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Biomedical subjects

C Gentili

Publications and source records attributed to C Gentili.

At least 37 records · Page 2Linked to original sources
PubMed1995

Production of angiogenesis inhibitors and stimulators is modulated by cultured growth plate chondrocytes during in vitro differentiation: dependence on extracellular matrix assembly.

Secretion of angiogenesis inhibitors and stimulators is modulated during in vitro differentiation of embryonic chick growth plate chondrocytes. Supernatants from dedifferentiated cells undergoing maturation to hypertrophic chondrocytes in suspension progressively inhibited vascular cell random migration and invasion of basement membrane matrix by endothelial cells. Maximal inhibition was exhibited by conditioned medium from hypertrophic chondrocytes. The same medium also repressed vascular cell migration induced by highly angiogenic Kaposi's sarcoma cell supernatants and prevented formation of an anastomosed network of tube-like structures by endothelial cells plated on matrigel. On the contrary, when the suspension culture of hypertrophic chondrocytes was supplemented with ascorbic acid, a condition leading to the formation of a mineralized tissue similar to calcified cartilage, a dramatic switch to production of angiogenic activity was observed. Medium conditioned by osteoblast-like cells derived from hypertrophic chondrocytes also induced vascular cell migration and invasion of basement membrane matrix. The presence of angiogenic activity in the conditioned medium was assessed also by an in vivo assay in mice using reconstituted basement membrane associated with heparin. Therefore, interactions of chondrocytes with their extracellular matrix are an absolute requirement for the expression of angiogenic activities by hypertrophic chondrocytes at late developmental stages.

Animals↗
PubMed1994

Ovotransferrin and ovotransferrin receptor expression during chondrogenesis and endochondral bone formation in developing chick embryo.

Ovotransferrin expression during chick embryo tibia development has been investigated in vivo by immunocytochemistry and in situ hybridization. Ovotransferrin was first observed in the 7 day cartilaginous rudiment. At later stages, the factor was localized in the articular zone of the bone epiphysis and in the bone diaphysis where it was concentrated in hypertrophic cartilage, in zones of cartilage erosion and in the osteoid at the chondro-bone junction. When the localization of the ovotransferrin receptors was investigated, it was observed that chondrocytes at all stages of differentiation express a low level of the oviduct (tissue) specific receptor. Interestingly, high levels of the receptor were detectable in the 13-d old tibia in the diaphysis collar of stacked-osteoprogenitor cells and in the layer of derived osteoblasts. High levels of oviduct receptor were also observed in the primordia of the menisci. Metabolic labeling of proteins secreted by cultured chondrocytes and osteoblasts and Northern blot analysis of RNA extracted from the same cells confirmed and completed the above information. Ovotransferrin was expressed by in vitro differentiating chondrocytes in the early phase of the culture and, at least when culture conditions allowed extracellular matrix assembly, also by hypertrophic chondrocytes and derived osteoblast-like cells. Osteoblasts directly obtained from bone chips produced ovotransferrin only at the time of culture mineralization. By Western blot analysis, oviduct receptor proteins were detected at a very low level in extract from differentiating and hypertrophic chondrocytes and at a higher level in extract from hypertrophic chondrocytes undergoing differentiation to osteoblast-like cells and from mineralizing osteoblasts. Based on these results, the existence of autocrine and paracrine loops involving ovotransferrin and its receptor during chondrogenesis and endochondral bone formation is discussed.

Animals↗
PubMed1993

Cell proliferation, extracellular matrix mineralization, and ovotransferrin transient expression during in vitro differentiation of chick hypertrophic chondrocytes into osteoblast-like cells.

Differentiation of hypertrophic chondrocytes toward an osteoblast-like phenotype occurs in vitro when cells are transferred to anchorage-dependent culture conditions in the presence of ascorbic acid (Descalzi Cancedda, F., C. Gentili, P. Manduca, and R. Cancedda. 1992. J. Cell Biol. 117:427-435). This process is enhanced by retinoic acid addition to the culture medium. Here we compare the growth of hypertrophic chondrocytes undergoing this differentiation process to the growth of hypertrophic chondrocytes maintained in suspension culture as such. The proliferation rate is significantly higher in the adherent hypertrophic chondrocytes differentiating to osteoblast-like cells. In cultures supplemented with retinoic acid the proliferation rate is further increased. In both cases cells stop proliferating when mineralization of the extracellular matrix begins. We also report on the ultrastructural organization of the osteoblast-like cell cultures and we show virtual identity with cultures of osteoblasts grown from bone chips. Cells are embedded in a dense meshwork of type I collagen fibers and mineral is observed in the extracellular matrix associated with collagen fibrils. Differentiating hypertrophic chondrocytes secrete large amounts of an 82-kD glycoprotein. The protein has been purified from conditioned medium and identified as ovotransferrin. It is transiently expressed during the in vitro differentiation of hypertrophic chondrocytes into osteoblast-like cells. In cultured hypertrophic chondrocytes treated with 500 nM retinoic acid, ovotransferrin is maximally expressed 3 d after retinoic acid addition, when the cartilage-bone-specific collagen shift occurs, and decays between the 5th and the 10th day, when cells have fully acquired the osteoblast-like phenotype. Similar results were obtained when retinoic acid was added to the culture at the 50 nM "physiological" concentration. Cells expressing ovotransferrin also coexpress ovotransferrin receptors. This suggests an autocrine mechanism in the control of chondrocyte differentiation to osteoblast-like cells.

Alkaline Phosphatase↗
PubMed1992

Expression, regulation, and tissue distribution of the Ch21 protein during chicken embryogenesis.

The Ch21 protein is one of the marker proteins whose synthesis and secretion by differentiating tibia chondrocytes is progressively increased during chicken embryogenesis (Descalzi-Cancedda, F., Manduca, P., Tacchetti, C., Fossa, P., Quarto, R. and Cancedda, R. (1988) J. Cell Biol. 107, 2455-2463). We report the corresponding full-length cDNA sequence and the complete primary structure of the protein, which contains a 20-residue signal peptide. The synthesis of the protein is directed by a 1450-base mRNA characterized by an unusually long 5'-untranslated leader sequence and is regulated only at the transcriptional level as shown by run-off transcription assays. During differentiation, maximal expression of the protein characterizes stage II hypertrophic chondrocytes. In situ hybridization on embryo sections reveals that the protein is expressed by several structures derived from the chondrogenic lineage and that, in addition, it is a major translational product in granulocytes. High cell density largely influences the expression of the Ch21 protein in chondrocyte cultures. When embryonic avian cells of different origin are grown to confluency, the expression of the Ch21 protein is observed in only some of the cell lines. Thus quiescence per se is not the primary factor determining the expression of the protein.

Amino Acid Sequence↗
PubMed1992

Efficacy of intravenous propafenone in acute atrial fibrillation complicating open-heart surgery.

Early postoperative atrial fibrillation (AF) is a frequent complication of major cardiovascular surgery. To assess the effectiveness of intravenous propafenone in this setting, we studied 50 patients who developed AF within 48 hours after open-heart surgery. Intravenous propafenone (2 mg/kg in 10 minutes) was administered 15 minutes after the onset of the arrhythmia. Sinus rhythm was restored in 35 patients (70%) after a mean time of 22 +/- 6 minutes after the beginning of the infusion. The conversion was obtained in 28 of 32 patients (88%) who had a coronary artery bypass graft and in 7 of 18 patients (39%) who had valvular or septal surgery (p less than 0.01). In those whose arrhythmia did not convert to sinus rhythm, the ventricular rate was reduced from 142 +/- 14 beats/min to 108 +/- 9 beats/min (p less than 0.01). In patients whose arrhythmia was converted to sinus rhythm, mean cardiac index increased from a mean baseline value of 2.7 +/- 0.4 L/min/m2 to 3.4 +/- 0.1 L/min/m2 (p less than 0.05), while it remained virtually unchanged in those whose arrhythmia did not convert. No significant side effects were observed. We conclude that intravenous propafenone is effective in converting to sinus rhythm the majority of patients with AF complicating open-heart surgery. Heart rate was reduced in those who did not convert to sinus rhythm and no side effects nor hemodynamic deterioration were observed in any case.

Acute Disease↗
PubMed1992

Hypertrophic chondrocytes undergo further differentiation in culture.

Conditions have been defined for promoting growth and differentiation of hypertrophic chondrocytes obtained in culture starting from chick embryo tibiae. Hypertrophic chondrocytes, grown in suspension culture as described (Castagnola P., G. Moro, F. Descalzi Cancedda, and R. Cancedda. 1986. J. Cell Biol. 102:2310-2317), when they reached the stage of single cells, were transferred to substrate-dependent culture conditions in the presence of ascorbic acid. Cells showed a change in morphology, became more elongated and flattened, expressed alkaline phosphatase, and eventually mineralized. Type II and X collagen synthesis was halted and replaced by type I collagen synthesis. In addition the cells started to produce and to secrete in large amount a protein with an apparent molecular mass of 82 KD in reducing conditions and 63 KD in unreducing conditions. This protein is soluble in acidic solutions, does not contain collagenous domains, and is glycosylated. The Ch21 protein, a marker of hypertrophic chondrocytes and bone cells, was synthesized throughout the culture. We have defined this additional differentiation stage as an osteoblast-like stage. Calcium deposition in the extracellular matrix occurred regardless of the addition of beta glycerophosphate to the culture medium. Comparable results were obtained both when the cells were plated at low density and when they were already at confluence and maintained in culture without passaging up to 50 d. When retinoic acid was added to the hypertrophic chondrocyte culture between day 1 and day 5 the maturation of the cells to the osteoblast-like stage was highly accelerated. The switch in the collagen secretion was already observed after 2 d and the production of the 63-kD protein after 3 d. Mineralization was observed after 15-20 d.

Animals↗
PubMed1989

Effectiveness of intravenous propafenone for conversion of atrial fibrillation and flutter of recent onset.

The efficacy of intravenous propafenone (2 mg/kg) was assessed in 83 consecutive patients: 68 with atrial fibrillation (AF) and 15 with atrial flutter lasting less than 15 days. Conversion to sinus rhythm occurred in 47 patients (57%), including 42 (62%) of those with AF and 5 (33%) of those with atrial flutter (p less than 0.05). The mean time to conversion was 29 +/- 24 minutes. The success rate was strongly affected by arrhythmia duration. Thus, conversion occurred in 40 patients (71%) among the 56 with arrhythmia lasting less than 48 hours but in 7 patients (26%) among the 27 with a longer lasting arrhythmia (p less than 0.0005). Left atrial size (determined echocardiographically in 56 patients) was significantly larger in nonconverters (49 +/- 12 vs 39 +/- 7 mm, p less than 0.0005). In nonconverters the mean ventricular rate decreased from 141 +/- 26 to 104 +/- 22 beats/min (p less than 0.0005). Except for reversible low output state in 3 patients already hemodynamically compromised, no significant side effects were observed. In conclusion, (1) intravenous propafenone allows a quick restoration of sinus rhythm in the majority of patients with AF of recent onset, whereas it seems less effective in atrial flutter; (2) its efficacy is influenced by the duration of the arrhythmia and by left atrial dimensions; (3) the drug allows control of ventricular rate; and (4) its use seems to be safe except in patients with severe cardiac failure.

Adult↗
PubMed1989

Beta-endorphin in experimental canine spinal ischemia.

Plasma and cerebrospinal fluid beta-endorphin concentrations were radioimmunologically assayed in dogs subjected to spinal cord ischemia induced by infrarenal aortic ligature and in control sham-operated dogs. Plasma beta-endorphin levels rose significantly following surgery in control dogs but were unaffected by spinal ischemia. On the other hand, a significant increase in cerebrospinal fluid beta-endorphin concentration occurred after spinal ischemia, while surgical stress had no significant effect. Thus, the origins of plasma and cerebrospinal fluid beta-endorphin may be different, with the former secreted from the hypophysis and the latter from nervous tissue. Observed changes in cerebrospinal fluid beta-endorphin concentration could be related to the ischemic lesion of nervous tissue while the changes in plasma levels may reflect general stressing factors such as the surgery in our experiments.

Animals↗
PubMed1981

Cell proliferation and its relationship to clinical features and relapse in breast cancers.

The relationship between primary tumor proliferative activity and clinical and pathologic characteristics was analyzed in relation to menopausal status for 541 breast cancer patients. The thymidine-3H labeling index (LI) showed significantly higher median values in cancers from premenopausal (4.2%) and paramenopausal (4.2%) patients in comparison to that of cancers from postmenopausal (1.8%) patients. The LI was not generally correlated to tumor size. The only significant correlation was limited to tumors with negative axillary lymph nodes from premenopausal patients. The proliferative activity of primary tumors was neither correlated to the presence nor the extension of axillary metastasis. The prognostic significance of the primary tumor LI was assessed in 145 untreated patients with cancers without axillary metastases. A higher median value of LI was observed in tumors from patients who relapsed (5.7%) within 52 months than in tumors from those who did not relapse (2%). However, the difference was statistically significant (P less than 0.01) in premenopausal patients, but not in postmenopausal patients. Similarly, a significantly (P less than 0.0005) higher rate of relapse (67.4%) was observed in patients with tumors that had a LI above the median value of 4.6% in comparison to that (0%) of tumors with a LI below the median value in premenopausal patients. No statistically significant relationship was observed between proliferative activity of the primary tumor and risk of relapse in postmenopausal patients.

Adult↗
PubMed1980

[Uncommon evolution of aneurysm of the ascending aorta in Marfan syndrome. A case report (author's transl)].

The Authors report a case of aneurysm of the ascending aorta in Marfan syndrome, with fatal outcome (2 months after the onset of the symptoms), caused neither by dissection nor by rupture of the aorta, but by serious myocardial involvement due to anoxic damage and acute volume overload of left ventricle. The Authors describe the possible mechanisms of this evolution and point out the usefulness of the identification of this uncommon evolution for a useful and opportune surgical therapy.

Aortic Aneurysm↗
PubMed1979

Ethical problems in psychopharmacological research.

1. Scientific research poses considerable ethical problems which in human psychopharmacological studies are frequently faced by singling out consent as the only reliable source of human respect, although it is never free, spontaneous, or informed. 2. On the other hand, various ethical problems present in the "life" of a new substance in the case of industry and preclinical, clinical and mass experiments, are left behind. 3. Thus there arise justified protests which go so far as disowning science and technology. To criticize science and technology is of no use: incorrect use of them must be prevented. 4. Such a guarantee can only come from an international control committee, capable of coping with a multinational power such as industry, supported by peripheral elective committees, which grant the citizens a direct participation in the administration of health.

Ethics, Medical↗