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L Guerrini

Publications and source records attributed to L Guerrini.

27 records · Page 2Linked to original sources

Regulation of asparagine synthetase gene expression by amino acid starvation.

We have studied the regulation of expression of the asparagine synthetase (AS) gene in ts11 cells, a mutant of BHK hamster cells which encodes a temperature-sensitive AS and therefore does not produce endogenous asparagine at 39.5 degrees C. Incubation of ts11 cells at the nonpermissive temperature drastically increases the level of AS mRNA, and the stimulation of AS mRNA expression is effectively suppressed by the addition of asparagine to the medium. We show here that regulation of AS gene expression involves cis-acting elements which are contained in the mRNA as well as in the 5' genomic region. When a plasmid containing the human AS cDNA under the control of the human AS promoter region was stably transfected into ts11 cells, the expression of human AS RNAs was regulated as that of the endogenous hamster transcripts, indicating that this construct contained all cis elements necessary for regulation. Expression of the AS cDNA in ts11 cells under the control of a constitutive foreign promoter was also regulated by the concentration of asparagine, and this regulation required translation. When we introduced by mutagenesis a number of stop codons in the AS cDNA, the mutant mRNAs with short open reading frames were expressed at low levels that were not increased by asparagine deprivation. Inhibition of protein and RNA synthesis also prevented down-regulation of AS mRNA levels by high concentrations of asparagine. In a parallel series of experiments, we showed that an AS DNA fragment including the promoter and first exon can also regulate RNA expression in response to asparagine concentration. Furthermore, similar increases in the levels of AS RNAs are produced not only by asparagine deprivation in ts11 cells but also by deprivation of human and wild-type BHK cells of leucine, isoleucine, or glutamine. Thus, regulation of AS gene expression is a response to amino acid starvation through mechanisms which appear to involve both changes in RNA stability and change in the rates of transcription initiation or elongation.

Amino Acids↗

Do calcium channel blockers have any influence on the immunological status of renal graft recipients on ciclosporin therapy?

We have assessed the peripheral distribution of T cells, using the monoclonal antibodies OKT3, OKT4, OKT8 and LEU7 and the proliferative response to phytohaemagglutinin (PHA), in 10 renal transplant recipients. In each patient, the immunological pattern was evaluated twice, both before and after 1 month of calcium antagonist (calcium channel blockers, CaA) treatment. During treatment with CaA, we have observed both a significant decrease in the mitogenic response to PHA and a significant increase in OKT8 cells. Our data support the hypothesis that CaAs per se may have an immunomodulatory effect on T cell distribution independently of changes in ciclosporin (CS) blood levels. These results could also provide a cellular basis for synergism between CS and CaA.

Adjuvants, Immunologic↗

The evaluation of effect of radiotherapy on T and B lymphocytes with standard methods and monoclonal antibodies: results at 30 months.

We examined and evaluated the immunologic status of 15 patients suffering from neoplastic, not ematologic, diseases, who underwent external beam radiation therapy. We determined the total lymphocyte count, the percentage of E and EAC rosettes, surface membrane immunoglobulins, the lymphocyte reactivity to PWM and PHA, and T-lymphocyte subpopulations by means of monoclonal antibodies (OKT3-OKT4-OKT8). Besides we evaluated the percentage of LEU7 and OKM1 cells and lymphocytes response to MLR. Blastogenesis tests (PHA and MLR), after 18 months, were performed with and without monocytes. We found out that the amount of T and B lymphocyte subpopulations, which was extremely variable during and after radiotherapy, gradually returned to initial value. After 30 months, the functional impairment seems to be almost completely recovered. At 18 months from the beginning of radiation treatment, the mixed lymphocyte reaction was normal. The presence of monocytes doesn't change either MLR or PHA responses. LEU7+ cells are normal, while OKM1+ cells increased.

B-Lymphocytes↗

The mid-term effects of radiotherapy on T and B lymphocytes: an evaluation of cellular immunity with standard methods and monoclonal antibodies.

The mid-term effects of radiotherapy on T and B peripheral lymphocytes of 15 patients treated for various malignancies were evaluated. All patients had a significant impairment of lymphocyte functions, as measured by blastogenesis after stimulation with phytohemagglutinin and pokeweed mitogen. Such impairment lasted for 1 year after the completion of radiotherapy, when numerical variability of T and B subpopulations, observed during and after radiation treatment, was restored to initial values.

B-Lymphocytes↗

Impaired distribution of T-lymphocyte subsets in patients with haemophilia.

The distribution of T-lymphocyte subsets was assessed using monoclonal antibodies in 20 symptom-free patients with haemophilia. In 15 patients, the T-cell subsets appear substantially balanced with only a moderate reduction in the proportion and absolute number of OKT4 positive cells. In the remaining 5, all with a reversed OKT4/OKT8 ratio, the proportion and absolute number of OKT4 positive cells was significantly reduced (p less than 0.0002) while the absolute number of OKT8 positive cells was normal or reduced although the proportion of these cells appeared increased. Functional studies, testing the proliferative response to PHA and PWM, were normal in all cases including those with immunological abnormalities. These results suggest that a proportion of patients with classic haemophilia show some immunological abnormalities similar to those observed in patients with acquired immunodeficiency syndrome and that regular evaluation of several immunological parameters is warranted in these patients.

Adolescent↗

Testicular peritubular myoid cells are a target for adrenomedullin.

Adrenomedullin (AM) is a recently cloned vasorelaxing peptide that belongs to the calcitonin gene-related peptide family. AM inhibits the contraction of several types of smooth muscle cells and is present in the testis as well as in many other organs. The authors investigated whether testicular peritubular myoid cells (PMC) possess specific receptors for AM. Binding of AM to PMC was saturable in a time-dependent manner and 125I-AM binding was effectively displaced by cold AM. The study documents that testicular peritubular myoid cells are a target for adrenomedullin and suggests a role for this peptide in the paracrine regulation of the testis.

Adrenomedullin↗

Is it possible to define a better ASCUS class in cervicovaginal screening? A review of 187 cases.

OBJECTIVE: To try to better define the cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS) in a cervical screening protocol. STUDY DESIGN: Smears from 187 patients with cytologic diagnoses of ASCUS and histologic or two years' cytologic/colposcopic follow-up were reviewed. When an ASCUS diagnosis was confirmed, it was done strictly on the basis of the morphologic criteria recommended by the Regione Emilia Romagna Screening Protocol in 1997, trying also to subclassify ASCUS into favor reactive or favor neoplasia. RESULTS: Seventy ASCUS cases were negative (37.4%). Three cases (1.6%) were low grade squamous intraepithelial lesion, and seven (3.8%) were high grade squamous intraepithelial lesion. One hundred seven ASCUS cases (57.2%) were confirmed. Among the 70 negative cases, 36 (51.4%) had reactive changes on biopsy, 30 (42.9%) koilocytosis, 3 cervical intraepithelial neoplasia (CIN 1) and one CIN not otherwise specified (5.7% total). CONCLUSION: Reclassification of ASCUS cases using tighter criteria reduced them to a rate of 57.2% but missed 30 patients with histologic diagnoses of koilocytosis and 4 with histologic diagnoses of CIN.

Biopsy↗