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Biomedical subjects

Y Mu

Publications and source records attributed to Y Mu.

At least 55 records · Page 3Linked to original sources
PubMed1998

Selectivity of effects of vasoactive intestinal peptide on macrophages and lymphocytes in compartmental immune responses.

The major immunoregulatory effects of vasoactive intestinal peptide (VIP) are mediated by structurally distinct type I (VIPR1) and II (VIPR2) G protein-associated receptors on many different types of immune cells. VIP is released in functionally relevant concentrations during many immunologic and inflammatory responses. Mast cells (VIPR1), macrophages (VIPR1 and VIPR2), B cells, and T cells (VIPR1, VIPR2, or VIPR1 and VIPR2) recognize and respond to VIP in patterns that are controlled by the relative levels of expression of VIPR1 and VIPR2. VIPR2 transduces human T-cell chemotaxis, expression of matrix metalloproteinases (MMPs) 2 and 9 and consequently basement membrane and connective tissue transmigration, while signaling suppression of proliferation and cytokine production. In contrast, VIPR1 fails to transduce T-cell chemotaxis but mediates suppression of chemotaxis and MMP expression elicited by some cytokines and chemokines. The relative representation of each type of VIPR, which is presumed to be under cytokine control, thus may determine T-cell responses to VIP and other immune mediators in tissue compartments innervated by VIPergic nerves.

Animals↗
PubMed1998

Rapid growth of cutaneous metastases after surgical resection of thrombospondin-secreting small blue round cell tumor of childhood.

In animal models, the importance of tumor-derived antiangiogenic factors in controlling metastases has been demonstrated by the growth acceleration of distant metastases after surgical excision of a primary tumor mass. We report the case of an infant who developed rapidly growing cutaneous metastases after surgical resection of a neoplasm of an upper extremity. The tumor was undifferentiated, with some morphological features of primitive neuroectodermal tumor. To test the possibility that the primary tumor was secreting an angiogenic inhibitor, cells from the primary tumor were grown in culture, and the culture medium was tested with an in vitro endothelial cell migration assay and Western blot. The cultured cells secreted sufficiently high levels of an angiogenic inhibitor to overcome the inducing ability of vascular endothelial growth factor and basic fibroblast growth factor. One of the secreted proteins was thrombospondin-1, a potent antiangiogenic glycoprotein. The rapid dissemination of distant metastases after resection of the primary tumor in this case suggests that tumor-derived angiogenic inhibitors are important in maintaining the local net balance of angiogenic mediators controlling the growth of micrometastasis.

Cells, Cultured↗
PubMed1998

Molecular determinants of NF-kappaB-inducing kinase action.

NF-kappaB corresponds to an inducible eukaryotic transcription factor complex that is negatively regulated in resting cells by its physical assembly with a family of cytoplasmic ankyrin-rich inhibitors termed IkappaB. Stimulation of cells with various proinflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), induces nuclear NF-kappaB expression. TNF-alpha signaling involves the recruitment of at least three proteins (TRADD, RIP, and TRAF2) to the type 1 TNF-alpha receptor tail, leading to the sequential activation of the downstream NF-kappaB-inducing kinase (NIK) and IkappaB-specific kinases (IKKalpha and IKKbeta). When activated, IKKalpha and IKKbeta directly phosphorylate the two N-terminal regulatory serines within IkappaB alpha, triggering ubiquitination and rapid degradation of this inhibitor in the 26S proteasome. This process liberates the NF-kappaB complex, allowing it to translocate to the nucleus. In studies of NIK, we found that Thr-559 located within the activation loop of its kinase domain regulates NIK action. Alanine substitution of Thr-559 but not other serine or threonine residues within the activation loop abolishes its activity and its ability to phosphorylate and activate IKKalpha. Such a NIK-T559A mutant also dominantly interferes with TNF-alpha induction of NF-kappaB. We also found that ectopically expressed NIK both spontaneously forms oligomers and displays a high level of constitutive activity. Analysis of a series of NIK deletion mutants indicates that multiple subregions of the kinase participate in the formation of these NIK-NIK oligomers. NIK also physically assembles with downstream IKKalpha; however, this interaction is mediated through a discrete C-terminal domain within NIK located between amino acids 735 and 947. When expressed alone, this C-terminal NIK fragment functions as a potent inhibitor of TNF-alpha-mediated induction of NF-kappaB and alone is sufficient to disrupt the physical association of NIK and IKKalpha. Together, these findings provide new insights into the molecular basis for TNF-alpha signaling, suggesting an important role for heterotypic and possibly homotypic interactions of NIK in this response.

Amino Acid Sequence↗
PubMed1998

Human T-cell leukemia virus type 1 Tax induction of NF-kappaB involves activation of the IkappaB kinase alpha (IKKalpha) and IKKbeta cellular kinases.

Tax corresponds to a 40-kDa transforming protein from the pathogenic retrovirus human T-cell leukemia virus type 1 (HTLV-1) that activates nuclear expression of the NF-kappaB/Rel family of transcription factors by an unknown mechanism. Tax expression promotes N-terminal phosphorylation and degradation of IkappaB alpha, a principal cytoplasmic inhibitor of NF-kappaB. Our studies now demonstrate that HTLV-1 Tax activates the recently identified cellular kinases IkappaB kinase alpha (IKKalpha) and IKKbeta, which normally phosphorylate IkappaB alpha on both of its N-terminal regulatory serines in response to tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) stimulation. In contrast, a mutant of Tax termed M22, which does not induce NF-kappaB, fails to activate either IKKalpha or IKKbeta. Furthermore, endogenous IKK enzymatic activity was significantly elevated in HTLV-1-infected and Tax-expressing T-cell lines. Transfection of kinase-deficient mutants of IKKalpha and IKKbeta into either human Jurkat T or 293 cells also inhibits NF-kappaB-dependent reporter gene expression induced by Tax. Similarly, a kinase-deficient mutant of NIK (NF-kappaB-inducing kinase), which represents an upstream kinase in the TNF-alpha and IL-1 signaling pathways leading to IKKalpha and IKKbeta activation, blocks Tax induction of NF-kappaB. However, plasma membrane-proximal elements in these proinflammatory cytokine pathways are apparently not involved since dominant negative mutants of the TRAF2 and TRAF6 adaptors, which effectively block signaling through the cytoplasmic tails of the TNF-alpha and IL-1 receptors, respectively, do not inhibit Tax induction of NF-kappaB. Together, these studies demonstrate that HTLV-1 Tax exploits a distal part of the proinflammatory cytokine signaling cascade leading to induction of NF-kappaB. The pathological alteration of this cytokine pathway leading to NF-kappaB activation by Tax may play a central role in HTLV-1-mediated transformation of human T cells, clinically manifested as the adult T-cell leukemia.

Adult↗
PubMed1998

Amino acids and peptides. XXXI. Preparation of analogs of the laminin-related peptide YIGSR and their inhibitory effect on experimental metastasis.

Analogs of a partial sequence peptide of laminin, i.e., Tyr-Ile-Gly-Ser-Arg (YIGSR) analogs and Cys-Asp-Pro-Gly-Tyr-Ile-Gly-Ser-Arg (CDPGYIGSR) analogs, were prepared by the solid-phase method and their inhibitory effects on experimental metastasis of B16-BL6 melanoma cells were examined. YIGSR analogs in which Ile was replaced by other hydrophobic amino acids (Met, Leu, Phe) were inhibitory. Cys-containing analogs of YIGSR were also prepared, but were less active than the parent peptide, YIGSR. Among them, CYIGSR was easily oxidized to form a disulfide bond. A Cys-containing YIGSR analog cyclized through a disulfide bond, cyclo(CYIGSRC)G, was prepared. The disulfide bond formation was performed on the resin by the silyl chloride-sulfoxide method and by the iodine oxidation method. The yield of the silyl chloride-sulfoxide method was much better than that of the iodine oxidation method.

Animals↗
PubMed1998

[Histologic study on the pulpal response after complete crown preparation].

Protecting pulp health during preparation procedures is one of the key factors for prosthesis success. The histological sections of dental pulp showed the disruption of odontoblastic layer, blood vessels hyperemia and local bleeding. Dental histological sections of 40 healthy teeth which would need to be detracted because of orthodontical treatment were made to observe the pulp response in vivo during different tooth preparation time, including four groups: before preparation, after preparation, one week after being covered with temporary crown and two weeks after being covered with temporary crown. when air-water spray was used during crown preparation, Healing of the pulp was apparent 2 weeks following preparation, when the prepared teeth were covered with temporary crown and cemented with zinc oxide eugenol.

Crowns↗
PubMed1997

Amino acids and peptides. XXXII: A bifunctional poly(ethylene glycol) hybrid of fibronectin-related peptides.

An amino acid type poly(ethylene glycol) (aaPPEG) was prepared and its application to a drug carrier was examined. The peptides, Arg-Gly-Asp (RGD) and Glu-Ile-Leu-Asp-Val (EILDV) which were reported as active fragments of Fibronectin (a cell adhesion protein), were conjugated with aaPEG (molecular weight, 10,000). The hybrid, RGD-aaPEG-EILDV, was prepared by a combination of the solid-phase method and the solution method. Antiadhesive activity of the peptides was not lost by its hybrid formation with the large aaPEG molecule. A mixture of RGD (0.43 mmol) and EILDV (0.43 mmol) did not demonstrate an antiadhesive effect, but the hybrid containing 0.43 mmol of each peptide did exhibit this effect.

Carrier Proteins↗
PubMed1997

Bruceine B, a potent inhibitor of leukocyte-endothelial cell adhesion.

Leukocyte adhesion to vascular endothelial cells is an essential step in the development of inflammatory diseases. We have searched for inhibitors of leukocyte-endothelial cell adhesion that could be used as anti-inflammatory drugs and found that bruceine B (0.2 microgram/ml; 0.44 microM) inhibited human neutrophil or T cell adhesion to tumor necrosis factor-alpha (TNF) stimulated human umbilical vein endothelial cells (HUVEC). The inhibition of neutrophil adhesion to TNF-stimulated HUVEC by bruceine B was not derived from cytotoxic effects, as determined by measurement of the level of lactate dehydrogenase (LDH) activity in conditioned medium. The effect of bruceine B on neutrophil adhesion to HUVEC was not seen when the neutrophils were preincubated with bruceine B. However, inhibitory effects were evident when the HUVEC were preincubated with bruceine B. Bruceine B also inhibited neutrophil adhesion to lipopolysaccharide-stimulated HUVEC and T cell adhesion to TNF-stimulated HUVEC. These findings suggest that bruceine B may have anti-inflammatory activity.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Amino acids and peptides. XXX. Preparation of Arg-Gly-Asp (RGD) hybrids with poly(ethylene glycol) analogs and their antimetastatic effect.

Hybrids of a fibronectin-related peptide[Arg-Gly-Asp (RGD)] with poly(ethylene glycol) (PEG) analogs were prepared by a simple and easy procedure. Two amino-PEG analogs were used as carriers for hybrid formation of the RGD. One was poly(oxyethylene)dipropylamine and the other was Jeffamine ED type, which has branched chains. RGD peptides were formed stepwise on PEG analogs by the diisopropylcarbodiimide method. The synthetic intermediates were easily purified by molecular-sieve gel chromatography and the final products were purified by molecular-sieve gel chromatography, followed by HPLC. This simple and easy preparation procedure using molecular-sieve gel chromatography for purification of synthetic intermediates is advantageous for the preparation of peptide-polymer hybrids. We found that PEG is stable to HF treatment at 0 degree C for 1 h. The inhibitory effect of the RGD hybrids on experimental metastasis of B16-BL6 was examined in mice. The Jeffamine type hybrid showed no inhibitory effect at the dose of 1 mg/mouse, but poly(oxyethylene)dipropylamine type hybrid was inhibitory at the same dose. The effect of the latter hybrid was about the same as that of 1 mg of RGD. One mg of the hybrid contains 0.18 mumol of RGD and 1 mg of RGD is 2.38 mumol. Thus it can be said that the inhibitory effect of RGD was potentiated by hybrid formation with poly(oxyethylene)diisopropylamine.

Animals↗
PubMed1996

Thymocyte apoptosis in response to low-dose radiation.

Thymocyte apoptosis was assessed by counting apoptotic bodies with flow cytometry (FCM) and measuring DNA fragmentation with fluorescence spectrophotometry (FSP). J-shaped dose-response curves were obtained after both whole-body irradiation (WBI) of mice and in vitro irradiation of EL4 cells with doses ranging from 0.025 to 4 Gy X-rays. There was a significant reduction of apoptosis rate to below control level with doses within 0.2 Gy, and a dose-dependent increase in apoptosis with doses above 0.5 Gy. When thymocytes were cultured 24 h after WBI with 75 mGy X-rays in complete RPMI 1640 medium, a reduction in apoptosis was observed in the course of incubation for 72 h, and the presence of Con A in the medium accentuated this reduction in a dose- and time-dependent manner. The implications of these observations and the possible molecular mechanisms for future studies are proposed.

Animals↗
PubMed1996

Amino acids and peptides. XXIX. Synthesis and antimetastatic effects of peptides and peptide-poly(ethylene glycol) hybrids related to the core sequence of the type III connecting segment domain of fibronectin.

Peptides (H-Glu-Ile-Leu-Asp-Val-NH2, H-Glu-Ile-Leu-Asp-Val-Pro-Ser-Thr-NH2, H-Arg-Glu-Asp-Val-NH2) and their poly(ethylene glycol) (PEG) hybrids related to the core sequence of the type III connecting segment domain of fibronectin A chain were prepared by the solution method or the solid phase method. Their inhibitory effects on the adhesion and migration of B16-BL6 melanoma cells to fibronectin were assessed in vitro, and their therapeutic potency against tumor metastasis were also examined. Anti-adhesive and anti-migrative effects of the synthetic fibronectin-related peptids were superior to those of their PEG hybrids, so we found that the in vitro bioactivity of peptides decreased by PEGylation. In the in vivo assay, we found that the synthetic peptides containing Glu-Ile-Leu-Asp-Val and Arg-Glu-Asp-Val sequences exhibited an inhibitory effect on the experimental metastasis of B16-BL6 melanoma. Of the synthetic peptides, H-Glu-Ile-Leu-Asp-Val-NH2 exhibited the most potent inhibitory effect. Hybrid formation of Arg-Glu-Asp-Val with poly(ethylene glycol) resulted in potentiation of the inhibitory effect of the parent peptides. A mixture composed of PEG hybrids of Glu-Ile-Leu-Asp-Val, Arg-Glu-Asp-Val and Tyr-Ile-Gly-Ser-Arg dramatically inhibited tumor metastasis.

Animals↗
PubMed1996

[Effects of ear acupuncture on beta-adrenoreceptor in lung tissues of guinea-pigs with experimental asthma].

The maximal binding volume (Bmax) of beta-adrenoreceptor in the lung tissues of guinea-pigs in health group, experimental asthma group and ear acupuncture treatment group was determined with radiological ligand binding analysis. The results were as follows: (1) the Bmax of beta-adrenoreceptor in lung tissues of guinea-pigs in asthma group (52.4 +/- 20.1 fmol/mg protein) was significantly lower than that of healthy group (106.8 +/- 14.0 fmol/mg protein) (P < 0.01); (2) the Bmax in the lung tissues of guinea-pigs in ear acupuncture treatment group (84.5 +/- 35.1 fmol/mg protein) was significantly higher than that of asthma group (P < 0.02), and was similar to that of healthy group(P > 0.05). These suggested it was one of the mechanisms of ear acupuncture treatment on asthma to increase the number of beta-adrenorecepor in the lung tissues.

Animals↗
PubMed1995

Amino acids and peptides. XXXIX. Synthesis of iNoc-Gln-Val-Val-Ala-Ala-pNA and its action on thiol proteinases.

Based on the results of X-ray analysis of the complex between Suc-Gln-Val-Val-Ala-Ala-pNA, a fairly potent thiol proteinase inhibitor, and papain, iNoc-Gln-Val-Val-Ala-Ala-pNA was designed and prepared and its inhibitory activity against thiol proteinases was examined. iNoc-Gln-Val-Val-Ala-Ala-pNA inhibited cathepsin L fairly specifically, although its potency is not high.

Amino Acid Sequence↗
PubMed1995

[Damage effects of methylmercury on cell membrane].

Damage to cell membrane system caused by methylmercury (Me-Hg) and its mechanism were studied with biochemical and cell biological methods experimentally. Results showed erythrocyte membrane and activities of T-ATPase, Mg(++)-ATPase and Na(+)-K(+)-ATPase of microsome membrane in brain, liver and kidney of the exposed animals decreased more significantly than of controls with a dose-effect pattern. Activities of Mg(++)-ATPase and Na(+)-K(+)-ATPase of erythrocyte membrane correlated positively with those of microsome membrane in brain and kidney. Sulfhydryl content of erythrocyte membrane and brain microsome membrane decreased significantly in the exposed animals (P < 0.01). Sulfhydryl content correlated inversely with the activities of above three kinds of ATPase in kidney, but so did in brain positively. Fluorescent polarization of membranes of erythrocytes and microsome in brain, liver and kidney increased, membrane fluidity decreased, LDH activities increased in plasma and decreased in cells and cell permeability increased in the exposed animals. Activities of respiratory enzymes of mitochondrion in exposed animals were lower than those in controls (P < 0.05). 3H-TdR incorporation was inhibited in spleen, liver and brain in exposed animals. Abilities of DNA synthesis and UDS repair were inhibited with high-dose of Me-Hg, and stimulated with low-dose. SCE frequency in bone marrow cells increased with dose of Me-Hg (P < 0.001). Proportion of splenocyte from G0/G1 to S phases increased and those from S to G2/M phases lowered, and it suggested DNA synthesis had been inhibited.

Animals↗
PubMed1995

[Analysis of luteinizing hormone pulses in men with idiopathic hypogonadotropic hypogonadism].

In order to test the defect of luteinizing hormone (LH) pulses and its relationship with sexual development in patients with idiopathic hypogonadotropic hypogonadism (IHH), fourteen male IHH patients and five healthy adult men were investigated. Blood samples were withdrawn at 10 minute intervals for 24h for analysis of LH pulse. LH pulse frequency ranged from 0-13 pulses/24h. Testosterone (T) level was 1.3-8.7 nmol/L in the 14 IHH patients and higher in the 5 healthy controls (all P < 0.01). Two of the patients with IHH had no detectable LH pulsations (apulsatile pattern), no history of puberty and a small testicular volume of less than 1ml. Most of the IHH patients (n = 9) had less pulse frequency (4-13 pulses/24h) and lower mean amplitude (1.3-2.2IU/L) than the healthy controls (14-20 pulses/24h and 3.81-2.46IU/L, P < 0.01). A patient with IHH had 10 pulses/24h and more or less the same mean amplitude (4.2 +/- 1IU/L) as the healthy controls; his T level was the lowest among the 14 patients due probably to biological inactivity of LH. Two IHH patients had detectable LH pulsations with normal mean amplitude (P > 0.05) present predominantly during the night, this pattern of LH pulse resembles that of peripuberty boy. Our results indicate that (1) LH pulse pattern varies widely among IHH patients and it is related to the sex characteristics; (2) frequency of LH pulses is essential for sexual development. but adequate amplitude is more important in this respect.

Adolescent↗