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Biomedical subjects

F Santini

Publications and source records attributed to F Santini.

At least 37 records · Page 2Linked to original sources
PubMed1999

Preservation of the aortic valve in acute type A dissection complicated by aortic regurgitation.

BACKGROUND: The aim of the present study was to verify the efficacy of preserving the aortic valve in patients with acute type A aortic dissection complicated by significant aortic regurgitation. METHODS: From January 1979 to December 1996, 178 patients (125 males; mean age 57 +/- 9 years) underwent emergency surgery for acute type A aortic dissection, with an overall operative mortality rate of 21%. Based on a retrospective analysis of the preoperative angio- or echocardiographic findings, the 141 survivors were divided into 2 groups: Group 1 (G1) included 80 patients (57%) with no or mild aortic regurgitation, and Group 2 (G2) the remaining 61 patients with moderate-to-severe aortic regurgitation. The native aortic valve was preserved by means of a uniform technique consisting of reconstruction of the aortic root and sinotubular junction in 99 patients (70%) [68 in G1 (85%) and 31 in G2 (51%)]. Forty-two patients required aortic valve (8 patients; 6%) or total root replacement (34 patients; 24%). RESULTS: At a mean follow-up of 4 +/- 3.6 years (range, 6 months to 19 years), 19 of the 99 patients with a preserved aortic valve developed moderate-to-severe aortic insufficiency [19%; 7/68 in G1 (10%) and 12/31 in G2 (39%)]. Multivariate analysis revealed that moderate-to-severe preoperative aortic valve insufficiency was a significant risk factor for development of postoperative aortic valve regurgitation (p = 0.008). Reoperation was necessary in 7 G1 patients (10%) and in 8 G2 patients (26%), with an actuarial freedom from reoperation at 5 and 10 years of 93% +/- 7% and 80% +/- 9% in G1 patients, and 81% +/- 8% and 40% +/- 15% in G2 patients (p = 0.045). CONCLUSIONS: Preservation of the aortic valve and aortic root is recommended in patients with acute type A aortic dissection and absent or mild aortic insufficiency. Patients presenting with moderate-to-severe aortic regurgitation and treated conservatively present an increased risk of recurrent valvular insufficiency.

Adolescent↗
PubMed1999

Routine left atrial catheterization for the post-operative management of cardiac surgical patients: is the risk justified?

OBJECTIVE: To assess the risk/benefit ratio, including cost, associated with routine left atrial catheterization for the post-operative management of patients after cardiac surgery. METHODS: From November 1991 to June 1998, out of 6187 open heart procedures performed at our institution, 5815 patients (94%) receive a left atrial monitoring line inserted invasively by a unique and reproducible technique. Catheters were removed on the first or second postoperative day before chest tube removal. A subgroup of 385 patients (7%) were switched to a Swan-Ganz catheter postoperatively. RESULTS: A total of 14 patients suffered a complication related to the left monitoring line (0.24%). Bleeding necessitating transfusion occurred in 10 patients (0.17%), seven of whom required surgical reexploration (0.12%). Catheter retention occurred in four cases (0.07%), requiring a mediastinal reexploration in one and a minimally invasive procedures in three, for removal. No other complications related to the presence of a left atrial line emerged in this series. Apart from providing crucial hemodynamic information on a routine basis, in nine selected patients (0.15%) in a low cardiac output state with increased pulmonary vascular resistance and right ventricular failure, the left atrial line was used as a preferential route for catecholamine infusion, with significant hemodynamic improvement. CONCLUSIONS: Complications of left atrial monitoring catheters in cardiac surgery do occur but at a very low and acceptable rate. No mortality was correlated to their use in our series. Complication rate can be further lowered by a meticulous management of the device. The wealth of information and therapeutic options offered by this line appears to outweigh the associated risk.

Cardiac Catheterization↗
PubMed1999

Spatial control of coated-pit dynamics in living cells.

Here we visualize new aspects of the dynamics of endocytotic clathrin-coated pits and vesicles in mammalian cells by using a fusion protein consisting of green fluorescent protein and clathrin light chain a. Clathrin-coated pits invaginating from the plasma membrane show definite, but highly limited, mobility within the membrane that is relaxed upon treatment with latrunculin B, an inhibitor of actin assembly, indicating that an actin-based framework may be involved in the mobility of these pits. Transient, motile coated vesicles that originate from coated pits can be detected, with multiple vesicles occasionally appearing to emanate from a single pit. Despite their seemingly random distribution, coated pits tend to form repeatedly at defined sites while excluding other regions. This spatial regulation of coated-pit assembly and function is attributable to the attachment of the coated pits to the membrane skeleton.

Animals↗
PubMed1999

Serum iodothyronines in the human fetus and the newborn: evidence for an important role of placenta in fetal thyroid hormone homeostasis.

UNLABELLED: The pattern of circulating iodothyronines in the fetus differs from that in the adult, being characterized by low levels of serum T3. In this study, concentrations of various iodothyronines were measured in sera from neonates of various postconceptional age (PA). Results obtained in cord sera at birth (PA, 24-40 weeks), reflecting the fetal pattern, were compared with those found during extrauterine life in newborns of 5 days or more of postnatal life (PA, 27-46 weeks). The main findings are: Starting at 30 weeks of PA, serum levels increase linearly during extrauterine life; and at 40 weeks, they are more than 200% of those measured in cord sera from newborns of equivalent PA. Serum reverse T3 (rT3) levels during fetal life are higher than those measured during extrauterine life; but they significantly decrease, starting at 30 weeks of PA. Serum T3 sulfate (T3S) does not significantly differ between the two groups, showing the highest values at 28-30 weeks of PA, and significantly decreasing at 30-40 weeks. T3S levels are directly correlated with rT3, both in fetal and extrauterine life, whereas a significant negative correlation between T3S and T3 is found only during extrauterine life. IN CONCLUSION: 1) changes in serum concentrations of iodothyronines in umbilical cord and during postnatal life indicate that maturation of extrathyroidal type I-iodothyronine monodeiodinase (MD) accelerates, starting at 30 weeks of PA; 2) high levels of type III-MD activity in fetal tissues prevent the rise of serum T3, whereas they maintain high levels of rT3 during intrauterine life; 3) an important mechanism leading to the transition from the fetal to the postnatal thyroid hormone balance is a sudden decrease in type III-MD activity; iv) because placenta contains a high amount of type III-MD, it is conceivable that placenta contributes to maintain low T3 and high rT3 serum concentrations during fetal life and that its removal at birth is responsible for most changes in iodothyronine metabolism occurring afterwards.

Female↗
PubMed1999

Mid-term results after heart valve replacement with the CarboMedics bileaflet prosthesis: experience with 785 implants.

BACKGROUND: The aim of the study was to evaluate our clinical experience with the CarboMedics Heart Valve Prosthesis. METHODS: Between October 1991 and December 1997, six hundred seventy-two consecutive patients (361 men, 54%; 311 women, 46%; mean age 57 +/- 12 year, range 6-73 years) underwent mechanical valve implantation at the Division of Cardiac Surgery of the University of Verona. Preoperatively, 69% of the patients were in NYHA FC III or IV. Eighty-one patients (12%) had undergone a previous cardiac operation and 14.5% had an ejection fraction less than 35%. We performed an aortic valve replacement in 309 patients (78 valved-conduits for replacement of the entire aortic root), a mitral valve replacement in 250, and a double valve in 113. 52 patients (8%) underwent associated myocardial revascularization. RESULTS: Early mortality was 2.8% (5/309 aortic, 1.6%; 11/250 mitral, 4.4%; 3/113 double, 2.6%). Late mortality was 4.4%. Actuarial survival at 5 years was 89.3% (aortic, 91.1%, mitral 86.4%, double 90.5%). Thromboembolism occurred in 26 patients (3.9%) and major hemorrhagic events in 20 (3%). Nine patients (1.3%) required a reoperation, in 3 cases (0.4%) after endocarditis (Staphylococcus epidermidis). No structural deterioration occurred in our series. CONCLUSION: Our study appears to confirm the safety and reliability of the CarboMedics mechanical valve prosthesis, even in old age groups. This bileaflet prosthesis demonstrates no structural deterioration, a low incidence of complications, and good hemodynamic performance.

Adolescent↗
PubMed1999

Factors influencing outcome after emergency surgical repair of acute type A aortic dissection.

OBJECTIVE: We retrospectively reviewed our more recent experience with acute type A aortic dissection in order to identify possible risk factors influencing current surgical results. METHODS: Between January 1990 and January 1998, 122 patients (86 males and 36 females; mean age 60 +/- 12 years) underwent emergency repair of acute type A aortic dissection using a standard surgical approach. Seventy-four (61%) patients required isolated replacement of the dissected ascending aorta, 27 (22%) required additional replacement of the aortic arch and 21 (17%) required total aortic root replacement. Surgical outcome was evaluated in terms of operative mortality and morbidity. Results of patients presenting with preoperative complications (Group C) (i.e. cardiac tamponade, cerebral stroke, cardiogenic shock, acute myocardial infarction, anuria or visceral ischemia) were compared with those of uncomplications cases (Group U) and with a calculated risk of expected operative mortality (EOM-rate) based on an analysis of each patient set of preoperative risk factors. Sixteen preoperative and 18 perioperative variables were also analyzed to identify conditions influencing morbidity and mortality. RESULTS: Fifty-seven patients (47%) presented with preoperative complications (Group C) and 65 (53%) did not (Group U). Overall operative mortality was 22% (27 patients). Mortality within subgroups was 40 and 6% for complicated and uncomplications cases, respectively (p < 0.001). The 85% of the overall mortality occurred in Group C patients. During the experience, the operative mortality rate actually observed ranged from 0 to 38% and was similar to the calculated expected risk, thus proving a direct relationship with the amount of complicated cases operated on each year. Multivariate analysis revealed that older age and hemopericardium significantly increased the risk of operative death, while male gender, preoperative complications, postoperative bleeding, duration of circulatory arrest and aortic cross-clamp time significantly predicted morbidity (p = 0.02). CONCLUSIONS: Current results of emergency repair of acute type A aortic dissection are strictly dependent on the number of complicated cases referred for operation. Earlier diagnosis and prompt referral before development of preoperative complications appear essential to improve surgical results.

Adult↗
PubMed1999

Diagnosis and early surgical management of traumatic thoracic aortic disruption.

OBJECTIVE: Traumatic rupture of the thoracic aorta is a major cause of death. Survival greatly depends on early diagnosis, degree of injuries to other districts and timing of repair. To address the controversial aspects of this condition, we retrospectively reviewed our experience. METHODS: Between April 1984 and December 1998, 39 patients (31 males, 79%), with a mean age of 33 +/- 7 (range, 17 to 59 years), underwent surgical repair at our institution. Final diagnosis of aortic disruption was achieved in 33 patients (85%) by aortogram, and in 6 (15%) by transesophageal echocardiography (TEE) alone. Four patients (8%) had a false negative chest X-ray on admission. Twenty-four patients (61.5%) had additional major injuries to other districts (n = 4, cranial trauma; n = 13, cranial trauma + pelvic fracture; n = 5, lesions to abdominal viscera; n = 2, lesions to abdominal viscera + pelvic fracture). Surgical techniques included simple aortic cross-clamping in 7 patients (18%), partial femoral-femoral bypass in 17 (44%), and partial left heart bypass in 15 (38%). Two patients underwent direct aortic suture (5%), whereas 37 (95%) had interposition of a vascular graft. RESULTS: Three patients (8%) died after major hemorrhaging during the early phases of our experience. Paraplegia occurred in 1 patient (2.5%) in the single aortic cross-clamping group. There was no morbidity directly attributable to the administration of heparin for cardiopulmonary bypass. CONCLUSION: Although aortography is still the gold standard to achieve diagnosis, the use of TEE as a method of detecting traumatic injury to the thoracic aorta appears feasible in critical patients, advantageously saving time. With a meticulous surgical approach and the use of an effective method for distal aortic perfusion during repair, it is possible to achieve good outcomes.

Adolescent↗
PubMed1998

Results of Biocor stentless valve replacement for infective endocarditis of the native aortic valve.

The mid-term results in a selected group of 9 patients with native aortic valve endocarditis managed by aortic valve replacement (with or without complex annular reconstruction) using a totally biological stentless valve are outlined. At a mean follow-up of 48 months, there are currently 7 survivors (2 late noncardiac deaths) with 100% freedom from reoperation, valve-related complication, and endocarditis.

Adult↗
PubMed1998

Mitral valve replacement associated with massive left atrial calcification.

Massive calcification of the atrial walls is a rare condition that entails important implications for mitral valve operations. Endoatriectomy is the procedure of choice in this situation. A technique of total replacement of the left atrium and mitral valve by means of a valved, T-shaped graft is presented as a possible alternative when a more conventional approach is not feasible.

Aortic Valve↗
PubMed1998

Aortic root replacement in adolescents and young adults: composite graft versus homograft or autograft.

BACKGROUND: Aortic root replacement (ARR) is a technically demanding procedure that can be performed using a variety of prosthetic devices. Root replacement in the young, but grown-up, patient poses unique problems in terms of the long-term outcome and active lifestyle that must be guaranteed by this operation. To identify the "ideal" substitute for ARR in the young, clinical results in teenagers and young adults (<35 years) operated on in the past two decades were reviewed. METHODS: Thirty-eight patients younger than 35 years underwent ARR between January 1980 and December 1996. Eighteen patients, aged 30+/-5 years, had ARR with composite graft (group 1), whereas 20 patients, aged 28+/-6 years, had ARR with aortic homografts or pulmonary autografts (group 2). Primary indication for the operation was aortic insufficiency with anuloaortic ectasia (12 of 18) in group 1 and aortic insufficiency with or without anuloaortic ectasia (16 of 20) in group 2. Urgent ARR was required in 3 (17%) group 1 patients and 1 (5%) group 2 patient (p = 0.01). RESULTS: Operative deaths were 2 (11%) in group 1, caused by hemorrhage and low output, and none in group 2. There were 4 (25%) late deaths in group 1, caused by embolism (2), hemorrhage, and myocardial infarction, and 1 (5%) in group 2, caused by arrhythmia. Survival was 81% +/- 9%, and 55%+/-18% at 2 and 10 years in group 1 versus 94%+/-5% at 2 years in group 2 (p = 0.04). Freedom from valve-related events was 93%+/-6% and 62%+/-18% at 2 and 10 years in group 1 versus 100% at 2 years in group 2 (p = 0.02). Freedom from reoperation in group 1 was 75% +/- 22% at 10 years, whereas no reoperations were done in group 2. Seven (58%) group 1 patients versus 1 (5%) group 2 patient were on cardiac medications (p = 0.001), and 11 (92%) group 1 patients versus no group 2 patients were on warfarin therapy at follow-up. All survivors were back to school or prior employment. CONCLUSIONS: Survival early after ARR does not differ depending on the type of prosthesis. Valve-related events are common, and reoperation may be needed late after ARR with composite grafts. Despite limited follow-up with biologic devices, the prevalence of complications with composite grafts makes homograft or autograft ARR preferable in adolescents and young adults.

Adolescent↗
PubMed1998

Hancock versus stentless bioprosthesis for aortic valve replacement in patients older than 75 years.

BACKGROUND: Stented aortic bioprostheses are routinely used in elderly patients. The stent, however, is obstructive and implies several hazards. Stentless aortic valves appear to be hemodynamically advantageous. However, their implantation is longer and technically more demanding, and durability is still under investigation. METHODS: Between January 1993 and December 1996, 77 patients (28 men) were prospectively randomized to undergo aortic valve replacement using the Hancock valves (group A: 40 patients, 16 men; age, 77+/-3 years; body surface area, 1.7+/-0.17 m2) or a stentless bioprostheses (group B: 37 patients, 12 men; age, 76+/-2 years; body surface area, 1.7+/-0.15 m2; Biocor, 17; Toronto SPV, 20). Preoperative variables were not significantly different between the two groups. Bypass time was 123+/-46 versus 133+/-51 minutes, and aortic cross-clamp time was 83+/-26 versus 95+/-24 minutes for group A and group B, respectively (not significant). Seven patients in group A (17.5%) and 5 in group B (13.5%) had enlargement of the aortic annulus. Valve size normalized to body surface area was 13.7+/-1.5 versus 14.1+/-1.6 mm/m2 for group A and group B, respectively (not significant). Eleven patients in group A (27.5%) and 5 in group B (13.5%) had concomitant myocardial revascularization. RESULTS: Overall perioperative mortality was 5% in group A (low cardiac output in 2 patients), and 8% in group B (low cardiac output in 1; major neurologic event in 2). Follow-up is 97% complete (group A, 14.5+/-10 months; group B, 18.5+/-12 months). One patient in group B died at 28 months of myocardial infarction. Actuarial survival at 12 and 24 months is 92% versus 91% and 92% versus 81% for group A and group B, respectively. At 6 months, patients in group A showed a peak transaortic gradient of 25+/-7 versus 20+/-9 mm Hg in group B. Progressive regression of left ventricular mass expressed as a percentage of preoperative value was 10.5% and 19% for group A and group B at 1 year postoperatively (not significant). CONCLUSIONS: Stentless valves represent a valuable alternative to conventional prostheses in patients older than 75 years, although no great advantages with their use emerge from this study. Continued evaluation particularly with regard to evidence of left ventricular remodeling and valve degeneration in the long term is warranted.

Actuarial Analysis↗
PubMed1998

Risk of late reoperations in patients with acute type A aortic dissection: impact of a more radical surgical approach.

OBJECTIVE: To evaluate the incidence and risk factors for reoperations on the pre-isthmic aorta after repair of type A acute aortic dissection. METHODS: From January 1979 to December 1996, 178 patients (125 males and 53 females with a mean age of 57 +/- 9 years) underwent emergency surgery for acute type A aortic dissection with an overall operative mortality rate of 21%. One hundred and forty-one patients (100 males and 41 females, aged 58 +/- 12 years), were discharged after successful replacement of the ascending aorta in 136 cases (96%) with extension to the transverse arch in 22 (16.2%) and associated total root or aortic valve replacement in 31 (22.8%) and 6 (4.4%) cases, respectively. Intimal tear resection and direct primary anastomosis of the aorta were performed in 5 patients (4%). Total follow-up was 690 patient-years, mean 5.1 +/- 4.1 years, with an actuarial survival rate at 5,10 and 15 years of 88%, 73% and 42%, respectively. RESULTS: Nineteen patients (13%), 13 males and 6 females, aged 50 +/- 10 years, required a total of 22 reoperations with an actuarial freedom from reoperation at 5, 10 and 15 years of 94%, 64% and 35%, respectively. Initial repair consisted of replacement of the ascending aorta in 16 (84%) cases, with total root replacement in 2 (12%) and isolated aortic valve replacement in 1 (6%). Three patients (16%) were treated by intimal tear resection and direct primary anastomosis of the aorta. Mean interval between initial repair and reoperation was 5.2 +/- 3.1 years and indication to re-do surgery were severe aortic regurgitation in 2 (11%), aneurysmal evolution of the false lumen in 4 (21%) or both in 13 (68%). Extensive aortic reconstruction comprising simultaneous graft replacement of the aortic root, ascending aorta and aortic arch was necessary in 13 cases (68%), isolated replacement of the ascending aorta in 3 (16%), aortic valve in 2 (11%) and aortic arch in 1 (5%). There were 1 hospital (5%) and 2 late (11%) deaths at a mean follow-up of 2.5 +/- 2.4 years, with an actuarial survival at 5 years of 88%. Retrospective analysis of our total experience revealed that the introduction of the open distal anastomosis technique since 1990, reduced the incidence of reoperation from 11/46 (24%) to 8/95 (8.4%) (P < 0.05). However, also with this strategy 8/73 (11%) patients surviving replacement limited to the ascending aorta required reoperation versus none of the 22 patients surviving repair extended to the aortic arch. Three out of 5 (60%) patients undergoing intimal tear resection and primary anastomosis of the aorta early in our experience, required reoperation. CONCLUSIONS: Management of patients with acute type A aortic dissection may include one or more surgical procedures after the initial emergency repair. Reoperations carry a low operative risk with good long-term survival and their incidence is reduced by routine open distal anastomosis and aggressive replacement of the aortic arch. Intimal tear resection and primary anastomosis of the aorta appear to be associated with increased risk of reoperation.

Acute Disease↗
PubMed1998

Endocytic clathrin-coated pit formation is independent of receptor internalization signal levels.

The mechanisms responsible for coated pit formation in cells remain unknown, but indirect evidence has argued both for and against a critical role of receptor cytoplasmic domains in the process. If the endocytic motifs of receptors are responsible for recruiting AP2 to the plasma membrane, thereby driving coated pit formation, then the level of constitutively internalized receptors at the membrane would be expected to govern the steady-state level of coated pits in cells. Here we directly test this hypothesis for broad classes of receptors containing three distinct constitutive internalization signals. Chimeric proteins consisting of an integral membrane reporter protein (Tac) coupled to cytoplasmic domains bearing tyrosine-, di-leucine-, or acidic cluster/casein kinase II-based internalization signals were overexpressed to levels that saturated the internalization pathway. Quantitative confocal immunofluorescence microscopy indicated that the number of plasma membrane clathrin-coated pits and the concentration of their structural components were invariant when comparing cells expressing saturating levels of the chimeric receptors to nonexpressing cells or to cells expressing only the Tac reporter lacking cytoplasmic internalization signals. Biochemical analysis showed that the distribution of coat proteins between assembled coated pits and soluble pools was also not altered by receptor overexpression. Finally, the cellular localizations of AP2 and AP1 were similarly unaffected. These results provide a clear indication that receptor endocytic signals do not determine coated pit levels by directly recruiting AP2 molecules. Rather, the findings support a model in which coated pit formation proceeds through recruitment and activation of AP2, likely through a limited number of regulated docking sites that act independently of endocytic signals.

Adaptor Protein Complex 1↗
PubMed1998

Cost effectiveness of screening for subclinical hypothyroidism in the elderly. A decision-analytical model.

OBJECTIVE: The value of early detection of subclinical hypothyroidism is the object of a long lasting debate. In this study, we assessed the cost effectiveness of a policy based upon screening for this condition through thyroid-stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) serum level measurements in the elderly. DESIGN: A Markov model was developed where hypothetical elderly patients (i.e. > or = 60 years of age), who attend general practitioner (GP) clinics for periodic health examinations in a primary-care setting in Italy, made transitions between health states at annual interval for 15 years, thus allowing an estimation of the average cost and of the expected average number of quality-adjusted life-years (QALY). In this model, patients were assumed to be seen at annual intervals by GPs for clinical examination and serum cholesterol level measurement, to which a TSH, T3 and T4 serum measurement was added. In the base-case analysis, TSH was measured every 5 years and, if abnormal, T3 and T4 serum levels were also determined. Costs were analysed from the perspective of the Italian National Health Service (NHS) and reflected 1996 values. MAIN OUTCOME MEASURES AND RESULTS: In the base-case analysis, the additional benefit estimated from testing a female population for subclinical hypothyroidism every 5 years was 0.36 QALY, with a cost per QALY gained of 668,298 lire (L). The expected gain in QALY for men was 0.20 and the cost per QALY gained was L270,322. In general, the best cost-effectiveness profile was seen with testing every 3 years. Results were sensitive to variations in the prevalence of disease among the target population, both in men and women. CONCLUSIONS: Our study indicates that a screening policy for subclinical hypothyroidism in the elderly population could be worthwhile. However, as the costs could be significant when applied at the population level, this policy deserves further assessment through well-designed primary research.

Aged↗
PubMed1998

[Transient congenital hypothyroidism: physiopathology and clinica].

The fetus and the newborn are more sensitive than adults to a reduced environmental iodine supply, and in iodine-deficient areas, transient neonatal hypothyroidism is frequently observed. This transient thyroid failure may be associated with neonatal goiter and elevated serum thyroglobulin levels at birth. Borderline elevated neonatal serum TSH concentrations frequently occur in newborns in iodine deficient areas, and result in a higher recalling rate at the screening for congenital hypothyroidism. Minor defects in mental performances and neurological development are observed in children living in areas of mild to moderate iodine deficiency, and result from the concomitant effects of iodine deficiency in the mother during pregnancy and transient neonatal hypothyroidism. Endemic cretinism is the severe and irreversible neurological consequence of iodine deficiency during fetal and neonatal life. Iodine prophylaxis is highly effective in preventing the development of iodine deficiency disorders including transient neonatal hypothyroidism. Since iodine prophylaxis in Italy is inadequate, variable degrees of iodine deficiency are still present all-over the country, and are responsible of a higher incidence of transient neonatal hypothyroidism or hyperthyrotropinemia.

Adult↗
PubMed1997

Modulation of the arrestin-clathrin interaction in cells. Characterization of beta-arrestin dominant-negative mutants.

We recently demonstrated that nonvisual arrestins interact via a C-terminal binding domain with clathrin and function as adaptor proteins to promote beta2-adrenergic receptor (beta2AR) internalization. Here, we investigated the potential utility of a mini-gene expressing the clathrin-binding domain of beta-arrestin (beta-arrestin (319-418)) to function as a dominant-negative with respect to beta2AR internalization and compared its properties with those of beta-arrestin and beta-arrestin-V53D, a previously reported dominant-negative mutant. In vitro studies demonstrated that beta-arrestin-V53D bound better to clathrin than beta-arrestin but was significantly impaired in its interaction with phosphorylated G protein-coupled receptors. In contrast, whereas beta-arrestin (319-418) also bound well to clathrin it completely lacked receptor binding activity. When coexpressed with the beta2AR in HEK293 cells, beta-arrestin (319-418) effectively inhibited agonist-promoted receptor internalization, whereas beta-arrestin-V53D was only modestly effective. However, both constructs significantly inhibited the stimulation of beta2AR internalization by beta-arrestin in COS-1 cells. Interestingly, immunofluorescence microscopy analysis reveals that both beta-arrestin (319-418) and beta-arrestin-V53D are constitutively localized in clathrin-coated pits in COS-1 cells. These results indicate the potential usefulness of beta-arrestin (319-418) to effectively block arrestin-clathrin interaction in cells and suggest that this construct may prove useful in further defining the mechanisms involved in G protein-coupled receptor trafficking.

Animals↗
PubMed1997

Usefulness of bicuspid homograft reconstruction of the right ventricular outflow tract in infants with complex congenital heart disease.

Homograft supply is limited especially for those sizes required for neonatal and infant cardiac operations. Surgically downsized homografts have been successfully used for right ventricular outflow tract reconstruction in 5 children (mean weight 6.2 kg) with evidence of good hemodynamic performance of the conduits at a mean follow-up time of 3.7 years.

Bioprosthesis↗