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Biomedical subjects

G Rizzo

Publications and source records attributed to G Rizzo.

At least 73 records · Page 4Linked to original sources

Expression of caveolin-1 is required for the transport of caveolin-2 to the plasma membrane. Retention of caveolin-2 at the level of the golgi complex.

Caveolins-1 and -2 are normally co-expressed, and they form a hetero-oligomeric complex in many cell types. These caveolin hetero-oligomers are thought to represent the assembly units that drive caveolae formation in vivo. However, the functional significance of the interaction between caveolins-1 and -2 remains unknown. Here, we show that caveolin-1 co-expression is required for the transport of caveolin-2 from the Golgi complex to the plasma membrane. We identified a human erythroleukemic cell line, K562, that expresses caveolin-2 but fails to express detectable levels of caveolin-1. This allowed us to stringently assess the effects of recombinant caveolin-1 expression on the behavior of endogenous caveolin-2. We show that expression of caveolin-1 in K562 cells is sufficient to reconstitute the de novo formation of caveolae in these cells. In addition, recombinant expression of caveolin-1 allows caveolin-2 to form high molecular mass oligomers that are targeted to caveolae-enriched membrane fractions. In striking contrast, in the absence of caveolin-1 expression, caveolin-2 forms low molecular mass oligomers that are retained at the level of the Golgi complex. Interestingly, we also show that expression of caveolin-1 in K562 cells dramatically up-regulates the expression of endogenous caveolin-2. Northern blot analysis reveals that caveolin-2 mRNA levels remain constant under these conditions, suggesting that the expression of caveolin-1 stabilizes the caveolin-2 protein. Conversely, transient expression of caveolin-2 in CHO cells is sufficient to up-regulate endogenous caveolin-1 expression. Thus, the formation of a hetero-oligomeric complex between caveolins-1 and -2 stabilizes the caveolin-2 protein product and allows caveolin-2 to be transported from the Golgi complex to the plasma membrane.

Biological Transport↗

An automatic classification technique for attenuation correction in positron emission tomography.

In this paper a clustering technique is proposed for attenuation correction (AC) in positron emission tomography (PET). The method is unsupervised and adaptive with respect to counting statistics in the transmission (TR) images. The technique allows the classification of pre- or post-injection TR images into main tissue components in terms of attenuation coefficients. The classified TR images are then forward projected to generate new TR sinograms to be used for AC in the reconstruction of the corresponding emission (EM) data. The technique has been tested on phantoms and clinical data of brain, heart and whole-body PET studies. The method allows: (a) reduction of noise propagation from TR into EM images, (b) reduction of TR scanning to a few minutes (3 min) with maintenance of the quantitative accuracy (within 6%) of longer acquisition scans (15-20 min), (c) reduction of the radiation dose to the patient, (d) performance of quantitative whole-body studies.

Brain↗

Hamartoma of the urinary bladder: case report and review of the literature.

Bladder hamartoma is a rare benign entity with only eight cases reported in the literature thus far, and whose general imaging features have not, to our knowledge, been previously discussed. The purpose of this report is to review the literature and to discuss the imaging findings in one case of bladder hamartoma where US features were those of an inhomogeneous solid mass with an unechogenic center, which was in accordance with the CT findings of a soft tissue mass with central inhomogeneous enhancement due to central necrosis.

Adult↗

Interferon alpha-2B and ribavirin in combination for patients with chronic hepatitis C who failed to respond to, or relapsed after, interferon alpha therapy: a randomized trial.

PURPOSE: To assess the efficacy of interferon alpha-2b and ribavirin in combination in the treatment of patients with chronic hepatitis C who had either failed to respond to therapy with interferon alpha (nonresponders), or who had relapsed after interferon therapy (relapsers). SUBJECTS AND METHODS: Four hundred patients with chronic hepatitis C (200 nonresponders and 200 relapsers) were randomly assigned in equal numbers to receive either subcutaneous administration of recombinant interferon alpha-2b (3 million units three times per week) and ribavirin (1,000 to 1,200 mg/daily orally) or interferon alpha-2b alone (6 million units three times per week). Both ribavirin and interferon alpha-2b were given for 24 weeks. The patients were then followed for an additional 24 weeks. RESULTS: At the end of the treatment period, normalization of serum alanine aminotransferase levels and absence of hepatitis C virus RNA were seen in 21% of nonresponders and in 39% of relapsers who were treated with interferon alpha-2b and ribavirin, compared with 5% of nonresponders (P = 0.001) and 9% of relapsers treated with interferon alpha-2b alone (P <0.001). At the end of follow-up, 14% of nonresponders and 30% of relapsers treated with the combination therapy had a sustained response, compared with 1% of nonresponders (P = 0.001) and 5% of relapsers treated with interferon alpha alone (P <0.001). CONCLUSIONS: A 24-week course of treatment with interferon alpha-2b and ribavirin offers a chance of sustained response, whereas retreatment with interferon alpha-2b alone does not give satisfactory results. The role of long-term therapy in inducing prolonged remission remains to be explored.

Adolescent↗

A morphometric and ultrastructural study of the changes in the lamina propria in adolescents with varicocele.

OBJECTIVE: To verify if changes in the lamina propria and its components, reported in adults with varicocele, are already present in adolescents with idiopathic varicocele, using a morphometric and ultrastructural study. MATERIALS AND METHODS: Twenty testicular biopsies from adolescents (mean age 15.6 years) were obtained during surgery for left idiopathic varicocele; five testicular biopsies from adolescents (mean age 16 years) undergoing surgery for hydrocele or inguinal hernia were used as controls. Biopsy specimens were processed for light and transmission electron microscopy; the sections were evaluated morphometrically using computerized image analysis. RESULTS: Morphometric and ultrastructural examination of the testes with varicocele showed an increased thickness in the lamina propria, caused principally by an increase in the extracellular matrix components, and deep invaginations towards the germinal epithelium. CONCLUSION: There is detectable damage of the lamina propria in adolescents affected by left idiopathic varicocele, although not as well developed or as severe as in adults.

Adolescent↗

Ependymoma of the fourth ventricle presenting with hemifacial spasm. Report of a case.

According to Gardner's hypothesis (1962) later confirmed by Jannetta (1982, 1985), hemifacial spasm can usually be related to a "vascular conflict" which takes place inside the cerebellopontine angle (CPA). Occasionally, the causative lesion can be identified as a mass encasing the facial nerve at its root exit zone (REZ) from the brain stem. The hemifacial spasm has been rarely reported in presence of a contralateral CPA mass ("false localising sign"). Hemifacial spasm in patients with masses in anatomical regions other than the CPA has to be considered exceptional. The case of an adult man harboring an ependymoma of the fourth ventricle whose only neurological sign was a left hemifacial spasm is reported. The rarity of such a condition prompted us to review the literature. Particular attention has been paid to the possible pathogenetic mechanisms and their therapeutic implications.

Brain Neoplasms↗

[Integration of computerized tomography imaging with single photon emission in a commercial system for developing radiotherapy fields: application to conformational irradiation for lung carcinoma].

PURPOSE: Single photon emission computed tomography (SPECT) of lung perfusion permits to map functioning lung parenchyma with higher sensitivity than CT. Delivering higher radiation doses is used to increase local control in lung carcinoma; this strategy is based on radiobiological and clinical studies. Lung parenchyma is a dose-limiting tissue in patients irradiated for lung cancer. Functional mapping based on SPECT and CT findings permits to design radiation beams such as to minimize irradiation of functioning lung. MATERIAL AND METHODS: CT and SPECT were used to examine a patient with non small cell lung carcinoma (stage IIIB, T4N0, left lung) candidate to conformal irradiation. Images were spatially correlated based on lung contours and using CT findings as reference. SPECT images were normalized to mean right lung value and expressed as perfusion (functional) contours. CT images and perfusion contours were transferred to the treatment planning system (Cadplan V 2.79, Varian-Dosetek Oy): in this way both functional (SPECT) and anatomical (CT) data were available for planning. A comparison was made between two irradiation techniques defined at TPS with (technique B) or without (technique A) SPECT contour information. The prescribed dose was 70.2 Gy. Rival plans were compared using dose volume histograms of target and risk organs. Both functional and anatomical regions were considered in the lung, together with single lung(s) and lung parenchyma. A second perfusion SPECT was obtained 5 months after irradiation and correlated with pretreatment CT images. RESULTS: SPECT lung scans showed marked heterogeneity in the left lung, which was found neither at CT nor at classic lung function tests. The lung volume with perfusion exceeding 80% of average corresponds to about 70% of the anatomical volume. Mean doses to anatomical and to functional lung parenchyma were 24 Gy and 19 Gy, respectively, with technique A and 23 Gy and 18 Gy, respectively, with technique B. Thirty-five percent and 20%, respectively of anatomical and functional lung parenchyma received > or = 25 Gy (V25) with technique B. The figure for functional lung parenchyma was reduced by 5% with technique B. Optimal design of irradiation field geometry decreased the area of functional parenchyma given high doses, which sparing was greater with smaller irradiation volumes. CONCLUSIONS: We have integrated the functional data provided by SPECT lung perfusion into a commercial irradiation planning system. Lung function mapping permits to design irradiation portals sparing larger areas of functional lung parenchyma.

Carcinoma, Non-Small-Cell Lung↗

Aspecific inflammatory lesion (histiocytosis?) simulating intramedullary astrocytoma. Case report.

We report an exceptional case of aspecific inflammatory lesion of the thoracic spinal cord simulating an intramedullary glial tumor. Patient history was characterized by progressive spastic paraparesis with urinary incontinence; MR imaging (T4-T5) showed an enhancing intrinsic mass lesion. Myelotomy enabled partial resection of grayish astrocytoma-like tissue. Only light microscope examination was possible and disclosed aspecific inflammatory tissue composed of eosinophils, lymphocytes and histiocytes. After the operation, the patient improved promptly and no further therapy was administered. Control MRI after four months, one year and two years showed complete disappearance of the intramedullary mass lesion and the patient remained clinically stable with no other signs of disease. Since electron microscopic as well as immunohistochemical studies were not available, a definitive histological diagnosis was not possible. However on the basis of some clinical similarities with cases of isolated histiocytosis X of the CNS reported in the literature, we suggest that a diagnosis of isolated intramedullary eosinophilic granuloma could be reasonable.

Astrocytoma↗

FDG/PET and spiral CT image fusion for medistinal lymph node assessment of non-small cell lung cancer patients.

BACKGROUND: To assess the potential usefulness of 18F-FDG/PET and spiral-CT images concurrent assessment and coregistration in staging mediastinal lymph node involvement in patients with non small cell lung cancer. METHODS: 28 patients waiting to undergo surgical treatment underwent spiral-CT and PET examinations on the same day. The results of the two studies were interpreted separately, together (CT&PET) and following their fusion in a single image (CT+PET). Results of spiral-CT, PET, CT&PET and CT+PET were assessed with respect to the histological diagnosis. RESULTS: A correct assessment of mediastinal lymph nodes was achieved by spiral-CT in 21 of the 28 patients, in 22 of the 28 patients by PET, in 24 patients by CT&PET and in 25 patients by CT+PET. CONCLUSIONS: CT+PET is more accurate than spiral-CT and PET alone in staging mediastinal lymph node involvement in lung cancer patients, with possible implications for their prognosis and therapy.

Aged↗

Cell proliferation and ku protein expression in ageing humans.

Previous studies on DNA repair in ageing have demonstrated increased frequencies of single and double strand breaks in lymphocytes from elderly subjects and, as a consequence, decreased efficiency in DNA replication. We have investigated the relationship between cell proliferation and the nuclear expression of ku protein in a human population of 43 subjects of different ages. Ku is an heterodimeric protein composed of two subunits of 70 and 80 kDa, which is involved in the early steps of DNA damage recognition. In the present study, PBL from subjects of different ages were PHA-activated to evaluate the stimulation index and the production of Th1- and Th2-type cytokines. Moreover, nuclear extracts were obtained from activated lymphocytes to evaluate by a gel retardation assay the presence and the functional activity of the heterodimer ku 70/80. Our results indicate that ageing affects the mitotic responsiveness and cytokine production to a significant extent, but only marginally the expression of ku 70/80. These findings suggest that the age-related impairment in DNA repair mechanisms are only in part related to the reduced expression of ku protein able to recognize DNA damage.

Adult↗

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↗

The effect of glucocorticoid therapy on fetal lung maturity indices in hypertensive pregnancies.

OBJECTIVE: To assess fetal lung maturity tests in hypertensive pregnancies and to examine the effect of glucocorticoid therapy. METHODS: In a cohort study involving 68 pregnant women with hypertension, 34 received antenatal betamethasone before amniocentesis and 34 did not. Controls were 68 women with uncomplicated pregnancies, matched for gestational age at amniocentesis and fetal gender. Amniotic fluid (AF) samples were analyzed by lamellar body count, planimetric and stechiometric lecithin-sphingomyelin ratio (L/S), and presence of phosphatidylglycerol. RESULTS: Fetal lung maturity, as determined by lamellar body counts and by planimetric L/S, was lower in hypertensive pregnancies not treated with steroids than in controls (19,600 +/- 14,500 versus 39,800 +/- 22,700, P < .009, and 1.9 +/- 0.6 versus 3.9 +/- 1.8, P < .01, respectively). In the period of 24 to 33 weeks' gestation, the percentage of untreated pregnancies with mature lamellar body counts and mature L/S was significantly lower than that of controls (13% versus 33%, P < .001; 6% versus 40%, P < .002 and P < .003, respectively). In contrast, in patients treated with betamethasone, the percentage of cases with mature indices for both tests was not significantly different from that of controls, but was higher than that of untreated hypertensive patients (40% versus 13%, P < .001; 33% versus 6%, P < .001). Phosphatidylglycerol did not differ among groups. From 34 to 38 weeks, no difference was found in the percentage of mature cases for lamellar bodies in pregnant women with hypertension not treated with steroids in comparison with controls (68% versus 84%), nor between cases treated and controls (74% versus 84%). In the same period, no difference in L/S values was found among groups, and the percentage of cases positive for phosphatidylglycerol was lower in hypertensive pregnancies than in controls (47% versus 95%, P < .001) and was not affected by steroid treatment (37% versus 95%, P < .001). CONCLUSION: Fetal lung maturity, as reflected in AF tests, is delayed in hypertensive pregnant patients, and steroids increase all lung maturity indices except phosphatidylglycerol between 24 and 33 weeks' gestation.

Adult↗

The value of transvaginal ultrasonographic examination of the uterine cervix in predicting preterm delivery in patients with preterm premature rupture of membranes.

The objective of this study was to compare the value of ultrasonographic assessment of the uterine cervix and amniotic fluid tests in the prediction of the interval from admission to delivery in patients with preterm premature rupture of membranes. Ninety-two patients admitted to the hospital for preterm premature rupture of membranes between 24 and 32 weeks of gestation underwent both transabdominal amniocentesis and transvaginal ultrasonographic evaluation of the uterine cervix. Amniotic fluid analyses included cultures for aerobic and anaerobic bacteria, mycoplasmas and ureaplasmas, white blood cell count and glucose and interleukin-6 determinations. The ultrasonographic variables evaluated were cervical length, presence of funneling and cervical index ((funnel length + 1)/cervical length). The outcome measure was the interval from admission to delivery. The median interval from admission to delivery was 4.5 days (range 0-36). An abnormal uterine cervix was associated with a short time interval (cervical length < or = 20 mm, median 2 days, range 0-14 vs. median 6 days, range 0-36; p < or = 0.0001; presence of funneling, median 3 days, range 1-31 vs. median 8 days, range 0-36; p < or = 0.001; cervical index > 0.50, median 2 days, range 0-7 vs. median 8 days, range 1-36; p < or = 0.0001). However, interleukin-6 concentration in the amniotic fluid was the best predictor of the interval from admission to delivery when compared to the ultrasonographic indices and to all the amniotic variables considered. Moreover, when a multiple model was applied, the cervical index significantly and independently improved the performance of interleukin-6 in the prediction of the interval from admission to delivery. These data suggest that the combined use of the amniotic fluid interleukin-6 assay and the cervical index in patients with preterm premature rupture of membranes provides a good prediction of the interval from admission to delivery, thus identifying a subgroup of patients at high risk of imminent delivery.

Adult↗

Doppler echocardiography of the main stems of the pulmonary arteries in the normal human fetus.

The objective of this study was to describe the normal blood flow velocity waveforms in the main branches of the right and left pulmonary arteries in the human fetus and to establish reference ranges for different Doppler parameters during the second half of pregnancy. Cross-sectional data were collected from 86 healthy human singleton fetuses between 18 and 38 weeks of gestation. With advancing gestation a significant increase (p < 0.001) in the peak systolic velocity, time averaged velocity and time velocity integral was observed. The pulsatility index decreased significantly (p < 0.05) in the same period, suggesting a decrease in the pulmonary arterial vascular resistance. The acceleration time (AT) and the ratio of AT to ejection time (AT/ET), described in postnatal cardiology as having an inverse correlation with mean arterial pressure, increased significantly (p < 0.001). This is possibly the result of decreased pulmonary arterial pressure. The data show that Doppler examination of blood flow in the main stem of both the right and the left pulmonary arteries of the fetus is feasible, and increases insight into the lung perfusion of the human fetus. The observed changes throughout gestation are in accordance with animal experiments showing an increase in perfusion as well as a decrease in the vascular resistance and pressure.

Blood Flow Velocity↗