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F Pasquali

Publications and source records attributed to F Pasquali.

At least 37 records · Page 2Linked to original sources
PubMed1991

Roberts syndrome: phenotypic variation, cytogenetic definition and heterozygote detection.

Five cases of Roberts syndrome (RS) in four nuclear families are reported and the wide range of phenotypic variation among them is described. This is in contrast with the remarkable uniformity of the cytogenetic findings. Indirect immunofluorescence with seric antibodies from patients with CREST, revealed that the centromeric structures are normal in RS thus confirming J. German's assumption that the chromatid repulsion is confined to the heterochromatin. The authors quantified the phenomenon of centromeric heterochromatin separation (as occasionally revealed by C-bands in normal subjects) in obligate heterozygotes and possible heterozygotes for RS. The results are indicative of the possibility to screen for heterozygotes. The nosology of RS and related syndromes is discussed in view of the cytogenetic findings and the natural history of the disease.

Abnormalities, Multiple↗
PubMed1990

Transformation by ras oncogene induces nuclear shift of protein kinase C.

We measured protein kinase C (PKC) activity in normal and ras-transformed Balb/3T3 fibroblasts; cytosolic and nuclear-associated PKC activity was determined either as phorbol ester binding, PKC-dependent phosphorylation of histone III-S, or phosphorylation of endogenous nuclear proteins. Results demonstrate that ras-transformed fibroblasts show down-regulation of cytosolic PKC accompanied by increase of nuclear-associated PKC. These results provide evidence linking transformation to PKC nuclear shift with consequent phosphorylation of nuclear proteins.

Animals↗
PubMed1990

Interaction between endogenous circulating sulfated-glycosaminoglycans and plasma proteins.

Interaction between endogenous 35S-labelled plasma glycosaminoglycans and proteins in murine plasma was demonstrated by coelution from gel chromatography of circulating 35S-labelled glycosaminoglycans with a wide range of plasma proteins. Autoradiography of electrophoretic tracing of proteins from 35S-sulfate labelled plasma showed that labelled glycosaminoglycans were associated with alpha 1, alpha 2, beta globulins and albumin, but not with gamma globulins. Analysis by gel chromatography on Sepharose CL-6B of delipidated 35S-labelled plasma after either proteolysis or beta-elimination, suggested that 35S-labelled glycosaminoglycan chains were covalently bound to proteins. Lipids were probably involved in the supramolecular assembly of GAGs with plasma proteins, as shown by hydrophobic interaction chromatography. In addition, strong, non-covalent interaction between glycosaminoglycan chains and proteins was responsible for the difficulty in extracting 'free' glycosaminoglycans from plasma. Consistently, ion-exchange chromatography of 35S-sulfate labelled delipidated plasma after alkali treatment, revealed that the anionic properties of glycosaminoglycans were hampered when plasma proteins were present.

Animals↗
PubMed1990

Inhibition of BC3H-1 cell growth by heparin is related to decreased mitogenic signalling.

We examined the effect of heparin and heparin fragments on BC3H-1 muscle cell proliferation. Heparin significantly inhibited BC3H-1 cell growth and this inhibitory effect was related to the ability of heparin to bind to cell surface; low molecular weight heparins were poorly efficient in binding and inhibiting proliferation. Analysis by gel filtration of heparin bound to cell surface showed selective binding of the high molecular weight fraction. Heparin inhibited serum-stimulated incorporation of [3H]thymidine; this effect, however, was only evident when heparin was administered concomitantly with serum. Similarly, heparin inhibited serum-induced inositol lipid turnover only when present with serum. Heparin fragments unable to inhibit cell growth did not affect the metabolism of inositol lipids. Taken together these data suggest that heparin inhibits cell growth by interfering with growth factor-mediated mitogenic signalling.

Cell Division↗
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

Gene dosage effect in acquired monosomy 7: distinct behaviour of beta-glucuronidase and phosphoserine phosphatase.

Evidence for gene dosage effect for beta-glucuronidase (GUSB) and phosphoserine phosphatase (PSP), whose genes are mapped on chromosome 7, was searched in a group of 13 patients with myeloproliferative disorders and acquired monosomy 7. The monosomy 7 was the sole anomaly in nine patients and was associated with other chromosome changes in four. A group of 19 patients with similar diseases but with normal karyotype or with anomalies not involving chromosome 7 served as control. beta-galactosidase and arylsulphatase A, whose genes are not on chromosome 7, were tested as control enzymes. We obtained evidence for a gene dosage effect for GUSB, but not for PSP. When all cases with monosomy 7 were compared with controls, no dosage effect was observed for PSP, but when this group was split into two, according to the presence of anomalies additional to the monosomy 7, the values of activity in the group with additional anomalies were significantly lower than in the controls. Thus, in the case of PSP, the loss of one allele is not followed immediately by reduction in activity, and this could be due to the specific importance of PSP in nucleic acid metabolism. We postulate that some regulatory mechanisms are able to keep normal levels of PSP even in the presence of only one allele, and that they are overwhelmed only when additional chromosome changes are present. These changes tend to involve chromosomes carrying genes for enzymes involved in a metabolic pathway closely related to PSP functions, and only then is a gene dosage effect for PSP detectable.

Alleles↗
PubMed1989

Synthesis of diacylglycerol de novo is responsible for permanent activation and down-regulation of protein kinase C in transformed cells.

We measured the synthesis of diacylglycerol de novo in normal NIH/3T3 fibroblasts and in cells transformed by ras, src, sis and abl oncogenes. Analysis of the incorporation of glucose-derived 14C into diacylglycerol indicated that neosynthesis of diacylglycerol was constitutively active in the transformed cell lines. Elevated levels of diacylglycerol and persistent activation/down-regulation of protein kinase C reduced the binding of phorbol dibutyrate to transformed cells. This phenomenon could be reversed by blocking the glycolytic pathway, thus indicating that neosynthesized diacylglycerol was responsible for persistent activation and down-regulation of protein kinase C. In transformed cells, protein kinase C activity could not be stimulated by the addition of diolein; however, inhibition of glycolysis restored the ability of transformed cells to respond to diolein. Taken together these data indicate that constitutive synthesis of diacylglycerol de novo is responsible for activation and down-regulation of protein kinase C in transformed cells, and it may play a role in altered mitogenic signalling.

Animals↗
PubMed1989

Signal transduction in EJ-H-ras-transformed cells: de novo synthesis of diacylglycerol and subversion of agonist-stimulated inositol lipid metabolism.

We examined the level of 1,2-diacylglycerol and inositol phosphates in normal and EJ-H-ras-transformed BALB/3T3 fibroblasts by prelabelling the cells with [3H]glycerol, [3H]inositol, [14C]glucose, [14C]arachidonic acid, and [14C]palmitic acid. Steady-state level of inositol phosphates, however, was the same in control and transformed cells. Diacyglycerol labelling by [14C]arachidonic acid was the same in control and transformed cells. Insulin dramatically increased diacylglycerol labeling by [14C]glucose in normal cells, whereas it did not affect ras-transformed fibroblasts. Neurotransmitter-induced inositol lipid turnover was greatly enhanced in ras-transformed cells; conversely, platelet-derived growth factor and thrombin-stimulated normal cells to a greater extent than transformed fibroblasts. Taken together these results suggest that ras transformation may induce multifarious effects on signal transduction: it may cause de novo synthesis of diacylglycerol and subversion of neurotransmitter and growth factor receptor coupling to inositol lipid metabolism.

Animals↗
PubMed1988

Binding, internalization and degradation of heparin and heparin fragments by cultured endothelial cells.

We have studied the binding to bovine adrenal capillary endothelial cells cultured in vitro of heparin from different sources (porcine heparin Ep. 152 P, Av.M.W. 15.9 Kd and bovine heparin Ep. 756 P, Av.M.W. 12.9 Kd) and heparin fractions of various molecular weights (low molecular weight heparin, LMW 2123 OP, Av.M.W. 4.5 Kd and very low molecular weight heparin, VLMW 1027/45 OP Av.M.W. 2.1 Kd). The binding was specific for heparin; heparan sulphate showed some competition whereas dextran sulphate and glycosaminoglycans did not. We determined the affinity of heparin and heparin fragments for endothelial cells by means of displacement of bound 3H-labeled heparin in response to increasing concentration of unlabeled compounds. The binding of the different heparin fractions depends on their molecular weights. VLMW 1027/45 OP was unable to bind to the cells, whereas LMW 2123 OP showed an affinity 10 times lower then porcine heparin. Bovine adrenal capillary endothelial cells incubated with unfractionated 3H-labeled heparin selectively bound internalized and degraded high molecular weight heparin fractions, as shown by gel filtration of the 3H-labeled heparin both after binding to the cells and after internalization.

Adrenal Glands↗
PubMed1988

Transposition of c-abl oncogene in a case of masked Ph chromosome duplicated in blastic phase.

A female with chronic myelocytic leukemia (CML) in blastic phase (BP) showed a masked Ph chromosome that had originated by a translocation between chromosomes 8 and 22, with no obvious involvement of chromosome 9. A duplication of the masked Ph and trisomy 13 were present as additional anomalies. The karyotype on peripheral blood unstimulated cultures was 48,XX,t(8;22)(p12;q11),+13,+der(22) t(8;22)/47,XX,t(8;22)(p12;q11),+der(22)t(8;22). While the duplication of the Ph is a frequent finding in BP of CML, we did not find any other case in the literature with duplication of a masked Ph. In situ hybridization with c-abl and bcr probes showed that a 3' bcr sequence was translocated to the der(8) chromosome, while the c-abl oncogene was transposed to the masked Ph.

Blast Crisis↗
PubMed1988

Modulation of growth of melanoma.

Combined heparin-cortisone treatment induces regression of growth in a variety of murine tumors including melanoma. We injected 92 inbred C 57 b1/6 male mice each with 5 X 10(5) melanoma cells (B16, B16 F1, and B16 A6 lines) with different metastatic potential. Heparin (400 U/ml) and cortisone acetate (250 mg/kg SC injections) were given daily. Control experiments were performed both with the administration of no drugs and with administration of cortisone alone. Plasminogen activator activity, which is notoriously related to tumor growth, was evaluated using fibrin plate technique in 10 fragments taken before and 20 days after the combined heparin-cortisone treatment of B16 F1 and B16 A6 melanomas. The combined heparin-cortisone treatment slowed tumor growth, but no tumour regression was observed. Cutaneous fibrinolytic activity appeared increased in all specimens after the treatment.

Animals↗
PubMed1988

Ataxia-without-telangiectasia in two sisters with rearrangements of chromosomes 7 and 14.

Two sisters, 11 and 9 years old respectively, had the clinical features of a progressive neurological disorder similar to the ataxia-telangiectasia (AT) syndrome. The two patients have ataxia and chromosome instability with rearrangements of chromosomes 7 and 14 but no telangiectasia, nor the range of immunological anomalies typical of AT. Comparison with similar cases from the literature leads to the conclusion that either there is a specific disorder characterized by ataxia-without-telangiectasia and with the same cytogenetic pattern of AT, or AT shows a wider variability of phenotypic expression than thought before.

Ataxia Telangiectasia↗
PubMed1987

Cytogenetic findings in a case of anaplastic carcinoma of the pancreas.

A cytogenetic study was performed on a short-term culture of a biopsy from a primary anaplastic carcinoma of the pancreas. The modal chromosome number was 60. Six numerical clonal anomalies involving chromosomes #2, #6, #7, #10, #15, and #16 were found, and marker chromosomes involving #1, #3, #5, #8, #11, #12, #13, #15, #16, #18, #20, #22, and X. Premature chromosome condensation (PCC) was observed with a high frequency. The results are discussed with reference to the scarce literature on chromosome changes in pancreatic cancer.

Carcinoma↗
PubMed1987

Polyphosphoinositide metabolism is rapidly stimulated by activation of a temperature-sensitive mutant of Rous sarcoma virus in rat fibroblasts.

We have examined polyphosphoinositide turnover in a Rat-1 fibroblast line infected with a temperature-sensitive mutant (ts LA24) of the Rous sarcoma virus (RSV). When ts LA24-infected cells are shifted from the non-permissive to the permissive temperature, a rapid and sustained activation of phospholipase C (PLC) is observed. Normal and wild-type RSV-infected Rat-1 cells do not show any PLC activation upon temperature shiftdown. Pre-treatment of ts LA24-infected fibroblasts with tetrodotoxin (a Na+ channel inhibitor) or incubation in Na+-free medium significantly prevent temperature shiftdown-induced PLC activation. Therefore, we conclude that PLC activation occurs concomitantly with pp60v-src expression, and hypothesize that pp60v-src-related membrane depolarization is the causal link between pp60v-src tyrosine kinase activity and stimulation of polyphosphoinositide metabolism. Finally, we discuss the relationship between the phenomena we have observed and the mechanism of action of the ras oncogene.

Animals↗
PubMed1987

The 47,XXY karyotype and unrelated malformative patterns: an unusual association.

47,XXY chromosome complement is relatively frequent (1/750-1000 male newborns) but has so far not been reported in association with malformative syndromes. Three cases of 47,XXY karyotype associated with an unrelated malformative pattern, the Silver-Russell syndrome in two cases and Noonan syndrome in one case are reported. The possibility of a phenotypic alteration of patients with the XXY karyotype by these malformative syndromes is considered.

Abnormalities, Multiple↗
PubMed1986

High-degree abnormalities of nuclear DNA distribution in SIg negative acute lymphoblastic leukemia with vacuolated blasts.

Among 65 consecutive patients with untreated adult acute lymphoblastic leukemia (ALL), six had peculiar clinical and cytologic features. Bone marrow and circulating blasts were large and showed prominent vacuolization, with variable degree of granular periodic acid-Schiff positivity in the cytoplasm. All patients had marked spleen and liver enlargement with cholestasis and without either lymph node or central nervous system disease. They achieved complete response to chemotherapy, and their median survival was longer than 12 months. Blast cells were studied for immunologic markers, propidium iodide flow cytofluorometric DNA content, and in vitro tritiated thymidine labeling index (3H-TdR LI). These showed a "null" phenotype in two cases, contained intracytoplasmic immunoglobulins (Cy mu) in two and were positive for CALL and Ia antigens in two others (one of which also contained Cy mu). Surface immunoglobulins (SIg) were found on less than 12% of cells, and T-cell markers were absent. In five cases, one or two stem lines with highly abnormal modal DNA content were found to coexist with diploid blasts. The 3H-TdR LI was high (8.5%-15.5%). Abnormal cell lines, after being cleared by chemotherapy, were found again at relapse. Additional cell lines appeared during the course of the disease in one patient, having different sensitivity to cytostatics. These cases of ALL apparently derive from B-cells not yet expressing SIg and have an exceptionally high incidence of aneuploid cell lines.

Adolescent↗