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Biomedical subjects

G Russo

Publications and source records attributed to G Russo.

At least 163 records · Page 9Linked to original sources
PubMed1995

TCL1 oncogene activation in preleukemic T cells from a case of ataxia-telangiectasia.

The TCL1 oncogene on human chromosome 14q32.1 is involved in chromosome translocations [t(14;14)(q11;q32.1) and t(7;14)(q35;q32.1)] and inversions [inv14(q11;q32.1)] with TCR alpha/beta loci in T-cell leukemias, such as T-prolymphocytic (T-PLL). It is also involved in T-acute and -chronic leukemias arising in cases of ataxia-telangiectasia (AT), an immunodeficiency syndrome. Similar chromosomal rearrangements occur also in the clonally expanded T cells in AT patients before the appearance of the overt leukemia. We have analyzed the expression of TCL1 mRNA and protein in peripheral blood lymphocytes (PBLs) from four AT cases and from healthy controls. We found that the TCL1 gene was overexpressed in the PBLs of an AT patient with a large clonal T-cell population exhibiting the t(14;14) translocation but not in the lymphocytes of the other cases. Fluorescence in situ hybridization of the TCL1 genomic locus to lymphocyte metaphases from the AT patient with the T-cell clonal expansion showed that the breakpoint of the t(14;14) translocation lies within the TCL1 locus and is accompanied by an inverted duplication of the distal part of chromosome 14. These data indicate that TCL1 is activated in preleukemic clonal cells as a consequence of chromosome translocation involving sequences from the TCR locus at 14q11. Deregulation of TCL1 is the first event in the initiation of malignancy in these types of leukemias and represents a potential tool for clinical evaluation.

Adolescent↗
PubMed1995

5'-Deoxy-5'-methylthioadenosine phosphorylase and p16INK4 deficiency in multiple tumor cell lines.

5'-Deoxy-5'methylthioadenosine phosphorylase (MTA-Pase) gene is localized at the 9p21 region linked to the recently identified putative tumor suppressor gene, p16INK4, which appears implicated in the control of cell division cycle. The phosphorylase is a housekeeping enzyme involved in the purine and amino acid metabolism whose activity is evidentiable in all the normal tissues. Chromosomal deletions encompassing both MTAPase and p16INK4 genes cause the total absence of the enzymatic activity only in malignant cells, thus resulting in defined metabolic differences between malignant and normal cells. MTAPase deficiency was investigated by direct radiochemical assay method and by immunochemical techniques in 35 different human malignant cell lines established from several tumor types. The enzyme-deficient cells derived from breast, lung, ovary and liver cancer, malignant melanomas, malignant gliomas and liposarcomas. Two of the MTAPase-deficient cell preparations (from a liver carcinoma and from a melanoma) are primary cultures thus directly representing the original cancer genotypes. Several of the MTAPase-negative cells were studied for p16INK4 gene deletions and for p16INK4 protein deficiency. In all the examined samples a full correlation exists between the lack of MTAPase and that of p16INK4. A similar result was obtained analysing extracts of Vero cell line, which is a fibroblast MTAPase-negative cell line established from the kidney of a normal adult monkey. Conversely, Cos cells, which also are fibroblasts derived from monkey kidney, show both MTAPase and p16INK4 protein. These results: (i) demonstrate that the phosphorylase deficiency is distributed among almost all the most important human cancers; (ii) confirm and extend the tumor types were p16INK4 gene inactivation is observable and (iii) suggest that deletions at 9p21 (in humans) or at syntenic chromosomes (in other species) might represent a general mechanism of p16INK4 gene loss of function and possibly, in turn, of cancer development and/or progression.

Animals↗
PubMed1995

Isolation of A-type K+ current in hair cells of the frog crista ampullaris.

Different procedures to isolate the K+ A-type current (IA) from other membrane currents were tested on the complex inactivating outward K+ current generated in hair cells from the peripheral regions of the frog crista ampullaris. Experiments were performed in thin slices of epithelium using the whole-cell configuration of the patch-clamp technique. The conventional conditioning voltage protocol did not allow a satisfactory isolation of IA, due to the presence of other K+ currents showing overlapping steady-state inactivation properties. An attempt to block other K+ currents using calcium-free saline containing 50 mM TEA also failed to provide a satisfactory isolation of IA, due to contamination by a residual sustained current, probably consisting of a slow delayed outward K+ current (IK). Use of the selective A-channel blocker 4-aminopyridine (4-AP) at concentrations < 12 mM was also unsatisfactory because at these concentrations 4-AP produced a voltage-dependent blockade. Conversely, use of 4-AP at concentrations of 15-20 mM allowed a good separation of an uncontaminated IA. These results indicate that IA in hair cells of vestibular epithelium can be isolated most effectively by the 4-AP procedure, provided that sufficiently high concentrations of the A-channel blocker are used.

Animals↗
PubMed1995

Semiquantitative anti-HBc IgM detection in children with chronic hepatitis B: a long-term follow-up study.

Serum anti-HBc IgM titres were monitored monthly by a semiquantitative method in 14 children with HBeAg positive chronic hepatitis B followed up for 18-65 months. All patients, but one, were treated with alfa-interferon (IFN) at different times. On the whole, 12 flare-up episodes were observed and 7 patients cleared HBV-DNA and seroconverted to anti-HBe. Seroconversion occurred only in patients with pretreatment anti-HBc IgM index greater than 0.15 and serum HBV-DNA concentration below 100 pg/ml; the pretreatment alanine aminotransferase (ALT) value was not predictive of response. Combining anti-HBc IgM results and serum HBV-DNA levels observed during the pre-IFN period allowed a precise identification of patients who were likely to respond to IFN therapy. Patients who seroconverted to anti-HBe showed a progressive reduction in serum anti-HBc IgM titres within 6 months. Interestingly, one child, in whom HBV-DNA reappeared and who reconverted to HBeAg 7 months after treatment, showed no anti-HBc IgM decrease after the transient clearance of HBV-DNA and anti-HBe seroconversion. Semiquantitative anti-HBc IgM detection is a useful tool in the decision making process for children with chronic hepatitis B.

Adolescent↗
PubMed1995

Identification of O-sulphate substituents on D-glucuronic acid units in heparin-related glycosaminoglycans using novel synthetic disaccharide standards.

The two disaccharides, methyl 4-O-(2-O-sulpho-beta-D-glucopyranosyl-uronic acid)-2-deoxy-2-amino-alpha-D-glucopyranoside and methyl 4-O-(3-O-sulpho-beta-D-glucopyranosyluronic acid)-2-deoxy-2-amino-alpha-D-glucopyranoside, were prepared by de novo synthesis, and converted to the corresponding 2,5-anhydro-D-[1-3H]mannitol derivatives by deamination with nitrous acid followed by reduction with NaB3H4. The resultant labelled products were used as standards in the identification, by anion-exchange high-performance liquid chromatography (HPLC), of disaccharides generated by HNO2/NaB3H4 treatment of heparan sulphate isolated from human brain. The two standards, containing 2-O- and 3-O-sulphated glucuronic acid, respectively, were clearly separated by the HPLC procedure. Comparison with the deamination products derived from heparan sulphate showed that the mono-O-sulphated disaccharide species containing a sulphated glucuronic acid unit co-eluted with the 2-O-sulphated standard. The corresponding component isolated from other heparan sulphate preparations, or from heparin, also eluted at the same position. No disaccharide derived from heparin or heparan sulphate appeared at the elution position of the 3-O-sulphated standard. It is concluded that D-glucuronic acid units in heparin-related glycosaminoglycans may be sulphated at C2, whereas no evidence has been found for sulphation at C3. By contrast, analysis of mono-O-sulphated disaccharides derived from a chemically sulphated, bacterial capsular polysaccharide (generated by Escherichia coli K5) clearly demonstrated the occurrence of O-sulphate groups at C-3 of D-glucuronic acid units.

Carbohydrate Sequence↗
PubMed1995

Frequency, clinical and laboratory features of thyroiditis in girls with Turner's syndrome. The Italian Study Group for Turner's Syndrome.

A total of 478 patients, mean age 15.5 (3.6-25.3) years, suffering from Turner's syndrome, were studied in order to determine the frequency of autoimmune thyroiditis, which is defined as the presence of antithyroid antibodies (AT-Ab) and typical ultrasound findings. We found 106 (22.2%) patients positive for AT-Ab and of those 49 (10%) also had positive ultrasound findings, and were therefore considered to be affected by thyroiditis. This frequency is significantly higher (p < 0.001) than that seen in the normal population. Goitre was detected on clinical examination in only 16 (33%) and by ultrasound in 19 (39%) patients. Hormonal evaluation showed that 17 patients were euthyroid, 27 had compensated hypothyroidism, 2 were hypothyroid and 3 were in a hyperthyroid phase. Clinical signs or symptoms of hypothyroidism were absent in all hypothyroid patients. In patients with thyroiditis, neither a higher frequency of malformations and autoimmune diseases nor a correlation with karyotype, oestrogens or growth hormone therapy was found.

Adolescent↗
PubMed1995

The effect of mechanical ventilation on oxygen consumption in critically ill patients.

We measured oxygen consumption (VO2) during spontaneous breathing with continuous positive airway pressure (CPAP), assist control ventilation (AC), and control ventilation during muscle relaxation (AC-MR) in eight patients undergoing resuscitation from cardiopulmonary failure. VO2 decreased in all eight patients between CPAP and AC-MR; mean VO2 (255 +/- 92 ml/min) on CPAP exceeded that on AC-MR (209 +/- 79 ml/min) (p < 0.005). Compared with CPAP, AC without MR reduced VO2 in five of eight patients and mean VO2 (227 +/- 59 ml/min) tended to decrease (p = 0.14); clinical examination did not distinguish patients requiring MR to reduce VO2 further. If VO2 on CPAP approximates VO2 during spontaneous breathing, the difference between CPAP and AC-MR (VO2resp) represents the decrement of VO2 that can be obtained during muscle rest. Both VO2resp and the mechanical work performed by the ventilator on the respiratory system were increased to about five times the efficiencies reported for normal patients, but VO2resp did not correlate with the mechanical work because of a wide range of respiratory muscle efficiencies. These efficiencies are less than those reported in normal patients, which may reflect the effect of sepsis, acidemia, hypoxia, or other conditions in these patients. We conclude that mechanical ventilation with muscle relaxation reduces VO2 by more than 20%; beyond stabilizing pulmonary gas exchange, these interventions preserve limited O2 delivery (QO2) for other vital organs.

Adult↗
PubMed1994

Identification of the TCL1 gene involved in T-cell malignancies.

The TCL1 locus on chromosome 14q32.1 is frequently involved in chromosomal translocations and inversions with one of the T-cell receptor loci in human T-cell leukemias and lymphomas. The chromosome 14 region translocated or rearranged involves approximately 350 kb of DNA at chromosome band 14q32.1. Within this region we have identified a gene coding for a 1.3-kb transcript, expressed only in restricted subsets of cells within the lymphoid lineage and expressed at high levels in leukemic cells carrying a t(14;14)(q11;q32) chromosome translocation or a inv(14)(q11;q32) chromosome inversion. The cognate cDNA sequence reveals an open reading frame of 342 nt encoding a protein of 14 kDa. The TCL1 gene sequence, which, to our knowledge, shows no sequence homology with other human genes, is preferentially expressed early in T- and B-lymphocyte differentiation.

Amino Acid Sequence↗
PubMed1994

Characterization and localization of the TCL-1 oncogene product.

The TCL-1 gene maps at chromosome 14q32.1 and is activated in T cell leukemias and lymphomas by either chromosome translocations or inversions that juxtapose the TCL-1 gene to the alpha/delta or the beta locus of the T cell receptor. The open reading frame of the TCL-1 gene, coding for a protein of 114 amino acids, was expressed in bacteria and antisera were raised against it. The antibodies recognized the predicted TCL-1 M(r) 14,000 protein product in cells expressing TCL-1 mRNA. Cell fractionation experiments indicated that the TCL-1 protein is present in the microsomal fraction. These results were confirmed by confocal microscopy. The TCL-1 protein has considerable sequence similarities to the product of the MTCP-1 gene on chromosome Xq28, which is involved in T cell lympho-proliferative diseases. Thus, TCL-1 may represent a member of a novel family of genes involved in lymphoid proliferation and/or survival and in T cell malignancies.

Amino Acid Sequence↗
PubMed1994

Regulation of leukemia inhibitory factor synthesis in cultured human astrocytes.

We have examined the ability of human astrocytes to synthesize and secrete leukemia inhibitory factor (LIF), which is a multifunctional cytokine that controls cell proliferation and differentiation in many tissues, including the nervous system. Astrocyte-enriched cultures, prepared from 8- to 9-wk-old embryonic brains, expressed LIF mRNA and secreted LIF protein. LIF synthesis was significantly increased by the cytokines IL-1 beta, TNF-alpha, and TGF-beta 1, but not by IFN-gamma, IL-6, or LPS. No major differences in basal and cytokine-inducible LIF production were detected among astrocyte populations obtained from different brain areas. LIF synthesis was lower in serum-free than in serum-containing astrocyte cultures. A role for protein kinase C in the regulation of astrocyte LIF production was suggested by the findings that phorbol esters induced both LIF mRNA and protein and that the cytokine-induced LIF increase was partially antagonized by relatively selective inhibitors of protein kinase C such as H7 and staurosporine. Human leptomeningeal fibroblasts also expressed LIF gene and protein. Astrocytes produced LIF and responded to cytokines with increased LIF synthesis only after being subcultured, and not when grown in primary cultures in close contact with neurons. Our findings suggest that in vivo induction of astrocyte LIF secretion might occur in pathologic conditions as a consequence of both alterations of neuronal-glial interactions and a local increase in the level of inflammatory cytokines.

Astrocytes↗