Recognition of persistent left superior vena cava in non-congenital patients undergoing cardiac surgery.

Persistent left superior vena cava (PLSVC) represents the most frequent congenital malformation of the thoracic venous drainage system. In adults referred to surgery for an acquired cardiac disease, abnormal venous drainage may be missed if not carefully researched. Discovering a previously undiagnosed PLSVC during cardiopulmonary bypass (CPB) may present some inconvenience for both the perfusionist and the surgeon, especially during a minimally invasive approach. The authors believe PLSVC probably may represent an under-reported condition. A careful screening of patients undergoing cardiac surgery may prove helpful. In particular, a complete echocardiographic study may help to better diagnose this condition before surgery. Different signs may raise the suspicion of PLSVC and should be carefully researched during preoperative patient work-up.

Calcified disease of the mitral annulus: a spectrum of an evolving disease.

Mitral annulus calcification may appear under different forms depending from its evolution stage: mitral annulus calcification; homogeneous calcified mass of the mitral valve; liquefaction necrosis of the mass; reduction or stability of the mass dimension. We report a large calcified mass located in between the posterior mitral valve leaflet and adjacent left ventricular myocardium suggesting the homogeneous calcified phase of the disease.

Quadricuspid morphology of the aortic valve.

Quadricuspid aortic valve is a rare congenital heart defect. It may be isolated or associated to other cardiac anomalies. It may cause aortic valve dysfunction, commonly aortic regurgitation. Management of patients with quadricuspid aortic valve is represented by strict follow-up, because they may require aortic valve replacement in later life. We report the case of a 37-year old male patient, occasionally diagnosed to have quadricuspid aortic valve. Diagnosis and management are discussed.

Cardiac allograft vasculopathy : complications and imaging studies.

Cardiac allograft vasculopathy (CAV) is an accelerated form of coronary artery disease affecting both intramyocardial and epicardial coronary arteries and is observed in patients during long-term survival after cardiac transplantation. We report a case of CAV complicated with silent transmural myocardial infarction and massive left ventricular thrombus formation associated with silent pericarditis and with ischemic and non-ischemic scar tissue, as detected by cardiac magnetic resonance imaging (CMRI). The authors suggest CMRI as an additional technique along with echocardiography during follow-up of heart transplant recipients. CMRI may contribute to the early identification of areas of myocardial wall abnormalities suggestive of CAV, thus guiding diagnosis and prompt percutaneous treatment.

Defective DNA repair genes in a primary culture of human renal cell carcinoma.

PURPOSE: Genomic stability is maintained by error-free DNA replication, repair, and recombination. To determine if repair genes contribute to genomic instability, we used a newly established cell line RCC-AJR (from clear-cell renal cell carcinoma) to examine hMSH2 (a mismatch-repair gene) and the gene encoding DNA beta polymerase (polbeta; a known contributor to base-excision repair). METHODS: Coding sequences of hMSH2 and polbeta were amplified by the polymerase chain reaction (PCR) using RNA from RCC-AJR cells and matched normal kidney (NK) cells from the same patient. Nucleotide sequences of the PCR products were determined by the dideoxy-DNA method and direct sequencing. Expressions of repair genes were assayed by Western blotting. Microsatellite stability in RCC-AJR cells was assayed by alteration in (CA)n repeats. RESULTS: In the RCC-AJR cells, we detected (a) a deletion of 1476 bp encoding 492 amino acids of hMSH2 cDNA, (b) an 87-bp deletion in the polbeta coding sequence, (c) truncated forms of hMSH2 and polbeta proteins, and (d) microsatellite instability. CONCLUSIONS: This study provides evidence of alterations in hMSH2 and polbeta in the homogeneous cell population of an RCC-AJR tumor culture. The data indicate that repair genes may help preserve genomic stability in this cell line. We believe that this new primary RCC-AJR cell line will prove a useful model for investigating the cascade of genetic events in renal cells that leads to renal carcinogenesis.

[Reversal left diastolic ventriculo-atrial flow induced by asynchronism in a patient with dilated cardiopathy and VVI pacemaker]. / Reflusso diastolico ventricolo-atriale sinistro indotto dall'asincronismo atrio-ventricolare in paziente con cardiopatia dilatativa portatore di pacemaker VVI.

We studied a case of reversal atrioventricular diastolic flow in a 74-year-old patient suffering from chronic heart failure for six years, following double myocardial infarction on the inferior (in 1985) and the anterior wall (in 1992). During his last hospitalization, he had an arrhythmic complication (advanced atrioventricular block) that required a definitive implantation of a VVI-pacemaker. The patient, a working man in good hemodynamic condition over the past several years, acknowledged symptoms of progressive functional decline three to six months prior to coming to our observation for a medical check-up. The surface electrocardiogram showed normal electrical PM activity. Echo-Doppler examination beyond the improved systolic function of left ventricle showed a variable E/A velocity ratio of mitral valve flow, due to the casual relationship between spontaneous atrial electrical activity and ventricular stimulation. In addition, at the surface ECG we frequently observed a retrograde atrioventricular flow during mean phase of diastole each time the P wave occurred at the end of T wave. This event did not occur when the T-P interval was longer (a few more milliseconds) and was thus similar to a normal atrioventricular ECG sequence. To summarize, we can affirm that in patients with dilated cardiomyopathy and improved systolic function requiring pacemaker implantation, the sequential mode of ventricular stimulation must be preferred, especially if there is normal electrical activity in the right atrium.

The adenovirus E1A 289R and 243R proteins inhibit the phosphorylation of p300.

A protein of 300 kDa (p300) associates with the adenovirus E1A proteins and has been implicated in the control of cell cycle progression. In mammalian cells, p300 is actively phosphorylated in both quiescent and proliferating cells and its level of phosphorylation increases as it travels from late G1 into M phase. E1A requires p300 for the induction of cellular DNA synthesis and the repression of enhancer mediated transcription, suggesting that p300 may be involved in pathways that are important to cell proliferation and gene expression. Since the activities of most cell cycle regulatory proteins depend on their phosphorylation state, the possibility exists that certain activities of p300 might also be controlled by phosphorylation and that E1A might in fact be affecting these events. We show here by in vitro analysis that E1A inhibits the phosphorylation of p300 by decreasing the rate of incorporation of phosphate into p300. We also show that p300 can be used as a substrate for the cyclin-dependent p33cdk2 and p34cdc2 kinases, and propose that E1A might be antagonistic to these enzymes in phosphorylating p300. Thus, these results indicate a possible novel function by which E1A can interfere with cellular pathways.

Structure-function analysis of DNA polymerase-beta using monoclonal antibodies: identification of a putative nucleotide binding domain.

DNA polymerase-beta was purified from Novikoff hepatoma and used as an antigen in an in vitro immunization system to produce monoclonal antibodies. These reagents surprisingly showed cross-reactivity to a number of proteins, including several DNA polymerases. Nearly all of these proteins possess nucleotide binding sites, which suggested the potential value of using the monoclonals to elucidate structure-function relationships within polymerase-beta. Furthermore, these antibodies were able to partially neutralize (40-50%) polymerase-beta activity, and this effect could be blocked by dNTP1 but not by dNMP or rNTP. The limited neutralization phenomenon is at least partially explained by the weak binding affinity of these antibodies. Scatchard analysis of immunoprecipitation data predicted a Kd of 1.8 x 10(-8) M. Epitope mapping studies showed that the region of polymerase-beta recognized by one of the monoclonal antibodies is within residues 235-335, and sequence homology studies indicated that the epitope is probably located in the region of amino acids 283-320. At least a portion of this area, namely residues 301-308 and 311-315, appears to be part of a nucleotide binding domain which has sequence homology with a portion of the highly conserved ATP binding site in adenylate kinase.

Relationship between the increase in liver nuclear triiodothyronine-receptor sites and malic enzyme activation by dexamethasone.

Previous works have indicated that a glucocorticoid excess results in an increase in the maximal binding capacity of nuclear T3-receptors (MBC) and in the activity of cytosolic malic enzyme (ME) in the liver of the rat. In this paper, studies were undertaken to evaluate the degree of dependency between the changes in the nuclear T3-receptor number and the induction of a specific metabolic response of T3 evaluated by the activity of ME. The injection of graded daily doses of dexamethasone to adrenalectomized animals (Ax) induced a dose-related increase in MBC and ME activity, and their maximal values were reached with the same dose of dexamethasone. The time-related changes in MBC and ME after the administration of a daily dose of dexamethasone indicated that both parameters followed a progressive-time increase which was evident 24 h after the glucocorticoid until the highest level's were reached. MBC and ME were measured in thyroidectomized (Tx) rats and Tx plus Ax rats injected with dexamethasone (Tx + Ax + D). MBC increased significantly in Ax animals treated with dexamethasone (Ax + D) and in Tx + Ax + D compared with the Tx and control groups. ME activity was very low in Tx animals and dexamethasone injection to Tx + Ax animals did not increase the enzyme activity as occurred in the Ax group where the serum T3 level was in the normal range. These data indicate that the increase in ME activity by dexamethasone administration was associated to a simultaneous increase in the number of liver nuclear T3-receptors. Dexamethasone injected to hypothyroid animals failed to induce a ME activation as it was found in animals with normal T3 levels, suggesting a T3-mediated action of dexamethasone on ME activity by modification of the nuclear T3-receptor number.

Relationship between the increase in liver nuclear triiodothyronine-receptor sites and malic enzyme activation by dexamethasone.

Previous works have indicated that a glucocorticoid excess results in an increase in the maximal binding capacity of nuclear T3-receptors (MBC) and in the activity of cytosolic malic enzyme (ME) in the liver of the rat. In this paper, studies were undertaken to evaluate the degree of dependency between the changes in the nuclear T3-receptor number and the induction of a specific metabolic response of T3 evaluated by the activity of ME. The injection of graded daily doses of dexamethasone to adrenalectomized animals (Ax) induced a dose-related increase in MBC and ME activity, and their maximal values were reached with the same dose of dexamethasone. The time-related changes in MBC and ME after the administration of a daily dose of dexamethasone indicated that both parameters followed a progressive-time increase which was evident 24 h after the glucocorticoid until the highest levels were reached. MBC and ME were measured in thyroidectomized (Tx) rats and Tx plus Ax rats injected with dexamethasone (Tx + Ax + D). MBC increased significantly in Ax animals treated with dexamethasone (Ax + D) and in Tx + Ax + D compared with the Tx and control groups. ME activity was very low in Tx animals and dexamethasone injection to Tx + Ax animals did not increase the enzyme activity as occurred in the Ax group where the serum T3 level was in the normal range. These data indicate that the increase in ME activity by dexamethasone administration was associated to a simultaneous increase in the number of liver nuclear T3-receptors. Dexamethasone injected to hypothyroid animals failed to induce a ME activation as it was found in animals with normal T3 levels, suggesting a T3-mediated action of dexamethasone on ME activity by modification of the nuclear T3-receptor number.

Nuclear triiodothyronine receptors and metabolic response in perinatally protein-deprived rats.

Pregnant rats from day 14 of pregnancy and pups were fed a control diet (24% casein) or a deprived diet (8% casein) to obtain a control and a pre- and post-natal protein-deprived group. From 50 days of age, all groups were fed a balanced commercial stock diet for different periods. A significant reduction in body weight was observed in the perinatally protein-deprived group (PPD) after the different periods of nutritional recovery studied. Maximal binding capacity (MBC) and apparent affinity constant (Ka) of liver nuclear T3-receptors in the PPD group were similar to those in the control group. Mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) and cytosolic malic enzyme (ME) activity were significantly increased in the PPD group in all the periods of nutritional recovery studied, except in the 8 months old group where it was non-significant. Plasma T3 levels were higher in rats 3 and 15 days after the removal of the hypoprotein diet while it was normal after longer periods of nutritional recovery. Serum T4 was not modified in any group. The results indicate that protein undernutrition during perinatal life may induce an activation of hepatic T3-dependent enzymes which persists even after long periods of nutritional recovery. The lack of modification at the nuclear T3-receptor level, where supposedly the first T3-signal takes place, raises the possibility of an amplification of this signal at a step beyond the receptor.

Selective alterations in hepatic nuclear T3-receptors and enzyme responses by glucocorticoid deficit or excess.

Glucocorticoid deficit in rats induced by adrenalectomy for a 10-day period resulted in an increase in the apparent association constant (Ka) of the liver nuclear T3-receptor while maximal binding capacity (MBC) remained unaltered compared to the intact (sham-operated) animals and to adrenalectomy plus dexamethasone (Sx + D) animals. In addition, a significant increase in the basal activity of liver mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) was observed, while cytosolic malic enzyme (ME) activity was not modified in this situation. Dexamethasone injection (5 mg/kg/day for 4-5 days) to previously adrenalectomized animals (Sx + D) induced a significant increase in MBC of nuclear T3-receptors. On the other hand, Ka value and alpha-GPD activity were restored to the values found in the control group. However, basal activity of ME as well as the response of this enzyme to a saturating dose of T3 was substantially increased by dexamethasone treatment. A non-specific in vitro effect of dexamethasone on MBC and ME was excluded as these parameters were not modified when dexamethasone was added immediately before the in vitro assays. The present study indicates that glucocorticoid deficit or excess is able to induce changes at the level of the nuclear T3-receptor site. The increase in the activity of cytolic ME induced by dexamethasone injection was associated with a simultaneous increase in the T3-receptor capacity.(ABSTRACT TRUNCATED AT 250 WORDS)