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Biomedical subjects

M Galloni

Publications and source records attributed to M Galloni.

At least 19 recordsLinked to original sources

The mesorectum: hypothesis on its evolution.

BACKGROUND: Two points are controversial in the anatomy of the mesorectum: (1) its origin; and (2) the existence of the lateral ligaments. We studied these structures in animals and in human fetuses. METHODS: Dissections were performed on quadrupedal mammals (29 dogs and 32 pigs) and 28 primates (Macaca apes). Moreover, macroslices of Macaca ape and of 182 human fetuses were examined histologically. RESULTS: In quadrupedal mammals, we found no traces of any adipose masses comparable to the human mesorectum nor were there ligaments of suspension. In the ape, the adipose tissue in the mesosigmoid forms an adipose cuff that completely surrounds the extraperitoneal rectum. Two dense connective bands were found between the lateral wall of the pelvis and the perirectal tissue. Both the mesorectum and the lateral ligaments were clearly identified in the sections of human fetus only at the end of the fifth month but not earlier. CONCLUSIONS: On the basis of our analysis of 3 animal species, we conclude that the mesorectum and lateral ligaments are absent in quadrupedal mammals but are present in primates. Therefore, we hypothesize that these structures appeared with the attainment of the upright position, even though other hypotheses are possible.

Animals↗

Nitinol Carbofilm coated stents for peripheral applications: study in the porcine model.

PURPOSE: Testing the safety and foreign body reaction (FBR) of a nitinol self-expandable carbon-coated stent system in the porcine animal model at different follow-up (FU) periods. METHODS: Fifteen minipigs received 30 carbon-coated self-expandable nitinol stents in iliac arteries. Explants were carried out at 7 (3 animals), 30 (4 animals), 90 (4 animals) and 180 (4 animals) day FU, for evaluation of acute, sub-acute and chronic biological response to the implanted devices. Histological, immunohistochemical, histomorphometric and scanning electron microscopy (SEM) analyses were performed to assess inflammatory reaction, endothelialization process, neointimal growth and cellular composition. RESULTS: Thirty stents were successfully implanted. No mural thrombi were observed at gross examination or by angiography. Histologically no significant inflammatory reaction was detected: the stents appeared covered by a thin monolayer of endothelial cells even at 7 day FU. The neointima presented homogeneous growth and moderate thickness after 30, 90 and 180 days explants (0.38+/- 0.36 mm, 0.33+/- 0.30 mm, 0.27+/- 0.25 mm respectively). Internal and external elastic laminae were intact in 95% of stented arteries. Histological data validations of vessel endothelialization was obtained with SEM for the seven day follow-up group. CONCLUSIONS: This study showed good remarkable technical performances, minimal FBR and biocompatibility comparable with other available pre-clinical experimentations.

Alloys↗

The Fab-8 boundary defines the distal limit of the bithorax complex iab-7 domain and insulates iab-7 from initiation elements and a PRE in the adjacent iab-8 domain.

The Drosophila bithorax complex Abdominal-B (Abd-B) gene specifies parasegmental identity at the posterior end of the fly. The specific pattern of Abd-B expression in each parasegment (PS) determines its identity and, in PS10-13, Abd-B expression is controlled by four parasegment-specific cis-regulatory domains, iab-5 to iab-8, respectively. In order to properly determine parasegmental identity, these four cis-regulatory domains must function autonomously during both the initiation and maintenance phases of BX-C regulation. The studies reported here demonstrate that the (centromere) distal end of iab-7 domain is delimited by the Fab-8 boundary. Initiators that specify PS12 identity are located on the proximal iab-7 side of Fab-8, while initiators that specify PS13 identity are located on the distal side of Fab-8, in iab-8. We use transgene assays to demonstrate that Fab-8 has enhancer blocking activity and that it can insulate reporter constructs from the regulatory action of the iab-7 and iab-8 initiators. We also show that the Fab-8 boundary defines the realm of action of a nearby iab-8 Polycomb Response Element, preventing this element from ectopically silencing the adjacent domain. Finally, we demonstrate that the insulating activity of the Fab-8 boundary in BX-C is absolutely essential for the proper specification of parasegmental identity by the iab-7 and iab-8 cis-regulatory domains. Fab-8 together with the previously identified Fab-7 boundary delimit the first genetically defined higher order domain in a multicellular eukaryote.

Animals↗

Cell-autonomous and non-autonomous growth-defective mutants of Drosophila melanogaster.

During animal development, growth of the various tissues and organs that make up the body must be coordinated. Despite recent progress in understanding growth control within the cell unit, the mechanisms that coordinate growth at the organismal level are still poorly understood. To study this problem, we performed a genetic screen for larval growth-defective mutants in Drosophila melanogaster. Characterization of these mutants revealed distinct types of larval growth defects. An allelic series for the translation initiation factor, Eif4A, showed different growth rates and suggests that Eif4A could be used as a dose-dependent growth regulator. Two mutants that fail to exit cellular quiescence at larval hatching (milou and eif4(1006)) have a DNA replication block that can be bypassed by overexpression of the E2F transcription factor. A mutation (bonsaï) in a homolog of the prokaryotic ribosomal protein, RPS15, causes a growth defect that is non-cell-autonomous. Our results emphasize the importance of translational regulation for the exit from quiescence. They suggest that the level of protein synthesis required for cell cycle progression varies according to tissue type. The isolation of non-cell-autonomous larval growth-defective mutants suggests that specialized organs coordinate growth throughout the animal and provides new tools for studies of organismal growth regulation.

Animals↗

Chromatin domain boundaries in the Bithorax complex.

Eukaryotic chromosomes are thought to be organized into a series of discrete higher-order chromatin domains. This organization is believed to be important not only in the compaction of the chromatin fibre, but also in the utilization of genetic information. Critical to this model are the domain boundaries that delimit and segregate the chromosomes into units of independent gene activity. In Drosophila, such domain boundaries have been identified through two different approaches. On the one hand, elements like scs/scs' and the reiterated binding site for the SU(HW) protein have been characterized through their activity of impeding enhancer-promoter interactions when intercalated between them. Their role of chromatin insulators can protect transgenes from genomic position effects, thereby establishing independent functional domains within the chromosome. On the other hand, domain boundaries of the Bithorax complex (BX-C) like Fab-7 and Mcp have been identified through mutational analysis. Mcp and Fab-7, however, may represent a specific class of boundary elements; instead of separating adjacent domains that contain separate structural genes. Mcp and Fab-7 delimit adjacent cis-regulatory domains, each of which interacts independently with their target promoters. In this article, we review the genetic and molecular characteristics of the domain boundaries of the BX-C. We describe how Fab-7 functions to confine activating as well as repressive signals to the flanking regulatory domains. Although the mechanisms by which Fab-7 works as a domain boundary remain an open issue, we provide preliminary evidence that Fab-7 is not a mere insulator like scs or the reiterated binding site for the SU(HW) protein.

Animals↗

Twelve-year follow up with the Sorin Pericarbon bioprosthesis in the mitral position.

BACKGROUND AND AIMS OF THE STUDY: The aim of this study was to evaluate the long-term follow up of the Pericarbon pericardial bioprosthesis implanted in the mitral position. METHODS: Between January 1985 and January 1991, 78 patients (26 males, 52 females; mean age 56.9 +/- 7.8 years) underwent isolated mitral valve replacement with a Pericarbon valve. All bioprostheses were size 29 mm and implanted by the same surgeon. RESULTS: Total follow up was 663.2 pt-years and it was 97% complete. Early mortality was 1.3% (1/78); two minor cerebral embolisms were observed as early complications. At 12 years the overall survival rate was 85.0 +/- and valve-related survival 93.1 +/- 3.0%; freedom from embolic events was 83.0 +/- 4.5% and from endocarditis 98.7 +/- 1.3%. Freedom from primary tissue failure was 56.8 +/- 6.6%; it was 86.3 +/- 7.5% in patients aged > 60 years and 36.8 +/- 8.2% in younger patients. There were 27 reoperations, 26 for primary tissue failure, one for endocarditis. Comparison between basal and follow up echocardiographic studies showed a significant stenotic deterioration of the bioprosthesis and a negligible incidence of regurgitation. Morphological findings of explanted bioprostheses were characterized by stenotic and diffuse microcalcification, but no tissue tear was observed. CONCLUSIONS: These results confirm that the Pericarbon bioprosthesis is structurally safe and free from the fatigue problems which afflicted the first and second generation of pericardial valves. As with other tissue valves, the rate of calcification is age-dependent, suggesting preferential use of the Pericarbon prosthesis in elderly people.

Bioprosthesis↗

[Mitral valve bioprosthesis from bovine pericardium. Color Doppler echographic study and long-term follow up].

Pericardial heart valve bioprostheses have been utilized for 20 years. In spite of encouraging initial results, long-term follow-up showed a higher incidence of structural failures and primary tissue failures than porcine bioprostheses. Pericarbon represents the newest generation of bovine pericardial bioprostheses. Aim of this study is the long-term evaluation with echocardiographic and color Doppler technique of an innovative bioprostheses, in particular, its morfological and functional characteristics. From 1985 to 1989, 78 consecutive patients (21 males, 57 females, mean age 56.5 +/- 8.16 years) underwent mitral valve replacement with Pericarbon 29, by the same operator, who preserved the mitral posterior leaflet. One month after operation, 21 of these patients underwent echo-color Doppler evaluation, in normalized hemodynamic conditions (normality ranges). In 1995, at the end of the followup, 30 of the remaining 54 patients underwent new echo-color Doppler evaluation and these data were compared with normality ranges values. Leaflets' thickness increased from 0.98 +/- 0.09 to 2.87 +/- 0.73 mm (anterior leaflet; p < 0.0001) and from 1.02 +/- 0.08 to 2.71 +/- 0.45 mm (posterior leaflet; p < 0.0001) 43.3% of anterior leaflet and 53.3% of posterior leaflet showed fibrocalcic lesions. Mean transvalvular gradient increased from 3.4 +/- 0.2 to 6.6 +/- 3.4 mmHg (p < 0.0001); also functional area decreased (p < 0.0001). We have found no paraprosthetic regurgitation and a very low number of central prosthetic regurgitation. Left ventricular function, evaluated by ejection fraction and regional kinesis, remained substantially preserved.

Aged↗

Morphological comparison of mitral and aortic bioprostheses explanted from the same patient for primary tissue failure.

Host factors might influence the fate of tissue prostheses. We have analyzed the tissue failure phenomenon in mitral and aortic porcine bioprostheses explanted from the same patient so as to avoid the bias of host factors. The 50 bioprostheses of this study were explanted from 25 patients reoperated on because of malfunctioning due to primary tissue failure. Bioprostheses explanted were photographed, radiographed and observed in polarizing light. All lesions analyzed received a score on the basis of morphological criteria. No difference was observed in the occurrence of pannus, tears or cells infiltrates. Calcifications occurred more extensively in mitral position (p=0.0031). Creep of the stent was significantly greater in mitral position (p=0.0324). Since the model of our study removed other individual factors, we may conclude that there is evidence for an earlier and more extensive calcific degeneration in the mitral than in the aortic position.

Aortic Valve↗

The Trithorax-like gene encodes the Drosophila GAGA factor.

Little is known about the way higher-order chromatin structure influences gene expression and chromosome topology in general. Genetic analysis in Drosophila has led to the discovery of two classes of genes, the regulators of homeotic genes and the modifiers of position-effect variegation, which seem to be good candidates for encoding some of the factors regulating chromatin functions. The Trithorax-like gene we described here is required for the normal expression of the homeotic genes and is a modifier of position-effect variegation. We found that Trithorax-like encodes the GAGA factor which is involved in the formation of an accessible chromatin structure at promoter sequences. Our genetic analysis suggests that the chromatin modelling function of the GAGA factor is not restricted to promoter regions.

Animals↗

Mcp and Fab-7: molecular analysis of putative boundaries of cis-regulatory domains in the bithorax complex of Drosophila melanogaster.

A very large cis-regulatory region of approximately 300 kb is responsible for the complex patterns of expression of the three homeotic genes of the bithorax complex Ubx, abd-A and Abd-B. This region can be subdivided in nine parasegment-specific regulatory subunits. Recent genetic and molecular analysis has revealed the existence of two novel cis-regulatory elements Mcp and Fab-7. Mcp is located between iab-4 and iab-5, the parasegment-specific regulatory subunits which direct Abd-B in parasegments 9 and 10. Similarly, Fab-7 is located between iab-6 and iab-7, the parasegment 11 and 12-specific regulatory units. Mcp and Fab-7 appear to function as domain boundaries that separate adjacent cis-regulatory units. We report the analysis of two new Mcp mutant deletions (McpH27 and McpB116) that allow us to localize sequences essential for boundary function to a approximately 0.4 kb DNA segment. These essential sequences closely coincide to a approximately 0.3 kb nuclease hypersensitive region in chromatin. We also show that sequences contributing to the Fab-7 boundary appear to be spread over a larger stretch of DNA, but like Mcp have an unusual chromatin structure.

Animals↗

Mitral valve replacement with the Biocor stentless mitral valve: early results.

Chordal preservation during mitral valve replacement is thought to greatly preserve left ventricular function. Recently a stentless mitral valve (Biocor) became available for clinical use. It is a porcine mitral valve with the entire chordal apparatus, the sewing ring being reinforced by a bovine pericardial ring and the chordae being sutured together onto two pericardial patches. During a six months period, seven patients undergoing mitral valve replacement for mitral insufficiency (four cases), mitral stenosis (two cases) or mixed lesions (one case) received a stentless mitral valve. Their mean age was 66.3 +/- 4.8. The valve was implanted by suturing the pericardial patches onto the papillary muscles and the sewing ring onto the mitral annulus. Echocardiography control immediately after surgery showed good valve function. Three valves failed after a period of seven days, seven and 12 months respectively. The valve lesions were similar and consistent with an excessive tension on the chordae and on the valvular tissue. There were tears along the posterior annulus and at the level of the commissures, often accompanied by chordal rupture. Histology and scanning electron microscopy showed good integration of the prosthesis with the patients own tissues. There were areas of overgrowing tissue without endothelial cells especially in the area of papillary muscle -pericardial patch interaction. The remaining four patients continue to do well after a mean follow up of two years. The apparent excessive tension on the valve tissues leading to the premature failure of the prosthesis could be due to the variability in the distance between mitral annulus and papillary muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Seven-year experience with chordal replacement with expanded polytetrafluoroethylene in floppy mitral valve.

Among 106 patients operated on for implantation of artificial mitral chordae (expanded polytetrafluoroethylene), usually associated with other traditional procedures, 82 had degenerative valve disease. Two of them had the valve replaced during the same operation because of residual regurgitation, and one patient died (1.3%) of respiratory insufficiency. Seventy-nine patients left the hospital and were followed up to 84 months. No late deaths and only one valve-related complication were reported. This occurred in a patient who required reoperation after 18 months for sudden recurrence of mitral regurgitation caused by the rupture of natural chordae, which had been shortened during the first procedure, whereas the artificial chordae had retained their function. The clinical experience confirms positive experimental data, because this technique was reliable with lasting results. Application of artificial chordae, associated with other traditional techniques, is useful to improve the results and to extend the indications for mitral valve repair.

Adolescent↗

The bluetail transposon: evidence for independent cis-regulatory domains and domain boundaries in the bithorax complex.

An extremely large cis-regulatory region generates the parasegment-specific expression patterns of the homeotic genes in the bithorax complex. We present evidence supporting the idea that this cis-regulatory region is subdivided into independent cis-regulatory domains. We describe a Ubx-lacZ transposon which is inserted into one of these domains, iab-7. The PS12-specific pattern of LacZ expression from this reporter indicates that it is subject to the control of the iab-7 cis-regulatory domain, but is protected from the effects of adjacent regulatory domains. Protection on the proximal side appears to be provided by the Fab-7 boundary element. Deletion of this boundary results in the ectopic activation of iab-7 in PS11 (where the iab-6 cis-regulatory domain normally functions). We show that the Fab-7 boundary, like other boundaries, has an unusual chromatin structure.

Animals↗

Surgical technique for artificial mitral chordae implantation.

Failure of reconstructive procedures of the mitral valve is often ascribed to diffuse alteration of the subvalvular apparatus, which prevents the utilization of well-established techniques such as chordal transposition or shortening. For this reason, in 1986 after 2 years of animal experiments, we started the clinical use of expanded-polytetrafluoroethylene mitral chordae. Details of the surgical procedure are presented. Our experience is based on 51 patients with a mean follow-up of about 20 months (range 3-57). Four patients had the valve replaced during the same operation: one patient died later of cardiac failure and two underwent reoperation, 8 and 18 months after operation. Forty-one patients are in New York Heart Association Functional Class I and three in Class II. We suggest this technique in association with other traditional procedures to increase the number of mitral valves repaired, mostly because of degenerative etiology.

Adult↗

Calcification of chemically treated bovine pericardium.

One of the most important problems arising in cardiac bioprostheses made with bovine pericardium and, more generally, with biologically-derived tissues is tissue calcification. The present study assessed four chemical treatments on patches of bovine pericardium, intended to avoid or minimize calcification. Pericardium specimens were treated with: A) 0.5% glutaraldehyde; B) 0.5% glutaraldehyde + 4% formaldehyde; C) same as A, but with a further neutralization treatment; D) acylation of fresh bovine pericardium. Circular samples of 1 cm diameter were subcutaneously implanted in the abdominal region of three groups of six rats. The explants were retrieved after 2, 4 and 8 weeks. The calcium content and the histological results showed better behaviour for C and D samples than with the commonly used fixation methods (A and B). The lowest calcification was observed with treatment D, even though its morphological structures were somewhat modified with homogenation of collagen bundles. Among the glutaraldehyde-based treatments, treatment C appears to be the most promising because the pericardium shows slower calcium accumulation with a diffusive pattern.

Animals↗

Artificial mitral valve chordae: experimental and clinical experience.

Failure of mitral valve reconstructive procedures often may be ascribed to severe or progressive alterations of subvalvar apparatus. Expanded polytetrafluoroethylene sutures were used to replace anterior leaflet mitral valve chordae in 8 animals (hypertensive dogs and growing sheep). After the positive results obtained during a 13-month follow-up, 5-0 sutures of the same material were introduced in clinical practice to replace mitral valve chordae. Twelve patients had two to six anterior leaflet chordae replaced for degenerative or rheumatic disease. In 3 patients, the intraoperative result was not acceptable and a prosthetic valve was inserted during the same operation. One case of late failure has been recorded so far (18 months after the procedure), owing to rupture of a natural chorda shortened at operation. Since that event, we have implanted supportive artificial chordae in case of diffuse alteration of natural chordae. The remaining patients show satisfactory hemodynamic results, and no valve-related events have been recognized up to 30 months after operation. We suggest use of 5-0 polytetrafluoroethylene sutures in replacing anterior leaflet chordae in degenerative, rheumatic, and congenital mitral valve diseases.

Adult↗