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Biomedical subjects

Z Tu

Publications and source records attributed to Z Tu.

At least 19 recordsLinked to original sources
PubMed2001

I kappa B kinase is critical for TNF-alpha-induced VCAM1 gene expression in renal tubular epithelial cells.

The expression of VCAM1 is up-regulated in renal proximal tubular epithelial cells (TEC) in a variety of inflammatory renal diseases, a prominent example of which is acute renal allograft rejection. VCAM1 may play an important role in these diseases because it binds to the integrins very late Ag-4 and alpha(4)beta(7) on lymphocytes and monocytes, thereby providing a potential mechanism to recruit these leukocytes to sites of inflammation. The molecular mechanisms underlying VCAM1 regulation in renal TEC are essentially unknown. We now report that VCAM1 mRNA is dramatically up-regulated in C1, a cell line derived from renal TEC, on exposure to TNF-alpha. Two NF-kappaB binding sites in the VCAM1 promoter are critical for the TNF-alpha-induced VCAM1 transcriptional up-regulation, and both sites bind to p65-p50 NF-kappaB complexes. TNF-alpha induces activation of inhibitor of NF-kappaB (IkappaB) kinase-beta (IKK-beta), a protein kinase that phosphorylates the NF-kappaB inhibitor IkappaB, and thereby targets the latter for degradation via the ubiquitin-proteasome pathway. Moreover, dominant negative versions of IKK inhibit TNF-alpha activation of a VCAM1 promoter reporter. We conclude that the IKK/NF-kappaB pathway is critical in the TNF-alpha-induced up-regulation of VCAM1 mRNA in renal TEC.

Animals↗
PubMed2001

Eight novel families of miniature inverted repeat transposable elements in the African malaria mosquito, Anopheles gambiae.

Eight novel families of miniature inverted repeat transposable elements (MITEs) were discovered in the African malaria mosquito, Anopheles gambiae, by using new software designed to rapidly identify MITE-like sequences based on their structural characteristics. Divergent subfamilies have been found in two families. Past mobility was demonstrated by evidence of MITE insertions that resulted in the duplication of specific TA, TAA, or 8-bp targets. Some of these MITEs share the same target duplications and similar terminal sequences with MITEs and other DNA transposons in human and other organisms. MITEs in A. gambiae range from 40 to 1340 copies per genome, much less abundant than MITEs in the yellow fever mosquito, Aedes aegypti. Statistical analyses suggest that most A. gambiae MITEs are in highly AT-rich regions, many of which are closely associated with each other. The analyses of these novel MITEs underscored interesting questions regarding their diversity, origin, evolution, and relationships to the host genomes. The discovery of diverse families of MITEs in A. gambiae has important practical implications in light of current efforts to control malaria by replacing vector mosquitoes with genetically modified refractory mosquitoes. Finally, the systematic approach to rapidly identify novel MITEs should have broad applications for the analysis of the ever-growing sequence databases of a wide range of organisms.

Africa↗
PubMed2001

Maque, a family of extremely short interspersed repetitive elements: characterization, possible mechanism of transposition, and evolutionary implications.

Database analysis revealed a novel family of very short interspersed repetitive elements named Maque in the African malaria mosquito, Anopheles gambiae. Past mobility of Maque was demonstrated by evidence of its insertion that resulted in a target duplication. Approximately 220 copies of Maque were present in the A. gambiae genome. Although only approximately 60 bp long, Maque has the appearance of a distinct transposition unit. Eleven of the 12 Maque elements found in the database were flanked by 9-14 bp direct repeats, indicating that their transposition was relatively recent. Sequence comparison and phylogenetic analyses suggest that there are at least two subgroups within the Maque family, suggesting that they may have been originated from more than one source. Five of the 12 Maque elements had at least one other repetitive element nearby. Three of the Maque elements were found near genes. However, Maque was not found in the coding regions of genes or in any of the expressed sequence tags (ESTs), which is consistent with its significantly biased distribution toward A + T rich regions. Several characteristics of Maque indicate that it is likely a non-autonomous retro-element. The evolutionary origin of Maque and the differences between Maque and other known retro-elements including short interspersed repetitive elements (SINEs) are discussed. A hypothesis is proposed in which short sequences containing just the reverse transcriptase recognition signal (RTRS) could potentially contribute to exon shuffling and the genesis of some primordial SINEs.

Animals↗
PubMed2001

Possible horizontal transfer of a transposable element from host to parasitoid.

Full-length mariner-like elements (MLEs) were identified from both a parasitoid wasp, Ascogaster reticulatus, and its moth host, Adoxophyes honmai. MLEs were detected in two related Tortricid moths, but not in another Ascogaster species. The MLEs of A. reticulatus and A. honmai were 97.6% identical in DNA sequence. This high similarity suggests a recent horizontal transfer, probably from the moth host to the wasp parasitoid, facilitated by the intimacy of the host-parasitoid relationship.

Amino Acid Sequence↗
PubMed2000

Colon interposition.

In the anatomy of the colon vasculature, the ascending branch of the left colic artery is the primary supplying vessel (96.91%). Isoperistaltic transposition of the transverse colon is preferred (83.58%). Riolan's vascular arcade is not a major vessel of the colon. It can only be found in less than 10% of patients, and whether or not this arcade is complete cannot be used as criterion to judge colon blood supply. Animal experiments and clinical studies have confirmed the superiority of one-layer over two-layer anastomosis. The former is simpler, safer, and more reliable, with a lower incidence of anastomotic leak or stricture. Based on a comprehensive evaluation of the disease type, patient age, heart and lung functions, nutritional status, and accompanying diseases, three colon transposition routes are available (anterosternal subcutaneous tunnel, retrosternal tunnel, and esophageal bed passage). The advantages and disadvantages of each route are analyzed, and the left-middle-left retrosternal route is described. The indications for esophageal reconstruction with colon operation (ERC) were collected and verified, increasing the number of indications to seven categories of diseases. The main complications of ERC, i.e., colon segment necrosis, anastomotic leak, recurrent laryngeal nerve injury, and intestinal obstruction were systematically studied, and their causes and prevention are detailed. The number of patients is the highest in a single unit among all the published reports. The incidence of complications and deaths are the lowest.

Adolescent↗
PubMed2000

Synthesis and biological characterization of stable and radioiodinated (+/-)-trans-2-hydroxy-3-P[4-(3-iodophenyl)piperidyl]-1,2,3,4-tetrahydronaphthalene (3'-IBVM).

The vesamicol analogue (+/-)-trans-2-Hydroxy-3-[4-(3-iodophenyl)piperidyl]-1,2,3,4-tetrahydronaphthalene (3'-IBVM), a potent ligand for the vesicular acetylcholine transporter (VAChT), was evaluated as a potential radiotracer for studying VAChT density in vivo. In radioligand binding experiments, 3'-IBVM displays subnanomolar affinity for VAChT and 100-fold selectivity for VAChT over sigma1 and sigma2 receptors. Consistent with this profile, radioiodinated (+/-)-3'-IBVM distributed heterogenously in the rat brain following a bolus IV injection, displaying high concentrations in the striatum and moderate to low concentrations in the cortex and cerebellum, respectively. However, co-injection of the radiotracer with the sigma ligand haloperidol resulted in significant reductions of radiotracer levels in all brain regions examined. Therefore, radioiodinated (+/-)-IBVM appears to bind to both VAChT and sigma receptors in vivo.

Acetylcholine↗
PubMed2000

Molecular and evolutionary analysis of two divergent subfamilies of a novel miniature inverted repeat transposable element in the yellow fever mosquito, Aedes aegypti.

A novel family of miniature inverted repeat transposable elements (MITEs) named Pony was discovered in the yellow fever mosquito, Aedes aegypti. It has all the characteristics of MITEs, including terminal inverted repeats, no coding potential, A+T richness, small size, and the potential to form stable secondary structures. Past mobility of PONY: was indicated by the identification of two Pony insertions which resulted in the duplication of the TA dinucleotide targets. Two highly divergent subfamilies, A and B, were identified in A. aegypti based on sequence comparison and phylogenetic analysis of 38 elements. These subfamilies showed less than 62% sequence similarity. However, within each subfamily, most elements were highly conserved, and multiple subgroups could be identified, indicating recent amplifications from different source genes. Different scenarios are presented to explain the evolutionary history of these subfamilies. Both subfamilies share conserved terminal inverted repeats similar to those of the Tc2 DNA transposons in Caenorhabditis elegans, indicating that Pony may have been borrowing the transposition machinery from a Tc2-like transposon in mosquitoes. In addition to the terminal inverted repeats, full-length and partial subterminal repeats of a sequence motif TTGATTCAWATTCCGRACA represent the majority of the conservation between the two subfamilies, indicating that they may be important structural and/or functional components of the Pony elements. In contrast to known autonomous DNA transposons, both subfamilies of PONY: are highly reiterated in the A. aegypti genome (8,400 and 9, 900 copies, respectively). Together, they constitute approximately 1. 1% of the entire genome. Pony elements were frequently found near other transposable elements or in the noncoding regions of genes. The relative abundance of MITEs varies in eukaryotic genomes, which may have in part contributed to the different organizations of the genomes and reflect different types of interactions between the hosts and these widespread transposable elements.

Aedes↗
PubMed2000

Recognition of sentences in noise by normal-hearing listeners using simulations of speak-type cochlear implant signal processors.

To assess whether more channels are needed to understand speech in noise than in quiet, we processed speech in a manner similar to that of spectral peak-like cochlear implant processors and presented it at a +2-dB signal-to-noise ratio to normal-hearing listeners for identification. The number of analysis filters varied from 8 to 16, and the number of maximum channel amplitudes selected in each cycle varied from 2 to 16. The results show that more channels are needed to understand speech in noise than in quiet, and that high levels of speech understanding can be achieved with 12 channels. Selecting more than 12 channel amplitudes out of 16 channels did not yield significant improvements in recognition performance.

Adult↗
PubMed2000

Rat hepatocellular apoptosis induced by glycodeoxycholate.

OBJECTIVE: To explore the relationship between glycodeoxycholate (GDC) and rat hepatocellular apoptosis. METHODS: GDC was used to treat rat hepatocytes cultured in vitro and the apoptotic cells were observed and analyzed with light microscope, transmission electron microscope, TUNEL in situ hybridization, DNA agarose gel electrophoresis and flow cytometry. RESULTS: When rat hepatocytes were incubated with GDC (final concentration of 100 micromol/L) for 2h, apoptotic hepatocytes were observed with light and transmission electron microscope, and TUNEL in situ hybridization. When the hepatocytes were incubated with GDC (final concentration of 50, 100, 150 micromol/L, respectively) for 2h, or with GDC (final concentration of 100 micromol/L) for 2, 4, 6, 8h, respectively, agarose gel electrophoresis of the hepatocytes DNA demonstrated the typical ladder patterns. CONCLUSION: GDC with final concentration of 50, 100, 150 micromol/L could induce rat hepatocellular apoptosis.

Animals↗
PubMed2000

[Protein expression of human progesterone receptor isoforms A and B in uterine leiomyoma].

OBJECTIVE: To investigate the role of two isoforms of human progesterone receptor A (hPR-A) and B (hPR-B) in the development of uterine leiomyoma, their distribution and expression in leiomyoma were detected. METHODS: The tissues of leiomyoma and normal myometrium from 30 uteri, which were excised for leiomyoma, were used for the localization and quantification of protein of the two isoforms. Immunohistochemistry and Western blot were applied respectively. RESULTS: Both hPR-A and hPR-B were nuclear receptors. Concentrations of hPR-(A + B) and hPR-A in leiomyoma were higher than those in normal myometrium (295,796 +/- 90,856, 256,275 +/- 98,560; P = 0.042, P = 0.000,563). Both isoforms were presented in leiomyoma and normal myometrium, with a consistent dominance of hPR-B over hPR-A. More expression of hPR-A was found during secretive phase than proliferative phase, not only in leiomyoma but also in normal myometrium (P = 0.037, P = 0.024). CONCLUSIONS: The development of uterine leiomyoma seems to be related with the progesterone receptor isoforms, especially hPR-A.

Adult↗
PubMed1999

Sphingosine 1-phosphate-induced cell rounding and neurite retraction are mediated by the G protein-coupled receptor H218.

Sphingosine 1-phosphate (SPP) is a lipid second messenger that also acts as a first messenger through the G protein-coupled receptor Edg-1. Here we show that SPP also binds to the related receptors H218 and Edg-3 with high affinity and specificity. SPP and sphinganine 1-phosphate bind to these receptors, whereas neither sphingosylphosphorylcholine nor lysophosphatidic acid compete with SPP for binding to either receptor. Transfection of HEK293 cells with H218 or edg-3, but not edg-1, induces rounded cell morphology in the presence of serum, which contains high levels of SPP. SPP treatment of cells overexpressing H218 cultured in delipidated serum causes cell rounding. A similar but less dramatic effect was observed in cells overexpressing Edg-3 but not with Edg-1. Cell rounding was correlated with apoptotic cell death, probably as a result of loss of attachment. Nerve growth factor-induced neuritogenesis in PC12 cells was inhibited by overexpression of H218 and to a lesser extent Edg-3. SPP treatment rapidly enhanced neurite retraction in PC12 cells overexpressing Edg-1, Edg-3, or H218. Thus, H218, and possibly Edg-3, may be the cell surface receptors responsible for cell rounding and neurite retraction induced by SPP. Moreover, the identification of these two additional SPP receptors indicates that a family of highly specific receptors exists that mediate different responses to SPP.

Animals↗
PubMed1999

MosquI, a novel family of mosquito retrotransposons distantly related to the Drosophila I factors, may consist of elements of more than one origin.

A novel family of non-long-terminal-repeat (non-LTR) retrotransposons, named MosquI, was discovered in the yellow fever mosquito, Aedes aegypti. There were approximately 14 copies of MosquI in the A. aegypti genome. Four of the five analyzed MosquI elements were truncated at the 5' ends while one of them, MosquI-Aa2, was full-length. All five MosquI elements ended with 4-10 TAA tandem repeats, as the Drosophila I factors do. Interestingly, MosquI elements were often found near genes and other repetitive elements. The 6,623-bp MosquI-Aa2 contained two open reading frames (ORFs) flanked by a 404-bp 5' untranslated region and a 326-bp 3' untranslated region. The two ORFs code for nucleocapsids, endonuclease, reverse transcriptase, and RNase H domains. Although overall structural and sequence comparisons suggest that MosquI is highly similar to the Drosophila I factors, phylogenetic analysis based on the reverse transcriptase domains of 40 non-LTR retrotransposons indicate that MosquI and I factors are likely paralogous elements which may have been separated before the split between the ancestors of mollusca and arthropoda. Pairwise comparisons between the four truncated MosquI elements showed 96.7%-99.5% identity at the nucleotide level, while comparisons between the full-length MosquI-Aa2 and the truncated copies showed only 80.2%-81.8% identity. These comparisons and preliminary phylogenetic analyses suggest that the full-length and truncated MosquI elements may belong to two subfamilies originating from two source genes that diverged a long time ago. In contrast to the defective I factors in Drosophila melanogaster, which are likely very old components of the genome, the truncated MosquI elements seem to have been recently active. Finally, the genomic distribution and evolution of MosquI elements are analyzed in the context of other non-LTR retrotransposons in A. aegypti.

Aedes↗
PubMed1999

Genomic and evolutionary analysis of Feilai, a diverse family of highly reiterated SINEs in the yellow fever mosquito, Aedes aegypti.

Five short interspersed repetitive elements (SINEs) were found fortuitously in the introns of a steroid hormone receptor AaHR3-2 gene of the yellow fever mosquito, Aedes aegypti, constituting a novel family of tRNA-related SINEs named Feilai. In addition, nine other Feilai elements were found in currently available sequences in Ae. aegypti, six of which were also near genes. Approximately 5.9 x 10(4) copies of Feilai were present in Ae. aegypti, equivalent to 2% of the entire genome. An additional 35 Feilai elements were isolated from a genomic library. Of the total 49 Feilai elements, 20 were full-length. Sequence comparisons and phylogenetic analyses of the full-length elements strongly suggest that there are at least two subfamilies within the Feilai family. There is a high degree of conservation within the two subfamilies. However, sequence divergence between the subfamilies, along with the presence of highly degenerate Feilai elements, suggests that Feilai is likely a diverse family of SINEs that has existed in Ae. aegypti for a long time. Many Feilai elements were closely associated with other transposons, especially with fragments of non-LTR retrotransposons and miniature inverted-repeat transposable elements. The 500-bp sequences immediately flanking a Feilai element were highly A + T-rich, which is consistent with the fact that no Feilai has been found in the coding regions of genes. It is likely that the highly reiterated and interspersed Feilai elements are partially responsible for the pattern of short-period interspersion of the Ae. aegypti genome. The evolutionary relationship between Feilai and the Ae. aegypti genome is likely complex.

Aedes↗
PubMed1999

On the number of channels needed to understand speech.

Recent studies have shown that high levels of speech understanding could be achieved when the speech spectrum was divided into four channels and then reconstructed as a sum of four noise bands or sine waves with frequencies equal to the center frequencies of the channels. In these studies speech understanding was assessed using sentences produced by a single male talker. The aim of experiment 1 was to assess the number of channels necessary for a high level of speech understanding when sentences were produced by multiple talkers. In experiment 1, sentences produced by 135 different talkers were processed through n (2 < or = n < or = 16) number of channels, synthesized as a sum of n sine waves with frequencies equal to the center frequencies of the filters, and presented to normal-hearing listeners for identification. A minimum of five channels was needed to achieve a high level (90%) of speech understanding. Asymptotic performance was achieved with eight channels, at least for the speech material used in this study. The outcome of experiment 1 demonstrated that the number of channels needed to reach asymptotic performance varies as a function of the recognition task and/or need for listeners to attend to fine phonetic detail. In experiment 2, sentences were processed through 6 and 16 channels and quantized into a small number of steps. The purpose of this experiment was to investigate whether listeners use across-channel differences in amplitude to code frequency information, particularly when speech is processed through a small number of channels. For sentences processed through six channels there was a significant reduction in speech understanding when the spectral amplitudes were quantized into a small number (< 8) of steps. High levels (92%) of speech understanding were maintained for sentences processed through 16 channels and quantized into only 2 steps. The findings of experiment 2 suggest an inverse relationship between the importance of spectral amplitude resolution (number of steps) and spectral resolution (number of channels).

Acoustic Stimulation↗
PubMed1999

Primary choledochorrhaphy after common bile duct exploration.

AIM: To prove further the safety of primary closure of the common bile duct. METHOD: Twenty patients among 99 common bile duct explorations underwent primary closure. Pre- and postoperative liver function test, ultrasound and intraoperative cholangiography data, operation time, postoperative complications and the length of postoperative stay were recorded. RESULTS: Nineteen patients did not suffer any biliary complication. One had bile leakage and bile peritonitis, and another had duodenal leakage. One case was complicated by gastric ulcer perforation. The mean postoperative hospital stay except for the 2 patients with complications was 8.72 +/- 0.75 days. Preoperative abnormal liver function tests recovered within 2-3 weeks after the operation. Postoperative ultrasound scan of the biliary tract within 2 months revealed no stenosis and residual stone. CONCLUSION: Primary common bile duct closure is a safe alternative to routine biliary drainage in selected patients.

Adult↗
PubMed1999

Identification and functional analysis of novel human melanocortin-4 receptor variants.

Inactivation of the melanocortin-4 receptor (MC4-R) by gene-targeting results in mice that develop maturity-onset obesity, hyperinsulinemia, and hyperglycemia. These phenotypes resemble common forms of human obesity, which are late-onset and frequently accompanied by NIDDM. It is not clear whether sequence variation of the MC4-R gene contributes to obesity in humans. Therefore, we examined the human MC4-R gene polymorphism in 190 individuals ascertained on obesity status. Three allelic variants were identified, including two novel ones, Thr112Met and Ile137Thr. To analyze possible functional alterations, the variants were cloned and expressed in vitro and compared with the wild-type receptor. One of the novel variants, Ile137Thr, identified in an extremely obese proband (BMI 57), was found to be severely impaired in ligand binding and signaling, raising the possibility that it may contribute to development of obesity. Furthermore, our results also suggest that sequence polymorphism in the MC4-R coding region is unlikely to be a common cause of obesity in the population studied, given the low frequency of functionally significant mutations.

Adolescent↗