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Biomedical subjects

S Ferrari

Publications and source records attributed to S Ferrari.

At least 289 records · Page 16Linked to original sources
PubMed1991

Primary lymphoma of bone: long term results in patients treated with vincristine--adriamycin--cyclophosphamide and local radiation.

Primary lymphoma of bone (PLB) is an unusual but well-recognized extranodal presentation of non-Hodgkin's lymphoma. In most series treatment with radiotherapy alone results in a cure rate of approximately 40%. Between January 1972 and December 1982, 26 patients with biopsy proven PLB were treated at the Rizzoli Institute with radiotherapy (4000-5,500 rad) and chemotherapy (vincristine, cyclophosphamide and adriamycin). The minimal clinical staging included complete blood cell counts and serum chemistries, bone radiography, full lung tomography, isotope bone scan, bone marrow biopsy and bipedal lymphoangiograms. At a median follow-up of 13 years (8.5-18.5) there were only three relapses (2 cases of meningeal involvement and 1 recurrence in another bone). No local recurrences nor second tumor in the irradiated field were observed. We conclude that the addition of chemotherapy to radiotherapy results in an excellent cure rate for patients with PLB.

Adolescent↗
PubMed1991

Mitochondrial DNA deletion in oculoskeletal myopathy.

The case of a patient showing bilateral ophthalmoplegia with proximal limb weakness, severe dysphagia and short stature, without family history, is described. The diagnosis of Kearns-Sayre syndrome was excluded because of the absence of pigmentary retinopathy and of all other common manifestations except short stature. The analysis of mitochondrial DNA of the patient's muscle revealed a deleted form accounting for 65% of the total mitochondrial DNA. The deletion, undetectable in the mitochondrial DNA of peripheral blood leukocytes, was apparently indistinguishable from that already described by others in a far more severe form of classic Kearns-Sayre syndrome.

Adult↗
PubMed1991

Decrease of proliferation rate and induction of differentiation by a MYCN antisense DNA oligomer in a human neuroblastoma cell line.

The effects of an antisense oligodeoxynucleotide to codons 2-7 of the oncogene MYCN on the human neuroblastoma cell line LAN-5 were studied. Treated cells showed a decreased MYCN protein expression and synthesis by immunoperoxidase staining and immunoprecipitation. At the same time, the replication rate was inhibited, and the phenotype was modified toward a more differentiated type. Our data suggest the involvement of oncogene MYCN in both proliferative and differentiative processes.

Base Sequence↗
PubMed1991

Non-metastatic Ewing's sarcoma: results in 98 patients treated with neoadjuvant chemotherapy.

From June 1983 to December 1987, 98 patients with non-metastatic Ewing's sarcoma of bone were treated by a protocol of neoadjuvant chemotherapy consisting of two months of preoperative chemotherapy with vincristine, adriamycin, and cyclophosphamide followed by local treatment and one year of chemotherapy aimed at preventing recurrence using the same drugs plus dactinomycin. Local treatment consisted of surgery in 39 cases (40%), radiation in 34 (34%), and both surgery and radiation in 25 (26%). After an average follow-up of five years, 51 patients (52%) had remained continuously disease-free (CDF), 46 had developed metastasis, of which 20 with local recurrence, and one had developed a radioinduced sarcoma. The site of the tumor (61% of patients with Ewing's sarcoma of the extremities were CDF vs. 35% with tumor of the pelvis) and the kind of local treatment (61% of patients who underwent surgery with or without radiation therapy were CDF vs. 35% of patients treated with radiation therapy alone) were important prognostic factors. These results are similar to those obtained in 59 patients treated from 1979 to 1982 (average follow-up, 10 years) using the same drugs administered according to adjuvant chemotherapy procedure as well as those reported in the only other large study on this subject in the literature (the multi-institution German study CESS-81). The authors conclude that even though neoadjuvant chemotherapy makes surgery possible and easier in Ewing's sarcoma, it does not significantly increase survival when compared to traditional adjuvant treatment.

Adolescent↗
PubMed1990

Primary chemotherapy and delayed surgery for malignant fibrous histiocytoma of bone in the extremity.

Between March 1983 and September 1988, 22 patients with non-metastatic malignant fibrous histiocytoma MFH of bone of the extremities were treated with two regimens of neo-adjuvant chemotherapy successively activated. Preoperatively, the patients received moderate doses of methotrexate and cisplatinum-Regimen 1- or high dose methotrexate, cisplatinum and adriamycin-Regimen 2. Cisplatinum was delivered intraarteriously, the other drugs intravenously. Limb salvage surgery was performed in 20 patients, and 2 patients were amputated. The surgical margins were adequate (radical or wide) in 18 cases and inadequate (marginal) in 4. The histologic response to chemotherapy was good (90% or more tumor necrosis) in 8 patients. In both regimens postoperative chemotherapy was tailored according to the grade of necrosis determined by preoperative treatment on the primary tumor. At an average follow-up of 40 months (15-70), 15 patients (68%) remained continuously disease-free and 7 relapsed with metastases. No local recurrences were observed. Regimen 2 was slightly more effective than Regimen 1 in terms of good histologic response (5/10 vs 1/12) and continuous disease-free survival (8/10 vs 7/127). The results demonstrate that, as in osteosarcoma, in non-metastatic malignant fibrous histiocytoma of bone in the extremities a high percentage of patients can be cured with neoadjuvant chemotherapy and that in most of them limb sparing surgery is possible and safe.

Adolescent↗
PubMed1990

Noncoordinated expression of S6, S11, and S14 ribosomal protein genes in leukemic blast cells.

The steady state levels of mRNAs codying for the ribosomal proteins S6, S11, and S14 have been evaluated in quiescent and proliferating human fibroblasts and in resting and proliferating human peripheral blood mononuclear cells. It was found that the amounts of ribosomal protein mRNA are very similar and are not increased by serum or mitogen stimulation. The constitutive expression of these genes appears to be coordinately regulated and it is not modified after protein synthesis inhibition by cycloheximide. The ribosomal protein mRNA was also assayed in 15 different populations of human leukemic blast cells. In these populations the abundance of each ribosomal protein mRNA is remarkably different from the other. The results of our present experiments indicate that the expression of the three ribosomal protein genes undergoes independent noncoordinated changes in the large majority of the leukemic populations studied.

Blast Crisis↗
PubMed1990

Protein phosphorylation in rat liver mitochondria.

Incubation of rat liver mitochondria in the presence of either [32P] Pi or [y32-P] ATP resulted in a phosphorylation of four proteins with Mr 50, 47, 44 and 36 kDa, respectively. The endogenous phosphorylation of these proteins in the presence of [32P] Pi was markedly influenced by the osmolarity of the incubation medium and differentially affected by various effectors of mitochondrial functions, such as Ca2+, oligomycin, FCCP, arsenite and dichloroacetate. In particular, the 36 kDa protein, unlike the other proteins, appears to be phosphorylated also by direct incorporation of [32P], independently of respiratory chain-linked ATP synthesis. The four proteins, located in the mitoplasts, seem to be phosphorylated by different protein kinases, as suggested by the observation that the endogenous phosphorylation of 36 kDa protein resulted selectively increased by addition of exogenous protein kinases, such as casein kinases S and TS. A tentative identification of these phosphorylatable protein is discussed.

Adenosine Triphosphate↗
PubMed1990

Identification of chicken calbindin D28K pre-messenger RNA sequences by polymerase chain reaction.

A transcribed RNA sequence encompassing the junction between the first intron and the second exon of the chicken calbindin D28K gene was copied in a cDNA fragment and subsequently amplified by polymerase chain reaction. When intestinal RNA is used as template, the appearance of the 161 bp amplified fragment is strictly dependent on the vitamin D status of the animal. In fact no amplified fragment is obtained when the RNA is extracted from the intestine of vitamin D-deficient chickens, while it is easily detected when the RNA is extracted only 30 min after injection with 1,25-dihydroxycholecalciferol. Conversely, the amplified fragment is obtained, irrespectively of the vitamin D status of the animal, when the RNA template is extracted from the brain. The appearance of unspliced RNA sequences upon vitamin D induction is followed, after a 30 min lag, by the appearance of the corresponding mature mRNA sequences.

Animals↗
PubMed1990

Ratios between the abundance of messenger RNA and the corresponding protein of two growth-related genes, c-myc and vimentin, in leukemia blast cells.

The abundance of the mRNAs of two growth-related genes, vimentin and c-myc, and that of the corresponding proteins have been studied in unstimulated and phytohemagglutinin-stimulated lymphocytes as well as in 18 populations of leukemic blast cells. The quantitative assay was carried out by densitometric scanning of Northern and Western blots. In normal lymphocytes the mRNA and the protein of both genes were almost undetectable. The phytohemagglutinin stimulation led to a sharp increase of the mRNA and the proteins of vimentin and c-myc. The increase was followed by a progressive fall of the gene products. The rate of decrease of the two mRNAs was similar to that of the corresponding proteins. In some leukemic populations very similar amounts of the vimentin protein were accompanied by amounts of the mRNA differing at least 25 times. Not unlikely, very similar amounts of p62c-myc corresponded to mRNA abundances differing at least 16 times. The coordinated biogenesis of both messenger RNAs and proteins, which occurs in mitogen-stimulated lymphocytes, is substituted, in approximately 30% of the leukemic blast cell populations, by molecular events leading to the accumulation of an excess of mRNA.

Blast Crisis↗
PubMed1990

Complement-mediated demyelination in patients with IgM monoclonal gammopathy and polyneuropathy.

We investigated the role of complement in the pathogenesis of the demyelinating polyneuropathy that occurs in some patients with IgM monoclonal gammopathy. Seven patients with chronic sensorimotor polyneuropathy and IgM monoclonal gammopathy were examined. In six patients, the monoclonal protein recognized an epitope shared by myelin-associated glycoprotein and two peripheral-nerve glycolipids, whereas in one patient, IgM bound to an unidentified myelin antigen. Direct and indirect immunofluorescence and immunoperoxidase assays showed colocalization along the myelin sheaths of peripheral-nerve fibers of monoclonal protein with complement components C1q, C3d, and C5. In addition, terminal-complement complex that was not associated with S protein was detected in myelin sheaths. It appeared that alterations in myelin geometry caused by the separation of myelin lamellae corresponded to sites at which terminal-complement complex was deposited. We conclude that demyelination in polyneuropathy associated with IgM monoclonal gammopathy may be mediated by complement.

Aged↗
PubMed1990

Transmembrane cation fluxes and fatty acid composition of erythrocytes in psoriatic patients.

Cation transport systems and lipid composition of erythrocyte membrane were studied in 27 psoriatic patients and in 34 healthy individuals. Whereas intracellular Na and K content, Na- and K-passive permeability and Li-Na countertransport of psoriatics did not show any statistical difference from normals, the Na/K ATPase pump activity was significantly higher and Na-K cotransport was significantly lower. Membrane lipid composition of psoriatics was different from normals: an increase in arachidonic acid and in unsaturated (poly- and total unsaturated) fatty acid content was found. A positive correlation was demonstrated between unsaturated/saturated fatty acid ratio and Na/K ATPase pump activity. These results demonstrate an alteration of erythrocyte Na/K ATPase pump and Na-K cotransport in psoriasis. These alterations of cation transport are associated with a perturbation of membrane fatty acid composition which appears a widespread phenomenon in cells of psoriatic patients.

Adult↗
PubMed1990

Differentiation-dependent expression of apolipoprotein A-I in chicken myogenic cells in culture.

Northern blot hybridization experiments showed that Apolipoprotein A-I (Apo A-I) mRNA is present at high concentration in chicken myotubes cultured in vitro, while it is virtually absent in fibroblasts and myoblasts. Myotubes are also capable of translating and secreting in the culture medium a protein which is specifically immunoprecipitated by anti-Apo A-I antibodies and has the same electrophoretic mobility as Apo A-I purified from circulating high-density lipoproteins. The appearance of Apo A-I mRNA in myotubes depends on the transcriptional activation of the corresponding gene, as it was shown by hybridizing 32P-labeled RNA synthesized in isolated nuclei to Apo A-I cDNA. The activation of the Apo A-I gene is regulated by the muscle cell coordinately with muscle-specific genes. In fact, treatment with TPA, a powerful inhibitor of differentiation, efficiently prevents myoblasts from producing Apo A-I mRNA, as well as muscle actin mRNA, and causes myotubes to quickly cease Apo A-I mRNA synthesis. The existence of a strict relationship between Apo A-I mRNA concentration and myogenic cell differentiation was also confirmed by experiments with quail myoblasts transformed with a temperature-sensitive mutant of the Rous Sarcoma Virus. Cells raised at the permissive temperature (undifferentiated phenotype) do not contain Apo A-I as well as alpha-actin mRNAs, while shifting to the nonpermissive temperature (differentiated phenotype) causes a rapid increase in Apo A-I and alpha-actin mRNA concentration.

Actins↗
PubMed1990

Overexpression of the MPO gene occurring in a case of APL without unusual genotypic characteristics.

Northern blot analysis of four typical cases of acute promyelocytic leukemia showed that one of the cell population examined was characterized by a very high level of expression of the myeloperoxidase (MPO) gene. Western blot analysis confirms that the protein content of the cells corresponded to the levels of the MPO mRNA. Southern blot studies of the DNA of this cell population ruled out the presence of any genome amplification or rearrangement. Chromosome hybridization studies in situ confirmed that the MPO gene was translocated on the long arm of chromosome 15. The observation that a typical genomic pattern may or may not be associated with the MPO overexpression leads us to believe that so far it is impossible to reach any conclusion about the significance of the translocation in the genesis of MPO overexpression.

Blotting, Southern↗
PubMed1990

Cloning of the mitogen-activated S6 kinase from rat liver reveals an enzyme of the second messenger subfamily.

Recently we reported the purification of a mitogen-activated S6 kinase from Swiss mouse 3T3 fibroblasts and rat liver. The rat liver protein was cleaved with cyanogen bromide or trypsin and 17 of the resulting peptides were sequenced. DNA primers were generated from 3 peptides that had homology to sequences of the conserved catalytic domain of protein kinases. These primers were used in the polymerase chain reaction to obtain a 0.4-kilobase DNA fragment. This fragment was either radioactively labeled and hybridized to Northern blots of poly(A)+ mRNA or used to screen a rat liver cDNA library. Northern blot analysis revealed four transcripts of 2.5, 3.2, 4.0, and 6.0 kilobases, and five S6 kinase clones were obtained by screening the library. Only two of the clones, which were identical, encoded a full-length protein. This protein had a molecular weight of 56,160, which correlated closely to that of the dephosphorylated kinase determined by SDS/PAGE. The catalytic domain of the kinase resembles that of other serine/threonine kinases belonging to the second messenger subfamily of protein kinases.

Amino Acid Sequence↗
PubMed1990

The importance of dose-intensity in neoadjuvant chemotherapy of osteosarcoma: a retrospective analysis of high-dose methotrexate, cisplatinum and adriamycin used preoperatively.

The relationship between dose-intensity and outcome was retrospectively analyzed in 125 patients with osteosarcoma of the extremities treated at our institution with neoadjuvant chemotherapy between 1986 and 1988. Before surgery, chemotherapy was performed with high-dose methotrexate (HDMTX) i.v. followed by cisplatinum (CDP) i.a. and adriamycin (ADM) i.v. Postoperative chemotherapy was tailored according to the necrosis induced by preoperative treatment. Patients who were "good responders" had 31-weeks of chemotherapy with the same drugs utilized preoperatively, while "poor responder" patients received a longer treatment (40 weeks) in which ifosfamide and etoposide (VP-16) were added to HDMTX, CDP and ADM. At a median follow-up of 2 years (1-3 years) 100 patients (80%) remained continuously disease-free and 25 patients relapsed: 24 with lung metastases and 1 with local recurrence. According to the real dose-intensity received, calculated as a percentage of the dose intensity projected by the protocol, the continuously disease-free survival was 87% in the 82 patients who received 80% or more of the scheduled dose-intensity and only 65% for the 43 patients who received less than 80% of the projected dose-intensity. This difference is highly significant (P less than 0.01). These results suggest that in neoadjuvant chemotherapy of osteosarcoma the real dose-intensity delivered is a determinant of treatment outcome and therefore every effort should be made to avoid reductions of doses and delays of cycles of chemotherapy in these patients.

Adolescent↗
PubMed1990

Cell membrane lipid composition in CAPD patients.

We analyzed the erythrocyte membrane lipid composition in 11 non-diabetic CAPD patients on treatment for 3-78 months and in a control group of 12 subjects. The mean total values of both saturated fatty acids and unsaturated fatty acids were not statistically different in CAPD patients and in controls but the composition of fatty acids of in cell membranes was altered. In fact, CAPD patients had a higher percentage of monounsaturated fatty acids and a lower percentage of polyunsaturated fatty acids than controls. This increase MUFA/PUFA ratio might reflect either a preferential cell membrane uptake of MUFA or a relative PUFA deficiency due to an increased lipid peroxidation.

Aged↗
PubMed1990

Modification of serum and membrane lipid composition induced by diet in patients with chronic renal failure.

Disorders of lipid metabolism during chronic renal failure (CRF) play a crucial role in the pathogenesis of early cardiovascular complication of this syndrome. In addition, some experimental evidence suggests that hyperlipidemia may accelerate progression of renal disease. We have studied 65 patients with CRF (S-creatinine 1.5-9.0 mg/dl), 52.3% of whom were hypertensive. Patients were divided in 2 groups matched for age, sex and degree of renal failure: group 1 was kept for 36 +/- 8 months on a free diet; group 2 was kept for 39 +/- 6 months on a low-protein diet with an elevated polyunsaturated/saturated fatty acid (PUFA/SFA) ratio. We found significantly higher levels of triglycerides (TG) and lower levels of esterified cholesterol in high density lipoprotein (HDL-C) in group 1 than in group 2. Patients on the diet had a lower percentage of membrane SFA and a higher percentage of PUFA than patients on free diet. Only in group 1 a direct correlation between cholesterol/phospholipid (Chol/P) ratio and age was observed; in group 2, a negative correlation between levels of PUFA and TG and between linoleic/oleic (Lin/Ol) ratio and serum Chol was shown. S-creatinine levels were directly correlated with Chol/P ratio in group 1 and indirectly with Lin/Ol ratio and PUFA in group 2. These data show that a low-protein diet, containing an elevated PUFA/SFA ratio, is able to counteract lipid abnormalities in patients with CRF and the normalization of this pattern is associated with significant improvement of membrane lipid composition and, presumably, of "functional" activity of cell membranes with a better control of supposed "renal lipoprotein toxicity".

Adult↗