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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

[Study of the pulmonary heart disease computer-aided diagnosis system based on combining neural network].

We have constructed an expert sub-system for diagnosing pulmonary heart disease with back-propagation (BP) model of typical artificial neural network and BP-Hamming. The system can obtain and represent clinical data, and it has solved the problems such as obtaining automatic knowledge, representation and self-learning. The results of testing demonstrate that the method of neural network can be regarded as an expert sub-system to make intelligent diagnosis of pulmonary heart disease.

Algorithms↗

National survey on prevalence of cancer pain.

OBJECTIVE: To collect nationwide basic data about cancer related pain. METHODS: Sixty cancer patients in each province were randomly selected to participate in this survey. The subjects represented all stages of cancer, tumor sites, and different demographic characteristics. Two self-designed structured questionnaires including reasons, types of pain and pain management were used by patients and physicians respectively. Subjects were asked to report whether he/she had experienced any type of cancer related pain and filled out the equivalent questionnaire. The severity of pain was assessed by using "visual analogue scale". Original data input and analysis were using EPI-INFO software package. RESULTS: The result showed that 61.6% (958/1555) of patients had different types of cancer related pain. Majority of pain (85.1%) were caused by advanced cancer. The major reasons (64.4%) for poor management or impedimental factors of pain care are due to patient including over-concern on opioid analgesic addiction, reluctance to report pain or refused to use opioid analgesic until at times when pain is intolerable; 26.8% belonged to physician's reasons including fear to cause addiction on opioid and lack of knowledge about cancer pain management; 16.2% are due to lack of different kinds of opioid analgesic for use and 16.1% belonged to drug regulation. CONCLUSIONS: The results showed that majority of patients (61.6%) had different types of cancer related pain. In most of patients, cancer pain was relieved when they were treated. The major reason for under-treatment or impeded factors for effective relief of cancer pain was fear of opioid addiction by both medical professionals and patients.

Adolescent↗

Antitumor activity of tumor necrosis factor-alpha conjugated with polyvinylpyrrolidone on solid tumors in mice.

We attempted the development of a novel polymer conjugation to further improve the therapeutic potency of antitumor cytokines compared with PEGylation for clinical application. Compared with native tumor necrosis factor (TNF)-alpha in vitro, specific bioactivities of polyvinyl-pyrrolidone (PVP)-modified TNF-alphas (PVP-TNF-alphas) were decreased by increasing the degree of PVP attachment. PVP-TNF-alpha fraction 3, Mr 101,000, had the most effective antitumor activity of the various PVP-TNF-alphas in vivo. PVP-TNF-alpha fraction 3 had >200-fold higher antitumor effect than native TNF-alpha, and the antitumor activity of PVP-TNF-alpha fraction 3 was >2-fold higher than that of MPEG-TNF-alpha (Mr 108,000), which had the highest antitumor activity among the polyethylene glycol (PEG)-conjugated TNF-alphas. Additionally, a high dose of native TNF-alpha induced toxic side effects such as body weight reduction, piloerection. and tissue inflammation, whereas no side effects were observed after i.v. administration of PVP-TNF-alpha fraction 3. The plasma half-life of PVP-TNF-alpha fraction 3 (360 min) was about 80- and 3-fold longer than those of native TNF-alpha (4.6 mm) and MPEG-TNF-alpha (122 min), respectively. The mechanism of increased antitumor effect in vivo caused the prolongation of plasma half-life and increase in stability. These results suggested that PVP is a useful polymeric modifier for bioconjugation of TNF-alpha to increase its antitumor potency, and multifunctionally bioconjugated TNF-alpha may be a potentiated antitumor agent for clinical use.

Animals↗

A bis-cyclodextrin diselenide with glutathione peroxidase-like activity.

A diselenide, 2,2'-diseleno-bis-beta-cyclodextrin (2-SeCD), was synthesized to imitate the antioxidant enzyme glutathione peroxidase (GPX). The GPX mimic accepts a variety of hydroperoxides as substrates. The GPX activities, reduction of H(2)O(2), tert-butyl hydroperoxide and cumenyl hydroperoxide by glutathione, are 7.4, 4.5 and 10.2 U/micromol, respectively. In contrast to ebselen (PZ51), the diselenide displays high GPX-like activity. The reduction of hydroperoxide by glutathione in the presence of a radical trap shows that the mimic catalyzes the reaction via a non-radical mechanism. A ping-pong mechanism was observed in the steady-state kinetic studies of the 2-SeCD-catalyzed reaction.

Animals↗

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↗

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↗

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↗

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↗

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↗

[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↗

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↗

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↗

[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↗

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↗

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↗

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↗

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↗