lower (0.3%). In patients with non-interstitial lung disease HCV antibody prevalence was 6.1%. In all eight patients with IPF found to be anti-HCV positive by ELISA, HCV antibodies were also detected by RIBA. Furthermore, all were HCV-RNA positive by PCR assay. HCV genotypes were identified in four of these eight patients. In all four genotype II was present and in two it was associated with genotype III and/or genotype IV. In the remaining four cases the genotype was not identified. CONCLUSION: Italian patients with IPF show an increased prevalence (approximately 13%) of HCV infection and viral replication, but the prevalence of anti-HCV antibodies does not differ from other lung diseases.

Adult↗
PubMed1996

Reduced striatal dopamine receptors in Alzheimer's disease: single photon emission tomography study with the D2 tracer [123I]-IBZM.

Many patients with Alzheimer's disease (AD) develop parkinsonian symptoms, suggesting an overlapping between AD and Parkinson's disease (PD). However, pathologic and neurochemical studies indicate that the involvement of the dopamine system may be different in the two conditions. Using single photon emission tomography, we determined the relative specific striatal uptake (striatum to cerebellum ratio) of the D2 receptor ligand [123I]-IBZM in 15 AD patients without overt extrapyramidal symptoms (three subjects presented mild rigidity and bradykinesia) and nine age-matched controls. Mean specific activity in striatal regions of AD patients (1.35 +/- 0.09) was significantly reduced from control mean (1.59 +/- 0.03). Because such changes were evident even in the absence of overt parkinsonian symptomatology, our data indicate that alterations of striatal D2 receptors may be part of the pathologic abnormalities of AD. In addition, the mechanisms underlying extrapyramidal symptoms in AD (decline of postsynaptic striatal dopamine receptors) appear different from the prevalent presynaptic nigrostriatal alterations typical of PD.

Aged↗
PubMed1995

Hydroxyapatite-based porous aggregates: physico-chemical nature, structure, texture and architecture.

At the request of medical teams from the maxillofacial sector, a highly porous ceramic support based on hydroxyapatite of around 70-80% porosity was produced with a pore size distribution similar to bone texture (< 10 microns, approximately 3 vol%; 10-150 microns, approximately 110 vol%; > 150 microns, approximately 86 vol%). The ceramic substrates were conceived not only as a fillers for bone cavities, but also for use as drug dispensers and as supports to host cells to produce particular therapeutic agents. A method is suggested to obtain a substrate of high porosity, exploiting the impregnation of spongy substrate with hydroxyapatite ceramic particles. X-ray and scanning electron microscopy analyses were carried out to evaluate the nature of the new ceramic support in comparison with the most common commercial product; pore size distribution and porosity were controlled to known hydroxyapatite ceramic architecture for the different possible uses.

Biocompatible Materials↗