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G Fiorelli

Publications and source records attributed to G Fiorelli.

At least 145 records · Page 8Linked to original sources
PubMed1990

Effect of heparin on proliferation and signalling in BC3H-1 muscle cells. Evidence for specific binding sites.

We studied binding and growth inhibitory properties of different glycosaminoglycans in growing and differentiated BC3H-1 muscle cells. Heparin (10 micrograms/ml) and heparan sulfate (10 micrograms/ml) significantly inhibited DNA synthesis in growing and differentiated cells, as monitored by [3H]thymidine incorporation. Binding of heparin to BC3H-1 cells was specific and time-dependent. Heparan sulfate was the only glycosaminoglycan able to displace [3H]heparin (IC50, 3.2 x 10(-7) M), although it was 10-fold less effective than heparin itself (IC50, 3.6 x 10(-8) M). Scatchard analysis revealed the existence of high-affinity heparin binding sites (Kd, 5 x 10(-8) M). Furthermore, heparin inhibited serum-induced stimulation of inositol lipid turnover. Taken together, these results indicate that heparin inhibits BC3H-1 cell growth by interacting with the cell surface, possibly disrupting the flow of growth factor-related mitogenic signalling.

Animals↗
PubMed1990

Erythrocyte ferritin in patients on chronic hemodialysis treatment.

Serum ferritin (SF) and erythrocyte ferritin (EF) were evaluated in 35 patients on chronic hemodialysis treatment (CHD), in 45 healthy subjects and in 22 nonnephropathic females with iron deficiency anemia. Twenty-five CHD patients with basal SF less than 500 micrograms/l were treated orally with 200 mg of Fe2+ for 2 months and the positive (hemoglobin increase greater than 1 g/dl) or negative response to the therapy was correlated to the basal levels of SF and EF. Three groups of CHD patients could be defined on the basis of their basal SF levels (hypo-, normo- or hyperferritinemic). Nine patients with increased SF levels had also EF levels significantly higher than the other CHD patients and controls since they were probably iron-overloaded. In the other 2 groups of CHD patients, EF levels were significantly higher than in controls for each level of SF probably because of the reduced utilization of iron by uremic bone marrow. Among the 25 treated CHD patients, only 5 responded to the therapy: 3 were hypoferritinemic while the other 2 responders had basal SF within the normal range. Four hypoferritinemic patients did not respond to the therapy. Four out of five responders had the lowest EF levels among CHD patients. EF measurement could be an important and useful test in detecting the presence of an iron deficiency erythropoiesis in CHD patients.

Adult↗
PubMed1990

Analysis of T helper and suppressor lymphocyte subsets in relation to the clinical stage of solid neoplasms.

Neoplastic disease affect the immunity in cancer patients. The immune alterations in human neoplasms, however, need to be further defined. The present study was carried out to analyze T lymphocyte subsets in patients with solid tumors. The study included 93 patients suffering from early or metastatic solid neoplasms. T helper and T suppressor subsets were measured on venous blood samples by using flow cytometry and monoclonal antibodies. As controls, 58 healthy subjects were included in the study. The T mean helper/suppressor ratio (CD4/CD8) was significantly lower in metastatic cancer patients with respect to that observed either in controls or in patients without metastases. A low CD4/CD8 ratio was seen in 25 of 93 cancer patients (26.9%), 8 of whom had no metastases, while the other 17 showed a metastatic disease. Within the nonmetastatic group, the decline in the CD4/CD8 ratio was due to increases in the T suppressor subset alone in 7. On the contrary, the percentage of cases with decreased T helper subset was significantly higher in metastatic than in the nonmetastatic patients. The results of this study suggest that the decrease in the CD4/CD8 ratio mainly depends on an increase in T suppressor cells in patients without metastases whereas it is due to a decrease in the T helper subset in most patients with metastatic diseases.

Adult↗
PubMed1990

Insulin-like growth factor-I receptors in nonfunctioning thyroid nodules.

We have recently demonstrated the production of insulin-like growth factor-I (IGF-I) as well as the presence of type I IGF receptors in human thyroid cells in primary culture. The role of IGF-I in the control of thyroid cell growth has been well established. In order to investigate the involvement of IGF-I in abnormal thyroid growth, the density of IGF-I receptors in solitary, cold, micro- and macro-follicular thyroid adenomas, and in extranodular histological normal tissue was studied. Forty-three euthyroid patients with isolated cold nodules were selected for the study. In 30 patients the presence of IGF-I receptors was evaluated by using quantitative immunohistochemistry; in 10 patients by using radioligand binding studies, and in 3 patients by using affinity labeling. Cross-linking and binding studies clearly demonstrated the presence of a homogeneous class of binding sites for type I IGF receptors. Furthermore, radioligand studies did not show any significant differences in receptor density between the 2 types of thyroidal tissues. Conversely, the computerized analysis of 900 fields of nodular and normal thyroid tissues immunostained with the monoclonal antibody alpha-IR3, strongly indicated that higher concentrations of IGF-I receptors were present in the epithelial cells of non-functioning thyroid nodules than in the adjacent extranodular thyroid tissues. These studies strongly suggest that the same type I IGF receptor is present in thyroid follicular adenomas as in histological normal thyroid tissue removed from the same patient. The higher concentration of IGF-I receptors as documented by immunostaining in the adenomas suggests that IGF-I may contribute to the abnormal growth of the neoplasms.

Adenoma↗
PubMed1990

[Otorhinological evaluations of patients undergoing rapid disjunction of the median palatine suture].

Seven young patients, who had been diagnosed to be oral breathers by an orthodontist, have been submitted to an ETN specialist examination, before and after the rapid expansion of the mid-palatal suture. Five of these patients had an actual reduction of nasal breathing capacity. Four patients presented a significant enlargement of the adenoids. One patient showed a transmission auditive deficiency. The ETN examination, two months after the maxillary expansion, has permitted to find out that all the patients who had an impaired nasal breathing before the maxillary expansion, had normalized their respiratory capacity. Moreover, those subjects who had enlarged adenoids, showed a normal adenoids volume in the second ETN examination. Finally also the patient with an auditive deficiency presented a normalization of this function at the second ETN examination.

Adenoids↗
PubMed1989

Immunohistochemical evidence for a lack of ferritin in duodenal absorptive epithelial cells in idiopathic hemochromatosis.

Patients with idiopathic hemochromatosis exhibit an unexplained increase in intestinal iron absorption. The aim of this work was to study immunohistochemical H- and L-ferritin distribution in duodenal mucosal cells of patients with idiopathic hemochromatosis, and of subjects with various degrees of iron loading. Biopsy sections of gastrointestinal mucosa from 24 patients with idiopathic hemochromatosis, 10 patients with secondary iron overload, 6 normal subjects, and 13 iron-deficient subjects were analyzed with monoclonal antibodies for the presence of immunohistochemical H and L ferritin types, and with Perls' stain for hemosiderin. Ferritin content of duodenal homogenates was evaluated in 5 cases. The absorptive duodenal cells were found to contain ferritin, mostly of the L type, in apical granules; these ferritin granules were present in all normal, iron-deficient, and iron-over-loaded subjects, but were absent in 21 (87%) of the patients with established idiopathic hemochromatosis. In cells other than those of the duodenal epithelium, such as lamina propria or antral mucosa, ferritin and hemosiderin contents were related to iron loading and no difference was evident between primary and secondary iron overload. These findings indicate that (a) idiopathic hemochromatosis is associated with an altered ferritin expression in the duodenal absorptive epithelial cells, (b) this alteration cannot be detected by analysis of duodenal homogenates, (c) idiopathic hemochromatosis does not affect ferritin accumulation in the other cell types analyzed, and (d) ferritin in absorptive duodenal cells may have a regulatory role in iron absorption.

Antibodies, Monoclonal↗
PubMed1989

HLA typing in 67 Italian patients with idiopathic hemochromatosis and their relatives.

The frequency of HLA A3 and B7 antigens was significantly higher in 67 unrelated patients with idiopathic hemochromatosis (IH) than in 700 controls (62.7% vs 22.5%, p less than 10(-8) and 26.9% vs 9.3%, p less than 10(-3), respectively). A3 B7, A3 B35 and A3 B5 were significantly more frequent in 72 haplotypes linked to IH gene than in 278 control haplotypes. The prevalence of B35 and A3 B35 was significantly higher in IH patients from North-Eastern Italy than from other regions (60% vs 21%, p less than .05 and 54.5% vs 8.2%, p less than 0.0001, respectively). All 15 siblings HLA identical to the respective proband were homozygous for IH with variable expression of the disease, whereas minor abnormalities of iron-related indexes were present in 23% of heterozygous relatives. Homozygous-heterozygous mating probably occurred in three of 40 families, accounting for the overt disease in three offspring and in one HLA semi-identical sibling; however, in this last case the possibility of a recombination event cannot be excluded.

Adult↗
PubMed1989

Different polymorphic variants of glucose-6-phosphate dehydrogenase (G6PD) in Italy.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in Italy and recent biochemical and kinetic studies have demonstrated the presence of polymorphic variants associated with severe or mild enzyme deficiency. We performed a biochemical characterization of G6PD in a large number of Italian G6PD deficient men in an attempt to identify the most reliable biochemical indices for discriminating polymorphic G6PD variants and to define their distribution throughout the country. Three polymorphic G6PD variants, respectively named Mediterranean, Cagliari and Sassari, were identified. The elution profile on DEAE-Sephadex column chromatography, substrate analogue utilization and the Michaelis constant for G6P were the most significant parameters to discriminate polymorphic variants among the variants with activity levels lower than 0.8 IU/g Hb. The distribution of the polymorphic variants, in relation to the origin of the subjects studied, differs throughout the country.

Chromatography, Ion Exchange↗
PubMed1989

Three-month treatment with a long-acting gonadotropin-releasing hormone agonist of patients with benign prostatic hyperplasia: effects on tissue androgen concentration, 5 alpha-reductase activity and androgen receptor content.

The intraprostatic concentrations of testosterone (T) and dihydrotestosterone (DHT) have been measured in only a few men. We measured, in prostatic tissue obtained at surgery from seven men with benign prostatic hyperplasia, the effects of 3-month treatment with a long-acting GnRH agonist on 1) the intraprostatic concentrations of T, DHT, and 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol); 2) prostatic 5 alpha-reductase activity; and 3) the prostatic content of androgen receptors (AR). Plasma T, DHT, and 3 alpha-diol levels also were measured. Prostatic tissue samples obtained at surgery from a group of untreated men with benign prostatic hyperplasia also were studied. The mean DHT and 3 alpha-diol concentrations in the prostatic tissue of the treated men were about 10% of those in untreated men (n = 19; P less than 0.01 for DHT and P less than 0.05 for 3 alpha-diol), and the mean intraprostatic T concentration in the treated men was about 25% of that in the control group (0.10 greater than P greater than 0.05). The mean in vitro formation of DHT by the prostatic tissue of the treated men was about 50% lower (P less than 0.05) than that by prostatic tissue of the untreated men (n = 9). The mean cytosolic AR content in the prostatic tissue of the treated men was significantly higher (P less than 0.05), whereas the mean nuclear content of both salt-extractable and salt-resistant AR was significantly lower (P less than 0.05) than that in the prostatic tissue of the untreated men (n = 8). The mean plasma T levels in treated men decreased from 4.77 +/- 1.79 (SD) ng/mL (16.5 +/- 6.2 nmol/L) to 0.27 +/- 0.42 ng/mL (0.9 +/- 1.5 nmol/L) after 1 month of therapy and remained in the castrate range thereafter. We conclude that pharmacological castration resulting from 3-month treatment with a long-acting GnRH agonist decreases the intraprostatic T concentration to about one fourth and those of DHT and 3 alpha-diol to about one tenth of the levels in untreated men. Thus, GnRH agonist treatment may not completely abolish intraprostatic androgen concentrations in metastatic prostatic cancer patients. The decrease in prostatic 5 alpha-reductase activity as well as the decrease in nuclear receptors are probably secondary to the decrease in plasma T concentrations.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1989

Epidermal growth factor receptors in human hyperplastic prostate tissue and their modulation by chronic treatment with a gonadotropin-releasing hormone analog.

We characterized the epidermal growth factor (EGF) receptor in the membrane fraction of prostatic tissue from men with benign prostatic hyperplasia (BPH). The maximum specific binding of [125I]EGF to the BPH membrane fraction was achieved after 30-min incubation at 35 C. Analysis of the binding data revealed two classes of binding sites, one of high affinity [Kd, 2.5 +/- 0.5 (+/- SE) x 10(-11) mol/L] and one of lower affinity (2.2 +/- 0.3 x 10(-9) mol/L). [125I]EGF binding was inhibited by excess EGF, but not by insulin, proinsulin, fibroblast growth factor, or insulin-like growth factors I and II. In prostatic tissue of men with BPH treated for 3 months with the GnRH agonist analog Goserelin (Zoladex, depot formulation), the binding capacities of both sites were significantly higher than those of BPH tissue from untreated men (P less than 0.001). These results demonstrate that prostatic tissue from men with BPH contains two classes of specific binding sites for EGF, and their levels are modulated by chronic GnRH agonists treatment.

Aged↗
PubMed1989

Two point mutations are responsible for G6PD polymorphism in Sardinia.

The human X-linked gene encoding glucose 6-phosphate dehydrogenase (G6PD) is highly polymorphic; more than 300 G6PD variants have been identified. G6PD deficiency in different geographical areas appears to have arisen through independent mutational events, but within the same population it may also be heterogeneous. One example is the island of Sardinia, where careful clinical and biochemical studies have identified four different G6PD variants. We cloned and sequenced the four G6PD variants from Sardinia and found that only two mutations are responsible for G6PD deficiency in this area: one mutation is the cause of the G6PD Seattle-like phenotype, a milder form of G6PD deficiency; the other mutation is responsible for all forms of very severe G6PD deficiency in Sardinia and, possibly, in the Mediterranean.

Cloning, Molecular↗
PubMed1988

Immunohistochemical evaluation of a panel of monoclonal antibodies for the diagnosis of small cell lung cancer.

Monoclonal antibodies (mAbs) with a high sensitivity and specificity for small cell lung cancer (SCLC) may be of potential diagnostic and therapeutic use. We selected five different mAbs generated against SCLC cell lines and tested them on paraffin-embedded SCLC and non SCLC (NSCLC) clinical samples in a retrospective study using immunohistochemical techniques. The results showed that the contemporary use of mAbs that react with different antigens allowed all the examined SCLC to be detected indicating that this panel of mAbs was extremely sensitive. Analysis of the reactivity of these mAbs with NSCLC showed that 4 of the 5 antibodies reacted also with a few NSCLC. Using higher dilutions of these mAbs their specificity improved substantially. The 5 different mAbs presented marked heterogeneity of antigenic expression within and between SCLC. This panel of antibodies may be very useful in the diagnosis of SCLC whereas their application, in vivo, in therapeutic trials, is limited by the heterogeneity of antigenic expression.

Antibodies, Monoclonal↗
PubMed1988

Characteristics and expression of binding sites specific for ferritin H-chain on human cell lines.

Purified recombinant human ferritin composed solely of H subunit was radiolabeled and incubated with proerythroleukemic K562 human cells. A specific binding was detected, and it could be displaced only by ferritins, natural or recombinant, containing large proportion of the H subunit. The specific ferritin H-chain binding was saturable, and cells showed 17,000 to 23,000 binding sites per cell. The affinity constant measured at 37 degrees C was of 3 x 10(8) M-1. Treatment with pronase eliminated the specific binding. The binding sites were expressed in a high number during the cellular exponential phase of growth and progressively decreased to disappear when cells reached the plateau phase. Treatment of the cells with desferrioxamine increased recombinant H-ferritin binding, while iron had little effect. K562 cells induced to differentiate by hemin failed to bind ferritin H. Ferritin H-chain binding capacity is present on various cell lines such as HL60, lung cancer, and hepatoma cells. Analysis of the binding sites by western blotting showed a peptide with apparent mol wt of about 100 kd.

Binding Sites↗
PubMed1987

Combined use of DNA probes in first-trimester prenatal diagnosis of hemophilia A.

First-trimester prenatal diagnoses of hemophilia A were heretofore obtained by using either intragenic factor VIII markers or linked extragenic polymorphic markers. Postulating that the combined use of all the available intragenic and extragenic markers can render such diagnoses more frequently feasible and more reliable, we carried out ten first-trimester prenatal diagnoses in male fetuses at risk for hemophilia A by DNA analysis of chorionic villus employing in combination the intragenic Bcl I polymorphism and the St 14 (DXS 52) or DX 13 (DXS 15) extragenic probes. A diagnosis of hemophilia was obtained in three fetuses, with a diagnosis of normal fetus obtained in the remaining seven. Seven diagnoses are confirmed by factor VIII assays carried out at the time of abortion, in the mid-trimester or at birth. A factor VIII probe recognizing Bcl I polymorphism was useful in 4 of 6 diagnoses; St 14, in 5 of 6; and DX 13 in 3 of 5. In two cases, St 14 was the only useful probe for diagnosis. Even though no recombination between extragenic probes and factor VIII gene was detected in this study, when only extragenic markers were informative we advised diagnostic confirmation on fetal plasma obtained by fetoscopy. Hence, first-trimester prenatal diagnosis of hemophilia A is feasible for the great majority of fetuses at risk through combined use of all the available intragenic and extragenic probes, providing key family members are available.

Adult↗