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Biomedical subjects

Y C Chiang

Publications and source records attributed to Y C Chiang.

At least 19 recordsLinked to original sources

Hepatic venous stenosis in partial liver graft transplantation detected by color Doppler ultrasound before and after radiological interventional management.

Hepatic outflow insufficiency remains one of the major complications causing postoperative graft failure especially among partial liver graft transplantations (PLT) including living donor liver transplantation (LDLT), reduced size liver transplantation (RLT), and split liver transplantation (SLT). These procedures are different from the whole liver graft transplantations (OLT), which include multiple vascular anastomoses. Color Doppler ultrasound (CDUS) was used to evaluate the hepatic venous outflow from grafts before and after radiological interventional management and to document treatment effects. From June 1994 to March 2003, our 136 cases of PLTs included 131 LDLTs, two RLTs, and three SLTs. Seven cases (six children and one adult) showed postoperative hepatic vein outflow obstruction and persistent massive ascites, as detected by color Doppler ultrasound (CDUS) and confirmed by interventional angiography. The CDUS showed a monophasic flat waveform with a relatively low hepatic vein average peak velocity (Va) in all cases (mean 11 cm/s). Successful interventional procedures included balloon dilatation in three cases and metallic stent replacement in four cases. CDUS was used with guidance during the procedure to confirm restoration of normal hepatic vein flow with a multiphasic waveform and an objective increase of average flow velocity (high to average 66 cm/s). Ascites disappeared dramatically after the procedure. In conclusion CDUS is the prime modality to diagnose and document a treatment response.

Adult↗

Purification and characterization of the 1.0 MDa CCR4-NOT complex identifies two novel components of the complex.

The CCR4-NOT complex is an evolutionarily conserved, transcriptional regulatory complex that is involved in controlling mRNA initiation, elongation and degradation. The CCR4-NOT proteins from Saccharomyces cerevisiae exist in two complexes, 1.9x10(6) Da and 1.0x10(6) Da (1.0 MDa) in size, and individual components of these complexes display such disparate functions as binding to and restricting TFIID functions, contacting SAGA and contributing to mRNA deadenylation. As a first step in characterizing the functional roles of the 1.0 MDa complex, we have purified it to near homogeneity. Mass spectrometric analysis was subsequently used to identify all the components of the complex. The 1.0 MDa complex was found to contain CCR4, CAF1, NOT1-5 and two new proteins, CAF40 and CAF130. CAF130 and CAF40 are two unique yeast proteins, with CAF40 displaying extensive homology to proteins from other eukaryotes. Immunoprecipitation and gel filtration experiments confirmed that CAF130 and CAF40 are components of both of the 1.9 MDa and 1.0 MDa CCR4-NOT complexes. Biochemical analysis indicated that the CAF40 and CAF130 proteins bind to the NOT1 protein and exist in a location separate from the two other subsets of proteins in the complex: the CCR4 and CAF1 proteins, and the NOT2, NOT4 and NOT5 proteins. Moreover, CAF40 was able to interact with human NOT1, suggesting that human CAF40 would also be a component of the recently identified human CCR4-NOT complex. Analysis of caf40 and caf130 deletions indicated that they elicited phenotypes shared by defects in other CCR4-NOT genes. The distinct location of CAF40 and CAF130 and the evolutionary conservation of CAF40 implicate them in novel roles in the function of the CCR4-NOT complex.

Binding Sites↗

Single imaging modality evaluation of living donors in liver transplantation: magnetic resonance imaging.

BACKGROUND: Liver graft size, anatomy of the bile duct and the vascular inflow and outflow are essential for living related liver transplantation (LRLT). Preoperative delineation of those variations that would change the operative procedure to achieve a successful result especially in an emergency condition. PURPOSE: Our aim was to develop a rapid and noninvasive imaging diagnostic method for the detection of anatomical variants that is mandatory for a safe operation when selecting potential liver transplant living donors. We used a different magnetic resonance (MR) imaging technique, which enabled to us to exploit the anatomical landmark of the liver, signal enhancement of blood flow in the abdomen, and the intrahepatic biliary routes inside the liver. Then, with the help of Advantage Window workstation reconstruction, the reconstructed single vascular or biliary systems were displaced in a three-dimensional fashion and the whole examination finished within 30 min. METHODS: Modification of the standard MR technique was performed on a superconductive 1.5T whole body image scanner, MR arteriogaphy, venography, and cholangiography with three-dimensional reconstruction in evaluating the anatomy of the hepatic arteries, hepatic veins, portal venous system, bile ducts, and liver size in potential liver transplant living donors. These anatomical structures were compared with traditional imaging methods. RESULTS: In all 38 cases, as well as delineation of the portal vein detail to the segmental level was satisfactorily obtained in this MR study. The images were well displayed in a three-dimensional fashion, which had good correlation with images from traditional imaging modalities and operative findings. In 86.8% cases, the MR arteriography was well matched with the celiac angiography. Of those 17 operative cases, estimation of liver volume was well correlated with the liver graft within 3.9-12.5% variation. In the major hepatic vein, we obtained 100% accuracy and 88.2% in the minor branches. Of 12 donors received intraoperative cholangiography during liver donation, good correlation of biliary anatomy was achieved. One donor was excluded from graft donation due to the complicated arterial supply to the left liver. According to the anatomical variation, surgical procedures in graft harvesting and anastomosis were readjusted and no major complications were found in those donors and all recipients survived after liver transplantation. CONCLUSION: MR volumetry, venography, angiography, and cholangiography with three-dimensional reconstruction is sufficient for all major imaging evaluation. It may replace the traditional conventional catheter angiography, computed tomography, sonography and endoscopic retrograde cholangiography as a single investigation in the evaluation of the potential liver transplant donors. Angiography is only valuable in suboptimal cases and intraoperative cholangiography is only performed in biliary ductile variants.

Adult↗

Significance of glutamate and dopamine neurons in the ventral pallidum in the expression of behavioral sensitization to amphetamine.

To explore the significance of ventral pallidum (VP) during the amphetamine sensitization, we first investigated if there are neurochemical alterations in the VP during amphetamine withdrawal period. Chronic amphetamine-treated (5 mg/kg x 14 days) rats displayed an apparent locomotion sensitization as compared with saline controls when challenged with 2 mg/kg amphetamine at withdrawal days 10-14. A microdialysis analysis revealed that output of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in the VP of amphetamine-sensitized rats increased approximately two-fold as compared to controls at both pre- and post-amphetamine challenge period. On the other hand, the in vivo glutamate output in the VP increased upon amphetamine challenge in the behaviorally sensitized rats, but not in the controls. To evaluate if drug manipulation in the VP would affect the behavioral sensitization, we treated both groups of rats with NMDA receptor antagonist, MK-801 (5 microg/microl for 5 days; bilateral) in the VP during withdrawal days 6-10. Animals were challenged with 2 mg/kg amphetamine at withdrawal day 11. The behavioral profile exhibited that MK-801 pre-treatment significantly blocked the locomotion hyperactivity in amphetamine-sensitized rats. Taken together, the current results suggest that the excitatory amino acid in the VP plays a significant role during the expression of behavioral sensitization to amphetamine.

Amphetamine↗

Interventional radiologic procedures in liver transplantation.

Postoperative biliary and vascular complications contribute significantly to morbidity and mortality in liver transplantation. Interventional radiologists are an integral part of the multidisciplinary team necessary for optimizing the management of these complications. During a 15-year period, 39 cadaveric and 25 living related liver transplantations were performed at the Chang Gung Memorial hospital, Taiwan. Of 64 liver transplant recipients, 9 (3 adult and 6 pediatric) underwent 13 interventional radiological procedures for the treatment of biliary sludge-casts (n = 2), bile duct occlusion or stenosis (n = 2), hepatic veins thrombosis (n = 1), hepatic veins stenosis (n = 1), portal vein stenosis with splenorenal shunting (n = 1), biloma (n = 1), and infected fluid collection or ascites (n = 4). Antegrade or retrograde interventional approach was used to successfully treat all biliary complications, and all percutaneous drainage procedures were effective in the control of intra-abdominal fluid collections. Portal vein stenosis was treated by balloon dilatation, and the associated splenorenal shunt was closed by metallic coil embolization via transhepatic catheterization of the portal vein. Hepatic vein stenosis was effectively treated by balloon dilatation and expandable metallic stent deployment via transfemoral and jugular venous approaches, respectively. Hepatic vein thrombosis was only partially lysed by transvenous streptokinase administration, and surgical thrombectomy was needed to achieve complete recanalization. The total success rate of the interventional procedures was 92 % with no procedure-related complications. The overall survival rate in this series is 89 %, and all patients who underwent living related liver transplantation maintain to date a 100 % survival rate. We can conclude that interventional radiological procedures are very useful for managing biliary and vascular complications after liver transplantation. These techniques provide a cure in most situations, thus obviating the need for further surgical intervention or re-transplantation.

Adolescent↗

Organelle DNA phylogeography of Cycas taitungensis, a relict species in Taiwan.

The phylogegraphic pattern of Cycas taitungensis, an endemic species with two remaining populations in Taiwan, was investigated based on genetic variability and phylogeny of the atpB-rbcL noncoding spacer of chloroplast DNA (cpDNA) and the ribosomal DNA (rDNA) internal transcribed spacer (ITS) of mitochondrial DNA (mtDNA). High levels of genetic variation at both organelle loci, due to frequent intramolecular recombination, and low levels of genetic differentiation were detected in the relict gymnosperm. The apportionment of genetic variation within and between populations agreed with a migrant-pool model, which describes a migratory pattern with colonists recruited from a random sample of earlier existing populations. Phylogenies obtained from cpDNA and mtDNA were discordant according to neighbour-joining analyses. In total four chlorotypes (clades I-IV) and five mitotypes (clades A-E) were identified based on minimum spanning networks of each locus. Significant linkage disequilibrium in mitotype-chlorotype associations excluded the possibility of the recurrent homoplasious mutations as the major force causing phylogenetic inconsistency. The most abundant chlorotype I was associated with all mitotypes and the most abundant mitotype C with all chlorotypes; no combinations of rare mitotypes with rare chlorotypes were found. According to nested clade analyses, such nonrandom associations may be ascribed to relative ages among alleles associated with the geological history through which cycads evolved. Nested in networks as interior nodes coupled with wide geographical distribution, the most dominant cytotypes of CI and EI may represent ancestral haplotypes of C. taitungensis with a possible long existence prior to the Pleistocene glacial maximum. In contrast, rare chlorotypes and mitotypes with restricted and patchy distribution may have relatively recent origins. Newly evolved genetic elements of mtDNA, with a low frequency, were likely to be associated with the dominant chlorotype, and vice versa, resulting in the nonrandom mitotype-chlorotype associations. Paraphyly of CI and EI cytotypes, leading to the low level of genetic differentiation between cycad populations, indicated a short period for isolation, which allowed low possibilities of the attainment of coalescence at polymorphic ancestral alleles.

Cycas↗

Phylogeography of Kandelia candel in East Asiatic mangroves based on nucleotide variation of chloroplast and mitochondrial DNAs.

Vivipary with precocious seedlings in mangrove plants was thought to be a hindrance to long-range dispersal. To examine the extent of seedling dispersal across oceans, we investigated the phylogeny and genetic structure among East Asiatic populations of Kandelia candel based on organelle DNAs. In total, three, 28 and seven haplotypes of the chloroplast DNA (cpDNA) atpB-rbcL spacer, cpDNA trnL-trnF spacer, and mitochondrial DNA (mtDNA) internal transcribed spacer (ITS) were identified, respectively, from 202 individuals. Three data sets suggested consistent phylogenies recovering two differentiated lineages corresponding to geographical regions, i.e. northern South-China-Sea + East-China-Sea region and southern South-China-Sea region (Sarawak). Phylogenetically, the Sarawak population was closely related to the Ranong population of western Peninsula Malaysia instead of other South-China-Sea populations, indicating its possible origin from the Indian Ocean Rim. No geographical subdivision was detected within the northern geographical region. An analysis of molecular variance (AMOVA) revealed low levels of genetic differentiation between and within mainland and island populations (phiCT = 0.015, phiSC = 0.037), indicating conspicuous long-distance seedling dispersal across oceans. Significant linkage disequilibrium excluded the possibility of recurrent homoplasious mutations as the major force causing phylogenetic discrepancy between mtDNA and the trnL-trnF spacer within the northern region. Instead, relative ages of alleles contributed to non-random chlorotype-mitotype associations and tree inconsistency. Widespread distribution and random associations (chi2 = 0.822, P = 0.189) of eight hypothetical ancestral cytotypes indicated the panmixis of populations of the northern geographical region as a whole. In contrast, rare and recently evolved alleles were restricted to marginal populations, revealing some preferential directional migration.

Alleles↗

Genetic evidence supports a role for the yeast CCR4-NOT complex in transcriptional elongation.

The CCR4-NOT complex is involved in the regulation of gene expression both positively and negatively. The repressive effects of the complex appear to result in part from restricting TBP access to noncanonical TATAA binding sites presumably through interaction with multiple TAF proteins. We provide here genetic evidence that the CCR4-NOT complex also plays a role in transcriptional elongation. First, defects in CCR4-NOT components as well as overexpression of the NOT4 gene elicited 6-azauracil (6AU) and mycophenolic acid sensitivities, hallmarks of transcriptional elongation defects. A number of other transcription initiation factors known to interact with the CCR4-NOT complex did not elicit these phenotypes nor did defects in factors that reduced mRNA degradation and hence the recycling of NTPs. Second, deletion of ccr4 resulted in severe synthetic effects with mutations or deletions in the known elongation factors RPB2, TFIIS, and SPT16. Third, the ccr4 deletion displayed allele-specific interactions with rpb1 alleles that are thought to be important in the control of elongation. Finally, we found that a ccr4 deletion as well as overexpression of the NOT1 gene specifically suppressed the cold-sensitive phenotype associated with the spt5-242 allele. The only other known suppressors of this spt5-242 allele are factors involved in slowing transcriptional elongation. These genetic results are consistent with the model that the CCR4-NOT complex, in addition to its known effects on initiation, plays a role in aiding the elongation process.

Alleles↗

Free anterolateral thigh flap for extremity reconstruction: clinical experience and functional assessment of donor site.

From August of 1995 through July of 1998, 38 free anterolateral thigh flaps were transferred to reconstruct soft-tissue defects. The overall success rate was 97 percent. Among 38 anterolateral thigh flaps, four were elevated as cutaneous flaps based on the septocutaneous perforators. The other 34 were harvested as myocutaneous flaps including a cuff of vastus lateralis muscle (15 to 40 cm3), either because of bulk requirements (33 cases) or because of the absence of a septocutaneous perforator (one case). However, vastus lateralis muscle is the largest compartment of the quadriceps, which is the prime extensor of the knee. Losing a portion of the vastus lateralis muscle may affect knee stability. Objective functional assessments of the donor sites were performed at least 6 months postoperatively in 20 patients who had a cuff of vastus lateralis muscle incorporated as part of the myocutaneous flap; assessments were made using a kinetic communicator machine. The isometric power test of the ratios of quadriceps muscle at 30 and 60 degrees of flexion between donor and normal thighs revealed no significant difference (p > 0.05). The isokinetic peak torque ratio of the quadriceps and hamstring muscles, including concentric and eccentric contraction tests, showed no significant difference (p > 0.05), except the concentric contraction test of the quadriceps muscle, which revealed mild weakness of the donor thigh (p < 0.05). In summary, the functional impairment of the donor thighs was minimal after free anterolateral thigh myocutaneous flap transfer.

Adult↗

Biliary complications in living related liver transplantation.

BACKGROUND: Biliary tract reconstruction has long been considered the Achilles' heel of liver transplantation as biliary complications can increase morbidity and mortality especially in partial liver graft transplantation. METHODS: Thirty-four living related liver transplants were performed at Chang Gung Memorial Hospital in Kaohsiung for 33 children and 1 adolescent during a 5.5-year period. All potential donors underwent a detailed preoperative imaging study of the vascular and biliary anatomy, including three-dimensional helical computed tomographic cholangiography (n = 20), magnetic resonance cholangiography (n = 14), and intra-operative cholangiography (n = 31) before graft retrieval. All hepatic artery anastomoses were performed in the standard microsurgery fashion and their patency was confirmed intra-operatively using Doppler ultrasound. RESULTS: The biliary complication rate was 8.8% (3/34), including multiple intrahepatic biliary stenosis of unknown origin (n = 1), bile leakage from the Roux-en-Y loop (n = 1), and a missed biliary radicle (n = 1) which were treated via interventional radiological and surgical procedures. The overall graft and patient survival rates were 100%. CONCLUSION: The biliary complication rate in this series was low compared to those of other experienced centers. Complete study of the variations of intrahepatic duct ramification pre-and-intra-operatively provided adequate information on the appropriate transection plane. Furthermore, intra-operative Doppler ultrasound verification of vessel patency helps prevent vascular complications, which has been identified as a cause of biliary complications.

Adolescent↗

Outflow tract reconstruction in living donor liver transplantation.

BACKGROUND: Hepatic venous reconstruction is critical in living donor liver transplantation because outflow obstruction may lead to graft dysfunction or loss. We describe our experience and analyze outcomes with a technique of creating a single outflow tract using venoplasties of the graft and recipient hepatic veins. PATIENTS AND METHODS: A retrospective study was done on 38 consecutive living donor liver transplants performed from June 1994 to March 2000. The grafts included 36 left-side grafts and 2 right-side grafts. Nine grafts had multiple hepatic veins and required a venoplasty of two or three hepatic veins to create a single outflow orifice. Triple recipient hepatic venoplasty was performed in 32 patients, double venoplasty in 5 and none in 1. RESULTS: There were four cases of outflow obstruction, three occurring in patients with a double recipient venoplasty. Two of the problems were remedied intraoperatively by adjusting the position of the graft although two were structural in nature and required the insertion of expandable metallic vascular stents. All donors and recipients with their original grafts are alive at a mean follow-up period of 27 months. CONCLUSION: A triple recipient venoplasty with a matching venoplasty of multiple graft hepatic veins to create a single wide outflow orifice is recommended in living donor liver transplantation using left side grafts.

Adolescent↗

Characterization of CAF4 and CAF16 reveals a functional connection between the CCR4-NOT complex and a subset of SRB proteins of the RNA polymerase II holoenzyme.

The CCR4-NOT transcriptional regulatory complex affects transcription both positively and negatively and consists of the following two complexes: a core 1 x 10(6) dalton (1 MDa) complex consisting of CCR4, CAF1, and the five NOT proteins and a larger, less defined 1.9-MDa complex. We report here the identification of two new factors that associate with the CCR4-NOT proteins as follows: CAF4, a WD40-containing protein, and CAF16, a putative ABC ATPase. Whereas neither CAF4 nor CAF16 was part of the core CCR4-NOT complex, both CAF16 and CAF4 appeared to be present in the 1.9-MDa complex. CAF4 also displayed physical interactions with multiple CCR4-NOT components and with DBF2, a likely component of the 1.9-MDa complex. In addition, both CAF4 and CAF16 were found to interact in a CCR4-dependent manner with SRB9, a component of the SRB complex that is part of the yeast RNA polymerase II holoenzyme. The three related SRB proteins, SRB9, SRB10, and SRB11, were found to interact with and to coimmunoprecipitate DBF2, CAF4, CCR4, NOT2, and NOT1. Defects in SRB9 and SRB10 also affected processes at the ADH2 locus known to be controlled by components of the CCR4-NOT complex; an srb9 mutation was shown to reduce ADH2 derepression and either an srb9 or srb10 allele suppressed spt10-enhanced expression of ADH2. In addition, srb9 and srb10 alleles increased ADR1(c)-dependent ADH2 expression; not4 and not5 deletions are the only other known defects that elicit this phenotype. These results suggest a close physical and functional association between components of the CCR4-NOT complexes and the SRB9, -10, and -11 components of the holoenzyme.

Adenosine Triphosphatases↗