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Biomedical subjects

Y Mu

Publications and source records attributed to Y Mu.

At least 37 records · Page 2Linked to original sources
PubMed2000

Metal ion release from titanium with active oxygen species generated by rat macrophages in vitro.

The release of metal ions due to active oxygen species generated by macrophages (Mphi) phagocytosing high-density polyethylene (HDPE) particles was studied in vitro to investigate the mechanism behind the release of metal ions from titanium implants into nearby tissues in the absence of wear and fretting in vivo. To determine the effects of Mphis on metal ion release, titanium disks were immersed in different solutions and the titanium ions released from the titanium disks into each solution were quantified. The results revealed that active oxygen species generated by Mphis induced the metal ion release. In particular, the ion release was accelerated with HDPE because the Mphis that phagocytosed HDPE generated more active oxygen species than Mphis that did not phagocytose any HDPE. Metal ions were also released by organic species in the absence of Mphis. These are some of the causes for metal ion release from titanium implants in the absence of wear and fretting in vivo.

Animals↗
PubMed2000

Thiazolidinedione suppresses the expression of erythroid phenotype in erythroleukemia cell line K562.

The activation of PPARgamma:RXR nuclear system induces monocytic differentiation of some myelogeneous leukemia cell lines. The present study was undertaken to examine the effect of PPARgamma ligand, TZD (troglitazone or pioglitazone) and/or RXR selective ligand, LG100268 on the erythroleukaemia cell line K562 which has both an erythroid character and a potential for differentiation into megakaryocytes. TZD suppressed cell proliferation and the erythroid phenotype of K562 cells. The suppression of erythroid phenotype of K562 cells by TZD was synergistically enhanced by the combined treatment with LG100268. Moreover, the marked suppression of erythroid phenotype in K562 cells was also accompanied by the downregulation of the erythroid lineage-transcription factor, GATA-1. These novel actions of troglitazone may provide a biochemical basis for anemia occasionally which is observed after the in vivo administration of TZD.

Cell Differentiation↗
PubMed2000

Protein kinase C-theta participates in NF-kappaB activation induced by CD3-CD28 costimulation through selective activation of IkappaB kinase beta.

The NF-kappaB/Rel family of eukaryotic transcription factors plays an essential role in the regulation of inflammatory, antiapoptotic, and immune responses. NF-kappaB is activated by many stimuli including costimulation of T cells with ligands specific for the T-cell receptor (TCR)-CD3 complex and CD28 receptors. However, the signaling intermediates that transduce these costimulatory signals from the TCR-CD3 and CD28 surface receptors leading to nuclear NF-kappaB expression are not well defined. We now show that protein kinase C-theta (PKC-theta), a novel PKC isoform, plays a central role in a signaling pathway induced by CD3-CD28 costimulation leading to activation of NF-kappaB in Jurkat T cells. We find that expression of a constitutively active mutant of PKC-theta potently induces NF-kappaB activation and stimulates the RE/AP composite enhancer from the interleukin-2 gene. Conversely, expression of a kinase-deficient mutant or antisense PKC-theta selectively inhibits CD3-CD28 costimulation, but not tumor necrosis factor alpha-induced activation of NF-kappaB in Jurkat T cells. The induction of NF-kappaB by PKC-theta is mediated through the activation of IkappaB kinase beta (IKKbeta) in the absence of detectable IKKalpha stimulation. PKC-theta acts directly or indirectly to stimulate phosphorylation of IKKbeta, leading to activation of this enzyme. Together, these results implicate PKC-theta in one pathway of CD3-CD28 costimulation leading to NF-kappaB activation that is apparently distinct from that involving Cot and NF-kappaB-inducing kinase (NIK). PKC-theta activation of NF-kappaB is mediated through the selective induction of IKKbeta, while the Cot- and NIK-dependent pathway involves induction of both IKKalpha and IKKbeta.

CD28 Antigens↗
PubMed2000

Facile synthesis of a chitosan hybrid of a laminin-related peptide and its antimetastatic effect in mice.

Laminin, a cell adhesion protein, consists of three peptide chains (alpha-1, beta-1 and gamma-1). The beta-1 chain contains a Tyr-Ile-Gly-Ser-Arg (YIGSR) sequence that has been found to inhibit experimental metastasis in mice. We have prepared a hybrid of a water-soluble chitosan and a laminin-related peptide, and have examined its inhibitory effect on experimental metastasis in mice. A laminin-related peptide, acetyl-Tyr-Ile-Gly-Ser-Arg-betaAla-OH (Ac-YIGSRbetaA-OH), was prepared by a solid-phase method. Ac-YIGSRbetaA-OH was then reacted with a water-soluble chitosan. BetaAla is a spacer and was placed to avoid racemization of the Arg residue when the peptide was coupled with chitosan. Although chitosan has amino groups, they did not react with the peptide. Four methods were tried to achieve a coupling reaction, the diphenylphosphoryl azide method, the diisopropylcarbodiimide/1-hydroxybenzotriazole method, the water-soluble carbodiimide (WSC), and the 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) method, but all four methods were unsuccessful. Therefore, a small spacer, tert-butyloxycarbonyl-Gly, was intercalated in chitosan, by the TBTU method, to facilitate its coupling with the peptide. After removal of the protecting group, the Gly-chitosan was coupled with Ac-YIGSRbetaA-OH by the water-soluble carbodiimide method to give Ac-YIGSRbetaAG-chitosan. Conjugation of the peptide with the larger chitosan molecule did not reduce the inhibitory effect of the peptide on experimental metastasis in mice, it actually potentiated the antimetastatic effect, demonstrating that chitosan may be effective as a drug carrier for peptides.

Animals↗
PubMed2000

24-hour blood pressure in Uygur, Kazakh and Han elderly subjects in China.

The Uygur in Hotan (Xinjiang, China) are reported to have a long life expectancy. The purpose of this study was to clarify the relationship between variations in blood pressure (BP) and longevity. Cross-sectional surveillance was carried out in both Hotan and Barkol. The subjects were divided into five groups: 1. Uygur longevity subjects in Hotan (103 subjects, age >90 yr); 2. Uygur elderly subjects in Hotan (107 subjects, age 65-70 yr); 3. Han elderly subjects in Hotan (41 subjects, age 65-70 yr); 4. Kazakh elderly subjects in Barkol (117 subjects, age 65-70 yr); 5. Han elderly subjects in Barkol (50 subjects, age 65-70 yr). BP was monitored and analyzed using the fourteen devices of ambulatory BP monitoring. The prevalence of hypertension was lowest in the Uygur (16.2% in Uygur elderly subjects in Hotan; 23.7% in Uygur longevity subjects in Hotan; 27.0% in Han elderly subjects in Hotan; 42.0% in Han elderly subjects in Barkol; 50.0% in Kazakh elderly subjects in Barkol). The ratio of dips in BP was largest in the Han (57% in Han elderly subjects in Barkol; 50% in Han elderly subjects in Hotan; 50% in Uygur longevity subjects in Hotan, 49% in Uygur elderly subjects in Hotan; 17% in Kazakh elderly subjects in Barkol). The 24-h mean systolic BP in Uygur longevity subjects in Hotan was not different from those in Uygur elderly subjects and Han elderly subjects in Hotan, nor did the 24-h mean diastolic BP differ from those in Uygur elderly subjects and Han elderly subjects in Hotan respectively. In conclusion, Uygur subjects seem to be less hypertensive, compared to Kazakh subjects. Uygur longevity subjects had more dipping in their BP variation than did the Kazakh subjects in Xinjiang, China.

Aged↗
PubMed2000

[Intraoperative endoscopic sphincterotomy for common bile duct stones during laparoscopic cholecystectomy].

OBJECTIVE: To assess the effects of approach-intraoperative endoscopic sphincterotomy (IOES) for common bile duct (CBD) stones during laparoscopic cholecystectomy (LC). METHODS: Twenty-seven patients with secondary CBD stones were treated by IOES during LC. Therapeutic effects were evaluated on the basis of the cure rate, early complications, and days of hospitalization. RESULTS: IOES was successfully performed in 26 (96.30%) of 27 cases, and their CBD stones were cleared completely. Two cases (7.69%) were complicated by mild acute pancreatitis. CONCLUSION: IOES as an alternative to the treatment of CBD stones during LC is safe and avoids reoperation.

Adult↗
PubMed1999

Bioconjugation of laminin-related peptide YIGSR with polyvinyl pyrrolidone increases its antimetastatic effect due to a longer plasma half-life.

Polyvinyl pyrrolidone (PVP) which can be radically synthesized and have a long blood residency was used to modify the laminin-related peptide YIGSR, and its inhibitory effect on experimental lung metastasis of B16-BL6 melanoma cells was examined. The antimetastatic effect of PVP-conjugated YIGSR (PVP-YIGSR) was more than 100-fold greater than that of native YIGSR. When injected intravenously, PVP-YIGSR showed more than a 15-fold longer plasma half-life relative to native YIGSR. In addition, the stability of YIGSR in plasma was increased by conjugation with PVP. These findings suggest that PVP is a useful polymeric modifier for increasing the antimetastatic activity of YIGSR.

Animals↗
PubMed1999

Novel farnesol and geranylgeraniol analogues: A potential new class of anticancer agents directed against protein prenylation.

Protein farnesyltransferase (FTase), the enzyme responsible for protein farnesylation, has become a key target for the rational design of cancer chemotherapeutic agents. Herein it is shown that certain novel prenyl diphosphate analogues are potent inhibitors of mammalian FTase. Furthermore, the alcohol precursors of two of these compounds are able to block anchorage-independent growth of ras-transformed cells. While 3-allylfarnesol inhibits protein farnesylation, 3-vinylfarnesol instead leads to abnormal prenylation of proteins with the 3-vinylfarnesyl group. In a similar manner, 3-allylgeranylgeraniol acts as a highly specific inhibitor of protein geranylgeranylation, while 3-vinylgeranylgeraniol restores protein geranylgeranylation in cells. This study indicates that certain prenyl alcohol analogues can act as prenyltransferase inhibitors in situ, via a novel prodrug mechanism. These analogues may prove to be valuable tools for investigating the therapeutic consequences of inhibiting geranylgeranylation relative to farnesylation. Furthermore, the 3-vinyl alcohol analogues can inhibit transformed cell growth through a mechanism not involving prenyltransferase inhibition.

Alkyl and Aryl Transferases↗
PubMed1999

[Linkage studies of a familial spastic paraplegia pedigree from Tibet].

OBJECTIVE: To study the location of disease-related gene in a hereditary spastic paraplegia family with autosomal dominant inheritance in Tibet. METHODS: The AD-HSP family in Tibet was analyzed by linkage studies using 9 highly polymorphic microsatellite DNA markers at three chromosomal regions. RESULTS: The maxium Lod- Score of D14S264 was 0.5163(theta=0.05); of D14S75, 2. 1072 (theta=0);+D14S69, 0.2840 (theta=0.10); of D14S266, 0.9311 (theta=0);of D14S66, 0.7991(theta=0);OF GABRB3, 0(theta =0.40);of D15S128, 0(theta=0.40); of D2S2255, 0 (theta=0.40);and of D2S2347,0(theta=0.40). CONCLUSION: In this Tibetian family, the disease-related gene is linked to D14S75 locus of SPG3 region.

Female↗
PubMed1999

Bioconjugation of laminin peptide YIGSR with poly(styrene co-maleic acid) increases its antimetastatic effect on lung metastasis of B16-BL6 melanoma cells.

A comb-shaped polymeric modifier, SMA [poly(styrene comaleic anhydride)], which binds to plasma albumin in blood was used to modify the synthetic cell-adhesive laminin peptide YIGSR, and its inhibitory effect on experimental lung metastasis of B16-BL6 melanoma cells was examined. YIGSR was chemically conjugated with SMA via formation of an amide bond between the N-terminal amino group of YIGSR and the carboxyl anhydride of SMA. The antimetastatic effect of SMA-conjugated YIGSR was approximately 50-fold greater than that of native YIGSR. When injected intravenously, SMA-YIGSR showed a 10-fold longer plasma half-life than native YIGSR in vivo. In addition, SMA-YIGSR had the same binding affinity to plasma albumin as SMA, while native YIGSR did not bind to albumin. These findings suggested that the enhanced antimetastatic effect of SMA-YIGSR may be due to its prolonged plasma half-life by binding to plasma albumin, and that bioconjugation of in vivo unstable peptides with SMA may facilitate their therapeutic use.

Animals↗
PubMed1999

High angiogenic activity in cells isolated from cystic hygroma: role of bFGF.

BACKGROUND: Cystic hygromas are characterized by a proliferation of small vessels and lymphatics with intervening fibrous tissue. Studies have shown malignant tumors and some benign neoplasms are dependent on angiogenesis, the induction of new capillaries from preexisting vessels. Growth and progression of these tumors are associated with a disturbance in the balance of angiogenic inducers and inhibitors. We have postulated that cells derived from cystic hygromas are angiogenic due to secretion of higher levels of angiogenic inducers that promote vascular proliferation. DESIGN: A large cystic mass was surgically removed and a portion of the sterile tumor was immediately placed in the medium. The tissue was minced, washed in phosphate-buffered saline, and grown to near confluence. Conditioned medium was collected under serum-free conditions after 48 hours. Secreted proteins were concentrated, quantitated, and analyzed in an in vitro endothelial cell migration assay and by Western blot. Antibody to factor VIII-related antigen was performed to confirm endothelial cell origin of the cultured cells. MAIN OUTCOME MEASURES: In vitro angiogenic activity of secreted proteins in a capillary endothelial migration assay was tested by using blocking antibodies to angiogenic inducer, basic fibroblast growth factor, and angiogenic inhibitor, thrombospondin-1. Total protein levels of thrombospondin-1 were determined by Western blot. RESULTS: Cells isolated from cystic hygroma are angiogenic in vitro and this angiogenic activity is due to secretion of high levels of angiogenic inducer, basic fibroblast growth factor, and lower levels of naturally occurring angiogenic inhibitor, thrombospondin-1. CONCLUSIONS: Cystic hygromas may represent another neoplasm dependent on angiogenesis. The angiogenic activity is due in part to elevated levels of potent angiogenic inducer, basic fibroblast growth factor. Antiangiogenic therapy directed at the endothelial cell may help suppress the growth of cystic hygromas.

Adolescent↗
PubMed1999

Captopril and platelet-activating factor (PAF) antagonist prevent cardiac allograft vasculopathy in rats: role of endogenous PAF and PAF-like compounds.

Accelerated coronary artery disease (CAD) is the leading cause of late mortality following cardiac transplantation. The vascular lesions are characterized by myointimal proliferation and perivascular mononuclear inflammatory infiltrates. Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent phospholipid mediator produced by inflammatory cells and activated endothelial cells. Angiotensin II is known to activate phospholipase A2, a critical enzyme in PAF synthesis. Using a rat heterotopic cardiac transplant model known to induce graft CAD, we previously reported that chronic administration of captopril, an angiotensin converting enzyme inhibitor, reduces intimal proliferation and maintains luminal patency. The purpose of the current study was to determine if captopril regulates vascular remodeling by suppressing PAF synthesis and whether administration of a PAF antagonist ameliorates graft CAD. Captopril was found to decrease levels of PAF and PAF-like compounds as well as reduce intimal lesions, decrease cellular rejection grade, and diminish allograft heart weights. Treatment with a PAF antagonist significantly decreased proliferation of the intimal component of the vasculopathy and caused regression of the cardiac hypertrophy, but had no significant effect on cellular rejection. In contrast, untreated animals had elevated plasma PAF levels, elevated heart weights, and severe myointimal proliferation with luminal stenosis 21 days post-transplantation. These observations suggest that graft CAD is mediated, in part, by PAF and PAF-like compounds, and suppression of endogenous PAF may prevent cardiac allograft vasculopathy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

The proto-oncogene Cot kinase participates in CD3/CD28 induction of NF-kappaB acting through the NF-kappaB-inducing kinase and IkappaB kinases.

The proto-oncogene Cot/Tpl-2 encodes a MAP3K-related serine-threonine kinase. Expression of wild type Cot activates the IkappaB kinases (IKK) leading to induction of NF-kappaB. Conversely, expression of kinase-deficient Cot inhibits CD3/CD28 but not TNF alpha induction of NF-kappaB. These findings suggest the selective involvement of Cot/Tpl-2 or a closely related kinase in the CD3/CD28 costimulatory pathway leading to induced nuclear expression of NF-kappaB. In contrast, a kinase-deficient mutant of the NF-kappaB-inducing kinase (NIK) inhibits both CD3/CD28 and TNF alpha signaling, indicating that these pathways converge at or prior to the action of NIK. Consistent with such a sequential function of these two kinases, Cot physically assembles with and phosphorylates NIK in vivo.

CD28 Antigens↗
PubMed1999

Increased expression of transforming growth factor-beta1 and thrombospondin-1 in congenital hepatic fibrosis: possible role of the hepatic stellate cell.

BACKGROUND: Congenital hepatic fibrosis is a rare disease characterized by portal tract fibrosis and biliary duct ectasia. It is associated with autosomal recessive polycystic kidney disease and rarely progresses to cirrhosis. The activated stellate cell has been implicated in the pathogenesis of alcohol- or inflammation-mediated cirrhosis through fibrogenic proteins such as transforming growth factor-beta1; however, the role of the stellate cell in pure, noninflammatory fibrosis is unknown. It has been hypothesized that fibrosis in congenital hepatic fibrosis may be caused by upregulation of transforming growth factor-beta1 and thrombospondin-1, and that the hepatic stellate cell may be the mediator of these proteins. METHODS: Human liver tissue samples from patients with congenital hepatic fibrosis (n = 9) and from normal patients (n = 3) were analyzed. Tissue homogenates from both groups were analyzed for transforming growth factor-beta1 protein and mRNA by Western blot analysis and in situ hybridization, respectively. Immunolocalization studies were performed in fixed tissue sections from both groups. Stellate cells were cultured from livers exhibiting congenital hepatic fibrosis and confirmed by desmin staining. The cells were cultured in serum-free medium for 48 hours, and media were collected and analyzed by Western blot analysis for thrombospondin-1 and transforming growth factor-beta1. RESULTS: Congenital hepatic fibrosis liver tissue homogenates had higher levels of thrombospondin-1 and transforming growth factor-beta1 protein than in normal livers. In congenital hepatic fibrosis tissue, transforming growth factor-beta1 was more highly expressed in the ectatic biliary epithelium and the perisinusoidal space, whereas thrombospondin-1 localized most intensely to the hepatocytes and spared the bile ducts. Congenital hepatic fibrosis-derived stellate cells secreted both thrombospondin-1 and transforming growth factor-beta1, in vitro. CONCLUSIONS: Transforming growth factor-beta1 and thrombospondin-1 may play a role in the pathogenesis of liver fibrosis in patients with congenital hepatic fibrosis. One potential source of these fibrogenic proteins is the hepatic stellate cell.

Blotting, Western↗
PubMed1999

Thiazolidinedione induces apoptosis and monocytic differentiation in the promyelocytic leukemia cell line HL60.

Thiazolidinedione (TZD) is known to be a potent activator of peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear receptor that constitutes a heterodimer with retinoid X receptor (RXR). Since a considerable amount of PPARgamma is expressed in various hematopoietic cells, the present study was undertaken to examine the effect of TZD in the absence or presence of LG100268, an RXR-selective ligand, on a cultured promyelocytic leukemia cell line, HL60. Treatment with TZD (25-50 microM troglitazone or pioglitazone) markedly suppressed cell proliferation of HL60. A cell cycle analysis revealed that the suppressive effect of troglitazone on HL60 cell proliferations was caused by G0/G1 cell cycle arrest as well as by an apoptotic effect. Treatment with the same concentration of troglitazone also induced the monocytic differentiation of HL60 cells. The apoptotic or the differentiating effect of TZD on HL60 cells was synergistically enhanced by the combined treatment with 1 microM LG100268, while LG100268 alone neither had an apoptotic nor a differentiating effect on HL60 cells. These results suggest that these actions are mediated through the nuclear receptor system constituted by the PPARgamma: RXR heterodimer.

Antineoplastic Agents↗
PubMed1999

Drug dependence and abuse potential of tramadol.

AIM: To assess the drug dependence and abuse liability of tramadol. METHODS: Subjects of opiate addicts with history of tramadol abuse were 219. Physical dependence of tramadol was assessed using opiate withdrawal scale (OWS), psychic dependence was assessed by association test of Addiction Research Center Inventory-Chinese Version (ARCI-CV); the degrees of craving experienced for tramadol was self-reported on visual analogue scale (VAS). RESULTS: The scores of OWS of tramadol were 0.05-1.07; 3 scores on scales in particular being used the identify euphoric effects--MBG, sedative effects--PCAG, and psychotomimetic effects--LSD of ARCI were 7.3, 6.1, and 3.4, respectively (F = 38.1, P < 0.01); 57.1% of tramadol abuse subjects had craving for tramadol (chi 2 = 75.86, P < 0.01). CONCLUSION: Tramadol produced high abuse potential among opiate addicts.

Adult↗
PubMed1998

Amino acids and peptides. XXXIII. A bifunctional poly(ethylene glycol) hybrid of laminin-related peptides.

A novel amino acid type poly(ethylene glycol) (aaPEG) was prepared and its application as a drug-carrier was examined. The peptides, Pro-Asp-Ser-Gly-Arg (PDSGR) and Tyr-Ile-Gly-Ser-Arg (YIGSR) which are active fragments of Laminin (a cell adhesion protein), were previously reported to be inhibitors of experimental metastasis. Both peptides were conjugated with aaPEG (average molecular weight, 3,000) to prepare a bifunctional peptide-PEG hybrid. The hybrid, PDSGR-aaPEG-YIGSR, was manually prepared by the solid-phase fluorenylmethyloxycarbonyl (Fmoc) strategy. The antimetastatic activity of the peptides in mice was not lost when conjugated to form a larger aaPEG molecule. YIGSR(375 nmol) and PDSGR (375 nmol and 750 nmol) did not demonstrate antimetastatic activity, but a mixture of PDSGR (187 nnmol) and YIGSR (187 nmol) exhibited an inhibitory effect. The inhibitory effect of the hybrid (187 nmol) was more potent than that of the mixture (PDSGR and YIGSR), indicating that the inhibitory effect of the peptides was potentiated by hybrid formation with aaPEG.

Animals↗