PubMed Health⌕ Search

Biomedical subjects

F Zito

Publications and source records attributed to F Zito.

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

Helicobacter pylori infection and the risk of myocardial infarction: role of fibrinogen and its genetic control.

The contribution of Helicobacter pylori (HP) infection to the risk of myocardial infarction was evaluated. The role of fibrinogen and its genetic control as a possible mechanism by which HP may influence myocardial infarction risk was explored in this context. A case-control study was performed in 101 patients with myocardial infarction and in 101 controls. HP infection was associated with an increased risk of myocardial infarction independently for confounding variables (OR 4.1, CI95: 1.8-9.4). HP infection was significantly associated with higher levels of fibrinogen, both in cases and in controls. Furthermore, there was an additive effect of HP infection and B2 allele of BclI fibrinogen polymorphism in increasing fibrinogen levels. HP infection showed a stronger effect on the risk of myocardial infarction in B2 allele carriers (OR 7.6, CI95: 1.8-31.6) as compared to subjects carrying the B1B1 genotype (OR 3.3, CI95: 1.2-9.2). We showed that a previous HP infection is a risk factor for myocardial infarction. An increase in fibrinogen levels is a possible mechanism by which HP may act. Concomitant conditions, like a genetic predisposition in increasing fibrinogen levels, seem to further increase the effect of HP on myocardial infarction risk.

Adult↗
PubMed1998

Purification of bovine P2 myelin protein with bound lipids.

The P2 protein is a neuritogenic, small basic protein present in PNS myelin. It belongs to the family of the cytoplasmic lipid-binding proteins and can be incorporated in lipidic bilayers. P2 has been purified and crystallized only in the lipid-free form. Here we show that the P2 protein can be purified with bound lipids by applying to PNS myelin the same procedure that as used to purify lipid-bound myelin basic protein from CNS myelin. SDS-PAGE showed a single band of 16.5 kDa, and TLC showed the presence of most of the myelin lipids associated with the protein. Lipid-bound P2 revealed different circular dichroism spectra from the corresponding lipid-free form, indicating that lipids influence P2 conformation.

Animals↗
PubMed1998

Glu78, from the conserved PEWY sequence of subunit IV, has a key function in cytochrome b6f turnover.

We have investigated the structure to function relationship at the Qo site in cytochrome b6f complexes in vivo. To this end, we created site-directed mutants of Chlamydomonas reinhardtii, at position 78 in the sequence of subunit IV. The target glutamic acid, present in the highly conserved 77PEWY80 sequence, was changed to residues of different polarities which did not prevent the functional assembly of cytochrome b6f complexes. Spectroscopic analysis performed in anaerobic conditions in vivo revealed distinct alterations in cytochrome b6f function, depending on the nature of the substituted residue. The semiconservative E78D substitution, in which only the length of the side chain is reduced, retained the functional features of the wild-type configuration. The E78K and E78L substitutions caused a significant decrease, by factors of 3 and 5, respectively, in the rate of the concerted oxidation process at the Qo site without a change in the affinity of Qo for reduced plastoquinones. The E78Q and E78N substitutions modified the characteristics of cytochrome b6f turnover under repetitive flash illumination. They caused a large increase in the electrogenicity of the electron-transfer reactions through the mutated cytochrome b6f complex. This increase was specifically sensitive to the electrical component of the proton-motive force. Surprisingly, despite the larger number of charges translocated across the membrane per charge injected in the high potential chain, the reduction phase for cytochrome b6 became barely detectable in the mutants, unless inhibitors at the Qi site were present. We show that similar functional characteristics can be observed with the cytochrome b6f complex in the wild-type in anaerobic conditions, provided a single flash illumination regime is used. These observations suggest that cytochrome b6f turnover may involve a mechanism implying an extra proton pumping activity.

Amino Acid Sequence↗
PubMed1998

Ectoderm cell--ECM interaction is essential for sea urchin embryo skeletogenesis.

Paracentrotus lividus sea urchin nectin (Pl-nectin) is an extracellular matrix (ECM) protein of the sea urchin embryo on the apical surface of the ectoderm and has been shown to be an adhesive substrate for embryonic cells. A monoclonal antibody (McAb) to Pl-nectin was generated that inhibits the adhesion of blastula cells to Pl-nectin-coated substrates in an in vitro functional assay. To examine for possible in vivo functions of Pl-nectin, Fab fragments (Fabs) of Pl-nectin McAb were added to early blastulae. Ingression of primary mesenchyme cells was not affected by Fabs. As control embryos reached the pluteus stage, treated embryos showed a severe inhibition of skeletal elongation and patterning. When the Fabs were injected directly into the blastocoel, even at higher concentration than was applied externally, skeletogenesis was normal. Therefore, the effect of the antibody on spiculogenesis was indirect. The treatment was partially reversible as embryos eventually seemed to recover and elongate spicules, although with an incorrect patterning. Migration of pigment cells was also affected by the Fabs, since they did not disperse throughout the ectoderm but remained clustered in ectopic areas. In contrast, the development of endoderm structures was not affected. Our results indicate that in the sea urchin embryo the appropriate contact of ectodermal cells with outer ECM components is essential for the correct morphogenesis of inner mesodermal structures.

Animals↗
PubMed1998

The oligomeric integrity of toposome is essential for its morphogenetic function.

Sea urchin embryos are uniquely suitable for the study of morphogenetic cell interactions. Efforts to identify the molecules responsible for morphogenetic cell adhesion led to the isolation of a 22S glycoprotein complex from Paracentrotus lividus sea urchin embryo, that has been called toposome. The biological activity of toposome in mediating cellular adhesion has been fully documented. Its function in determining positional guidance during the development of the sea urchin embryo has been proposed. Here studies on the molecular structure of toposome are reported showing that, under non-reducing conditions, it is resolved in sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) in a major band with an apparent molecular weight of 260 kDa, a doublet of 180-160 kDa and a lower band of 80 kDa. Digestion with EndoH endoglycosidase reduced the molecular sizes of the bands of 10%, 20% and 40%, respectively. In order to establish if the oligomeric integrity of toposome was essential for its function, the biological activity of each subunit on cells dissociated from sea urchin blastula embryos was tested. The resulting swimming embryoids were lacking skeleton, while reaggregating cells supplemented with native toposome developed into pluteus-like structures with skeletal elements.

Animals↗
PubMed1998

Differential distribution of striatal [123I]beta-CIT in Parkinson's disease and progressive supranuclear palsy, evaluated with single-photon emission tomography.

Functional imaging of the presynaptic dopaminergic activity using single-photon emission tomography (SPET) and iodine-123 labelled 2-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane ([123I]beta-CIT) is important for the assessment of disease severity and progression in patients with Parkinson's disease (PD). However, its capability to discriminate between different extrapyramidal disorders has not yet been assessed. The aim of this study was to evaluate the possibility of differentiating patients with PD and with progressive supranuclear palsy (PSP) by means of this method. The distribution of [123I]beta-CIT in the basal ganglia was assessed in six normal subjects, 13 petients with PD and five patients with PSP in whom the disease was mild. SPET images were obtained 24+/-2 h after i.v. injection of the tracer using a brain-dedicated system (CERASPECT). MR and SPET images were co-registered in four normal subjects and used to define a standard set of 16 circular regions of interest (ROIs) on the slice showing the highest striatal activity. The basal ganglia ROIs corresponded to (1) the head of caudate, (2) a region of transition between the head of caudate and the anterior putamen, (3) the anterior putamen and (4) the posterior putamen. A ratio of specific to non-displaceable striatal uptake was calculated normalising the activity of the basal ganglia ROIs to that of the occipital cortex (V3"). ANOVA revealed a global reduction of V3" in all ROIs of PD and PSP patients compared with normal controls (P<0. 0001). A Mann-Whitney U test showed that the difference between PD and PSP patients was statistically significant for the caudate region only (Z value: 2.6; P<0.01). By subtracting V3" caudate values from those of the putamen, differentiation from PSP was possible in 10/13 PD patients. In conclusion, analysis of [123I]beta-CIT distribution in discrete striatal areas provides information on the relative caudate-putamen damage, with different values being obtained in patients clinically diagnosed as having either PD or PSP.

Aged↗
PubMed1998

A protein of the basal lamina of the sea urchin embryo.

The purification, biochemical characterization and functional features of a novel extracellular matrix protein are described. This protein is a component of the basal lamina found in embryos from the sea urchin species Paracentrotus lividus and Hemicentrotus pulcherrimus. The protein has been named Pl-200K or Hp-200K, respectively, because of the species from which it was isolated and its apparent molecular weight in SDS-PAGE under reducing conditions. It has been purified from unfertilized eggs where it is found packed within cytoplasmic granules, and has different binding affinities to type I collagen and heparin, as assessed by affinity chromatography columns. By indirect immunofluorescence experiments it was shown that, upon fertilization, the protein becomes extracellular, polarized at the basal surface of ectoderm cells, and on the surface of primary mesenchyme cells at the blastula and gastrula stages. The protein serves as an adhesive substrate, as shown by an in vitro binding assay where cells dissociated from blastula embryos were settled on 200K protein-coated substrates. To examine the involvement of the protein in morphogenesis of sea urchin embryo, early blastula embryos were microinjected with anti-200K Fab fragments and further development was followed. When control embryos reached the pluteus stage, microinjected embryos showed severe abnormalities in arms and skeleton elongation and patterning. On the basis of current results, it was proposed that 200K protein is involved in the regulation of sea urchin embryo skeletogenesis.

Animals↗
PubMed1997

Mutations of cytochrome b6 in Chlamydomonas reinhardtii disclose the functional significance for a proline to leucine conversion by petB editing in maize and tobacco.

We have introduced a proline codon in place of a leucine codon at position 204 of the petB gene of Chlamydomonas reinhardtii. This gene modification mimics the presence of proline codons at the same position in the petB genes of maize and tobacco, which are subsequently edited to leucine codons at the RNA level. Following transformation, we observed no editing at this position in C. reinhardtii, independent of the type of proline codon we have used: the CCA codon, edited in maize, or a CCT codon. Strains carrying the introduced mutation were non phototrophic and displayed a block in photosynthetic electron transfer, consistent with a lack of cytochrome b6f activity. Thus the presence of a proline residue at position 204 in cytochrome b6 is detrimental to photosynthesis. We show that the mutant phenotype arose from a defective assembly of cytochrome b6f complexes and not from altered electron transfer properties in the assembled protein complex. Biochemical comparison of the proline-containing transformants with a cytochrome b6 mutant deficient in heme-attachment indicates that their primary defect is at the level of assembly of apocytochrome b6 with the bh heme, thereby preventing assembly of the whole cytochrome b6f complex.

Animals↗
PubMed1997

Diagnostic accuracy and predictive value of 201T1 SPET for the differential diagnosis of cerebral lesions in AIDS patients.

The use of 201T1 has been proposed for the differential diagnosis of lymphomas and non-neoplastic brain masses in AIDS patients. The aim of this study was to assess the diagnostic accuracy of three different semi-quantitative methods for the analysis of 201T1 SPET brain images in individuals with AIDS and brain lesions. Thirty-seven AIDS patients with contrast-enhancing brain lesions underwent 201T1 SPET. Three different lesion-to-background uptake indices were calculated: (1) small lesion/large background (SL/LB; i.e. counts in a 3 x 3 pixel ROI in the lesion/counts in a 7 x 7 pixel ROI in the contralateral healthy hemisphere); (2) small lesion/multiple small background (SL/MSL; i.e. counts in a 3 x 3 pixel ROI in the lesion/average counts of ten 3 x 3 ROIs over the highest background pixel values); (3) large lesion/large background (LL/LB; i.e. counts in an elliptic ROI in the lesion/counts in a contralateral mirrored ROI). Data analysis included a ROC curve analysis to identify the cut-off value corresponding to the highest accuracy value, and an analysis of the predictive value to classify the patients in three categories (high, intermediate and low risk of lymphoma). The greatest accuracy (71%) was achieved with the LL/LB method of analysis. Using this method, 62% of patients could be classified as either having lymphoma or not, whereas 38% could not be classified. LL/LB values > or = 2.9 are suggestive of the presence of lymphomas, whereas values < or = 2 are highly predictive of the presence of a lesion other than lymphoma. However, LL/LB values between 2 and 3 are not diagnostic and adjunctive tests should be carried out. In conclusion, 201T1 SPET was an adequate diagnostic tool in approximately 70% of the cases in this study.

AIDS-Related Opportunistic Infections↗
PubMed1997

Bcl I polymorphism in the fibrinogen beta-chain gene is associated with the risk of familial myocardial infarction by increasing plasma fibrinogen levels. A case-control study in a sample of GISSI-2 patients.

The aim of this study was to investigate the association of the Bcl I beta-chain fibrinogen polymorphism with the risk of acute myocardial infarction (AMI) and its relationship with fibrinogen levels in the Italian population. We studied 102 AMI patients, selected within the framework of the GISSI-2 trial, who had a familial history of arterial thrombosis (at least one first-degree relative suffering from AMI or stroke before 65 years) and 173 control subjects (with neither AMI nor personal or familial history of arterial thrombosis). All subjects were Italian. Patients showed fibrinogen levels higher than control subjects. There was a highly significant difference in allele frequency in cases versus control subjects, the B2 allele frequencies being respectively 0.28 versus 0.17 (P = .002). In multivariate analysis, adjusted for sex, age, smoking habits, and history of hyperlipidemia, hypertension, or diabetes, the (B1B2 + B2B2) genotype was associated with a higher risk of AMI (odds ratio 2.4, 95% confidence interval, 1.2 to 4.6). The Bcl I genotype was also associated with fibrinogen levels, independently of gender and smoking habits, the (B1B2 + B2B2) subjects showing the highest levels in both cases and control subjects. The difference in fibrinogen levels between cases and control subjects was significantly influenced by the genotype (significant interaction, P = .042). The B2 allele of the Bcl I polymorphism in the beta-chain of the fibrinogen gene is a new factor associated with the risk of familial AMI through its association with fibrinogen levels. These data provide evidence for a causal role of fibrinogen in familial AMI.

Case-Control Studies↗
PubMed1996

Single-photon emission tomographic quantification in spherical objects: effects of object size and background.

A method was set up for single-photon emission tomographic (SPET) quantification of radioactivity concentration in small anatomical structures. The method is based on the theoretical model proposed by Kessler et al. (J. Comput Assist Tomogr 1984; 8: 514-522) describing the effects of spatial resolution (partial volume effect and spillover) on the quantification of radioactivity concentration in small spherical objects. The model was validated here in SPET, by phantom experimental measurements, in relation to object size and source/background contrast. Good agreement was found between model-predicted and SPET-measured radioactivity concentration ratios in hot spots in hot background experiments. Accuracy of the method was assessed for comparison of model-corrected and true radioactivity concentration ratios and was found to be within 8.5% over the full range of object size (9.4-36.5 mm). The good agreement found indicates that the model can be used to correct for partial volume effect and spillover in specific clinical situations, when the anatomical structure under study can be approximated by a sphere of known size (e.g. neuroreceptor and tumour studies). The method was applied to a representative SPET monoclonal antibody patient study for the quantification of radioactivity concentration in ocular melanoma.

Eye Neoplasms↗
PubMed1996

Quantitative comparison of direct antibody labeling and tumor pretargeting in uveal melanoma.

UNLABELLED: SPECT radioimmunoscintigraphy with 99mTc-labeled anti-melanoma monoclonal antibodies (MAbs) 225.28S is being used to detect uveal melanoma. Recently, pretargeting methods have been described to reduce background activity and perform imaging in a shorter time interval. METHODS: We compared the three-step pretargeting method with conventional radioimmunoscintigraphy in 15 patients with a clinical and laboratory diagnosis of uveal lesion. High-resolution SPECT radioimmunoscintigraphy was performed in all patients with directly labeled MAbs and, 1 wk later, with the three-step pretargeting technique. Eleven patients underwent eye enucleation and specimens of uveal melanoma were available for histology, whereas four patients underwent conservative therapy. The percent injected dose (%ID) delivered to the tumor and the tumor-to-background ratio were calculated. RESULTS: In all three-step radioimmunoscintigraphy studies, there was a reduction of nonspecific nasopharyngeal background. The three-step radioimmunoscintigraphy tumor-to-nontumor ratio was 3.1 +/- 1.3 versus 1.5 +/- 0.5 of conventional radioimmunoscintigraphy, while the percent injected dose on the tumor was similar for the two methods (4.4 +/- 3.0 versus 3.8 +/- 2.8) x 10(-3). CONCLUSION: Improved SPECT imaging with the three-step radioimmunoscintigraphy results from reduced background and from higher counting statistics due to reduction of time interval between radiotracer administration and imaging, whereas the absolute amount of tracer delivered to the tumor by the two methods is comparable.

Antibodies, Monoclonal↗
PubMed1995

[Impulsive noise: PTS and anatomic correlations].

The EEH (Equal Energy Hypothesis) postulates that permanent hearing loss (PTS) produced by exposure to noise is a function of sound energy of the exposure. The validity of EEH for continuous noise exposure was confirmed by large scale demographic studies and experiments in controlled laboratory setting. However, for impulse noise, EEH may not be as valid. This study was designed to test the applicability of EEH in impulse noise exposure in chinchillas. 9 groups of chinchillas were exposed to impulse noise. The intensity of the impulses (113, 125 and 137 dB SPL) and the rate (900, 3,600 and 14,400 impulses/hour) of the 9 exposure conditions were counterbalanced so that the 9 groups received the same total energy. PTS was obtained at 0.5, 2. and 8.0 kHz, by recording the evoked potentials from a chronic electrode implanted in the inferior colliculus. The cochleas were dissected and evaluated using conventional histological surface preparations and examined through scanning electron microscopy (SEM) employing a JEOL 35 microscopy. In our experimental conditions only the 113 dB SPL exposures were consistent with EEH (PTS less than 20 dB). The 125 dB SPL peak level is a critical value in that the validity of EEH also depends on exposure duration. As duration increases, so does PTS. At a 137 dB SPL peak level, EEH is not applicable. The amount of PTS is higher than 50 dB. It slightly increases when the impulse rate per hour becomes higher. In all cases examined PTS is less at 0.5 kHz than at 2.0 or 8 kHz. In these animals excellent informations concerning the sensory cell losses and cells damage was obtained with SEM.

Animals↗
PubMed1994

Performance comparison of a state-of-the-art neuro-SPET scanner and a dedicated neuro-PET scanner.

The physical performances of two current state-of-the-art scanners dedicated to functional imaging of the brain, one a single-photon emission tomography (SPET) scanner and the other a positron emission tomography (PET) scanner, have been compared under identical conditions. The aim of the study was to compare the capabilities of the devices under conditions resembling the routine clinical environment, as well as to consider other issues such as radiation burden for some common investigations. Both systems have slightly less than 11-cm axial fields of view. The PET system can be operated in a septa-less (3D) mode as well as conventionally with septa (2D). The spatial resolution of both devices was less than 8 mm in all dimensions in scattering media. On average, the PET scanner's resolution was approximately 10%-15% better than the SPET system. Energy resolution on the SPET system was superior due the scintillator used [NaI(Tl)]. Sensitivity in air with a line source on the PET system was found to be approximately 150 times greater in 3D and approximately 25 times greater in 2D than with the SPET system. A normal subject was studied on each system in an attempt to obtain the highest quality data possible for a subjective comparison. It is clear that, while PET retains the advantages of more desirable radiopharmaceuticals and higher sensitivity, the quality obtainable from SPET devices has improved markedly. SPET may prove as useful for many clinical investigations.

Brain↗
PubMed1994

Pre-targeted immunodetection in glioma patients: tumour localization and single-photon emission tomography imaging of [99mTc]PnAO-biotin.

The imaging of cerebral gliomas with radiolabelled monoclonal antibodies (MoAbs) has been previously reported. However, previous studies have been hampered by the drawback of a low tumour to non-tumour ratio. In order to overcome this problem we have developed a three-step pre-targeting method using the avidin-biotin system. The rationale of this technique consists in vivo labelling of biotinylated MoAbs targeted onto tumour deposits, when most of the unbound antibodies have been cleared from the bloodstream as avidin-bound complexes. The anti-tenascin MoAb BC2, specific for the majority of gliomas, was biotinylated and 1 mg was administered i.v. in 20 patients with histologically documented cerebral lesions. After 24-36 h, 5 mg avidin was injected i.v. followed 24 h later by a third i.v. injection of 0.2 mg PnAO-biotin labelled with 15-20 mCi technetium-99m. No evidence of toxicity was observed. Whole-body biodistribution was measured at 20 min, 3 h and 5 h post-injection. [99mTc]PnAO-biotin had a fast blood clearance and was primarily excreted through the biliary system. A dedicated single-photon emission tomography system was used to acquire brain tomographic images 1-2 h after the administration of [99mTc]PnAO-biotin. Tumours were detected in 15/18 glioma patients with a tumour to non-tumour ratio of up 14:1. This three-step method, based on the sequential administration of anti-tenascin MoAb BC2, avidin and [99mTc]PnAO-biotin, can support computed tomography or magnetic resonance imaging for the diagnosis and follow-up of patients with glioma. Further studies are required to evaluate the potential of this technique for therapeutic application.

Astrocytoma↗
PubMed1994

Avidin-biotin system in radioimmunoguided surgery for colorectal cancer. Advantages and limits.

PURPOSE: Radiolabeled monoclonal antibodies (MAbs) have been reported to allow tumor intraoperative detection by means of a gamma-detecting probe. The technology is called the Radioimmunoguided Surgery (RIGS) system. The main inconveniences of the method are 1) the long interval needed for clearance of unattached MAbs from the patient's body, between the injection of the MAb and surgery, and 2) the low sensitivity of current MAbs used in detecting small tumors. We describe a new method to overcome these inconveniences using biotinylated MAbs and avidin in order to obtain a rapid blood clearance of the radiolabeled MAbs both anticarcinoembryonic antigen and antitumor-associated glycoprotein-72 MAbs. METHODS: Twenty patients with primary and recurrent colorectal cancer have been enrolled in the study; 125I-biotinylated MAbs FO23C5 (anticarcinoembryonic antigen) and B72.3 (antitumor-associated glycoprotein-72) followed by cold avidin were injected in 13 patients and 7 patients, respectively. RESULTS: A decrease of 94 +/- 3 percent of circulating radioactivity was achieved in 3 to 5 days. Patients underwent surgery approximately seven days after MAb injections rather than after four weeks. Tumors were localized in 14/20 (70 percent) patients (true positive), 2 (10 percent) were false negative, and 4 (20 percent) were true negative. The overall sensitivity level in early-stage primary cancers was 37 percent when related to the presence of disease and 75 percent when related to antigenic expression. The sensitivity for more advanced cancer and for recurrences was 100 percent. Moreover, the in vivo tumor targeting of biotinylated MAb was demonstrated in frozen tumor section by direct streptoavidin-peroxidase staining. CONCLUSIONS: The avidin-biotin system may enhance applicability and effectiveness of radioimmunoguided surgery (RIGS).

Antibodies, Monoclonal↗