Biomedical subjects

W F Shen

Publications and source records attributed to W F Shen.

At least 19 recordsLinked to original sources

PubMed2001

The HOX homeodomain proteins block CBP histone acetyltransferase activity.

Despite the identification of PBC proteins as cofactors that provide DNA affinity and binding specificity for the HOX homeodomain proteins, HOX proteins do not demonstrate robust activity in transient-transcription assays and few authentic downstream targets have been identified for these putative transcription factors. During a search for additional cofactors, we established that each of the 14 HOX proteins tested, from 11 separate paralog groups, binds to CBP or p300. All six isolated homeodomain fragments tested bind to CBP, suggesting that the homeodomain is a common site of interaction. Surprisingly, CBP-p300 does not form DNA binding complexes with the HOX proteins but instead prevents their binding to DNA. The HOX proteins are not substrates for CBP histone acetyltransferase (HAT) but instead inhibit the activity of CBP in both in vitro and in vivo systems. These mutually inhibitory interactions are reflected by the inability of CBP to potentiate the low levels of gene activation induced by HOX proteins in a range of reporter assays. We propose two models for HOX protein function: (i) HOX proteins may function without CBP HAT to regulate transcription as cooperative DNA binding molecules with PBX, MEIS, or other cofactors, and (ii) the HOX proteins may inhibit CBP HAT activity and thus function as repressors of gene transcription.

Amino Acid Motifs↗

PubMed2000

Functional cloning and characterization of a novel nonhomeodomain protein that inhibits the binding of PBX1-HOX complexes to DNA.

PBX1 is a homeodomain protein that functions in complexes with other homeodomain-containing proteins to regulate gene expression during developmental and/or differentiation processes. A yeast two-hybrid screen of a fetal liver-hematopoietic cDNA library using PBX1a as bait led to the discovery of a novel non-homeodomain-containing protein that interacts with PBX1 as well as PBX2 and PBX3. RNA analysis revealed it to be expressed in CD34(+) hematopoietic cell populations enriched in primitive progenitors, as is PBX1; search of the expressed sequence tag data base indicated that it is also expressed in other early embryonic as well as adult tissues. The full-length cDNA encodes a 731-amino acid protein that has no significant homology to known proteins. This protein that we have termed hematopoietic PBX-interacting protein (HPIP) is mainly localized in the cytosol and in small amounts in the nucleus. The region of PBX that interacts with HPIP includes both the homeodomain and immediate N-terminal flanking sequences. Strikingly, electrophoretic mobility shift assays revealed that HPIP inhibits the ability of PBX-HOX heterodimers to bind to target sequences. Moreover, HPIP strongly inhibits the transactivation activity of E2A-PBX. Together these findings suggest that HPIP is a new regulator of PBX function.

Amino Acid Sequence↗

PubMed2000

Changes in HOXB6 homeodomain protein structure and localization during human epidermal development and differentiation.

HOX homeodomain proteins are master developmental regulators, which are now thought to function as transcription factors by forming cooperative DNA binding complexes with PBX or other protein partners. Although PBX proteins exhibit regulated subcellular localization and function in the nucleus in other tissues, little data exists on HOX and PBX protein localization during skin development. We now show that the HOXB6 protein is expressed in the suprabasal layer of the early developing epidermis and throughout the upper layers of late fetal and adult human skin. HOXB6 signal is cytoplasmic throughout fetal epidermal development, but substantially nuclear in normal adult skin. HOXB6 protein is also partially nuclear in hyperproliferative skin conditions, but appears to be cytoplasmic in basal and squamous cell carcinomas. Although all three PBX genes are expressed in fetal epidermis, none of the three PBX proteins exhibit nuclear co-localization with HOXB6 in either fetal or adult epidermis. RNA and protein data suggest that a truncated HOXB6 protein, lacking the homeodomain, is expressed in undifferentiated keratinocytes and that the full-length protein is induced by differentiation. GFP-fusion proteins were used to demonstrate that the full-length HOXB6 protein is localized to the nucleus while the truncated protein is largely cytoplasmic. Taken together, these data suggest that during epidermal development the truncated HOXB6 isoform may function by a mechanism other than as DNA binding protein, and that most of the nuclear, homeodomain-containing HOXB6 protein does not utilize PBX proteins as DNA binding partners in the skin. Published 2000 Wiley-Liss, Inc.

Adult↗

PubMed1999

HOXA9 forms triple complexes with PBX2 and MEIS1 in myeloid cells.

Aberrant activation of the HOX, MEIS, and PBX homeodomain protein families is associated with leukemias, and retrovirally driven coexpression of HOXA9 and MEIS1 is sufficient to induce myeloid leukemia in mice. Previous studies have demonstrated that HOX-9 and HOX-10 paralog proteins are unique among HOX homeodomain proteins in their capacity to form in vitro cooperative DNA binding complexes with either the PBX or MEIS protein. Furthermore, PBX and MEIS proteins have been shown to form in vivo heterodimeric DNA binding complexes with each other. We now show that in vitro DNA site selection for MEIS1 in the presence of HOXA9 and PBX yields a consensus PBX-HOXA9 site. MEIS1 enhances in vitro HOXA9-PBX protein complex formation in the absence of DNA and forms a trimeric electrophoretic mobility shift assay (EMSA) complex with these proteins on an oligonucleotide containing a PBX-HOXA9 site. Myeloid cell nuclear extracts produce EMSA complexes which appear to contain HOXA9, PBX2, and MEIS1, while immunoprecipitation of HOXA9 from these extracts results in coprecipitation of PBX2 and MEIS1. In myeloid cells, HOXA9, MEIS1, and PBX2 are all strongly expressed in the nucleus, where a portion of their signals are colocalized within nuclear speckles. However, cotransfection of HOXA9 and PBX2 with or without MEIS1 minimally influences transcription of a reporter gene containing multiple PBX-HOXA9 binding sites. Taken together, these data suggest that in myeloid leukemia cells MEIS1 forms trimeric complexes with PBX and HOXA9, which in turn can bind to consensus PBX-HOXA9 DNA targets.

Animals↗

PubMed1997

The Abd-B-like Hox homeodomain proteins can be subdivided by the ability to form complexes with Pbx1a on a novel DNA target.

Previous studies showed that the Hox homeodomain proteins from paralog groups 1-8 display cooperative DNA binding with the non-Hox homeodomain protein Pbx, mediated by a canonical YPWM. Although the Abd-B-like Hox proteins in paralogs 9-13 lack this sequence, Hoxb-9 and Hoxa-10 were reported to bind with Pbx1a to DNA. We show that these interactions require a tryptophan 6 amino acids N-terminal to the homeodomain. Binding site selection for Hoxb-9 with Pbx1a yielded ATGATTTACGAC, containing a novel TTAC Hox-binding site adjacent to a Pbx site. In the presence of Pbx1a, Hoxb-9 and Hoxa-10 bound to targets containing either TTAC or TTAT. These data extend previous findings that interactions with Pbx define a Hox protein binding code for different DNA sequences across paralog groups 1 through 10. Members of the 11, 12, and 13 paralogs do not cooperatively bind DNA with Pbx1a, despite the presence of tryptophan residues N-terminal to the homeodomain in Hoxd-12 and Hoxd-13. Hoxa-11, Hoxd-12, or Hoxd-13, in the presence of Pbx1a, selected a TTAC Hox site but lacking a Pbx1a site. These data suggest that Abd-B-like Hox proteins bind to a novel TTAC site and can be divided by their cooperative binding to DNA with Pbx1a.

Amino Acid Sequence↗

PubMed1997

AbdB-like Hox proteins stabilize DNA binding by the Meis1 homeodomain proteins.

Recent studies show that Hox homeodomain proteins from paralog groups 1 to 10 gain DNA binding specificity and affinity through cooperative binding with the divergent homeodomain protein Pbx1. However, the AbdB-like Hox proteins from paralogs 11, 12, and 13 do not interact with Pbx1a, raising the possibility of different protein partners. The Meis1 homeobox gene has 44% identity to Pbx within the homeodomain and was identified as a common site of viral integration in myeloid leukemias arising in BXH-2 mice. These integrations result in constitutive activation of Meis1. Furthermore, the Hoxa-9 gene is frequently activated by viral integration in the same BXH-2 leukemias, suggesting a biological synergy between these two distinct classes of homeodomain proteins in causing malignant transformation. We now show that the Hoxa-9 protein physically interacts with Meis1 proteins by forming heterodimeric binding complexes on a DNA target containing a Meis1 site (TGACAG) and an AbdB-like Hox site (TTTTACGAC). Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b, while Hox proteins from other paralogs do not appear to interact with Meis1 proteins. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.

Animals↗

PubMed1996

Hox homeodomain proteins exhibit selective complex stabilities with Pbx and DNA.

Eight of the nine homeobox genes of the Hoxb locus encode proteins which contain a conserved hexapeptide motif upstream from the homeodomain. All eight proteins (Hoxb-1-Hoxb-8) bind to a target oligonucleotide in the presence of Pbx1a under conditions where minimal or no binding is detected for the Hox or Pbx1a proteins alone. The stabilities of the Hox-Pbx1a-DNA complexes vary >100-fold, with the proteins from the middle of the locus (Hoxb-5 and Hoxb-6) forming very stable complexes, while Hoxb-4, Hoxb-7 and Hoxb-8 form complexes of intermediate stability and proteins at the 3'-side of the locus (Hoxb-1-Hoxb-3) form complexes which are very unstable. Although Hox-b proteins containing longer linker sequences between the hexapeptide and homeodomains formed unstable complexes, shortening the linker did not confer complex stability. Homeodomain swapping experiments revealed that this motif does not independently determine complex stability. Naturally occurring variations within the hexapeptides of specific Hox proteins also do not explain complex stability differences. However, two core amino acids (tryptophan and methionine) which are absolutely conserved within the hexapeptide domains appear to be required for complex formation. Removal of N- and C-terminal flanking regions did not influence complex stability and the members of paralog group 4 (Hoxa-4, b-4, c-4 and d-4), which share highly conserved hexapeptides, linkers and homeodomains but different flanking regions, form complexes of similar stability. These data suggest that the structural features of Hox proteins which determine Hox-Pbx1a-DNA complex stability reside within the precise structural relationships between the homeodomain, hexapeptide and linker regions.

Amino Acid Sequence↗

PubMed1996

Comparative value of Doppler echocardiography and cardiac catheterization for management decision-making in patients with left-sided valvular regurgitation.

OBJECTIVE: The purpose of this study was to examine the value of non-invasive clinical and Doppler echocardiographic findings, compared to cardiac catheterization, in management decision-making for patients with left-sided valvular regurgitation. METHODS: One hundred and thirty-five consecutive patients with left-sided valvular regurgitation who underwent cardiac catheterization and detailed Doppler echocardiography were prospectively studied. Two independent groups of experienced cardiologists, given clinical information combined with either Doppler echocardiographic or cardiac catheterization data, decided to operate, not to operate, or remained uncertain. RESULTS: In 63 (81%) of 78 patients with mitral regurgitation, there was agreement on the decision for valve surgery or medical treatment between Doppler echocardiography and cardiac catheterization. Valve repair was performed in 22 patients, which agreed with the echocardiographic decision. In the remaining 15 patients, although the severity and type of mitral valve lesions and left ventricular functional status were confirmed by Doppler echocardiography, the clinical decision was uncertain; additional information concerning coronary anatomy (13 patients) and pulmonary artery pressure (one patient) or both (one patient) was required. In 47 of 57 patients (82%) with aortic regurgitation, there was agreement on their management as a result of Doppler echocardiography and cardiac catheterization findings. In 10 patients, the clinical decision reached with the help of Doppler echocardiography alone was uncertain and coronary (seven patients), left ventricular (two patients) angiography or aortography (one patient) were requested. Overall, there were no conflicting clinical decisions made by the two methods in patients with either mitral or aortic regurgitation. CONCLUSIONS: In every patient in whom it was considered that a decision could be reached by echocardiography alone (more than 80% of patients) there was 100% agreement from the cardiac catheterization assessment group on the management decision. Therefore, in patients with significant mitral or aortic regurgitation where echocardiographic data is adequate, cardiac catheterization can be safely omitted from the investigative process for surgery. Where echocardiographic indices are conflicting, or significant coronary artery disease is suspected, cardiac catheterization is required.

Adult↗

PubMed1996

Pbx modulation of Hox homeodomain amino-terminal arms establishes different DNA-binding specificities across the Hox locus.

Pbx cofactors are implicated to play important roles in modulating the DNA-binding properties of heterologous homeodomain proteins, including class I Hox proteins. To assess how Pbx proteins influence Hox DNA-binding specificity, we used a binding-site selection approach to determine high-affinity target sites recognized by various Pbx-Hox homeoprotein complexes. Pbx-Hox heterodimers preferred to bind a bipartite sequence 5'-ATGATTNATNN-3' consisting of two adjacent half sites in which the Pbx component of the heterodimer contacted the 5' half (ATGAT) and the Hox component contacted the more variable 3' half (TNATNN). Binding sites matching the consensus were also obtained for Pbx1 complexed with HoxA10, which lacks a hexapeptide but requires a conserved tryptophan-containing motif for cooperativity with Pbx. Interactions with Pbx were found to play an essential role in modulating Hox homeodomain amino-terminal arm contact with DNA in the core of the Hox half site such that heterodimers of different compositions could distinguish single nucleotide alterations in the Hox half site both in vitro and in cellular assays measuring transactivation. When complexed with Pbx, Hox proteins B1 through B9 and A10 showed stepwise differences in their preferences for nucleotides in the Hox half site core (TTAT to TGAT, 5' to 3') that correlated with the locations of their respective genes in the Hox cluster. These observations demonstrate previously undetected DNA-binding specificity for the amino-terminal arm of the Hox homeodomain and suggest that different binding activities of Pbx-Hox complexes are at least part of the position-specific activities of the Hox genes.

Animals↗

PubMed1996

[Can Doppler echocardiography help to avoid cardiac catheterization in the surgical decision-making in isolated left heart valve diseases?].

The aim of this study was to assess the value of non-invasive investigation based on clinical evaluation and Doppler echography in deciding the operative indications of patients with isolated left heart valvular lesions compared. Three hundred and thirty five patients were included in a prospective study: 78 had MR, 57 had AR, 150 had AS and 50 had MS. All underwent clinical. Doppler echography and catheter studies. The therapeutic decision was taken blind by two groups of 2 cardiologists. Group I took its decision based on clinical findings and results of Doppler echography whilst Group II took its decision on the clinical and catheter data. For each patient, one of the following three choices was proposed: 1) medical treatment: 2) surgery or valvuloplasty with balloon catheter; 3) request for further information. In addition, in group I, the need for coronary angiography was left to the appreciation of two cardiologists. The quantification of the valvular disease was concordant for groups I and II in 93, 97, 98.5 and 100% for MR, AR, AS and MS respectively. These percentages were respectively 97, 95, 92 and 100% for assessment of left ventricular function. The theoretical management decision was concordant between the two groups for 97% of MR, 94.7% of AR, 95.3% of AS and 94% of MS. Complementary information requiring invasive studies was required by group I in 3.9% of cases. A discordant opinion was obtained in 0.6% of cases (2 cases of AS). Coronary angiography was requested by the cardiologists of Group I in 34% of patients, identifying all patients who underwent coronary bypass surgery. These results show that cardiac catheterisation is no longer an essential diagnostic procedure for discussing the indications of valvular surgery in the majority of patients with isolated left heart lesions.

Adult↗

PubMed1995

Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of Hox proteins.

The human proto-oncogene PBX1 codes for a homolog of Drosophila extradenticle, a divergent homeo domain protein that modulates the developmental and DNA-binding specificity of select HOM proteins. We demonstrate that wild-type Pbx proteins and chimeric E2a-Pbx1 oncoproteins cooperatively bind a consensus DNA probe with HoxB4, B6, and B7 of the Antennapedia class of Hox/HOM proteins. Specificity of Hox-Pbx interactions was suggested by the inability of Pbx proteins to cooperatively bind the synthetic DNA target with HoxA10 or Drosophila even-skipped. Site-directed mutagenesis showed that the hexapeptide motif (IYPWMK) upstream of the Hox homeo domain was essential for HoxB6 and B7 to cooperatively bind DNA with Pbx proteins. Engraftment of the HoxB7 hexapeptide onto HoxA10 endowed it with robust cooperative properties, demonstrating a functional role for the highly conserved hexapeptide element as one of the molecular determinants delimiting Hox-Pbx cooperativity. The Pbx homeo domain was necessary but not sufficient for cooperativity, which required conserved amino acids carboxy-terminal of the homeo domain. These findings demonstrate that interactions between Hox and Pbx proteins modulate their DNA-binding properties, suggesting that Pbx and Hox proteins act in parallel as heterotypic complexes to regulate expression of specific subordinate genes.

Amino Acid Sequence↗

PubMed1995

Tyrosine phosphorylation is required for up-regulation of the HOX-11 (TCL-3) homeobox proto-oncogene in T cells.

HOX-11 (TCL-3) is a homeobox proto-oncogene isolated from the breakpoint region of the t(10;14) chromosomal translocation associated with pediatric T-cell acute leukemia. To better understand the transcriptional regulation of the HOX-11 gene in response to extracellular signals, the levels of HOX-11 RNA were examined in normal and leukemic human T cells upon phytohemagglutinin and hematopoietic growth factor stimulation. While individual hematopoietic growth factors tested did not show any effect on HOX-11 gene expression, a drastic increase in HOX-11 RNA was observed under the induction of phytohemagglutinin. In the presence of cycloheximide, a protein synthesis inhibitor, phytohemagglutinin-induced HOX-11 up-regulation was suppressed, indicating that HOX-11 acts as a delayed early response gene which requires protein synthesis. The HOX-11 gene expression was also suppressed by the tyrosine kinase inhibitors tryphostin and lavendustin A. Our data therefore suggest that the delayed early response of HOX-11 up-regulation in T cells requires a tyrosine phosphorylation signal.

Base Sequence↗

PubMed1995

[Does mitral insufficiency prevent spontaneous contrast phenomenon and formation of thrombi in the left atrium?].

The aim of this study was to assess the influence of mitral regurgitation on the prevalence of left atrial spontaneous echo contrast and thrombosis in 2,180 consecutive patients undergoing transthoracic and transoesophageal echocardiography. Two groups of patients were defined according to the absence (group I) or presence (group II) of grades 3 or 4 mitral regurgitation quantified by transoesophageal echocardiography. Group II was associated with a statistically significant lower frequency of spontaneous echo contrast (0.6 vs 11.2%; p < 0.0001), left atrial thrombosis (0.6 vs 4.2%; p < 0.03), ischaemic cerebrovascular accidents (1.2 vs 21%; p < 0.0001), transient ischaemic attacks (0 vs 12%; p < 0.0001) and systemic embolism (0 vs 4.6%; p < 0.01). Conversely, the prevalence of atrial fibrillation was higher in group II (28 vs 19%; p < 0.01) and there were more patients with left atrial dimensions > or = 5.5 cm (16 vs 6.7%; p < 0.0001). When mitral stenosis and valve prosthesis were excluded, there were no cases of spontaneous echo contrast (8.3 vs 0%; p < 0.001) or left atrial thrombosis (2.9 vs 0%; p < 0.05) in the group with grades 3 or 4 mitral regurgitation. The phenomenon of left atrial spontaneous echo contrast and/or thrombosis is rare in patients with grade 3 or 4 in native mitral valve regurgitation and explains the low incidence of systemic embolism in these cases.

Adolescent↗

PubMed1994

Noninvasive prediction of coronary artery disease by transesophageal echocardiographic detection of thoracic aortic plaque in valvular heart disease.

Clinical and angiographic features and transesophageal echocardiographic (TEE) findings were retrospectively analyzed in 105 consecutive patients with valvular heart disease to assess the value of TEE detection of thoracic aortic plaque for predicting coronary artery disease. In 19 patients with significant coronary artery stenosis (> or = 70% narrowing of the luminal diameter in the left anterior descending, left circumflex, or right coronary arteries, or > or = 50% stenosis of the left main coronary artery), 18 had thoracic aortic plaque on TEE study. In contrast, aortic plaque existed in only 10 of the remaining 86 patients with normal coronary arteries or mildly atherosclerotic coronary lesions. The presence of aortic plaque on TEE study had a sensitivity of 95% and a specificity study had a sensitivity of 95% and a specificity of 88% for significant coronary stenosis at angiography. The positive and negative predictive values were 64% and 99%, respectively. There was a close relation between the degree of aortic intimal changes and the severity of coronary artery disease (r = 0.65; p < 0.001). Multivariate stepwise regression analysis of patient age, sex, risk factors of cardiovascular disease, angina, and TEE findings revealed that atherosclerotic aortic plaque was the most significant independent predictor of coronary artery disease. This study indicates that TEE detection of atherosclerotic plaque in the thoracic aorta is useful in the noninvasive prediction of the presence and severity of coronary artery disease in patients with valvular heart disease.

Aged↗

PubMed1994

Quantitation of aortic valve area in aortic stenosis with multiplane transesophageal echocardiography: comparison with monoplane transesophageal approach.

The accuracy and reliability of two-dimensional monoplane and multiplane transesophageal echocardiography (TEE) in the quantitation of aortic valve area were compared in 54 patients with aortic stenosis. Fifty patients had aortic valve area calculated by the continuity equation and transthoracic Doppler echocardiography (TTE); 25 underwent cardiac catheterization. Two-dimensional echocardiograms adequate for quantitation of aortic valve area were obtained in 21 (39%) patients with monoplane TEE and in 51 (94%) with multiplane TEE. The mean aortic valve area determined by both TEE methods did not differ significantly from that derived from TTE and catheterization. The mean difference of aortic valve area measurements between monoplane TEE and TTE was -0.045 +/- 0.11 cm2; that between multiplane TEE and TTE was 0.001 +/- 0.11 cm2. Multiplane TEE provided a better correlation of aortic valve area measurements with either TTE (y = 0.97 x + 0.03; r = 0.96; SEE = 0.11 cm2) or catheterization (y = 0.84 x + 0.11; r = 0.90; SEE = 0.12 cm2) than the monoplane TEE (y = 0.88 x + 0.13; r = 0.83; SEE = 0.15 cm2 and y = 0.41 x + 0.42; r = 0.81; SEE = 0.15 cm2). Severe aortic stenosis with valve orifice area of < or = 0.75 cm2 during TTE examination was found by multiplane TEE with a sensitivity of 96% and a specificity of 96%. Thus aortic valve area can be directly and reliably measured by two-dimensional multiplane TEE in majority of patients with aortic stenosis.

Adult↗

PubMed1994

Mitral to aortic velocity-time integral ratio. A non-geometric pulsed-Doppler regurgitant index in isolated pure mitral regurgitation.

To determine the clinical value of a simple and non-geometric pulsed Doppler regurgitant index, namely the mitral to aortic velocity-time integral (VTI) ratio in the semiquantitative assessment of severity of isolated pure mitral regurgitation (MR), 109 patients with isolated pure MR and sinus rhythm prospectively underwent Doppler echocardiography within 48 h of cardiac catheterization. The eccentricity of regurgitant jets was assessed by Doppler colour flow imaging and the mitral and aortic VTI and its ratio were derived from the pulsed Doppler method. Angiographic grade of MR was evaluated in all patients with MR, but haemodynamic regurgitant fraction was determined in only 91 patients. Fifty patients in sinus rhythm and without valvular disease served as controls. In the control group, the mitral VTI (16.2 +/- 2.5 cm) was lower than the aortic VTI (20.6 +/- 2.8 cm) (P < 0.001), resulting in a mitral to aortic VTI ratio of 0.79 +/- 0.08. In patients with MR, the mitral VTI was significantly greater than the aortic VTI (23.1 +/- 6.8 vs 16.9 +/- 4.7 cm, P < 0.001). There was a close relationship between the mitral to aortic VTI ratio and the angiographic grading of MR (n = 109, r = 0.74, P < 0.001). A ratio > or = 1.3 classified patients with severe MR (grade III or IV) with a sensitivity of 87%, a specificity of 91%, and positive and negative predictive values of 93% and 84%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve↗

PubMed1994

[Assessment of coronary flow reserve in patients with angina pectoris].

Coronary flow reserve was assessed by using a computer-assisted method in 26 normal controls and 45 patients with significant coronary artery stenosis ( > or = 50% luminal narrowing) and 16 patients with syndrome X. After intracoronary administration of papaverine, the diameter, cross sectional area, blood velocity, flow volume and reserve capacity of both left anterior descending (LAD) and right coronary arteries (RCA) were lower in patients with significant coronary stenosis than in controls. Despite similar changes in the diameter and cross sectional area, the velocity, flow volume and reserve capacity of these two vessels were also lower in patients with syndrome X than in controls. We conclude that coronary flow reserve is reduced in patients with coronary artery stenosis or syndrome X due to different levels of coronary artery abnormalities.

Angina Pectoris↗

PubMed1993

[Contribution of transesophageal and transthoracic echography in the evaluation of the mechanism and quantification of regurgitation in mitral and aortic bioprosthetic valves].

The respective values of transoesophageal (TOE) and transthoracic echocardiography (TTE) in the evaluation of the mechanism and the quantification of pathological regurgitation of bioprosthetic heart valves were analysed in 23 patients (14 mitral, 9 aortic; duration of implantation 108 +/- 43.2 months). Surgical or pathological correlations were available in all cases and catheter data in 18 of the 23 patients. With regards to mitral bioprostheses, the TOE evaluations of the mechanism and site of regurgitation corresponded in all cases with the operative or pathological findings and quantification of mitral regurgitation concorded with angiography. There was an underestimation of the severity of mitral regurgitation in 30% of cases by TTE compared with angiography; prolapse was diagnosed in 7 of the 10 cases with cusp tears. It was not possible to accurately determine the intra or perivalvular site of regurgitation by TEE. With regards to aortic bioprostheses, TOE and TTE were equally useful in determining the mechanism of regurgitation, showing cusp prolapse in 6 of the 9 cases with cusp tears. However, TTE quantified regurgitation accurately in all cases with respect to angiography, whereas TOE was only contributive in 50% of cases. These results show that single plane TOE is superior to TTE in the quantification and determination of the mechanism of regurgitation in mitral bioprostheses, but that TTE remains better for the quantification of regurgitation of aortic bioprostheses.

Adult↗