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Biomedical subjects

M Fu

Publications and source records attributed to M Fu.

At least 37 records · Page 2Linked to original sources

Endogenous indoles as novel polyamine site ligands at the N-methyl-D-aspartate receptor complex.

High-throughput ligand displacement screens of a series of endogenous indoles revealed that tryptamine, serotonin and 5-methoxytryptamine readily displace [3H]spermidine and [3H]MK-801 from their respective binding sites in rat brain homogenate. These data, coupled with their potent inhibition of spermidine-potentiated [3H]MK-801 binding, suggest that certain endogenous indoles may act as ligands to one or more polyamine binding sites in the brain, including those on the N-methyl-D-aspartate receptor complex.

Animals↗

Zhang's ring-clamp modification of Duhamel's procedure: 30 years experience.

To evaluate the efficacy of the ring-clamp procedure (RCP) in the treatment of Hirschsprung's disease (HD) 435 RCPs were compared to 54 Kocher procedures performed between 1960 and 1990. The data were analyzed by chi-square test. The RCP resulted in much less blind-pouch syndrome (7%) compared to the Kocher's procedure (40%), and represents a valid alternative in the treatment of HD in children.

Child↗

Inhibition of egg hatching success and larvae survival of the scallop, Chlamys farreri, associated with exposure to cells and cell fragments of the dinoflagellate Alexandrium tamarense.

We report an apparently novel toxic effect of the dinoflagellate Alexandrium tamarense, manifested by inhibition of the egg hatching success of the scallop, Chlamys farreri. The hatching rate of C. farreri approached only 30% of controls when its fertilised eggs were exposed for 36h to A. tamarense cells or cellular fragments at a concentration of 100 cells/ml, and the hatching rate was just 5% after exposure to A. tamarense of 500 cells/ml. Similar exposures of the fertilised scallop eggs to two other algal species, the diatom Phaeodactylum tricornutum and the raphidophyte Heterosigma carterae, resulted in no such toxicity or inhibitory effects. Likewise, exposure of eggs to standard STX toxin, as well as to A. tamarense cell contents (supernant of re-suspended algal cells following ultrasonication and centrifugation), did not elicit this inhibitory response. However, exposure of the scallop eggs to cell cultures, intact algal cells, or cell fragments of A. tamarense produced marked toxicity. The alga also influenced larvae at early D-shape stage of scallop. The survival rates began to decrease significantly after exposed for 6 days at concentration of 3000 cells/ml and above; no larvae could survive after 14-day exposure to A. tamarense at 10,000 cells/ml or 20-day at 5000 cells/ml. The results indicated the production of novel substances from A. tamarense which can cause adverse effects on egg hatching and survival of the scallop larvae. The experiment also found that the developmental stages before blastula was the developmental period most sensitive to the A. tamarense toxin(s) and the alga at early exponential stage had the strongest effect on egg hatching comparing with other growth phases. The adverse effect of A. tamarense on early development of scallops may cause decline of shellfish population and may have further impact on marine ecosystem.

Animals↗

NF-kappaB and cell-cycle regulation: the cyclin connection.

The cyclins are a family of proteins that are centrally involved in cell cycle regulation and which are structurally identified by conserved "cyclin box" regions. They are regulatory subunits of holoenzyme cyclin-dependent kinase (CDK) complexes controlling progression through cell cycle checkpoints by phosphorylating and inactivating target substrates. CDK activity is controlled by cyclin abundance and subcellular location and by the activity of two families of inhibitors, the cyclin-dependent kinase inhibitors (CKI). Many hormones and growth factors influence cell growth through signal transduction pathways that modify the activity of the cyclins. Dysregulated cyclin activity in transformed cells contributes to accelerated cell cycle progression and may arise because of dysregulated activity in pathways that control the abundance of a cyclin or because of loss-of-function mutations in inhibitory proteins.Analysis of transformed cells and cells undergoing mitogen-stimulated growth implicate proteins of the NF-kappaB family in cell cycle regulation, through actions on the CDK/CKI system. The mammalian members of this family are Rel-A (p65), NF-kappaB(1) (p50; p105), NF-kappaB(2) (p52; p100), c-Rel and Rel-B. These proteins are structurally identified by an amino-terminal region of about 300 amino acids, known as the Rel-homology domain. They exist in cytoplasmic complexes with inhibitory proteins of the IkappaB family, and translocate to the nucleus to act as transcription factors when activated. NF-kappaB pathway activation occurs during transformation induced by a number of classical oncogenes, including Bcr/Abl, Ras and Rac, and is necessary for full transforming potential. The avian viral oncogene, v-Rel is an NF-kappaB protein. The best explored link between NF-kappaB activation and cell cycle progression involves cyclin D(1), a cyclin which is expressed relatively early in the cell cycle and which is crucial to commitment to DNA synthesis. This review examines the interactions between NF-kappaB signaling and the CDK/CKI system in cell cycle progression in normal and transformed cells. The growth-promoting actions of NF-kappaB factors are accompanied, in some instances, by inhibition of cellular differentiation and by inhibition of programmed cell death, which involve related response pathways and which contribute to the overall increase in mass of undifferentiated tissue.

Animals↗

Molecular therapy with recombinant antisense c-myc adenovirus for human gastric carcinoma cells in vitro and in vivo.

BACKGROUND AND AIMS: This study used a recombinant antisense c-myc adenovirus (Ad-ASc-myc) to evaluate how alterations of c-myc expression in the SGC7901 human gastric carcinoma cells could influence the proliferation, apoptosis and the growth of human gastric tumors in nude mice. METHODS: The human gastric carcinoma cell line, SGC7901, treated with Ad-ASc-myc or adenovirus recombinants carrying LacZ gene (Ad-LacZ) were analyzed by using X-gal stain, MTT, DNA ladder, TUNEL assay, flow cytometric analysis, polymerase chain reaction and western blot in vitro. The tumorigenicity and experimental therapy in nude mice models were assessed in vivo. RESULTS: The Ad-ASc-myc could strongly inhibit cell growth and induce apoptosis in SGC7901 cells. The proliferation of the Ad-ASc-myc-infected SGC7901 cells was reduced by 44.1%. The mechanism of killing gastric carcinoma cells by Ad-ASc-myc was found to be apoptosis, which was detected by the use of a DNA ladder, TUNEL and flow cytometric analysis. Infection of Ad-ASc-myc in nude mice showed that all three mice failed to form tumors from the 7 to 30 day period, compared with injection of Ad-LacZ and parent SGC7901 cells. Experimental therapy on the nude mice bearing subcutaneous tumors of SGC7901 cells showed that intratumor instillation of Ad-ASc-myc inhibited the growth of the tumors. Recombinant antisense c-myc adenovirus-treated tumors were inhibited by 68.9%, compared with tumors injected with Ad-LacZ and control (LacZ and phosphate-buffered saline). CONCLUSION: The expression of Ad-ASc-myc can inhibit growth and induce apoptosis of gastric cancer cells in vitro and in vivo and thus is a potential clinical utility in gene therapy for the treatment of gastric carcinoma.

Adenoviridae↗

Inhibition of cellular proliferation through IkappaB kinase-independent and peroxisome proliferator-activated receptor gamma-dependent repression of cyclin D1.

The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-regulated nuclear receptor superfamily member. Liganded PPARgamma exerts diverse biological effects, promoting adipocyte differentiation, inhibiting tumor cellular proliferation, and regulating monocyte/macrophage and anti-inflammatory activities in vitro. In vivo studies with PPARgamma ligands showed enhancement of tumor growth, raising the possibility that reduced immune function and tumor surveillance may outweigh the direct inhibitory effects of PPARgamma ligands on cellular proliferation. Recent findings that PPARgamma ligands convey PPARgamma-independent activities through IkappaB kinase (IKK) raises important questions about the specific mechanisms through which PPARgamma ligands inhibit cellular proliferation. We investigated the mechanisms regulating the antiproliferative effect of PPARgamma. Herein PPARgamma, liganded by either natural (15d-PGJ(2) and PGD(2)) or synthetic ligands (BRL49653 and troglitazone), selectively inhibited expression of the cyclin D1 gene. The inhibition of S-phase entry and activity of the cyclin D1-dependent serine-threonine kinase (Cdk) by 15d-PGJ(2) was not observed in PPARgamma-deficient cells. Cyclin D1 overexpression reversed the S-phase inhibition by 15d-PGJ(2). Cyclin D1 repression was independent of IKK, as prostaglandins (PGs) which bound PPARgamma but lacked the IKK interactive cyclopentone ring carbonyl group repressed cyclin D1. Cyclin D1 repression by PPARgamma involved competition for limiting abundance of p300, directed through a c-Fos binding site of the cyclin D1 promoter. 15d-PGJ(2) enhanced recruitment of p300 to PPARgamma but reduced binding to c-Fos. The identification of distinct pathways through which eicosanoids regulate anti-inflammatory and antiproliferative effects may improve the utility of COX2 inhibitors.

Binding Sites↗

SOX10 is abnormally expressed in aganglionic bowel of Hirschsprung's disease infants.

BACKGROUND: The primary pathology of Hirschsprung's disease (HD) is a congenital absence of ganglion cells in the caudal most gut. The spastic aganglionic bowel is often innervated by a network of hypertrophied nerve fibres. Recently, mutations of SOX10 have been identified in patients with HD but only in those with Waardenburg-Shah syndrome. AIMS: To understand the molecular basis for the pathogenesis of HD we intended to determine the specific cell lineages in the enteric nervous system which normally express SOX10 but are affected in disease conditions. METHODS: We studied colon biopsies from 10 non-syndromic HD patients, aged three months to four years, and 10 age matched patients without HD as normal controls. The absence of mutation in the SOX10 gene of HD patients was confirmed by DNA sequencing. Expression and cellular distribution of SOX10 in bowel segments of normal and HD infants were examined by reverse transcription-polymerase chain reaction and in situ hybridisation. RESULTS: We found that in normal infants and normoganglionic bowel segments of HD patients, SOX10 was expressed in both neurones and glia of the enteric plexuses and in the nerves among the musculature in normal colon. In the aganglionic bowel segments of patients, SOX10 expression was consistently lower and was found to be associated with the hypertrophic nerve trunks in the muscle and extrinsic nerves in the serosa. CONCLUSION: We conclude that SOX10 is normally required postnatally in the functional maintenance of the entire enteric nervous system, including neurones and glia. In non-syndromic HD patients who do not have the SOX10 mutation, the SOX10 gene expressed in the sacral region may be involved in the pathogenesis of the abnormal nerve trunks through interaction with other factors.

Case-Control Studies↗

Cyclin D1 binds the androgen receptor and regulates hormone-dependent signaling in a p300/CBP-associated factor (P/CAF)-dependent manner.

The androgen receptor (AR) is a ligand-regulated member of the nuclear receptor superfamily. The cyclin D1 gene product, which encodes the regulatory subunit of holoenzymes that phosphorylate the retinoblastoma protein (pRB), promotes cellular proliferation and inhibits cellular differentiation in several different cell types. Herein the cyclin D1 gene product inhibited ligand-induced AR- enhancer function through a pRB-independent mechanism requiring the cyclin D1 carboxyl terminus. The histone acetyltransferase activity of P/CAF (p300/CBP associated factor) rescued cyclin D1-mediated AR trans-repression. Cyclin D1 and the AR both bound to similar domains of P/CAF, and cyclin D1 displaced binding of the AR to P/CAF in vitro. These studies suggest cyclin D1 binding to the AR may repress ligand-dependent AR activity by directly competing for P/CAF binding.

Acetyltransferases↗

Unusual complication of retrograde dissection to the coronary sinus of valsalva during percutaneous revascularization: a single-center experience and literature review.

BACKGROUND: While coronary dissection, which is one of the most frequently occurring complications during interventional procedures, has various forms, extensive coronary dissection retrograde to the coronary sinus of Valsalva (CSV) is very rarely observed. METHODS AND RESULTS: Within the last 5 years, we retrospectively reviewed our experience with 4,700 consecutive patients who underwent angioplasty procedures, 7 of whom (0.15%) developed extensive coronary dissection retrograde to the CSV. Six of the seven patients developed retrograde dissection of the right CSV during angioplasty to the right coronary artery. One of the seven patents developed retrograde dissection of the left CSV during angioplasty to the left anterior descending artery. Retrograde dissection, which extended to the ascending aorta in two patients, was observed by transthoracic echocardiography and surgical findings, respectively. Five patients were successfully treated by coronary stenting. However, this complication caused four patients to have acute myocardial infarctions, resulting in emergency surgery for one patient and in-hospital death for another. CONCLUSIONS: Our experience increased our understanding of this very rare complication. However, this complication may be life threatening, and patients in this clinical setting may have a potential risk for acute myocardial infarction, emergency surgery, or even sudden cardiac death. Therefore, it is important to learn how to promptly diagnose and manage this complication.

Aortic Dissection↗

Effect of primary angioplasty on total or subtotal left main occlusion: analysis of incidence, clinical features, outcomes, and prognostic determinants.

BACKGROUND: Although acute left main coronary artery (LMCA) occlusion is a rare clinical entity, it carries a very high mortality rate. The purposes of this study were to evaluate the effect of primary angioplasty for a severely obstructed or totally occluded LMCA, and to determine the incidence, clinical features, outcome, and prognostic determinants in this clinical setting. MATERIALS AND METHODS: Between May 1993 and July 2000, a total of 740 patients with acute myocardial infarction underwent primary angioplasty in our hospital. Eighteen of 740 patients (2.4%) with a severely obstructed or totally occluded LMCA constituted the population of this study. RESULTS: Seventeen of 18 patients (94.4%) experienced pulmonary edema (including 14 patients in cardiogenic shock). Six patients (33.3%) sustained sudden death due to malignant ventricular tachyarrhythmias. Coronary angiography showed that there were variable grade flow of intercoronary collaterals in 12 patients (66.7%), a totally occluded LMCA in 8 patients (44.4%), an incompletely occluded LMCA in 10 patients (55.6%), and a dominant right coronary artery (RCA) in 16 patients (88.9%). Primary angioplasty of the LMCA was performed with a 72.2% procedural success rate. Four patients (22.2%) received coronary artery bypass surgery after angioplasty. Six patients (33.3%) died in the hospital. Two patients died after discharge. Ten of 18 patients (55.6%) survived in long-term follow-up (mean +/- SD, 44 +/- 14 months). Those patients who survived to be discharged had significantly higher combined coexisting incidence of intercoronary collaterals, dominant RCA, and incompletely occluded LMCA (100% vs 0.0%, p = 0.0006) than those patients who died in the hospital. CONCLUSIONS: Acute obstructive LMCA disease generally presented as pulmonary edema, cardiogenic shock, or sudden death. Only those who had combined coexistence of intercoronary collaterals, a dominant RCA, and an incompletely occluded LMCA could survive to be discharged. Our experience suggests that primary LMCA angioplasty is a feasible and effective procedure, and it may save lives in this clinical setting.

Adult↗

The frequency of occurrence of autoantibodies against beta1-adrenoceptors and its clinical relevance in patients with hepatitis virus myocarditis.

The aim of this study was to examine the frequency of occurrence of autoantibodies against beta1-adrenoceptors in patients with hepatitis virus myocarditis (HVM) and its possible correlation with clinical characteristics. A total of 103 patients with viral myocarditis were divided into a positive group (HVM group, n=29) and a negative group (Non-HVM group, n=74) according to the laboratory findings regarding their type of hepatitis virus. The study parameters included UCG, ECG, biochemical findings and screening of autoantibodies against beta1-adrenoceptor. It was shown that the positive rate of the hepatitis virus was 28.16% (29/103) in patients with viral myocarditis. The severity of myocardial or liver injuries and the frequency of occurrence of autoantibodies against beta1-adrenoceptors in patients with viral myocarditis were more pronounced, before treatment, in the HVM group than in the Non-HVM group. The positive rates of the antibodies against the hepatitis virus and the autoantibodies against beta1-adrenoceptors were highly consistent in patients with HVM (p<0.05). In conclusion, the frequency of occurrence of the autoantibodies against beta1-adrenoceptors may be one important marker of HVM and, thus, possibly involved in the pathogenesis of the HVM.

Adult↗

Primary angioplasty in acute inferior myocardial infarction with anomalous-origin right coronary arteries as infarct-related arteries: focus on anatomic and clinical features, outcomes, selection of guiding catheters and management.

BACKGROUND: Inferior wall myocardial infarction caused by obstruction of an anomalous-origin right coronary artery (RCA) is a rare angiographic finding; primary angioplasty to an anomalous-origin RCA has never been reported. METHODS: In 185 patients with acute inferior wall myocardial infarction resulting from RCA occlusion who underwent primary angioplasty, eight patients (4.3%) had anomalous-origin RCAs. RESULTS: Coronary angiography showed that all 8 patients had a dominant RCA. Six patients (75%) had an anomalous-origin RCA arising from the anterior aspect of the ascending aorta above the sinotubular line and the other 2 patients (25%) had an anomalous-origin RCA arising from the left sinus of Valsalva with a separate ostium from the left main coronary artery. The standard Judkins right guiding catheter did not offer adequate support in these patients. In the group of 6 patients, an Amplatz guiding catheter offered good support, while a standard Judkins left guiding catheter was adequate in the other 2 patients. Obstruction of the proximal RCA occurred in 6 patients (75%). Successful reperfusion was achieved in 6 patients (75%), resulting in an uneventful clinical course and long-term survival (mean follow-up, 24.9 +/- 16.5 months). Two patients (25%) had unsuccessful reperfusion and died from cardiogenic shock. CONCLUSIONS: In this small series, anomalous-origin RCAs were the dominant artery and predisposed to atherosclerosis at the proximal portions. We suggest that appropriate guide catheter selection and careful manipulation are essential for the success of revascularization. Complete reperfusion results in an excellent clinical and long-term outcome in patients with anomalous-origin RCAs.

Angioplasty, Balloon, Coronary↗

[Analysis of mandibular position of patients with angles Class I and Class II, division 1 malocclusion].

OBJECTIVE: To study changes of condyle position and occlusion between centric jaw relation and maximum intercuspation positions. METHODS: The power centric registration advocated by Roth was used to take centric relation bite registration for 50 patients (25 Class I and 25 Class II, Division 1) and diagnostic models were mounted and analysed with Panadent articulator and condyle position indicator. RESULTS: Nearly all patients had CR-MI differences in all three planes of space. 70% of the sagittal displacement was within 2.0 mm and 87% of the transverse displacement was within 1.0 mm. Most of the condyles moved posteriorly and inferiorly. 65% of the initial contacts in CR occured on the most posterior molar on single side. Correlation was found between some variables of condylar displacement and occlusion changes. No significant difference was observed in condylar position and occlusion changes between Class I and Class II, Dvision 1 patients. CONCLUSIONS: The occlusion in centric jaw relation should be analysed before treatment to reveal the disharmony between occlusion and jaw position.

Adolescent↗

Cytogenetic analysis in 61 couples with spontaneous abortions.

OBJECTIVE: To examine the relationship between spontaneous abortion and chromosomal abnormalities. METHODS: Couples who had one or more consecutive spontaneous abortions and had normal genitals were enrolled for cytogenetic karyotype analysis. RESULTS: In the 61 couples, the detected incidence was 11.5%, with five Robertsonian translocations, one reciprocal translocation, and one pericentric inversion of chromosome 7. CONCLUSION: Chromosomal abnormalities may play an important role in fetal wastage.

Abortion, Spontaneous↗