Biomedical subjects

Y Weng

Publications and source records attributed to Y Weng.

At least 109 records · Page 6Linked to original sources

PubMed1995

Accelerated degeneration of allografts in the first two years of life.

Between January 1988 and May 1994, 53 of 159 patients have received cryopreserved aortic and pulmonary allografts for reconstruction of the pulmonary circuit in the first 2 years of life with body weight ranging from 2.2 to 18 kg (mean, 8.2 +/- 3.4 kg). The implanted allografts ranged in internal diameter from 9 to 23 mm (mean, 16.3 +/- 3.5 mm). Of the 38 survivors who regularly had postoperative echocardiographic examinations 15 (39.5%) underwent cardiac catheterization 1 to 31 months after operation. Allograft dysfunction (gradient > or = 50 mm Hg with or without pulmonary insufficiency) was confirmed in 9 patients leading to reoperation in 5 and valvulo-angioplasty in 4. At 48 months actuarial survival was 64%. In the aortic and pulmonary allografts freedom from wall calcification at 20 months was 19% and 100%, respectively. Freedom from valve dysfunction in patients with aortic and pulmonary allografts was 53% and 88%, respectively; it was 49% in allografts with an internal diameter of 17 mm or smaller. Freedom from reoperation in all patients was 78%. In conclusion, young age, antigenicity (ABO compatibility), and type of allograft seemed to be independent risk factors for early allograft conduit degeneration and late valve dysfunction. Pulmonary allografts seemed to be more resistant to early wall calcification and valve dysfunction than aortic allografts.

Actuarial Analysis↗

PubMed1995

Expression of diverse and functional TCR gamma and Ig heavy chain transcripts in fetal liver cells cultured with interleukin-7.

We have previously shown that specific T cell receptor (TCR) gamma V regions genes (V gamma 4 and V gamma 6) are rearranged and expressed by murine fetal liver (FL) cells cultured with IL-7. The present studies determined that the sequences of the TCR V region gene transcripts expressed in response to IL-7 included diverse and functional sequences expressed by thymocyte and peripheral V gamma 4+ and V gamma 6+ T cells, indicating that the IL-7-induced expression of these genes is functionally relevant and mimics normal in vivo developmental events of gamma delta T cells. We found that more than 50% of these TCR transcripts had N region diversity. The presence of N region diversity indicates that these TCR rearrangements took place in vitro, presumably in response to IL-7, because fresh (uncultured) FL cells do not produce detectable terminal deoxynucleotidyl transferase (TdT) mRNA or protein. We also found that 100% of immunoglobulin (Ig) VH7183-JH4 transcripts from FL cells cultured with IL-7 had N region diversity at the V-DJ region, while only 40% of Ig VH7183-JH4 transcripts from FL cells cultured in the absence of IL-7 had N region diversity at this region. FL cell cultures supplemented for 7 days with IL-7 had increased TdT mRNA and protein levels. However, since 1-day culture of FL cells with or without IL-7 resulted in induction of expression of TdT, IL-7 probably does not directly stimulate TdT expression, but increases the development and expansion of TdT+ lymphoid cells. These findings implicate IL-7 as a regulator of the molecular signals involved in controlling TCR gamma rearrangement and diversity, and provide an in vitro system for studying the regulation of TdT and N region diversity in B and T lymphoid progenitors by environmental signals.

Animals↗

PubMed1995

Anomalous origin of the left coronary artery from the pulmonary artery in adults.

Between March 1986 and December 1994, four adult patients underwent surgery for anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) at the German Heart Institute Berlin. The patients, aged 27, 35, 54, and 60, were all females. ALCAPA was diagnosed 3 to 8 months before surgery. The patients presented with cardiac murmur (two patients), abnormal ECG pattern (two patients), arrhythmia (one patient), and acute myocardial infarction (one patient). During surgery a two coronary system was established either by Takeuchi operation (one patient), interruption of the anomalous vessel and aortocoronary saphenous vein bypass (two patients), or internal mammary artery bypass (one patient). There were no postoperative deaths, however, one patient had to be reoperated because of a recurrent shunt. Clinical improvement was observed in all four patients with disappearance of fatigue, angina, dyspnea, and ischemic ECG changes. Despite having this long-standing congenital heart defect, adult and elderly patients with ALCAPA may benefit from surgical intervention to establish a two coronary system.

Adult↗

PubMed1995

Purification and characterization of the Upf1 protein: a factor involved in translation and mRNA degradation.

mRNA degradation is an important control point in the regulation of gene expression and has been shown to be linked to the process of translation. One clear example of this linkage is the observation that nonsense mutations in a gene can accelerate the decay of the corresponding mRNA. In the yeast Saccharomyces cerevisiae, the product of the UPF1 gene, harboring zinc finger, NTP hydrolysis, and helicase motifs, was shown to be a trans-acting factor in this decay pathway. A UPF1 gene disruption results in stabilization of nonsense-containing mRNAs and leads to a nonsense suppression phenotype. As a first step toward understanding the molecular and biochemical mechanism of nonsense-mediated mRNA decay, we have purified Upf1p from a yeast extract and characterized its nucleic acid-dependent NTPase activity, helicase activity, and nucleic acid binding properties. The results presented in this paper demonstrate that Upf1p contains both RNA- and DNA-dependent ATPase activities and RNA and DNA helicase activities. In the absence of ATP, Upf1p binds to single-stranded RNA or DNA, whereas hydrolysis of ATP facilitates its release from single-stranded nucleic acid. Based on these results, the role of Upf1p's biochemical activities in mRNA decay and translation are discussed.

Acid Anhydride Hydrolases↗

PubMed1995

Performance of aortic and pulmonary homografts in the right ventricular outflow tract in children.

Cryopreserved homografts have been used at the German Heart Institute Berlin since October 1986. Until 31st May 1994, cryopreserved aortic (AA) or pulmonary (PA) homografts were implanted in the pulmonary position and followed up in 104 patients. The mean age at operation was 5.5 years. The patients were treated with 3-5 mg/kg aspirin daily after the operation for three months. They all had routine echocardiographic evaluation of their homografts, 47 patients were studied by heart catheterization. Excellent functional results of the homograft valves were found in 92 patients (88.5%). Early degeneration of the homograft conduit leading to reoperation was observed in 12 patients. Freedom from wall calcification was 18% in aortic and 78% in pulmonary homografts while freedom from valve dysfunction in aortic and pulmonary homografts at 60 months was 60% and 67%, respectively. Freedom from reoperation was 81% overall, 78% and 84% in patients with aortic and pulmonary homografts respectively (p < 0.05). In conclusion, pulmonary homograft has proved to be more durable than the aortic homograft in the pulmonary position, hence it is the preferential valve for RVOT reconstruction in children.

Age Factors↗

PubMed1995

[Study on chromosomal centromeric dots in couples with spontaneous abortion].

Chromosomal centromeric dots (Cd) of peripheral blood in 20 couples with spontaneous abortion and 10 normal couples were studied by Cd-banding technique. The frequencies of Cd loss and centromeric dots-nucleolar organizer region (Cd-NOR) fusion were 0.36 +/- 0.15/cell and 0.31 +/- 0.20/cell in the couples with abortion, 0.22 +/- 0.13/cell and 0.20 +/- 0.19/cell in normal couples respectively. These results showed that frequencies of Cd loss and Cd-NOR fusion in couples of spontaneous abortion were significantly higher than those in the normal couples. We suggested that the occurrence of spontaneous abortion in human might casually relate to the changes of Cd.

Abortion, Habitual↗

PubMed1995

Preservation of papillary muscles and chordae during mitral valve replacement: possibilities and limitations.

The various techniques of preserving the chordal apparatus in mitral valve replacement applied in 1,453 cases at a single institution between 1986 and 1994 are described. The techniques include preservation of chordal attachment to the posterior mitral leaflet only and to both leaflets with five different technical variations. The specific advantages and risks of these techniques are demonstrated and discussed. It is concluded, that preservation of the entire subvalvular structures is feasible in almost all cases. Different procedures should be employed according to the variety of mitral disease, in particular with respect to mitral leaflet mobility.

Chordae Tendineae↗

PubMed1994

Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma.

Mutational inactivation and allelic loss of the von Hippel-Lindau (VHL) gene appear to be causal events for the majority of spontaneous clear-cell renal carcinomas. We now show that hypermethylation of a normally unmethylated CpG island in the 5' region provides another potentially important mechanism for inactivation of the VHL gene in a significant portion of these cancers. This hypermethylation was found in 5 of 26 (19%) tumors examined. Four of these had lost one copy of VHL while one retained two heavily methylated alleles. Four of the tumors with VHL hypermethylation had no detectable mutations, whereas one had a missense mutation in addition to hypermethylation of the single retained allele. As would be predicted for the consequence of methylation in this 5' CpG island, none of the 5 tumors expressed the VHL gene. In contrast, normal kidney and all tumors examined with inactivating VHL gene mutations but no CpG island methylation had expression. In a renal cell culture line, treatment with 5-aza-2'-deoxycytidine resulted in reexpression of the VHL gene. These findings suggest that aberrant methylation of CpG islands may participate in the tumor-suppressor gene inactivations which initiate or cause progression of common human cancers.

Adenocarcinoma, Clear Cell↗

PubMed1994

GM-CSF and M-CSF expression is associated with macrophage proliferation in progressing and regressing rabbit atheromatous lesions.

Recent studies have documented that macrophages are a significant cell component of atherosclerotic lesions and may play a significant role in the pathogenesis of these lesions. It has also been documented that markers of cell proliferation (e.g., the proliferating cell nuclear antigen) can be expressed by macrophage subpopulations in atherosclerotic lesions, and there is great interest in identifying cell mediated factors which might be instrumental in macrophage proliferation in this context, perhaps accounting for the persistence of macrophages within this context. Important candidates for this function include granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF); the latter has been previously demonstrated to be expressed in human and rabbit atherosclerotic lesions. We have extended these studies by studying immunocytochemical localization of GM-CSF and M-CSF in progressing and regressing lesions of cholesterol-fed rabbits, documenting expression of these factors predominantly in macrophages, but also in some smooth muscle-cells and endothelial cells. The simultaneous documentation of macrophage subpopulations expressing the proliferating cell nuclear antigen in the same lesions provides evidence to support the hypothesis that macrophage GM-CSF and M-CSF production represents a factor underlying macrophage proliferation and accumulation in atherosclerotic lesions.

Animals↗

PubMed1994

Successful extracorporeal circulatory support after aortic reimplantation of anomalous left coronary artery.

The development of severe heart failure is the main cause of postoperative mortality after the surgical treatment of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). Two patients with ALCAPA who developed low cardiac output and could not be weaned from cardiopulmonary bypass (CPB) after aortic reimplantation of the anomalous left coronary artery were successfully treated with a centrifugal left ventricular assist device (LVAD) and extracorporeal membrane oxygenation (ECMO). The circulation of a 10-month-old infant with severe left ventricular dysfunction was supported 192 h postoperatively with a LVAD and a 9-year-old boy with severe right ventricular failure received ECMO support for 99 h following surgery. Both patients survived and, 4 and 9 months after surgery, are asymptomatic and have normal ventricular function. If CPB (up to 3 h) is not effective in improving ventricular function after surgery for ALCAPA, ECMO or LVAD must be used since myocardial recovery in these patients can occur only after prolonged extracorporeal circulatory support.

Cardiopulmonary Bypass↗

PubMed1994

Mutations of the VHL tumour suppressor gene in renal carcinoma.

Multiple, bilateral renal carcinomas are a frequent occurrence in von Hippel-Lindau (VHL) disease. To elucidate the aetiological role of the VHL gene in human kidney tumorigenesis, localized and advanced tumours from 110 patients with sporadic renal carcinoma were analysed for VHL mutations and loss of heterozygosity (LOH). VHL mutations were identified in 57% of clear cell renal carcinomas analysed and LOH was observed in 98% of those samples. Moreover, VHL was mutated and lost in a renal tumour from a patient with familial renal carcinoma carrying the constitutional translocation, t(3;8)(p14;q24). The identification of VHL mutations in a majority of localized and advanced sporadic renal carcinomas and in a second form of hereditary renal carcinoma indicates that the VHL gene plays a critical part in the origin of this malignancy.

Adenocarcinoma, Clear Cell↗

PubMed1994

cDNA cloning and expression of the human homolog of the sea urchin fascin and Drosophila singed genes which encodes an actin-bundling protein.

cDNA clones having extensive sequence identity with the sea urchin fascin and the Drosophila singed gene products were isolated from a human teratocarcinoma cDNA library. The human homolog, termed hsn, is a single-copy gene that was localized to human chromosome 7p22 by fluorescence in situ hybridization and is predicted to encode a 493-amino-acid product with a molecular mass of approximately 55,000. This protein would be similar in size to the fascin and singed proteins, as well as a previously described 55-kD actin-bundling protein that was purified from HeLa cells. Monoclonal antibodies directed against the 55-kD HeLa protein were reactive against a bacterially expressed hsn fusion protein, indicating that the hsn gene probably encodes the 55-kD protein. The hsn mRNA was variably expressed in all human tissues analyzed and was highly expressed in actively growing renal carcinoma cell lines and in activated, but not in resting, lymphocytes, suggesting a functional role for hsn in proliferation. The fascin family lacks homology with other characterized actin-binding proteins, and the high degree of evolutionary conservation of these proteins indicates a functional importance of their actin-bundling properties.

Amino Acid Sequence↗

PubMed1994

Improvement in left ventricular dysfunction after aortic reimplantation in 11 consecutive paediatric patients with anomalous origin of the left coronary artery from the pulmonary artery. Early results of a serial echocardiographic follow-up.

To study the potential for recovery of left ventricular function in patients with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) after aortic reimplantation, serial two-dimensional echocardiographic examinations were performed before and up to 9 months after operation in 11 consecutive paediatric patients (group 1: six infants; group 2: five children above the age of 1 year). End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), myocardial volume (MV), ratio of myocardial volume/end-diastolic volume (MVI), and regional wall motion of the left ventricle (LV) were studied. Pre-operatively, mean LVEDV was 339% of normal in group 1 and 289% in group 2 (P < 0.001); mean LVMV was about twice the normal value in both groups (P < 0.001); LVMVI was 0.79 +/- 0.23 in group 1 and 0.83 +/- 0.3 in group 2; LVEF was 28 +/- 10% in group 1 and 46 +/- 18% in group 2; regional wall motion was normal in two group 2 patients, the other showed uniform reduction in segmental shortening fraction. Postoperatively, mean LVEDV tended to become normal after 2 weeks in group 1 and after 3 months in group 2. In both groups mean LVEF reached the normal range after 3 months; LVMV as well as LVMVI normalized after 9 months. Three months after the operation, all infants had a nearly normal pattern of regional wall motion, while in three group 2 children a residual reduced shortening fraction could be observed in anterior or lateral segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta, Thoracic↗

PubMed1994

Anomalous origin of the left coronary artery from the pulmonary artery. Early results with direct aortic reimplantation.

Between January 1991 and June 1993, eleven children with anomalous origin of the left coronary artery from the pulmonary artery underwent direct aortic reimplantation of the left coronary artery at the German Heart Institute Berlin. The patients' ages ranged from 2.5 months to 10.5 years; six were infants. Three infants were intubated and their lungs ventilated before the operation, and one was resuscitated 2 days before the operation. The electrocardiograms of eight patients indicated deep Q waves. All but three of these patients had insufficient collaterals between the right and left coronary arteries. The entire group exhibited reduced left ventricular ejection fraction (minimum 15%) including mitral valve incompetence, which was moderate in six patients and severe in three. All six infants underwent emergency operations, and the remaining children, who were older, underwent elective operations involving moderate hypothermic perfusion and cold crystalloid cardioplegia. Aortic cross-clamping time ranged from 22 to 79 minutes (mean 54 minutes). A two-coronary artery system was established in all patients by direct reimplantation of the anomalous left coronary artery into the ascending aorta. Three patients who also exhibited severe mitral valve incompetence underwent modified Kay mitral valve annuloplasty. A delayed sternal closure procedure (closure performed 1 to 10 days after the operation) was used on eight patients. A 10-month-old patient was successfully treated after the operation with a centrifugal left heart assist device and a 9-year-old patient received extracorporeal membrane oxygenation because of severe heart failure. No postoperative deaths occurred. Left ventricular end-diastolic volume decreased dramatically after the operation and returned to near normal values 1 to 9 months postoperatively. At the same time, the preoperatively depressed left ventricular ejection fraction returned to normal and mitral valve incompetence decreased or vanished in eight patients. Color Doppler echocardiograms (eleven patients) and coronary angiograms (three patients) indicated that the reimplanted left coronary artery was patent in all eleven patients during the follow-up period. Reimplantation of the left coronary artery into the ascending aorta is an effective method of establishing a two-coronary artery system in children with anomalous origin of the left coronary artery from the pulmonary artery. Mitral valve annuloplasty is recommended for patients who also have severe mitral valve incompetence. Prolonged assisted circulation must be used in cases of severe postoperative heart failure.

Aorta↗

PubMed1994

Examination of human tumors for rhoA mutations.

rhoA encodes a ras-related GTP-binding protein that is thought to play a role in cytoskeletal organization. Recent evidence has suggested both that rhoA could act either as a dominant oncogene, since transfection of both normal and activated rho genes confer a transformed phenotype on fibroblast cells in culture, or as a recessive tumor suppressor gene, by virtue, in part, of its chromosomal location at 3p21, a site deleted in many human malignancies. In either case, a role for rhoA in the oncogenesis of human tumors would be supported by the finding of rhoA mutations in tumors. We therefore examined human tumors and cell lines for mutations in the protein coding regions of rhoA by RNAase protection analysis. We first examined the expression of rhoA in renal cell carcinoma cell lines in which 3p21 was heterozygously deleted or retained. We found no evidence for rhoA mutations in these specimens. We also examined RNA from lung, breast, colon or ovarian tumors and also found no evidence of activating rhoA mutations. Furthermore, there was no relation between the level of rhoA mRNA expression and the presence or absence of 3p21 deletions in the renal cell carcinoma specimens. Thus, although rhoA has transforming potential in vitro, there is no evidence that it is activated by mutation in human malignancies, or that it could act as a tumor suppressor gene in tumors in which 3p21 is deleted.

Carcinoma, Renal Cell↗

PubMed1993

Interleukin 7-induced expression of specific T cell receptor gamma variable region genes in murine fetal liver cultures.

We previously reported that culture of murine fetal liver (FL) cells with interleukin 7 (IL-7) results in expression of high levels of T cell receptor (TCR) gamma transcripts by a population of cells expressing Thy-1 and Pgp-1, suggesting that IL-7 promotes the growth and/or differentiation of pre-T cells. We demonstrate herein that culture of FL cells for 7 d with IL-7 caused the rearrangement and expression of TCR gamma variable (V) region genes V gamma 4 and V gamma 6, but not V gamma 5 or V gamma 7. Since this effect was not blocked by hydroxyurea, it appeared to represent induction of expression of these genes by IL-7 rather than expansion of a preexisting positive population. We also show that IL-7 induced RAG-1 and RAG-2 mRNA expression by FL cells. These data provide evidence that specific TCR gamma/delta V region genes can be rearranged and expressed by T lineage cells before their migration to the thymus, in response to IL-7.

Animals↗

PubMed1993

Developmental regulation of the base excision repair enzyme uracil DNA glycosylase in the rat.

The developmental regulation of the mammalian DNA-repair enzyme uracil DNA glycosylase was examined in the rat at specific intervals ranging from -4 days before to 106 days after birth. Enzyme activity was quantitated by in vitro biochemical assay. In the adult animal, as measured in crude cell extracts, three organs (liver, kidney and spleen) had significant levels of activity. In contrast, three organs (brain, heart and lung) had low activity. Partial purification of this enzyme identified one major species of molecular weight 32,700 Da, demonstrating the quantitation of the nuclear glycosylase. During development, with the exception of the liver, the specific activity of the glycosylase paralleled the regulation of DNA synthesis. In these organs the highest levels of the glycosylase and the rate of DNA replication were observed around the time of birth. In the liver, DNA replication was similarly regulated. However, glycosylase activity was minimal at early stages of life. Instead, maximal levels were observed at 14-21 days after birth. At that time DNA replication was severely reduced. These results demonstrate that individual organs express this DNA-repair enzyme in a distinct and specific pattern during development. Accordingly, the regulation of the uracil DNA glycosylase during development may provide a model system to examine the differential regulation of DNA-repair genes.

Age Factors↗

PubMed1993

Use of polytetrafluoroethylene surgical membrane as a pericardial substitute in the correction of congenital heart defects.

Patients who undergo repair of congenital heart defects have a high probability of eventually needing a repeat operation. In such cases, use of a pericardial substitute can preclude adhesion formation, thereby helping to avert the complications of a repeat sternotomy. This report describes our use of the GORE-TEX polytetrafluoroethylene surgical membrane in 321 patients who underwent repair of congenital heart disease at our hospital between May of 1989 and December of 1992 (these cases account for 37.1% of all such repairs performed during this period). The patients' ages ranged from 2 days to 31 years (mean, 5.9 years). Eighty-eight patients (27.4%) had at least 1 previous median sternotomy, and 234 (73.0%) had a moderate to high probability of reoperation. Seventy-eight patients (24.3%) received a homograft, which was positioned extracardially in 63 cases. During a maximum follow-up period of 43 months (mean, 26 +/- 5.6 months), 11 patients died, for an overall mortality of 3.4%. In no case was death attributable to membrane-related complications. Postoperative complications were encountered in 12 patients (3.7%), 10 of whom required an early repeat thoracotomy. One patient had mediastinitis, for an incidence of 0.3% (in contrast to 0.2% in 864 patients who underwent similar repair without the use of a surgical membrane). No complications were encountered in the 27 patients in whom the membrane was implanted during delayed sternal closure. Seventeen patients (5.5% of the survivors) underwent a repeat sternotomy, for further correction of congenital heart defects, a mean of 20 months after the original repair. At reoperation, major complications were encountered. Although the number of reoperations was low, we conclude that use of the polytetrafluoroethylene surgical membrane for pericardial closure in children is a safe procedure that helps prevent complications at reoperation.

Adolescent↗