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Biomedical subjects

A Lamberti

Publications and source records attributed to A Lamberti.

At least 19 recordsLinked to original sources
PubMed2004

The translation elongation factor 1A in tumorigenesis, signal transduction and apoptosis: review article.

An increasing number of evidences suggest the involvement of the eukaryotic elongation factor 1A, a core component of the protein synthesis machinery, at the onset of cell transformation. In fact, eEF1A is shown to be up-regulated in cell death; moreover, it seems to be involved in the regulation of ubiquitin-mediated protein degradation. In addition, eEF1A undergoes several post-translational modifications, mainly phosphorylation and methylation, that generally influence the activity of the protein. This article summarizes the present knowledges on the several extra-translational roles of eEF1A also in order to understand as the protein synthesis regulatory mechanisms could offer tools for cancer intervention.

Animals↗
PubMed2003

Prenatal ultrasound diagnosis of Nager syndrome.

Nager syndrome, or acrofacial dysostosis, is a rare malformation complex characterized by facial anomalies (external ear abnormalities and micrognathia) and limb defects (radial hypoplasia and absence of the thumb and/or other digits). Since its first description in 1948, more than 80 cases have been reported in the pediatric literature. However, there is only one previous report on the prenatal recognition of the syndrome, which was at 30 weeks of gestation. We report here a further case of Nager syndrome, prospectively diagnosed at 23 weeks of gestation.

Abortion, Induced↗
PubMed2001

The Rhizobium etli argC gene is essential for Arginine biosynthesis and nodulation of Phaseolus vulgaris.

A Tn5-induced mutant strain (CTNUX5) of Rhizobium etli unable to grow with ammonium as the sole nitrogen source was isolated and characterized. Sequence analysis showed that Tn5 is inserted into an argC-homologous gene. Unlike its wild-type parent (strain CE3), the mutant strain CTNUX5 had an absolute dependency on arginine to grow. The argC gene was cloned from the wild-type strain CE3, and the resulting plasmid, pAR207, after transformation was shown to relieve the arginine auxotrophy of strain CTNUX5. Unlike strain CE3 or CTNUX5-pAR207, strain CTNUX5 showed undetectable levels of N-acetyl-gamma-glutamylphosphate reductase activity. Unless arginine was added to the growth medium, strain CTNUX5 was unable to produce flavonoid-inducible lipo-chitin oligosaccharides (nodulation factors) and to induce nodules or nodulelike structures on the roots of Phaseolus vulgaris.

Aldehyde Oxidoreductases↗
PubMed2001

The Rhizobium GstI protein reduces the NH4+ assimilation capacity of Rhizobium leguminosarum.

We show that the protein encoded by the glutamine synthetase translational inhibitor (gstI) gene reduces the NH4+ assimilation capacity of Rhizobium leguminosarum. In this organism, gstI expression is regulated by the ntr system, including the PII protein, as a function of the nitrogen (N) status of the cells. The GstI protein, when expressed from an inducible promoter, inhibits glutamine synthetase II (glnII) expression under all N conditions tested. The induction of gstI affects the growth of a glutamine synthetase I (glnA-) strain and a single amino acid substitution (W48D) results in the complete loss of GstI function. During symbiosis, gstI is expressed in young differentiating symbiosomes (SBs) but not in differentiated N2-fixing SBs. In young SBs, the PII protein modulates the transcription of NtrC-regulated genes such as gstI and glnII. The evidence presented herein strengthens the idea that the endocytosis of bacteria inside the cytoplasm of the host cells is a key step in the regulation of NH4+ metabolism.

Bacterial Proteins↗
PubMed2000

Increased expression of CD40 ligand in activated CD4+ T lymphocytes of systemic sclerosis patients.

CD40-CD154 interactions play a key role in regulating immune response and are involved in the development of some autoimmune diseases. We analysed the expression of CD154 antigen in CD3-activated PBMC from 10 systemic sclerosis (SSc) patients and 10 control subjects by immunofluorescence. PBMC from SSc patients showed an increased expression of this molecule, since, 6 h following CD3 stimulation, the percentage of CD154(+)cells was of 17. 53+/-2.0 (mean+/-SE) in control and 25.33+/-2.93 in patient cells (P< 0.03). The higher expression of CD154 antigen was ascribible to CD4(+)cells. The enhanced induction of CD154 following CD3 stimulation depended on protein synthesis, since was abolished when the cells were stimulated via CD3 in the presence of cycloheximide. By analysing the expression of the CD40-induced antigen CD80, we verified that a blocking anti-CD40 antibody inhibited CD80 appearance in SSc activated monocytes, indicating that CD154 molecule was functional. These results show an enhanced expression of a functional CD154 molecule in SSc CD4(+)activated T lymphocytes.

Adult↗
PubMed2000

Early detection of Leishmania promastigotes in dog bone marrow cultures by acridine orange stain.

An acridine orange staining technique was evaluated in comparison with other well-known methods for the laboratory diagnosis of leishmaniasis. A higher number of promastigotes was found in Novy-MacNeal-Nicolle (NNN) cultures inoculated with canine bone marrow, when culture samples were stained with acridine orange vital stain, compared with those detected using either Giemsa staining or unstained wet mount examination. Based on our data the acridine orange stain is a useful and timely technique in reflecting the true numbers of microorganisms present in a culture and also enhances the visualization of the parasites. The present results warrant further studies with human samples from suspected leishmaniasis patients.

Acridine Orange↗
PubMed2000

Enhancement of cytosine arabinoside-induced apoptosis in human myeloblastic leukemia cells by NF-kappa B/Rel- specific decoy oligodeoxynucleotides.

The activity of NF-kappa B/Rel nuclear factors is known to inhibit apoptosis in various cell types. We investigated whether the subtraction of NF-kappa B/Rel activity influenced the response of 11 AML (M1, M2 and M4) patients' cells to AraC. To this end we used a phosphorothioate double-stranded decoy oligodeoxynucleotide (ODN) carrying the NF-kappa B/Rel- consensus sequence. Cell incubation with this ODN, but not its mutated (scrambled) form used as a control, resulted in abating the NF-kappa B/Rel nuclear levels in these cells, as verified by electrophoretic mobility shift assay (EMSA) of cells' nuclear extracts. We incubated the leukemic cells with AraC (32 or 1 microM), in either the absence or presence of the decoy or the scrambled ODN, and analyzed cell apoptosis. The spontaneous cell apoptosis detectable in the absence of AraC (<25%) was not modulated by the oligonucleotide presence in cell cultures. On the other hand, in 10 of the 11 samples tested, the decoy kappa B, but not the scrambled ODN significantly (P < 0.01 in a Student's t test) enhanced cell apoptotic response to AraC. Such an effect was particularly remarkable at low AraC doses (1 microM). These findings indicate that NF-kappa B/Rel activity influences response to AraC in human primary myeloblastic cells, and suggests that the inhibition of NF-kappa B/Rel factors can improve the effect of chemotherapy in AML. Gene Therapy (2000) 7, 1234-1237.

Antimetabolites, Antineoplastic↗
PubMed2000

Inhibition of glutamine synthetase II expression by the product of the gstI gene.

We report the identification of a previously unrecognized gene that is involved in the regulation of the Rhizobium leguminosarum glnII (glutamine synthetase II) gene. This gene, which is situated immediately upstream of glnII, was identified by means of a deletion/complementation analysis performed in the heterologous background of Klebsiella pneumoniae. It has been designated gstI (glutamine synthetase translational Inhibitor) because, when a complete version of gstI is present, it is possible to detect glnII-specific mRNA, but neither GSII activity nor GSII protein. The gstI gene encodes a small (63 amino acids) protein, which acts in cis or in trans with respect to glnII and is transcribed divergently with respect to glnII from a promoter that was found to be strongly repressed by the nitrogen transcriptional regulator NtrC. A mutated version of GstI lacking the last 14 amino acids completely lost its capacity to repress glnII expression. Our results indicate that gstI mediates the translation inhibition of glnII mRNA and, based on in silico analyses, a mechanism for GstI action is proposed.

Amino Acid Sequence↗
PubMed2000

Prenatal ultrasound diagnosis of congenital cystic adenomatoid malformation of the lung: a report of 26 cases and review of the literature.

OBJECTIVES: To evaluate the sonographic appearances and prenatal natural history of congenital cystic adenomatoid malformation of the lung. METHODS: In each case a detailed examination of the thoracic lesion and a complete fetal survey was performed. The pregnancies that elected to continue were followed to term. RESULTS: A total of 26 cases were identified. The pregnancy was electively terminated in nine cases (35%). All the remaining 17 pregnancies ended in liveborn infants (100%). The lesion disappeared completely in three fetuses (18%). Of the 14 infants in whom the lesion was confirmed at birth nine required surgery in the neonatal or post-natal period. Five children did not undergo surgery. CONCLUSIONS: Conservative management appears to be an adequate medical practice in cases of isolated congenital unilateral cystic adenomatoid malformation of the lung, in the absence of hydrops and/or acute polyhydramnios.

Adult↗
PubMed2000

Characterization and natural history of ventricular septal defects in the fetus.

OBJECTIVE: To characterize and describe the evolution of ventricular septal defects (VSD) from intra-uterine diagnosis to infancy in a population of fetuses with isolated defects. METHODS: Sixty-eight fetuses with isolated VSD represented the study population. Of these, 28 underwent termination of pregnancy, 14 died in utero or after birth and 26 reached 1 year of age. In this population, the following variables were evaluated: presence of extracardiac or chromosomal anomalies, site and size of the defect, pregnancy outcome. These variables were assessed against closure of the VSD up to 1 year of age. Necropsies were available for all fetuses following termination of pregnancy. All surviving neonates were followed up directly or by telephone until documented echocardiographic closure of the defect or until 1 year of age. RESULTS: There was a significant correlation between type of VSD and type of aneuploidy (P < 0.001). A total of 26 surviving fetuses reached 1 year of age: 46.1% (n = 12) of all defects closed in utero, 23.1% (n = 6) closed during the first year of life and 30.8% (n = 8) remained patent. Only three (15.8%) of the 19 VSDs < 3 mm remained patent in comparison with five (71.4%) of the seven defects > 3 mm (P < 0.05). None of the malalignment VSDs closed, in comparison to 69% of the peri-membranous and 60% of the muscular defects. CONCLUSION: Ventricular septal defect can undergo spontaneous closure during intra-uterine life and this process depends upon the site and the size of the defect. These data may provide useful additional information to aid prenatal counseling.

Adult↗
PubMed2000

Tissue Doppler imaging of the fetal heart.

OBJECTIVES: The objectives of this study were: (i) to assess the feasibility of a tissue Doppler imaging (TDI) evaluation in the fetus, (ii) to identify color-TDI patterns consistent with the various phases of the cardiac cycle; and (iii) to assess myocardial velocities and the myocardial velocity gradient. METHODS: Eighty-nine normal fetuses between the 17th and the 37th week of gestation were studied. Color-TDI was superimposed on an apical four-chamber view of the fetal heart and three cardiac cycles captured in cine-loop format. By reviewing the cine-loop strip, color patterns consistent with the various phases of the cardiac cycle were identified. The procedure was then repeated with a transverse four-chamber view. On each frame corresponding to mid-systole, early and late diastole, myocardial velocities were calculated at the subepicardial and subendocardial layer and regressed against gestational age. Statistics included correlation and regression analysis, calculation of the 95% confidence intervals and of the Cronbach's alpha reliability coefficient for repeated observations. RESULTS: TDI examination is acceptably reproducible in the fetus. We were able to identify color-TDI patterns depicting the systolic contraction wave, ventricular relaxation and atrial contraction. Statistical evaluation demonstrated that: all variables (systolic right and left subendocardial and subepicardial velocities, early diastolic right and left subendocardial and subepicardial velocities, end diastolic right and left subendocardial velocities, right subepicardial velocities) except end-diastolic right and left subepicardial velocities, showed a positive correlation with advancing gestational age; subendocardial velocities were higher than subepicardial ones throughout the cardiac cycle in both ventricles; systolic myocardial velocities were higher in the left ventricle whereas early diastolic velocities were higher in the right ventricle; and the ratio between early and late diastolic subendocardial velocities (EM/AM) was constantly < 1 and did not change with advancing gestational age. CONCLUSIONS: TDI evaluation of the fetal heart is feasible and reproducible. Color-TDI is able to identify the various phases of the cardiac cycle. Quantitative evaluation of myocardial velocities has shown also in the fetus the existence of the myocardial velocity gradient found in postnatal life.

Blood Flow Velocity↗
PubMed2000

Coeliac disease and unfavourable outcome of pregnancy.

BACKGROUND: Up to 50% of women with untreated coeliac disease experience miscarriage or an unfavourable outcome of pregnancy. In most cases, after 6-12 months of a gluten free diet, no excess of unfavourable outcome of pregnancy is observed. The prevalence of undiagnosed coeliac disease among pregnant women is not known. AIM: To determine the prevalence of untreated coeliac disease among women attending the obstetrics-gynaecological department. METHODS: Endomysial antibodies, which are specific and sensitive for coeliac disease, were evaluated in all women attending the obstetrics-gynaecology department of a large city hospital over a 90 day period. RESULTS: Of 845 pregnant women screened, 12 were identified as having coeliac disease. Three had previously been diagnosed but were not following a gluten free diet. The remaining nine underwent a small intestinal biopsy, which confirmed the diagnosis. The outcome of pregnancy was unfavourable in seven of these 12 women. Six healthy babies were born with no problems after the women had been on a gluten free diet for one year. CONCLUSIONS: Overall, 1 in 70 women was affected by coeliac disease, either not diagnosed (nine cases) or not treated (three cases). Their history of miscarriages, anaemia, low birth weight babies, and unfavourable outcome of pregnancy suggests that testing for coeliac disease should be included in the battery of tests prescribed for pregnant women. Coeliac disease is considerably more common than most of the diseases for which pregnant women are routinely screened. Unfavourable events associated with coeliac disease may be prevented by a gluten free diet.

Abortion, Spontaneous↗
PubMed2000

Randomized trial comparing cisplatin, gemcitabine, and vinorelbine with either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non-small-cell lung cancer: interim analysis of a phase III trial of the Southern Italy Cooperative Oncology Group.

PURPOSE: In our previous phase II study, the cisplatin, gemcitabine, and vinorelbine (PGV) regimen produced a median survival time (MST) of approximately 1 year in advanced non-small-cell lung cancer (NSCLC) patients. The present study was aimed at comparing the MST of patients treated with this triplet regimen with the MSTs of patients receiving cisplatin and vinorelbine (PV) or cisplatin and gemcitabine (PG). PATIENTS AND METHODS: From April 1997, patients with locally advanced or metastatic NSCLC, an age of < or = 70 years, and an Eastern Cooperative Oncology Group performance status < or = 1 were randomized to receive one of the following regimens: cisplatin 50 mg/m(2), gemcitabine 1,000 mg/m(2), and vinorelbine 25 mg/m(2) on days 1 and 8 every 3 weeks (arm A); cisplatin 100 mg/m(2) on day 1 and gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 every 4 weeks (arm B); or cisplatin 120 mg/m(2) on days 1 and 29 and vinorelbine 30 mg/m(2)/wk (arm C). According to the two-stage design for phase III trials, an interim analysis was planned when the first 60 patients per arm were assessable for survival. RESULTS: The survival data of 180 NSCLC patients (stage IIIB, 76 patients; stage IV, 104 patients) were analyzed in April 1999. Overall, 128 patients had died (PGV, n = 33; PG, n = 42; and PV, n = 53). The MST of patients in the PGV, PG, and PV arms was 51, 42, and 35 weeks, respectively, and the corresponding 1-year projected survival rates were 45%, 40%, and 34%, respectively. When only patients with stage IV disease were considered, an even stronger difference was seen between PGV (MST = 47 weeks) and both PG (34 weeks) and PV (27 weeks). At multivariate Cox analysis, the estimate hazard of death for patients receiving PGV compared with those receiving PV was 0.35 (95% confidence interval, 0.16 to 0.77; P <.01). The response rates were 47% in the PGV arm, 30% in the PG arm, 25% in the PV arm. Both hematologic and nonhematologic toxicities were not substantially worse in patients who received the PGV regimen. CONCLUSION: The PGV regimen is associated with a substantial survival gain (MST > 3 months longer) when compared with the PV combination. Because this difference in survival met one of the early stopping rules, the accrual in the PV arm has been stopped (null hypothesis rejected). Enrollment still continues in the PGV and PG arm to ascertain whether the PGV regimen can also produce a significantly longer survival than that obtained with the PG regimen.

Adult↗
PubMed2000

CD40 and B chronic lymphocytic leukemia cell response to fludarabine: the influence of NF-kappaB/Rel transcription factors on chemotherapy-induced apoptosis.

The levels of tumour necrosis factor receptor (TNF-R) superfamily members can be altered in lymphoid leukemias, indicating a possible role of such molecules in the biology of these neoplasias. In B chronic lymphocytic leukemia cells, the CD40/CD40L system has been shown to be effective in inhibiting the apoptotic response to fludarabine. The modulation of apoptosis relied on the CD40-induced activity of NF-kappaB/Rel transcription factors. The anti-apoptotic effect of CD40 was abolished using a phosphorothioate kappaB decoy oligodeoxynucleotide. These findings illustrate an example of the biological activity of TNF-R-like molecules in leukemias. They also show the influence of NF-kappaB/Rel activity on leukemic cell response to apoptogenic agents.

Antineoplastic Agents↗
PubMed2000

Interim analysis of a phase III trial comparing cisplatin, gemcitabine, and vinorelbine vs. either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non small-cell lung cancer. A Southern Italy Cooperative Oncology Group Study.

In a previous phase II randomized study, a cisplatin/gemcitabine/vinorelbine (PGV) regimen produced a 50-week median survival time (MST) in advanced non small-cell lung cancer (NSCLC) patients. The present trial was planned to randomly compare the outcome of patients treated with this new triplet regimen with those of patients receiving either cisplatin plus vinorelbine (PV) or cisplatin plus gemcitabine (PG) doublet combinations. One hundred eighty patients with stage IIIB (76) or IV (104) disease, aged <or= 70 years, and with Eastern Cooperative Oncology Group performance status (ECOG PS) <or= 1, were randomly allocated to receive: cisplatin, 50 mg/m2 plus gemcitabine, 1000 mg/m2 plus vinorelbine, 25 mg/m2 (PGV) on days 1 and 8 every 3 weeks; cisplatin, 100 mg/m2 on day 1 plus gemcitabine, 1000 mg/m2 (PG) on days 1, 8, and 15 every 4 weeks; cisplatin, 120 mg/m2 on days 1 and 29 plus vinorelbine, 30 mg/m2/week (PV). At the planned interim analysis, the MST of patients in the PGV, PG, and PV arms was 51, 42, and 35 weeks, respectively. The hazard of death (Cox analysis) for patients receiving PGV compared with those receiving PV was 0.35 (95% confidence index [CI], 0.16-0.77, P = 0.0058). The response rate was 47% in the PGV arm, 30% in the PG arm, and 25% in the PV arm. Severe neutropenia (75% vs. 45%), and vomiting (50% vs. 15%) significantly affected more patients in the PV than in the PGV arm. Since the difference in survival met early stopping rules, accrual to the PV arm was suspended. Enrollment still continues in the PGV and PG arms to ascertain whether the triplet regimen has a more significant effect on survival than that produced with the PG regimen.

Clinical Trial↗
PubMed1999

Amifostine inhibits hematopoietic progenitor cell apoptosis by activating NF-kappaB/Rel transcription factors.

We investigated the involvement of NF-kappaB/Rel transcription factors that reportedly can inhibit apoptosis in various cell types in the antiapoptotic mechanism of the cytoprotectant amifostine. In the nontumorigenic murine myeloid progenitor 32D cells incubated with amifostine, we detected a reduction of the IkappaBalpha cytoplasmic levels by Western blotting and a raising of nuclear NF-kappaB/Rel complexes by electrophoretic mobility shift assay. Amifostine inhibited by more than 30% the growth factor deprivation-induced apoptosis, whereas its effect failed when we blocked the NF-kappaB/Rel activity with an NF-kappaB/Rel-binding phosphorothioate decoy oligodeoxynucleotide. In human cord blood CD34(+) cells, the NF-kappaB/Rel p65 subunit was detectable (using immunofluorescence analysis) mainly in the cytoplasm in the absence of amifostine, whereas its presence was appreciable in the nuclei of cells incubated with the cytoprotectant. In 4 CD34(+) samples incubated for 3 days in cytokine-deficient conditions, cell apoptosis was reduced by more than 30% in the presence of amifostine (or amifostine plus a control oligo); the effect of amifostine was abolished in cultures with the decoy oligo. These findings indicate that the inhibition of hematopoietic progenitor cell apoptosis by amifostine requires the induction of NF-kappaB/Rel factors and that the latter can therefore exert an antiapoptotic activity in the hematopoietic progenitor cell compartment. Furthermore, the identification of this specific mechanism underlying the survival-promoting activity of amifostine lends support to the possible use of this agent in apoptosis-related pathologies, such as myelodysplasias.

Amifostine↗