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N Ferrari

Publications and source records attributed to N Ferrari.

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Nucleosomal repeat length in active and inactive genes.

Nucleosomal repeat lengths of total chromatin, H4 histone and beta-DR genes have been measured in logarithmically growing HeLa cells. We have detected significant differences in nucleosomal spacing between inactive chromatin and chromatin regions actively engaged in transcription. These differences are also maintained in metaphase chromosomes at times when transcription ceases although a shortening in nucleosomal repeat length is observed in active and inactive chromatin. These observations support a model where DNA-core histone interactions are temporarily altered to allow selective remodelling of chromatin organization.

Chromatin↗

Nucleosomal structure as probed by H3 histone thiol reactivity. Conformation of H3 histone variants is differently affected by thiol group reagents.

Two H3 histone variants are found in equal amount in HeLa cells, and they have been characterized by two-dimensional gel electrophoresis followed by reaction with specific antibodies. These molecules are the only cysteine-containing histones, and they have been used as the target for thiol-specific reagents, in intact nuclei, isolated nucleosomes, histone complexes, and purified histones. Cysteine residues are available to N-ethylmaleimide only when histones are disassembled from the core particles. Upon reaction with these reagents, one of the H3 variants undergoes profound conformational changes, as revealed by an altered electrophoretic mobility.

Acetylation↗

Availability of hyperacetylated H4 histone in intact nucleosomes to specific antibodies.

Specific antibodies against the tetra-acetylated form of H4 histone have been elicited in the rabbit. They do not cross-react with the non-, mono-, and di-acetylated forms of the histone molecule but a slight cross-reactivity with the tri-acetylated form of H4 histone is observed. Our studies also show that hyperacetylated H4 histones are recognized by the antibodies in intact nucleosomes.

Acetylation↗

Effects of retinol on chromatin structure.

The effect of retinol is studied in 3T3 cultured cells. The vitamin induces a decreased rate of cell proliferation and an augmented sensitivity of chromatin to DNase I digestion. Biochemical analyses of chromosomal components establish that the rates of radioactive acetate uptake and turnover on histones are increased leaving unaltered the steady-state level of histone acetylation. The presence of retinol in the culture medium also causes the disappearance of a protein of Mr 20 000, which is co-extracted with the high-mobility-group proteins. The observed changes in chromatin structure and composition are reversible when retinol is removed from the culture medium.

Acetylation↗

Characterisation and use of an intragenic polymorphic marker for detection of carriers of haemophilia B (factor IX deficiency).

DNA from 33 healthy White subjects was analysed with a 2 X 5 kilobase subgenomic DNA probe derived from the gene for coagulation factor IX, containing the exon "d" region of that gene. Intragenic Taq I restriction-fragment length polymorphism was revealed, with allelic frequencies estimated at 0 X 65 and 0 X 35 (SE = 0 X 06), also detectable by a cDNA probe. The genomic DNA probe is technically superior to the cDNA probe and has been used in three families with haemophilia B (factor IX deficiency). The polymorphic marker segregates with the deleterious mutation, allowing the identification or exclusion of carriers. The allelic frequencies of the Taq I polymorphism are virtually ideal. Therefore, such a polymorphism should be helpful both in genetic counselling of approximately 40% of affected families and in prenatal diagnosis.

Alleles↗

Effects of vitamin E on liver DNA.

Vitamin E, both in the form of dl-alpha-tocopherol and dl-alpha-tocopheryl acetate, was capable of inducing an increased alkaline elution rate of liver DNA from rats treated i.p. with the vitamin. This activity was clearly both dose- and time-dependent. A statistically significant effect was observed at dosages (1.25-5.00 mg/kg) that are in the range of biological activity of the vitamin in the rat (reabsorption-gestation bioassay). Moreover, the effect was observed at dosages that are clearly not toxic. An increased alkaline elution rate of DNA is usually interpreted as suggestive of DNA damage, however recent observations seem to indicate that functional modifications of chromatin packaging can also affect the elution rate of DNA.

Animals↗

Hospital malnutrition: incidence and prospective evaluation of general medical patients during hospitalization.

The incidence of malnutrition and the effect of hospitalization was evaluated in 100 consecutive admissions to the Clinical Pathology R Department of the University of Genoa. Nutritional deficiencies were evaluated at the time of admission and discharge from the Hospital, among patients hospitalized 2 weeks or longer, using the following nutrition-related parameters: body fat, muscle proteins, weigh, rate of weight loss plasma proteins level, vitamin B12 and folic acid plasma level, plasma iron and ferritin. We also considered the nutritional alterations in malnourished patients with relation to appetite decrease and to pathological status. At the admission to the hospital, the findings showed a high incidence (79%) of alterations in some nutritional parameters. In patients with nutritional impairments we observed a worsening of most of the nutritional parameters during hospitalization, especially in patients with severe appetite decrease and those affected by sepsis, neoplastic, gastric and renal diseases.

Anthropometry↗

[Clinical study of a prepared reducing diet: adequacy of the vitamin-mineral contribution in comparison to the nutritional and immunity status].

The Authors studied the effectiveness and safety of a commercial hypocaloric diet on 11 obese postmenopausal women. During the experimental period 1 meal/day has been replaced with a chemically defined low calories product. Different parameters have been evaluated to assess the nutritional status 1), anthropometric: weight, skinfold thickness, arm muscle circumference; 2) biochemical total plasma proteins, transferrin, vitamins A, E, C, B12, folic acid; plasma iron, hemoglobin, MCV, RBC; 3) immune status (T lymphocytes and immunoglobulins). Moreover blood sugar, cholesterol and triglyceride levels, as well as blood pressure have been taken into account. All the possible side effects and the diet acceptance for all the patients have been scored. After 1 month all the abnormal conditions (weight, cholesterol, blood pressure) improved, while the nutritional status and immune response remained at an optimal level.

Aged↗

Effect of retinol on macromolecular synthesis in cultured cell lines.

The effects of retinol on SK Mel 28 and HeLa cell lines were studied with regard to DNA and protein synthesis. It was found that vitamin A added to the culture media at a 50 microM concentration causes a 60% inhibition of DNA synthesis, that the inhibition is reversible and that this treatment does not select retinol-resistant clones. The synthesis of cytoplasmic, acid-soluble nuclear proteins and that of non-histone chromosomal proteins is inhibited as soon as the vitamin reaches the cell.

DNA Replication↗

Short-term antibiotic prophylaxis of mixed infections during hysterectomy.

Surgical procedures on contaminated tissues, such as hysterectomy with opened vagina, are frequently followed by local or systemic infections. It seems that a prolonged antibiotic prophylaxis is not justified because of possible induction of resistant mutants or dysmicrobisms. The administration of antibiotics only in a short pre- and postsurgical period appears to be more rational. We have carried out a controlled clinical trial with the aim of evaluating the efficacy of this prophylactic practice. One hundred forty-five patients submitted to vaginal and two hundred seventy-five to abdominal hysterectomy entered this study (started September 1977). All patients received local nitrofurantoin treatment and were then subdivided into four randomized groups: control group, groups treated with thiamphenicol, cephazolin, thiamphenicol plus cephazolin, respectively. Each antibiotic was administered in the dose of 1 gm one hour before and five and 12 hours after surgery. Antibiotics were chosen taking into consideration the usual vaginal microbial flora, notoriously mixed (aerobic and anaerobic). The three treated groups presented a significant decrease in the incidence and severity of infectious complications. The use of antibiotics in the postoperative period resulted in significantly reduced morbidity in the treated groups. Thiamphenicol appears to be the most effective drug. Bacteriological studies showed that local treatment of the vagina decreased the bacteria charge, but never brought about sterilization.

Adult↗

Antiangiogenic activity of chemopreventive drugs.

Tumors growing within the host form dynamic aberrant tissue that consists of host components, including the stroma, an expanding vasculature and often chronic inflammation, in addition to the tumor cells themselves. These host components can contribute to, rather than limit, tumor expansion, whereas deprivation of vessel formation has the potential to confine tumors in small, clinically silent foci. Therapeutic inhibition of vessel formation could be best suited to preventive strategies aimed at the suppression of angiogenesis in primary tumors in subjects at risk, or of micrometastases after surgical removal of a primary tumor. Our analysis of potential cancer chemopreventive molecules including N-acetylcysteine, green tea flavonoids and 4-hydroxyphenyl-retinamide has identified antiangiogenic activities that could account--at least in part--for the tumor prevention effects observed with these compounds. These drugs appear to target common mechanisms of tumor angiogenesis that may permit identification of critical targets for antiangiogenic therapy and antiangiogenic chemoprevention.

Acetylcysteine↗