Biomedical subjects

G Russo

Publications and source records attributed to G Russo.

At least 73 records · Page 4Linked to original sources

PubMed2000

Identification of the TCL6 genes within the breakpoint cluster region on chromosome 14q32 in T-cell leukemia.

A region on chromosome 14q32.1 is often involved in chromosomal translocations and inversions with one of the T-cell receptor loci in T-cell lymphoproliferative diseases. The breakpoints of the different rearrangements segregate into two clusters; a cluster due to inversion on the centromeric side and a cluster due to simple balanced translocations on the telomeric side. If the target gene activated by these different types of chromosomal rearrangements is the same, the gene must be localized between the two clusters of breakpoints in a region of around 160 kb. Within this breakpoint cluster region, we isolated two genes; namely, TCL1 and TML1/TCL1b genes. In the course of characterizing the TML1 gene, we further identified a third novel gene, which we named TCL6 (T-cell leukemia/lymphoma 6), from a region 7 kb upstream of the TML1 locus. The TCL6 gene expressed at least 11 isoforms through very complex alternative-splicing, including splicing with the TML1 gene. Those isoforms encode at least five open reading frames (ORFs) with no homology to known sequences. The localization of the proteins corresponding to these ORF was determined by fusing green fluorescence protein at the carboxyl terminal of each ORF. ORF141 and ORF72 were observed in the cytoplasmic region, while ORF105, ORF119, and ORF163 were predominantly localized in the nuclear region. Since the TCL6 gene was expressed in T-cell leukemia carrying a t(14;14)(q11;q32.1) chromosome translocation and was not expressed in normal T-cells (just like the TML1 and TCL1 genes), it is also a candidate gene potentially involved in leukemogenesis. Oncogene (2000).

Alternative Splicing↗

PubMed2000

Regulation of TCL1 expression in B- and T-cell lymphomas and reactive lymphoid tissues.

Chromosomal rearrangements observed in T-cell prolymphocytic leukemia involve the translocation of one T-cell receptor gene to either chromosome 14q32 or Xq28, deregulating the expression of cellular protooncogenes of unknown function, such as TCL1 or its homologue, MTCP1. In the human hematopoietic system, TCL1 expression is predominantly observed in developing B lymphocytes, whereas its overexpression in T cells causes mature T-cell proliferation in transgenic mice. In this study, using a newly generated monoclonal antibody against recombinant TCL1 protein, we extended our analysis mainly by immunohistochemistry and also by fluorescence-activated cell sorting and Western blot to a large tumor lymphoma data bank including 194 cases of lymphoproliferative disorders of B- and T-cell origin as well as reactive lymphoid tissues. The results obtained show that in reactive lymphoid tissues, TCL1 is strongly expressed by a subset of mantle zone B lymphocytes and is expressed to a lesser extent by follicle center cells and by scattered interfollicular small lymphocytes. In B-cell neoplasia, TCL1 was expressed in the majority of the cases, including lymphoblastic lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma, follicular lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma (60%), and primary cutaneous B cell lymphoma (55%). TCL1 expression was observed in both the cytoplasmic and nuclear compartments, as confirmed by Western blot analysis. Conversely, TCL1 was not expressed in Hodgkin/Reed-Sternberg cells, multiple myelomas, marginal zone B-cell lymphomas, CD30+ anaplastic large cell lymphoma, lymphoblastic T-cell lymphoma, peripheral T-cell lymphoma, and mycosis fungoides. These data indicate that TCL1 is expressed in more differentiated B cells, under both reactive and neoplastic conditions, from antigen committed B cells and in germinal center B cells and is down-regulated in the latest stage of B-cell differentiation.

Aged↗

PubMed2000

Tcl1 enhances Akt kinase activity and mediates its nuclear translocation.

The TCL1 oncogene at 14q32.1 is involved in the development of human mature T-cell leukemia. The mechanism of action of Tcl1 is unknown. Because the virus containing the v-akt oncogene causes T-cell lymphoma in mice and Akt is a key player in transduction of antiapoptotic and proliferative signals in T-cells, we investigated whether Akt and Tcl1 function in the same pathway. Coimmunoprecipitation experiments showed that endogenous Akt1 and Tcl1 physically interact in the T-cell leukemia cell line SupT11; both proteins also interact when cotransfected into 293 cells. Using several AKT1 constructs in cotransfection experiments, we determined that this interaction occurs through the pleckstrin homology domain of the Akt1 protein. We further demonstrated that, in 293 cells transfected with TCL1, the endogenous Akt1 bound to Tcl1 is 5-10 times more active compared with Akt1 not bound to Tcl1. The intracellular localization of Tcl1 and Akt1 in mouse fibroblasts was investigated by immunofluorescence. When transfected alone, Akt1 was found only in cytoplasm whereas Tcl1 was localized in the cytoplasm and in the nucleus. Interestingly, Akt1 was also found in the nucleus when AKT1 was cotransfected with TCL1, suggesting that Tcl1 promotes the transport of Akt1 to the nucleus. These findings were supported by the intracellular localization of Akt1 or Tcl1 when Tcl1 or Akt1, respectively, were confined to the specific cellular compartments. Thus, we demonstrate that Tcl1 is a cofactor of Akt1 that enhances Akt1 kinase activity and promotes its nuclear transport.

Animals↗

PubMed2000

Low frequency of alterations of the alpha (PPP2R1A) and beta (PPP2R1B) isoforms of the subunit A of the serine-threonine phosphatase 2A in human neoplasms.

The phosphatase 2A (PP2A) is one of the major cellular serine-threonine phosphatases. It was recently shown that the gene encoding for the beta isoform of its subunit A, PPP2R1B, is altered in human lung and colorectal carcinomas, suggesting a role in human tumorigenesis. Here, we report the detection of mutations in breast, lung carcinomas and melanomas in the genes of both alpha (PPP2R1A) and beta isoforms. Mutations affecting PPP2R1B were found in four breast carcinomas, while mutations in PPP2R1A were found in carcinomas of the breast and of the lung and in one melanoma. Most of the mutations affecting PPP2R1B were exons deletions, suggesting abnormal splicing. These splicing abnormalities were detected in tumor samples in the absence of the normal splicing product, and were not found in several normal controls. In one case, a homozygous deletion present in tumor DNA, and not in the matched normal control was demonstrated. Mutations affecting the PPP2R1A gene were nucleotide substitutions changing highly conserved amino acids and one frame-shift. Although the frequency of alterations is low, the inclusion of both isoforms of subunit A in the genes mutated in human cancer and the addition of breast cancer to the list of neoplasms in which PPP2R1B is altered, strengthen the potential role of PP2A in human tumorogenesis.

Amino Acid Substitution↗

PubMed2000

Cardiac syndrome X: an overview.

Not all patients with angina have myocardial ischemia. A sizable minority--up to 30% of angina patients studied at tertiary referral centers--have normal coronary angiograms. Such patients often undergo an expensive and extensive array of testing and treatment. Yet the prognosis is generally good, and symptomatic management may be effective.

Coronary Angiography↗

PubMed2000

Interferon beta-1a prevents the effects of lipopolysaccharide on embryonic brain microvessels.

By means of light and electron microscopy we have studied the effect of interferon beta-1a (IFNbeta-1a) in the optic tecta of 20-day-old chick embryos under normal conditions and after exposure to lipopolysaccharide (LPS) which mimics the blood-brain barrier (BBB) disruption in meningoencephalitis. Optic tecta were examined for: (i) ultrastructure by means of transmission electron microscopy; (ii) the immunohistochemical localization of HT7 antigen, a specific marker of differentiation of the brain microvessels; (iii) the brain microvessel permeability, by means of horseradish peroxidase (HRP) tracer; (iv) the expression of microvessel glycoconjugates, by means of lectin histochemistry, using Ricinus communis agglutinin-I (RCA-I), specific for beta-D-galactosyl moieties and Wheat Germ agglutinin (WGA) specific for sialyl and N-acetylglucosaminyl moieties. A morphometric evaluation of brain microvessel permeability and of glycoconjugate expression was also performed. In control- and in IFNbeta-1a-treated embryos, HRP was confined to the vessel lumina which were sealed by the interendothelial tight junctions. RCA-I binding sites were recognizable both in the basal membranes and in the tight junctions, while WGA sites were present on the luminal side of the endothelial cells. HRP was blocked in the vessels lumina by the interendothelial tight junctions. After LPS treatment, HRP showed an extravascular localization and the labeling of microvessels by anti-HT7 antibodies disappeared. RCA-I binding was only found ultrastructurally and appeared as irregularly clustered gold particles, in the cleft of damaged tight junctions, but were no longer detectable in the endothelial basement membranes. After pretreatment of LPS-treated embryos with IFNbeta-1a, the vessel permeability to HRP strongly decreased and the vessels showed the normal pattern of HT7 protein and of the RCA-I binding sites. These results indicate that the changes induced by LPS in the endothelial cells are prevented by IFNbeta-1a.

Animals↗

PubMed2000

Development of a new vaccine formulation that enhances the immunogenicity of tumor-associated antigen CaMBr1.

Aberrant glycosylation is one of the most constant traits of malignant cells. The CaMBr1 hexasaccharide antigen, originally defined on the human breast carcinoma cell line MCF7, is expressed on some normal tissues but overexpressed in a high percentage of human breast, ovary, prostate and lung carcinomas. CaMBr1 overexpression is associated with poor prognosis. The epitope consists of the tetrasaccharide Fuc(alpha1-2)Ga1(beta1-3)GalNAc(beta1-3)Ga1alpha-O-spacer, which has recently become available as a synthetic oligosaccharide. Here we report the CaMBr1 tetrasaccharide conjugation to two different carrier proteins (CRM197 and KLH) and the evaluation of conjugate immunogenicity in mice following their administration in various vaccine formulations with two adjuvants (MPL-SE and Detox-PC). Radioimmunoassay to determine the level and isotype of anti-tetrasaccharide antibodies in mouse sera, and cytofluorimetric analysis and 51Cr-release assay on human tumor cells, to evaluate specificity of binding and complement-dependent lysis respectively, identified CaMBr1-CRM197, in association with the MPL-SE adjuvant, as the best vaccine formulation. This combination induced (1) production of tetrasaccharide-specific antibodies, with negligible side-effects; (2) antibodies with complement-mediated cytotoxic activity on human CaMBr1-positive cells and (3) a high titer of IgG1 detected in sera obtained 3 months after the first injection, indicating that the anti-tetrasaccharide antibody response was mediated by T cell activation. The availability of CaMBr1-glycoconjugate in the minimal and functional antigenic structure and the identification of an efficacious vaccine formulation opens the way to exploring the activity of this glycoconjugate in a clinical setting.

ABO Blood-Group System↗

PubMed2000

Microvascular angina in patients with syndrome X.

Syndrome X (SX) is usually diagnosed in the presence of angina and normal coronary arteriograms. It is an heterogeneous syndrome which encompasses different pathogenic mechanisms. Whether myocardial ischaemia is responsible for the condition remains controversial. The term "microvascular angina" has been used to define the syndrome of chest pain and normal coronary arteries with heightened sensitivity of the coronary microcirculation to vasoconstrictor stimuli. It has been suggested that the abnormal vasodilator response of the coronary circulation in patients with SX is due to impaired endothelial function. Plasma levels of endothelin in patients with chest pain and normal coronary arteries were found to be significantly raised compared to normal controls. Endothelial dysfunction in SX is likely to be multifactorial and many cardiac risk factors, such as hypertension, hypercholesterolemia, oestrogen deficiency and smoking, can contribute to its development. As the majority of SX patients are women and most are post-menopausal, oestrogen deficiency has been proposed as a pathogenic factor. A large proportion of patients satisfying the stated criteria for SX have one or more coronary risk factors. Additional factors, such as abnormal pain perception, may contribute to the evolution of chest pain in patients with normal coronaries and endothelial dysfunction. Combined alteration of pain perception and microvascular dysfunction are likely to explain a proportion of all cases of SX. The treatment of this syndrome represents a major challenge for the cardiologist. Beta-blockers and calcium channel blockers are effective in controlling chest pain in SX patients. A very important therapeutic intervention in microvascular angina is the control of risk factors that can lead to endothelial dysfunction. Different approaches, including spinal cord stimulation and psychological treatment, have been proposed especially for those patients in whom a cardiac origin of pain is unlikely.

Antidepressive Agents, Tricyclic↗

PubMed2000

Quantitative assessment of cerebral vascular reserve by means of transcranial Doppler ultrasound and rebreathing maneuver: bedside test and mathematical modeling.

Cerebral vascular reserve was measured by means of the transcranial Doppler (TCD) technique from carbon dioxide (CO2) tests, in healthy individuals and patients with unilateral internal carotid artery (ICA) occlusion. The percentage changes in middle cerebral arteries blood flow velocity (VMCA) per mmHg of pCO2 variations (reactivity index, RI) were separately computed during hypocapnia and hypercapnia, the latter obtained by a rebreathing maneuver. Clinical data have been compared with predictions obtained using an original mathematical model of intracranial dynamics, in order to search a theoretical explanation of the hemodynamic events observed during clinical testing. This analysis has also been considered in order to support the choice between different CO2 tests for quantitative assessment of vascular reactivity. Clinical data and model simulations agree in showing that side-to-side reactivity differences (Irel) measured from hypercapnia test allow a good discrimination of patients with poor compensatory capacity. They suggest that an Irel significantly greater than 30% after hypercapnia test can be considered indicative of patients with poor compensatory capacity. These preliminary results encourage a long-term follow-up of cerebral vascular reserve by means of TCD during "rebreathing test", for selecting patients with poor vascular reserve that may benefit from brain revascularization.

Adolescent↗

PubMed2000

Distribution and antibiotic resistance of isolates from lower respiratory tract and blood cultures from patients in three Italian intensive care units: a 2-year comparison.

The distribution and antibiotic resistance of major pathogens isolated from patients in ICUs were studied by three Italian microbiological laboratories. Consecutive aerobic strains were collected over two different time periods from protected brushing bronchoscopy, broncho-alveolar lavage and blood cultures. A total of 420 strains were isolated during the first period (47.3% gram-negative and 52.7% gram-positive) and 412 over the second period (50.5% gram-negative and 49.5% gram-positive). Pseudomonas aeruginosa was the most frequently isolated organism from the respiratory tract followed by Staphylococcus aureus. Methicillin resistance was 47.9 and 44.5% in S. aureus and 63.0 and 65.1% in coagulase-negative staphylococci over the two periods. No glycopeptide-resistance was found in gram-positive organisms. Ceftazidime-resistance in Klebsiella pneumoniae was very high.

Anti-Bacterial Agents↗

PubMed2000

Opposite deletions/duplications of the X chromosome: two novel reciprocal rearrangements.

Paralogous sequences on the same chromosome allow refolding of the chromosome into itself and homologous recombination. Recombinant chromosomes have microscopic or submicroscopic rearrangements according to the distance between repeats. Examples are the submicroscopic inversions of factor VIII, of the IDS gene and of the FLN1/emerin region, all resulting from misalignment of inverted repeats, and double recombination. Most of these inversions are of paternal origin possibly because the X chromosome at male meiosis is free to refold into itself for most of its length. We report on two de novo rearrangements of the X chromosome found in four hypogonadic females. Two of them had an X chromosome deleted for most of Xp and duplicated for a portion of Xq and two had the opposite rearrangement (class I and class II rearrangements, respectively). The breakpoints were defined at the level of contiguous YACs. The same Xp 11.23 breakpoint was found in the four cases. That of the long arm coincided in three cases (Xq21.3) and was more proximal in case 4 (Xq21.1). Thus class I rearrangements (cases 1 and 2) are reciprocal to that of case 3, whilst that of case 4 shares only the Xp breakpoint. The abnormal X was paternal in the three cases investigated. Repeated inverted sequences located at the breakpoints of rearrangements are likely to favour the refolding of the paternal X chromosome and the recombination of the repeats. The repeat at the Xp11 may synapse with either that at Xq21.3 or that at Xq21.1. These rearrangements seem to originate as the Xq28 submicroscopic inversions but they are identifiable at the microscopic level and result from a single recombination event.

Adolescent↗

PubMed2000

Localisation of the gene responsible for fechtner syndrome in a region <600 Kb on 22q11-q13.

Fechtner syndrome is an autosomal dominant disorder which has been thought to be a variant of Alport syndrome. It is characterised by nephritis, sensorineural hearing loss and eye abnormalities, as well as by macrothrombocytopenia and polymorphonuclear inclusion bodies. Recently, the Fechtner syndrome has been mapped in a 5.5 Mb region on the long arm of chromosome 22 by linkage analysis in an extended Israeli family. We describe here the genetic refinement of the Fechtner critical interval to a region less than 600 Kb by linkage analysis performed in a large Italian pedigree. The presence of several recombination events allowed the disease gene to be localised between markers D22S278 and D22S426, in a region containing only two non-recombinant markers, D22S1173 and D22S283. This interval, spanning <600 Kb on genomic DNA, has been entirely sequenced and contains six known and three putative genes.

Abnormalities, Multiple↗

PubMed2000

Diphtheria in Latvia, 1986-1996.

After nearly two decades without a diphtheria case in Latvia, the disease reappeared in 1986. From 1990 to 1996, case counts were highest among adults 40-49 years of age, school-aged children, and adolescents. Nonetheless, the average annualized incidence of disease was highest among infants and preschoolers. In August 1995, mass vaccination efforts began to provide adults 25-60 years of age with at least one dose of vaccine. By the end of the year, a 77% coverage rate was achieved, resulting in a decrease of reported diphtheria cases by 1996. From February to September 1997, special outreach efforts were focused on hard-to-reach populations; as a result, by June 1997, 55% of adults had received three doses of vaccine. While decreases in the incidence of and morbidity from diphtheria have occurred, additional efforts still need to be concentrated on improving vaccination coverage in adults and children <2 years of age and in reducing mortality from diphtheria.

Adolescent↗

PubMed2000

Nonlinear dynamics optically induced in nematic liquid crystals

We report the analysis of the dynamical regimes induced in a homeotropically aligned nematic liquid-crystal layer when an s-polarized laser beam impinges at a small incident angle. These regimes are studied by analyzing the time series of the variation of the polarization state of a light probe beam, recorded at different light intensities. A detailed description of the dynamical regimes, based on the analysis of the wavelet transforms performed on the observed time series, is presented. We recognize a first Hopf bifurcation followed by a gluing bifurcation, and a further transition toward an irregular regime. Similarities between our experimental results and a scenario of transition to chaos via a sequence of gluing bifurcations have been discussed.

Journal Article↗

PubMed2000

Simple and safe method to prepare patients with prosthetic heart valves for surgical dental procedures.

Temporary discontinuation of high-intensity oral anticoagulant treatment is not recommended in patients undergoing dental surgery. This policy is not based on solid data from randomized clinical trials but on expert consensus. The alternative, i.e., to continue treatment and treat patients with tranexamic acid mouthwash, often is not applicable. A prospective cohort study was carried out to evaluate bleeding and thromboembolic complications in patients bearing prosthetic heart valves and registering International Normalized Ratio (INR) values between 2.0 and 4.5, who underwent dental procedures after a 2-day suspension of warfarin treatment. One hundred four consecutive patients receiving high-intensity anticoagulation underwent 123 dental procedures after 2 days' warfarin withdrawal. No major bleeding complications occurred in the week after the procedure; minor bleeding requiring local measures occurred in two patients. No thromboembolic events and no cases of bacterial endocarditis were recorded in the 3 months after the procedure. A mean decrease in INR by approximately 1.0 U (from 2.95+/-0,59 to 1.87+/-0,46) occurred after 2 days' warfarin suspension. Seven days after reinitiation of warfarin, INR values returned to the therapeutic range in 90% of cases. The calculated average time spent at INR less than 2.0 (critical value) was 28 hours. Two days' warfarin suspension is a simple and safe policy for patients with prosthetic heart valves undergoing dental surgery.

Adult↗

PubMed2000

Acquired chromosome 11q deletion involving the ataxia teleangiectasia locus in B-cell non-Hodgkin's lymphoma: correlation with clinicobiologic features.

PURPOSE: To study the clinicobiologic significance of acquired 11q deletions involving the ataxia teleangiectasia locus (ATM+/-) in B-cell non-Hodgkin's lymphomas (NHL). PATIENTS AND METHODS: Fifty-three indolent lymphomas and 82 aggressive lymphomas were studied by conventional cytogenetic analysis and by fluorescence in situ hybridization using an 11q22-23 probe recognizing ATM sequences. Pertinent clinical data were collected. RESULTS: A hemizygous ATM deletion was seen in 44% to 88% of the interphase cells in 15 cases (11.1%); four patients had an indolent lymphoma (follicular center cell lymphoma), and 11 patients had an aggressive lymphoma (five mantle-cell lymphomas [MCLs] and six diffuse large-cell lymphomas). Dual-color hybridization studies showed ATM deletion to be possibly a secondary aberration in three patients with MCL. Ten out of 15 ATM+/- patients had a complex karyotype, 11 out of 15 had more than 90% abnormal metaphases (AA karyotype status), and +12, 13q14 deletion, and 17p13 deletion were seen in seven, four, and five cases, respectively. Patients with ATM+/- more frequently had a complex karyotype (P =.01) and the AA karyotype (P =.04) compared with patients without ATM+/-. With the exception of a poor performance status (P =.001), no correlation was found between ATM+/-, initial clinical variables, and complete remission rate; whereas a highly significant association was found with shorter survival (P <.0001). This cytogenetic lesion maintained its prognostic importance in multivariate analysis (P =.0004), along with performance status (P =.0006), serum lactate dehydrogenase level (P =.03), splenomegaly (P =.01), and histologic grade (P =.03). When analyzing indolent lymphomas and aggressive lymphomas separately, ATM+/- maintained its prognostic importance as an independent variable in both histologic groups (P =.0001 and P =.016, respectively). CONCLUSION: Though possibly not representing a primary genetic lesion in the majority of cases, the acquired ATM+/- status has clinicobiologic importance in NHL, possibly representing a major cytogenetic determinant of outcome.

Ataxia Telangiectasia↗

PubMed2000

Precocious puberty and body composition: effects of GnRH analog treatment.

INTRODUCTION: Body composition changes with age and sex differences become significant only after puberty. Boys and girls before the age of 8 yr do not differ in fat, lean or bone mineral mass. Hormonal influences during pubertal development determine the physiological adult male and female body composition phenotype. AIM: The aim of our study was to evaluate body composition changes due to central precocious puberty (PP) and the specific effects of therapy on these modifications. SUBJECTS AND METHODS: Sixteen patients (14 girls, 2 boys) were included in the study. They were diagnosed as affected by idiopathic PP according to standard hormonal and clinical criteria; anatomic alterations of hypothalamus-hypophysis region were excluded by MRI. Mean age at diagnosis was 5.9 +/- 1.9 yr. All patients received GnRH analog (Leuprolide or Triptorelin) treatment subcutaneously every 4 weeks for at least 1 yr. Mean period of treatment was 3.4 +/- 1.9 yr. Standard anthropometry and body composition analysis were performed at baseline and every 6-12 months. A group of healthy subjects with normal timing of puberty was matched (for age or for pubertal stage) served as the control group (CA or CP, respectively). RESULTS: Patients with PP showed at baseline a significant increase of BMI and relative body weight; lean and fat compartments were also increased but not significantly. During treatment, the PP group showed increased fat mass compared to CA (p<0.05), while no difference was found between PP and CP. Lean mass was similar to CA but lower than in CP (p<0.05). During treatment a significant increase in lean mass (both as total as well as limb mass) was observed. After stopping treatment there was no difference between PP and CP, except for lower lean mass (p<0.04). CONCLUSION: When puberty occurs precociously, lean and fat mass are not significantly different from age-matched control subjects. Data collected during treatment confirm a shortening of prepubertal lean mass development and the block of further lean mass development due to puberty itself, while fat mass accumulation continues. The net result of these modifications determines a typical body composition pattern in PP patients, after the end of therapy: lean mass is reduced by a shortening of the prepubertal growing period and by the "menopausal effect" of treatment itself. Fat mass is increased as a consequence of therapy and could lead to future obesity.

Adipose Tissue↗

PubMed2000

[Malignant schwannoma of the small intestine: a report of 2 cases].

The authors report two cases of small bowel malignant schwannoma. It is an extremely rare disease and it is often difficult to diagnose malignancy. Histologic differentiation from other stromal tumors may require electron microscopy, although the preparation of immunohistochemical reactions now allows to identify forms which were previously diagnosed in different terms to be precisely classified. Diagnosis is often late and no preoperative test enables a correct clinical diagnosis to be made. The primary treatment is surgical and the resection is the only real therapy. Radiotherapy and chemotherapy are ineffective. Close postoperative observation is recommended because of the tendency to recurrence and metastasis.

Aged↗