PubMed Health⌕ Search

Biomedical subjects

M Campagna

Publications and source records attributed to M Campagna.

At least 19 recordsLinked to original sources
PubMed2006

Interaction of rotavirus polymerase VP1 with nonstructural protein NSP5 is stronger than that with NSP2.

Rotavirus morphogenesis starts in intracellular inclusion bodies called viroplasms. RNA replication and packaging are mediated by several viral proteins, of which VP1, the RNA-dependent RNA polymerase, and VP2, the core scaffolding protein, were shown to be sufficient to provide replicase activity in vitro. In vivo, however, viral replication complexes also contain the nonstructural proteins NSP2 and NSP5, which were shown to be essential for replication, to interact with each other, and to form viroplasm-like structures (VLS) when coexpressed in uninfected cells. In order to gain a better understanding of the intermediates formed during viral replication, this work focused on the interactions of NSP5 with VP1, VP2, and NSP2. We demonstrated a strong interaction of VP1 with NSP5 but only a weak one with NSP2 in cotransfected cells in the absence of other viral proteins or viral RNA. By contrast, we failed to coimmunoprecipitate VP2 with anti-NSP5 antibodies or NSP5 with anti-VP2 antibodies. We constructed a tagged form of VP1, which was found to colocalize in viroplasms and in VLS formed by NSP5 and NSP2. The tagged VP1 was able to replace VP1 structurally by being incorporated into progeny viral particles. When applying anti-tag-VP1 or anti-NSP5 antibodies, coimmunoprecipitation of tagged VP1 with NSP5 was found. Using deletion mutants of NSP5 or different fragments of NSP5 fused to enhanced green fluorescent protein, we identified the 48 C-terminal amino acids as the region essential for interaction with VP1.

Animals↗
PubMed2003

Diethylsulphate and methylnitrosourea affect different targets in Chinese hamster fibroblasts: possible mechanisms of aneuploidy induction by these agents.

It has been shown that the ethylating agent diethylsulphate (DES) induces centromere-containing micronuclei with kinetics suggesting that molecules other than DNA could be targets. In quiescent Chinese hamster fibroblasts CHEF/18, O6-alkylated bases inhibit ribosomal protein S6 kinase (S6K1), the terminal member of a kinase cascade responsible for an increased rate of protein synthesis, but not extracellular signal-activated kinases (ERK1/2) or terminal kinases of a second cascade which activates transcription. The inhibition correlates with the appearance of abnormal metaphases at the following mitosis, suggesting that alkylation of the nucleotide pool and inhibition of S6K1 could be one of the mechanisms leading to chromosome loss by alkylating agents. To clarify the role of protein kinases in chromosome loss induced by alkylating agents, we have studied the effects of DES and methylnitrosourea (MNU) on S6K1 and ERK1/2 activation by growth factors. The alkylating agents were studied in a battery of Chinese hamster fibroblasts (CHEF/18, CHO and ClB) with normal and mutated p53 to control for DNA damage-induced activation of p53, which could indirectly inhibit protein kinases. The role of repair in induction of micronuclei was studied in mismatch repair-proficient CHO and repair-deficient ClB cells. Our results indicate that DES induced micronuclei in a mismatch repair-independent manner, within 8 h of treatment, in agreement with a role for S6K1 inhibition in micronucleus formation. MNU induced centromere-containing micronuclei only in CHO cells, one cell cycle after treatment, without any detectable influences on either kinase cascade, suggesting a role for mismatch repair in chromosome loss.

Alkylating Agents↗
PubMed1999

Dual-colour FISH analysis to characterize a marker chromosome in cytochrome P450 2B1 recombinant V79 Chinese hamster cells.

Recombinant V79 Chinese hamster cell lines have been constructed for the expression of useful functions, e.g. cytochromes P450, in order to study metabolism-dependent toxicity. Recombinant cell lines are derived as single clones upon gene transfer and selection from the parental V79 cell line. It is of fundamental importance for a reliable application of the recombinant cell lines to show that the original biological characteristics of the parental line are maintained. As part of these efforts, fluorescence in situ hybridization with Chinese hamster chromosome-specific DNA libraries was performed in order to identify the origin of the chromosomes from which a marker chromosome present in the recombinant cell line V79MZr2B1 was derived, which could not be identified by standard cytogenetic techniques.

Animals↗
PubMed1998

Fragile sites at the centromere of Chinese hamster chromosomes: a possible mechanism of chromosome loss.

On the basis of our previous observations showing that fragile sites (FS) mapped essentially in the centromeric regions of Chinese hamster chromosomes, we consider the possibility that the presence of FS at the centromere might be a source of chromosome loss. In this model a centromeric FS causes a centromeric break giving rise to two chromosome arms which could be lost or maintained with different consequences on the ploidy of daughter cells. To test this hypothesis, Chinese hamster cells have been treated both with N-methyl-N-nitrosourea (MNU), a mutagenic agent which also induces aneuploidy, and vinblastin (VBL), a pure aneugen, used as a control compound, which is supposed not to interact with DNA. The results show that MNU induces the formation of translocated and/or truncated chromosomes, on the contrary VBL is not able to induce chromosome rearrangements. The sites most involved in MNU-induced breaks are the centromeric regions of chromosomes where FS are also present. These breaks cause essentially the loss of one chromosome arm, so that the resulting cells are numerically diploid but presenting partial monosomies. The implications of these results are discussed.

Animals↗
PubMed1992

Ionescu-Shiley valve failure. I: Experience with 125 standard-profile explants.

A group of standard-profile Ionescu-Shiley valve implants, 357 aortic and 190 mitral, was reviewed for cases of failure requiring surgical explantation. To date, 90 (25.2%) of the aortic and 35 (18.4%) of the mitral valves have failed, and are the subject of this analysis. Observations of these explants confirm previous suggestions about the clinical and pathologic patterns of the Ionescu-Shiley valve's failure, but are extended in this study to allow more confident statistical analyses. Cusp tear with insufficiency remains the most important reason for explantation, precipitating removal to date of 19.1% of the aortic and 10.0% of the mitral valves implanted. This difference, aortic versus mitral, is significant (p less than 0.006) and the reverse of observations made in other studies of pericardial valves. In this review there is no significant difference in the proportion of aortic and mitral valves that failed with calcification (2.2% and 3.1%, respectively). Aortic Ionescu-Shiley valves failing with tears had a mean of 3.1 tears per valve, whereas mitral valves had 1.2. Aortic valves also showed considerably more pretear wear than did mitral valves. Although the large number of these Ionescu-Shiley valve failures has been a profound clinical disappointment, it has provided an opportunity to observe and detail the pathology of their failure.

Adolescent↗
PubMed1992

Ionescu-Shiley valve failure. II: Experience with 25 low-profile explants.

A group of patients who had low-profile Ionescu-Shiley valves implanted, 237 aortic and 130 mitral, was reviewed for cases of bioprosthetic failure requiring explantation. Fourteen such aortic and 11 mitral valves were recovered at operation. The most common reason for explantation was valvular insufficiency due to cusp tears, accounting for 50.0% of aortic and 82.0% of mitral explants. Morphologic examination of the valves suggested a common mode of failure with tears, and this is illustrated. The clinical and pathologic patterns of this valve's failure are compared with those of the standard-profile Ionescu-Shiley valve, and many similarities exist. A tendency for a larger proportion of mitral valve failures with tears is, however, in contrast to observations of the standard-profile valve, in which aortic failures are more common. Additionally, low-profile valves, in either the aortic or mitral positions, fail after a shorter time in situ than their standard-profile counterparts, at a mean of 45.1 months versus 78.0 in the aortic position (p less than 0.01) and at 52.2 months versus 73.8 in the mitral position (p less than 0.05). These differences in the performance of the Ionescu-Shiley valve models may have implications for the design of future bioprostheses.

Adult↗
PubMed1992

Lambl's excrescences and papillary fibroelastomas: are they different?

OBJECTIVE: To determine if Lambl's excrescences (LEs) and papillary fibroelastomas (PFEs) differ histologically. SETTING: Materials were obtained from post mortem examinations performed at the Ottawa Civic Hospital, a tertiary care teaching hospital in Ottawa, Ontario. DESIGN AND PATIENTS: Hearts with grossly 'classic' PFEs (n = 10) or 'typical' LEs (n = 20) were examined. The patients with PFEs had a mean age of 63.5 years (range 24 to 79), similar to that of 68.1 years (range 47 to 83) for those with LEs. The LEs and PFEs were compared regarding their gross characteristics, sizes, locations and microscopic appearances. MAIN RESULTS: Lesions which were termed LEs had a similar microscopic appearance to grossly categorized PFEs; however, the LEs were smaller and broader-based. Some LEs and PFEs were microscopically indistinguishable. CONCLUSIONS: As LEs and PFEs may be virtually identical microscopically in some instances, separation of these two lesions may be artificial; however, this separation remains useful because it highlights the gross appearances, unusual locations and potential clinical sequelae of papillary fibroelastomas.

Adult↗
PubMed1991

Patterns of failure in Hancock pericardial bioprostheses.

A series of Hancock pericardial valve bioprostheses was reviewed for cases of primary valve failure. Thirteen mitral and 10 aortic valve explants were recovered from 21 adult patients. Mitral valves had been in place for a mean of 56.4 months, and aortic valves for 53.8 months. All valves failed with cusp tears from stents (with a mean of 1.7 for mitral valves and 2.6 for aortic valves) in a predictable pattern, suggesting that wear and stress at cusp stitch sites are important in their pathogenesis. The topography of these tears is illustrated as are the less common associates of primary failure, such as calcification, fibrosis, and thrombosis. Similarities and differences of this valve's failure compared with that of the Ionescu-Shiley pericardial valve are discussed.

Adult↗
PubMed1990

Severe mitral insufficiency post-balloon valvuloplasty: the late changes found in a disrupted mitral valve.

The case of a 45-yr-old woman who had balloon valvuloplasty for rheumatic mitral stenosis is presented. An anterior mitral leaflet tear occurred as a complication of the procedure. Both partial healing of the anterior mitral leaflet and gradual dilatation of the left atrium occurred which allowed the damaged valve to remain in situ for several months. Some of the late changes which occur after such a complicated valvuloplasty are illustrated here, as this patient eventually required surgery and valve excision for definitive repair.

Catheterization↗
PubMedDate not supplied

[From lead colic to moderate risk].

During the 20th century, occupational and environmental exposure to lead was among the main relevant issues studied by occupational physicians, hygienists, and public health administrators. During the different decades there was a progressive reduction in exposure levels and in the mean time a progressive reduction in the severity of clinical symptoms due to very high exposure to this metal. During thefirst forty years of the 20th century, a clear decrease in the frequency of encephalopathy and paralysis of the radial nerve was observed while abdominal colics and anaemia where frequently observed until the sixties. In the first part of the seventies, there was a clear change in the preventive approach to lead poisoning both in the field of research and in the clinical-preventive and legal field. These successful results where obtained despite the disagreement of outstanding physicians and international renowed researchers and industrial associations. Every successful battle allowed a great improvement in the field of occupational and environmental prevention, but the above-mentioned disagreements caused a great delay in the solution of the problem and did not improve workers', children's and teenagers' health. In Italy, there was a very deep interest in the prevention of lead poisoning which led to very good results in a relatively short period even though the current laws did not help and also nowadays do not help the occupational professionals studying and dealing with occupational health. Lead undoubtly represents one of the most largely studied environmental industrial toxics and shows a model, also suitable for other matters involving exposure to different industrial toxics. Nevertheless, there are still problems in the understanding of some pathogenetic aspects of lead and in the significance of some of its early effects which deserve further studies. These matters, strictly linked to low-dose exposure, still present numerous questions. For example, there should be a deep interest in the standardization of its internal dose indicators, in the study the role of the metal in the pathogenesis of cardiological and nephrological diseases, in the characterization of its genetic polymorphisms and in the assessment of its carcinogenicity. A lot of these issues, already examined in old studies concerning casistics of workers affected by lead poisoning, have been analyzed in the multidisciplinary study "Progetto MIUR Piombo" (Project on lead by the Italian Ministry of University and Research) conducted by six different Institutes of Occupational Health (Cagliari, Parma, Perugia, Bari, Ancona and Brescia) which will report their results during this Congress.

Colic↗