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Biomedical subjects

J Yuan

Publications and source records attributed to J Yuan.

At least 253 records · Page 14Linked to original sources
PubMed1996

Characterization of a novel member of the macrophage mannose receptor type C lectin family.

The recognition of a diversity of carbohydrates by the various calcium dependent (type C) lectin family members has been shown to be critical for a variety of processes ranging from cell adhesion to antigen presentation. Examination of the expressed sequence tag (EST) data base for novel type C lectins using E-selectin as a probe resulted in the identification of a distantly related short polypeptide sequence containing many of the conserved residues found in these carbohydrate-binding proteins. Cloning of the full-length murine cDNA containing this region revealed that this protein is a novel member of the family that includes the macrophage mannose, the phospholipase A2, and the DEC 205 receptors, with a cysteine-rich domain, a fibronectin type 2 domain, eight type C lectin domains, a transmembrane domain, and a short cytoplasmic carboxyl terminus. Genomic Southern analysis suggests that this is a conserved protein, and examination of a human homologue revealed a high degree of sequence homology with the murine form. Northern blot analysis revealed expression of a large transcript in a number of different human and murine tissues and tumor cells and an alternatively spliced smaller transcript with a divergent 5' sequence was expressed specifically in the human fetal liver. Analysis of the genomic structure revealed that the gene encoding this lectin was interrupted by a large number of introns, and the intron structure was similar to the macrophage mannose receptor gene. Finally, in situ hybridization analysis demonstrated that the transcript encoding this lectin was found in a number of highly endothelialized sites as well as in chondrocytes in cartilaginous regions of the embryo.

Amino Acid Sequence↗
PubMed1996

Identification and characterization of Ich-3, a member of the interleukin-1beta converting enzyme (ICE)/Ced-3 family and an upstream regulator of ICE.

We report here the isolation and characterization of a new member of the ice/ced-3 family of cell death genes, named ich-3. The predicted amino acid sequence of Ich-3 protein shares 54% identity with murine interleukin-1beta converting enzyme (ICE). Overexpression of ich-3 in Rat-1 and HeLa cells induces apoptosis, which can be inhibited by CrmA and Bcl-2. The mRNA and proteins of ich-3 are dramatically induced in vivo upon stimulation with lipopolysaccharide, an inducer of septic shock. The ich-3 gene product can be cleaved by cytotoxic T cells granule serine protease granzyme B, suggesting that Ich-3 may mediate apoptosis induced by granzyme B. Ich-3 does not process proIL-1beta directly but does promote proIL-1beta processing by ICE. These results suggest that Ich-3 may play a very important role in apoptosis and inflammatory responses and may be an upstream regulator of ICE.

Amino Acid Sequence↗
PubMed1996

Functional role of interleukin 1 beta (IL-1 beta) in IL-1 beta-converting enzyme-mediated apoptosis.

Prointerleukin-1 beta (pro-IL-1 beta) is the only known physiologic substrate of the interleukin-1 beta (IL-1 beta)-converting enzyme (ICE), the founding member of the ICE/ced-3 cell death gene family. Since secreted mature IL-1 beta has been detected after apoptosis, we investigated whether this cytokine, when produced endogenously, plays a role in cell death. We found that hypoxia-induced apoptosis can be inhibited by either the IL-1 receptor antagonist (IL-1Ra) or by neutralizing antibodies to IL-1 or to its type 1 receptor. IL-1Ra also inhibits apoptosis induced by trophic factor deprivation in primary neurons, as well as by tumor necrosis factor alpha in fibroblasts. In addition, during the G1/S phase arrest, mature IL-1 beta induces apoptosis through a pathway independent of CrmA-sensitive gene activity. We also demonstrate that Ice, when expressed in COS cells, requires the coexpression of pro-IL-1 beta for the induction of apoptosis, which is inhibited by IL-1Ra. Interestingly, we found that mature IL-1 beta has antiapoptotic activity when added exogenously before the onset of hypoxia, which we found is caused in part by its ability to downregulate the IL-1 receptor. Our findings demonstrate that pro-IL-1 beta is a substrate of ICE relevant to cell death, and depending on the temporal cellular commitment to apoptosis, mature IL-1 beta may function as a positive or negative mediator of cell death.

Animals↗
PubMed1996

Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4.

The tyrosine kinases Flt4, Flt1, and Flk1 (or KDR) constitute a family of endothelial cell-specific receptors with seven immunoglobulin-like domains and a split kinase domain. Flt1 and Flk1 have been shown to play key roles in vascular development; these two receptors bind and are activated by vascular endothelial growth factor (VEGF). No ligand has been identified for Flt4, whose expression becomes restricted during development to the lymphatic endothelium. We have identified cDNA clones from a human glioma cell line that encode a secreted protein with 32% amino acid identity to VEGF. This protein, designated VEGF-related protein (VRP), specifically binds to the extracellular domain of Flt4, stimulates the tyrosine phosphorylation of Flt4 expressed in mammalian cells, and promotes the mitogenesis of human lung endothelial cells. VRP fails to bind appreciably to the extracellular domain of Flt1 or Flk1. The protein contains a C-terminal, cysteine-rich region of about 180 amino acids that is not found in VEGF. A 2.4-kb VRP mRNA is found in several human tissues including adult heart, placenta, ovary, and small intestine and in fetal lung and kidney.

Amino Acid Sequence↗
PubMed1996

High-dose therapy/stem cell support: comparison of mice and humans.

A murine high-dose therapy/stem cell support model is described using female BALB/c mice bearing the EMT-6 mammary carcinoma. Peripheral blood cells were prepared in syngeneic donor animals mobilized by treatment with cyclophosphamide and rhG-CSF. The most effective support regimen includes administration of fluid by gavage, rhG-CSF twice per day for 12 days and peripheral blood cells administered i.v. on the day after cytotoxic therapy. Dose escalations of 2.2- to 13-fold over the usual conventional dose were possible in mice treated with single doses of cyclophosphamide, carmustine, melphalan, thiotepa, carboplatin or total body radiation, which compare favorably with dose escalations achievable in humans. Depletion and recovery rates of white blood cells and granulocytes in the mice were similar to those seen in humans. Rapid weight loss is a major factor in limiting further dose escalation. Single high-dose therapy with cyclophosphamide, melphalan, thiotepa and carboplatin, but not 5-fluorouracil, produced longer tumor growth delays than standard regimens of the same drugs. For melphalan and thiotepa, there was a direct correlation between drug dose, tumor growth delay and tumor surviving fraction. With cyclophosphamide, the tumor growth delay with high-dose therapy was greater than expected from the dose increase and the tumor surviving fraction data.

Animals↗
PubMed1996

Suppression of interleukin-1 beta-converting enzyme-mediated cell death by insulin-like growth factor.

COS cells are resistant to cell death induced either by interleukin-1beta-converting enzyme (*ICE) and ICE homolog (ICH-1L) overexpression or by serum deprivation. COS cells deprived of serum undergo apoptosis after transfection with an ICE expression construct, but not an ICH-1L construct. ICE-mediated apoptosis of COS cells in serum-free medium is suppressed by insulin-like growth factor (IGF)-1 and insulin. Viability of Rat-1 cell line (Rat-1/ICE) expressing low levels of ICE-LacZ fusion protein is lower than those of cell lines expressing either both Bcl-2 and ICE or mutant ICEGly-->Ser during serum deprivation. Enzymatic activation and processing of ICE are observed in cells induced to die by serum deprivation, which are suppressed by IGF-1. IGF-1 or insulin suppresses ICE-mediated cell death without affecting the expression levels of Bcl-2, Bcl-x, or Bax. Taken together, these results indicate that ICE is activated by growth factor deprivation, and IGF-1 is able to suppress ICE-mediated cell death through a mechanism independent of the expression of Bcl-2, Bcl-x, or Bax.

Amino Acid Sequence↗
PubMed1996

Abnormal assembly of membrane proteins in erythroid progenitors of patients with beta-thalassemia major.

The life threatening anemia in beta-thalassemia major (Cooley's anemia) is characterized by profound intramedullary lysis, the cause of which is incompletely understood. Using marrow obtained from beta thalassemia major patients undergoing allogeneic bone marrow transplantation in Pesaro Italy, it became possible to directly study the mechanism of the intramedullary hemolysis. Based on our previous studies, we hypothesized that the unmatched alpha globin chains would interfere with normal assembly of erythroid precursor membrane proteins. Patient and control erythroid precursors were reacted with monospecific polyclonal rabbit antibodies directed against spectrin, band 3, and band 4.1 and with a monoclonal anti-alpha globin chain antibody. Using laser confocal fluorescence microscopy, normal erythroid precursors show no alpha globin chain accumulation and exhibited uniformly smooth rim fluorescence of the three membrane proteins. In some thalassemic precursors, spectrin appeared to interact with large alpha globin accumulations, and in many of these cells the spectin appeared clumped and discontinuous. Band 4.1 interacted strongly with accumulations of alpha globin in thalassemic precursors to produce bizarrely clumped zones of abnormal band 4.1 distribution. Band 3 was incorporated smoothly into thalassemic erythroblast membranes. However, the proerythroblasts and basophilic erythroblasts were significantly deficient in band 3. Thus, accumulations of alpha globin in beta-thalassemia major colocalized with and disrupt band 4.1 and spectrin assembly into the membrane. The cause of deficient band 3 incorporation into thalassemic proerythroblast membranes remains unknown. These profound membrane alterations would likely contribute to the intramedullary lysis seen in Cooley's anemia.

Animals↗
PubMed1996

Evolutionary conservation of a genetic pathway of programmed cell death.

Genetic analysis of programmed cell death in Caenorhabditis elegans has led to the identification of 13 genes that constitute a developmental pathway of programmed cell death. Two of the three key genes in this pathway, ced-9, a cell death suppressor, and ced-3, a cell death inducer, were found to encode proteins that share structural and functional similarities with the mammalian proto-oncogene product Bcl-2 and interleukin-1 beta converting enzyme, respectively. These results suggest that the genetic pathway of programmed cell death may be evolutionarily conserved from worms to mammals.

Animals↗
PubMed1996

Fenfluramine-induced loss of serotonin transporters in baboon brain visualized with PET.

The present study sought to determine whether or not Positron Emission Tomography (PET) with the newly developed positron emitting serotonin (5-HT) transporter ligand, (+)[11C]McN-5652, could be used to detect fenfluramine-induced 5-HT neurotoxicity in the brain of living primates (baboons). Six PET imaging studies were performed: three before treatment with fenfluramine (5 mg/kg, s.c., twice daily for 4 days) and three after (18, 45, and 81 days after treatment). The dose of fenfluramine used in this study (5 mg/kg) is known to produce 5-HT neurotoxicity in primates, and to be approximately two times higher than a dose of fenfluramine reported to produce small and inconsistent weight loss in baboons (2 mg/kg). Following fenfluramine treatment, marked lasting reductions in regional brain specific binding of (+)[11C]McN-5652 were found by means of PET. Findings with PET corresponded well with post-mortem neurochemical findings indicative of serotonergic neurotoxicity (lasting depletions of regional brain 5-HT, 5-HIAA, and 5-HT uptake sites). These results suggest that PET imaging with (+)[11C]McN-5652 will be useful for evaluating the 5-HT neurotoxic potential of fenfluramine and related drugs in living humans.

Animals↗
PubMed1996

Age-related accumulation of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3- carboxylic acid in human lens.

A fluorescent beta-carboline, 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3- carboxylic acid (MTCA) was identified in human normal lenses and cataractous lenses. The mean total amounts of MTCA in normal lenses (n = 7), diabetic cataractous lenses (n = 15), and senile cataractous lenses (n = 15) were 0.64 +/- 0.76 ng, 1.79 +/- 0.94 ng, and 3.66 +/- 1.04 ng, respectively. The MTCA levels in human lenses increased linearly with the age of the lenses, and there was a significant correlation between the total amount of MTCA in human lenses and the age of the lens. In all types of lenses, the concentrations of MTCA in the insoluble-protein fraction [pg (mg protein)-1] were significantly higher than those in the water-soluble protein fraction. These results suggest that MTCA may be one of the age-related fluorogens. In vitro experiments revealed that MTCA, a condensation reaction product of tryptophan with acetaldehyde, can be formed in the mixture of tryptophan and glucose by low temperature heating. Furthermore, the MTCA levels in the homogenate of cataractous lenses were significantly increased with the heating time, when the homogenate without addition of glucose and tryptophan was heated at 60 degrees C. This indicates that enough material such as tryptophan for MTCA formation is present in human cataractous lenses. Therefore, it may be that MTCA is formed in human lens. However, we can not rule out the possibility that MTCA in the lens may be derived from other sources, and deposited in the lens since MTCA is reported to be present in various foodstuffs and alcoholic beverages.

Adolescent↗
PubMed1996

Evaluation of exposure level of N-methyl-beta-carboline-3-carboxamide (FG 7142), an anxiogenic agent in humans.

beta-Carboline-3-carboxylic acid methylamide (FG 7142), an anxiogenic agent, has been detected in human urine. The urinary excretion level of FG 7142 in non-smokers was found to be 0.503 +/- 0.25 ng per day (mean +/- S.D., n=10), while that in smokers was found to be 2.418 +/- 0.384 ng per day (n=10). This suggests that humans are exposed to FG 7142 and that smokers are exposed to higher levels of FG 7142 than non-smokers. Considering the previous findings that FG 7142 is present in cigarette smoke, indoor and outdoor air and smoke condensate of tree leaves, humans may be exposed to FG 7142 via the airways and lungs, although we cannot exclude the possibility of exposure via foodstuffs. Results of animal experiments suggest that FG 7142 which enters the bloodstream is excreted into the urine via the kidneys within 24 h in an unchanged form. Therefore, monitoring the level of FG 7142 in urine may be useful for monitoring the exposure level of FG 7142.

Journal Article↗
PubMed1996

The Pseudomonas syringae Hrp regulation and secretion system controls the production and secretion of multiple extracellular proteins.

Pseudomonas syringae pv. tomato DC3000 produces seven to eight major extracellular proteins (EXPs) in a minimal medium inducing hrp genes. Using a polyclonal antibody against DC3000 EXPs, we have determined that the production and secretion of five EXPs (EXP-60, EXP-45, EXP-43, EXP-22, and EXP-10) are under the control of the Hrp regulation and secretion system.

Amino Acid Sequence↗
PubMed1996

Immunity and morbidity in schistosomiasis japonicum infection.

Schistosomiasis japonica differs significantly from Schistosoma mansoni infection in several epidemiologic, immunologic, and operational characteristics for control. Because of numerous nonhuman hosts, transmission remains high despite aggressive case finding and treatment of human cases. Diagnosis of infection using the Kato-Katz stool technique is less sensitive and specific in this than in other species of human schistosomes, making case finding and treatment a less effective approach to control. Clinically, morbidity induced by S. japonicum appears unrelated to intensity of infection, and is more severe than that of S. mansoni in terms of liver pathology and stunting of child growth and development. Both hepatic enlargement and fibrosis appear to be reversible and preventable with aggressive treatment but several operational characteristics for control of infection due to S. japonicum make the community impact of case-finding and treatment with praziquantel less pronounced than would have been predicted by the analysis of individual cases. In the Philippines, rebound morbidity following reinfection mandates short treatment intervals between screening and treatment to have a significant impact on morbidity, while in China inapparent infection (infection not diagnosed by a single stool examination) appears to be a common cause for persistent hepatic pathology. The authors conclude that for S. japonicum, mass treatment or targeted mass treatment is a more cost-effective approach than case-finding and treatment for control.

Animals↗
PubMed1996

[Relationship between the state of intravascular bubbles and microcirculation system].

To confirm the hypothesis that air bubbles were unable to block the blood vessels and that the state of the intravascular bubbles was determined by the function of the circulatory system, 35 guinea pigs were pressurized then were decompressed to normal pressure. Microscopic observation was made of the bulbar conjunctival, dorsum auricular and subcutaneous vessels in 33 surviving animals. Air bubbles of different amounts, sizes and shapes were found in the dorsum auricular and subcutaneous vein of all the amimals and in the bulbar conjunctival oriridal artery of 16 animals, and in some cases the vessels were even filled with bubbles. The bubbles ran in the same direction and at the same speed as the blood flow. They could run in a backward, to-and-fro or sluggish flow. The bubbles looked shapeless and tended to break and divided into branch flows where the vessel branches. The bubbles were motionless at the proximal end of the artery occluded due to spasm or when the blood was stagnated. Under the action of the blood pressure the bubbles could expand the vessel and push forward. The bubbles showed a tendency of flowing with ease with the function of the vessel recovered. The results suggest that bubbles of any size in the vessel could easily change their shape under the action of the blood flow and pressure, and pass through vessels of any diameter and circulate with the blood. Only when a vessel was occluded due to spasm or the blood in a vessel was stagnated could the bubbles be motionless, but it was not that the bubbles blocked the vessel.

Animals↗