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Biomedical subjects

Y Tu

Publications and source records attributed to Y Tu.

At least 73 records · Page 4Linked to original sources
PubMed1999

The LIM-only protein PINCH directly interacts with integrin-linked kinase and is recruited to integrin-rich sites in spreading cells.

PINCH is a widely expressed and evolutionarily conserved protein comprising primarily five LIM domains, which are cysteine-rich consensus sequences implicated in mediating protein-protein interactions. We report here that PINCH is a binding protein for integrin-linked kinase (ILK), an intracellular serine/threonine protein kinase that plays important roles in the cell adhesion, growth factor, and Wnt signaling pathways. The interaction between ILK and PINCH has been consistently observed under a variety of experimental conditions. They have interacted in yeast two-hybrid assays, in solution, and in solid-phase-based binding assays. Furthermore, ILK, but not vinculin or focal adhesion kinase, has been coisolated with PINCH from mammalian cells by immunoaffinity chromatography, indicating that PINCH and ILK associate with each other in vivo. The PINCH-ILK interaction is mediated by the N-terminal-most LIM domain (LIM1, residues 1 to 70) of PINCH and multiple ankyrin (ANK) repeats located within the N-terminal domain (residues 1 to 163) of ILK. Additionally, biochemical studies indicate that ILK, through the interaction with PINCH, is capable of forming a ternary complex with Nck-2, an SH2/SH3-containing adapter protein implicated in growth factor receptor kinase and small GTPase signaling pathways. Finally, we have found that PINCH is concentrated in peripheral ruffles of cells spreading on fibronectin and have detected clusters of PINCH that are colocalized with the alpha5beta1 integrins. These results demonstrate a specific protein recognition mechanism utilizing a specific LIM domain and multiple ANK repeats and suggest that PINCH functions as an adapter protein connecting ILK and the integrins with components of growth factor receptor kinase and small GTPase signaling pathways.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Embolization of a giant torcular dural arteriovenous fistula in a neonate.

We treated a neonatal infant who presented with heart failure and a giant torcular dural arteriovenous fistula by staged transtorcular embolization with two guidewires, 95 platinum microcoils, and tissue glues through a needle-size craniotomy. Blood loss was minimal. The patient was stable without heart failure after a three-staged embolization. The lesion disappeared on the follow-up angiography done at the age of 3 years. This is the first documented case of neonatal giant torcular dural arteriovenous malformation cured by interventional neuroradiology. The dilemma and strategy in managing this patient will be presented and discussed.

Arteriovenous Fistula↗
PubMed1999

Estimation of the conduction velocity distribution of peripheral nerve trunks.

The distribution of the conduction velocity (DCV) of peripheral nerve fibers was estimated from two compound action potentials (CAPs) that were evoked at two sites by electrical stimulation and recorded at a different site. In this paper, a regularized least-squares method with a smoothness constraint and self-adaptation of the regularization parameter was adopted. Computer simulation showed it to be effective, especially for noisy CAP signals. In addition, the conduction lengths of nerve fibers were automatically determined by a Fibonacci search, since the conduction lengths of nerve fibers could not be measured accurately due to slack in fibers or changes in length associated with the contraction of adjacent muscles.

Action Potentials↗
PubMed1999

[Diagnosis and surgical treatment of idiopathic slow transit constipation].

OBJECTIVE: To investigate the pathogenesis, the diagnostic criteria, and the therapeutic method of idiopathic slow transit constipation. METHODS: History recording, bowel transit, anorectal dynamic, electromyography of the pelvic floor and defecography were performed before subtotal or total colectomy for severe constipation resistant to conservative treatment. RESULTS: The natural stool frequency was decreased and the time of bowel transit was delayed. The rectal sensation and the ability to reflect inhibition of the pelvic floor when attempting to defecate were damaged significantly compared with normal controls. pathological findings showed that the argyrophilic neurons in the myentenic and submucous plexus reduced quantitatively. All the patients were followed up for an average of 32.2 months. Satisfactory functional outcome was obtained in 91.8% of the patients receiving the operation. CONCLUSIONS: The severe damage colon transit function is due to the impairement of the myentenic and submucous plexus of the colon. It causes vary. The diagnosis of the disease is dependent on the typical clinic features and the bowel transit test. The symptoms of constipation could be relieved effectively by removal of the pathologic colon.

Adolescent↗
PubMed1999

[Study on activities of eight kinds of traditional Chinese medicine against urogential Chlamydia trachomatis].

In order to screen the susceptibilities of urogenital chlamydia trachomatis (CT) to 8 kinds of traditional Chinese medicine by microculture technigue of McCoy cell in Vitro. The results showed that 8 kinds of Chinese medicines all had activities against urogenital CT. Their minimal inhibitory concentrations (MIC) were from 0.49 mg/ml to 15.63 mg/ml. The number and the volume of inclusions were reducing gradually, disappeared finally. These traditional Chinese medicines hadn't any action of cytotoxicity to McCoy cell. The result of this study will be useful for the further study.

Animals↗
PubMed1999

[Omega-mercaptohexanoic acid self-assemble-modified gold electrode and its catalytic property for redox reaction of chlorophylls].

Omega-mercaptohexanoic acid (6-MHA) self-assemble-modified gold electrode has been made by the authors. The SERS spectrum and the variations of double-layer capacitance (Cd) which occurred in the formation of 6-MHA self-assembled monolayers (SAM) on gold electrode surface were studied. The structure model of this SAM was deduced. The results show that 6-MHA can form stable SAM on gold electrode, and this 6-MHA SAM electrode has obvious catalysis for the redox reaction of chlorophylls.

Caproates↗
PubMed1998

Sequence and time-dependent deamination of cytosine bases in UVB-induced cyclobutane pyrimidine dimers in vivo.

The mutational specificity of UV-light is characterized by an abundance of C to T transition mutations at dipyrimidines containing cytosine or 5-methylcytosine. A significant percentage of these mutations are CC to TT double transitions. Of the major types of UV-induced DNA lesions, the cis-syn cyclobutane pyrimidine dimers (CPDs) are thought to be the most mutagenic lesions, at least in mammalian cells. It has been proposed that the CPDs become mutagenic perhaps only after cytosine bases within these dimers deaminate to uracil and the resulting U-containing photolesions are correctly bypassed by DNA polymerases. In order to assess the significance of this proposed mutagenic mechanism, we have developed two methods to specifically measure deaminated CPDs in UV-irradiated human cells or DNA. The first method is based on enzymatic photoreversal of CPDs, followed by cleavage of the DNA with uracil DNA glycosylase, an AP lyase activity, and ligation-mediated PCR to map the resulting strand breaks. The second method, which can be used to detect double deamination events (CC to UU), is PCR amplification of photolyase-treated DNA using primers complemetary to the deaminated sequences. We have measured deamination events in the human p53 gene, which contains a large percentage of C to T transitions in skin cancers. The deamination reactions are specific for cytosine within CPDs, are negligible immediately after irradiation, and are time-dependent and DNA sequence context-dependent. Twenty four hours after irradiation of human fibroblasts with UVB light, between 10 and 60% of most CPD signals are converted to the deaminated form, depending on the sequence. Significant deamination occurs at skin cancer mutation sites in the p53 gene. Double deamination also occurs and this reaction can involve dimers containing 5-methylcytosine or cytosine. These double events are expected to occur more frequently in cells with a DNA repair defect because there is more time for deamination in unrepaired lesions. This may explain the relatively high frequency of CC to TT mutations in skin cancers from xeroderma pigmentosum patients. In summary, these novel detection techniques demonstrate that deamination of cytosine in pyrimidine dimers is a significant event that most likely contributes to the mutational specificity of UVB irradiation in human cells.

Carbon-Oxygen Lyases↗
PubMed1998

RGSZ1, a Gz-selective RGS protein in brain. Structure, membrane association, regulation by Galphaz phosphorylation, and relationship to a Gz gtpase-activating protein subfamily.

We cloned the cDNA for human RGSZ1, the major Gz-selective GTPase-activating protein (GAP) in brain (Wang, J., Tu, Y., Woodson, J., Song, X., and Ross, E. M. (1997) J. Biol. Chem. 272, 5732-5740) and a member of the RGS family of G protein GAPs. Its sequence is 83% identical to RET-RGS1 (except its N-terminal extension) and 56% identical to GAIP. Purified, recombinant RGSZ1, RET-RGS1, and GAIP each accelerated the hydrolysis of Galphaz-GTP over 400-fold with Km values of approximately 2 nM. RGSZ1 was 100-fold selective for Galphaz over Galphai, unusually specific among RGS proteins. Other enzymological properties of RGSZ1, brain Gz GAP, and RET-RGS1 were identical; GAIP differed only in Mg2+ dependence and in its slightly lower selectivity for Galphaz. RGSZ1, RET-RGS1, and GAIP thus define a subfamily of Gz GAPs within the RGS proteins. RGSZ1 has no obvious membrane-spanning region but is tightly membrane-bound in brain. Its regulatory activity in membranes depends on stable bilayer association. When co-reconstituted into phospholipid vesicles with Gz and m2 muscarinic receptors, RGSZ1 increased agonist-stimulated GTPase >15-fold with EC50 <12 nM, but RGSZ1 added to the vesicle suspension was <0.1% as active. RGSZ1, RET-RGS1, and GAIP share a cysteine string sequence, perhaps targeting them to secretory vesicles and allowing them to participate in the proposed control of secretion by Gz. Phosphorylation of Galphaz by protein kinase C inhibited the GAP activity of RGSZ1 and other RGS proteins, providing a mechanism for potentiation of Gz signaling by protein kinase C.

Amino Acid Sequence↗
PubMed1998

Intermittent administration of parathyroid hormone (1-34) stimulates matrix metalloproteinase-9 (MMP-9) expression in rat long bone.

Intermittent doses of parathyroid hormone (PTH) stimulate bone formation in animals and humans, but the molecular mechanisms underlying this phenomenon are not understood. Bone formation culminates with the expression of type I collagen, osteocalcin, and alkaline phosphatase, but genes that initiate and support the anabolic response are not known. To identify novel PTH-regulated genes in bone during the anabolic response, we used differential display-polymerase chain reaction (DDRT-PCR) to analyze RNA from young male rats injected with either human PTH (1-34) or vehicle control, once daily for 5 days. Total RNA was isolated from the distal femur metaphysis at 1, 6, and 48 h after the final injection and subjected to DDRT-PCR. We identified three PTH-responsive transcripts as matrix metalloproteinase-9 (MMP-9), creatine kinase, and the alpha1 (I) polypeptide chain (COL1A1) of type I collagen. The concomitant upregulation of MMP-9 and COL1A1 during bone formation was particularly intriguing. Further characterization of MMP-9 expression revealed that it was localized to osteoblasts, osteocytes, megakaryocytes, and cells of the bone marrow in the rat distal femur metaphysis. Northern analysis for MMP-9 expression in other tissues indicated that this transcript was present in the kidney and brain. In vitro, PTH regulated the protein synthesis of MMP-9 by osteoblasts of the primary spongiosa. We propose that PTH may promote bone formation by mediating the subtle variation in MMP activities, thus preparing the extracellular matrix for the subsequent bone cell migration and deposition of new osteoid.

Amino Acid Sequence↗
PubMed1998

Interleukin-6-induced inhibition of multiple myeloma cell apoptosis: support for the hypothesis that protection is mediated via inhibition of the JNK/SAPK pathway.

The mechanism by which interleukin-6 (IL-6) protects multiple myeloma (MM) plasma cells from apoptosis induced by anti-fas antibodies and dexamethasone was studied. Anti-apoptotic concentrations of IL-6 had no effect on cell-cycle distribution or activation of RAF-1 or ERK in dexamethasone- or anti-fas-treated 8226 and UCLA #1 MM cell lines. However, IL-6-dependent protection of viability correlated with an inhibition of dexamethasone- and anti-fas-induced activation of jun kinase (JNK) and AP-1 transactivation. To test the hypothesis that cytokine-induced protection was mediated through inhibition of JNK/c-jun, we also inhibited c-jun function in 8226 cells via introduction of a mutant dominant negative c-jun construct. Mutant c-jun-containing MM cells were also resistant to anti-fas-induced apoptosis but were significantly more sensitive to dexamethasone-induced apoptosis. These results support the notion that IL-6 protects MM cells against anti-fas through its inhibitory effects on JNK/c-jun but indicate protection against dexamethasone occurs through separate, yet unknown pathways.

Apoptosis↗
PubMed1998

The transcription-repair coupling factor CSA is required for efficient repair only during the elongation stages of RNA polymerase II transcription.

The known nucleotide excision repair (NER) defects of xeroderma pigmentosum (XP) and Cockayne syndrome (CS) cells can be exploited to analyze mechanisms of repair of UV-induced cyclobutane pyrimidine dimers (CPDs) at nucleotide (nt.) resolution. The two gene products of the CS complementation groups (CSA and CSB) have been implicated in the preferential repair of the transcribed strand of human genes. We had previously described very efficient repair of CPDs at sequences near the transcription initiation site of the human JUN gene in normal fibroblasts. Here, we have analyzed repair in a CSA fibroblast strain. CSA cells exhibited rapid repair near the transcription initiation site (positions -45 to +15) but were deficient in repair of sequences on the transcribed strand beginning around nt. +20. There was also no strand-selective repair of sequences further downstream of the start site (+260 to +450). The results suggest that the transcription-repair coupling factor (TRCF) CSA is required for efficient repair only during the elongation stages of RNA polymerase II transcription. We also discuss possible mechanisms of differential repair observed near the transcription initiation site in XP and CS cells and conclude that these in vivo repair data support some recent models obtained from nucleotide excision repair experiments in vitro.

Cell Line↗
PubMed1998

Analysis of differential gene expression in rat tibia after an osteogenic stimulus in vivo: mechanical loading regulates osteopontin and myeloperoxidase.

The skeleton has the ability to alter its mass, geometry, and strength in response to mechanical stress. In order to elucidate the molecular mechanisms underlying this phenomenon, differential display reverse transcriptase-polymerase chain reaction (DDRT-PCR) was used to analyze gene expression in endocortical bone of mature female rats. Female Sprague-Dawley rats, approximately 8 months old, received either a sham or bending load using a four-point loading apparatus on the right tibia. RNA was collected at 1 h and 24 h after load was applied, reverse-transcribed into cDNA, and used in DDRT-PCR. Parallel display of samples from sham and loaded bones on a sequencing gel showed several regulated bands. Further analysis of seven of these bands allowed us to isolate two genes that are regulated in response to a loading stimulus. Nucleotide analysis showed that one of the differentially expressed bands shares 99% sequence identity with rat osteopontin (OPN), a noncollagenous bone matrix protein. Northern blot analysis confirms that OPN mRNA expression is increased by nearly 4-fold, at 6 h and 24 h after loading. The second band shares 90% homology with mouse myeloperoxidase (MPO), a bactericidal enzyme found primarily in neutrophils and monocytes. Semiquantitative PCR confirms that MPO expression is decreased 4- to 10-fold, at 1 h and 24 h after loading. Tissue distribution analysis confirmed MPO expression in bone but not in other tissues examined. In vitro analysis showed that MPO expression was not detectable in total RNA from UMR 106 osteoblastic cells or in confluent primary cultures of osteoblasts derived from either rat primary spongiosa or diaphyseal marrow. Database analysis suggests that MPO is expressed by osteocytes. These findings reinforce the association of OPN expression to bone turnover and describes for the first time, decreased expression of MPO during load-induced bone formation. These results suggest a role for both OPN and MPO expression in bone cell function.

Animals↗
PubMed1998

BCL-X expression in multiple myeloma: possible indicator of chemoresistance.

Because murine myeloma plasma cells and normal human lymph node plasma cells express BCL-X, we evaluated BCL-X expression in malignant human plasma cells. BCL-X expression was detected in several human myeloma cell lines, as well as in CD38-sorted bone marrow cells obtained from some patients. Only the antiapoptotic long form of BCL-X (BCL-X-L), was detected. Because BCL-X-L expression can protect tumor cells from apoptotic death induced by chemotherapeutic agents, we tested the clinical relevance of expression in 55 archival bone marrow biopsies. The biopsies were stained by immunohistochemistry, and BCL-X expression was correlated with the subsequent response to treatment. BCL-X expression in malignant plasma cells strongly correlated with decreased response rates in patient groups treated with either melphalan and prednisone or vincristine, Adriamycin, and dexamethasone. Response rates were 83-87% in non-BCL-X-expressing cases and 20-31% in BCL-X-expressing cases. In addition, BCL-X expression was more frequent in specimens taken from patients at relapse (77%), when compared to those at initial diagnosis (29%). Further support for the association of drug resistance with BCL-X-L expression came from studies of the 8226 dox-40 cell line. This line, which expresses p-glycoprotein and serves as a model of multidrug resistance in multiple myeloma cells, demonstrated an up-regulated expression of BCL-X-L, which was relatively specific, in that BCL-2 or BAX expression was not altered. In addition, dox-40 cells demonstrated a generalized resistance to apoptosis that was induced by several different agents. These results indicate that malignant plasma cells can express BCL-X-L and that such expression may be a marker of chemoresistant disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Study on the hypercoagulable state in patients with angina and myocardial infarction.

The molecular markers of platelet activation, coagulation and fibrinolysis were detected in 60 cases of coronary heart disease (CHD), including 15 cases of stable angina (SA), 21 cases of unstable angina (UA) and 24 cases of acute myocardial infarction (AMI). The results showed that the platelet granule membrane protein 140 (GMP-140) level increased obviously in CHD groups compared with normal control, suggesting that platelet activation existed in CHD. Prothrombin fragment F1 + 2 and fibrinopeptide A (FPA) were examined to observe the activation of coagulation. No difference was found between SA group and normal controls, while their levels in both UA group and AMI group were significantly higher than in normal control and SA group (both P < 0.05). D-D dimer and alpha 2-plasma inhibitor (alpha 2-PI) were detected to observe fibrinolytic state. The results showed that no difference existed between SA group and normal controls, while both D-D dimer and alpha 2-PI in UA group and AMI group were significantly elevated than those in SA group and normal controls (P < 0.05).

Angina Pectoris↗
PubMed1998

In vitro cytoreductive effects on multiple myeloma cells induced by bisphosphonates.

In a double blind randomized study, the bisphosphonate drug Pamidronate (Aredia) significantly protected Durie-Salmon stage III multiple myeloma patients from osteolytic bone disease. In the patient sub-group on salvage chemotherapy. Pamidronate treatment was also significantly associated with prolonged survival. To test if this drug could induce direct antitumor effects, we exposed myeloma cells to increasing concentrations of Pamidronate or a more potent bisphosphonate, Zoledronate. A concentration- and time-dependent cytotoxic effect was detected on four of five myeloma cell lines as well as three specimens obtained directly from myeloma patients. Zoledronate-induced cytotoxicity was significantly greater than that of Pamidronate. Cytotoxicity could not be explained by bisphosphonate-induced chelation of extracellular calcium or secondary decrease in production of the myeloma growth factor interleukin-6. Morphological examination, DNA electrophoresis and cell cycle analysis indicated that the bisphosphonate-induced cytotoxic effect consisted of a combination of cytostasis and apoptotic myeloma cell death. Enforced expression of BCL-2 protected against the apoptotic death but not against cytostasis. Most cytotoxic effects were seen between 10 and 100 microM of drug. The results suggest a possible direct anti-tumor effect in myeloma patients treated with bisphosphonates which may participate in their significantly increased survival. This hypothesis should now be further tested in clinical trials.

Antineoplastic Agents↗