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Biomedical subjects

R Yan

Publications and source records attributed to R Yan.

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

AIT-082, a cognitive enhancer, is transported into brain by a nonsaturable influx mechanism and out of brain by a saturable efflux mechanism.

A fundamental feature of any drug designed to treat a disease of the central nervous system is the ability to cross the blood-brain barrier. Passage across the blood-brain barrier of AIT-082, a cognitive enhancer, was investigated in mice. [(14)C]AIT-082 crossed the blood-brain barrier in young male Swiss-Webster mice with a mean influx constant (K(i)) of 0.6 +/- 0.2 microl g(-1) min(-1). Furthermore, [(14)C]AIT-082 was transported into brain of both young and old male C57BL/6 mice with a K(i) of 0.35 +/- 0.06 and 0.33 +/- 0.02 microl g(-1) min(-1), respectively. There was no significant effect of age or strain on the movement of [(14)C]AIT-082 across the blood-brain barrier in mice. When 110- or 650-fold excess unlabeled AIT-082 was included in the injection solution, the K(i) was not significantly changed in either Swiss-Webster or C57BL/6 mice. This indicated that [(14)C]AIT-082 crossed the blood-brain barrier by a nonsaturable mechanism. The passage of AIT-082 into brain extracellular fluid was confirmed with capillary depletion and microdialysis. The efflux of [(14)C]AIT-082 from brain also was examined. After i.c.v. injection, [(14)C]AIT-082 levels in brain decreased over time with a t(1/2) of 20.0 +/- 1.0 min. Excess unlabeled AIT-082 (600-fold) increased the t(1/2) to 35.5 +/- 3.6 min. Together, these data indicate that AIT-082 moves into brain via a nonsaturable mechanism and is actively transported out of brain.

Age Factors↗
PubMed1999

Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity.

Mutations in the gene encoding the amyloid protein precursor (APP) cause autosomal dominant Alzheimer's disease. Cleavage of APP by unidentified proteases, referred to as beta- and gamma-secretases, generates the amyloid beta-peptide, the main component of the amyloid plaques found in Alzheimer's disease patients. The disease-causing mutations flank the protease cleavage sites in APP and facilitate its cleavage. Here we identify a new membrane-bound aspartyl protease (Asp2) with beta-secretase activity. The Asp2 gene is expressed widely in brain and other tissues. Decreasing the expression of Asp2 in cells reduces amyloid beta-peptide production and blocks the accumulation of the carboxy-terminal APP fragment that is created by beta-secretase cleavage. Solubilized Asp2 protein cleaves a synthetic APP peptide substrate at the beta-secretase site, and the rate of cleavage is increased tenfold by a mutation associated with early-onset Alzheimer's disease in Sweden. Thus, Asp2 is a new protein target for drugs that are designed to block the production of amyloid beta-peptide peptide and the consequent formation of amyloid plaque in Alzheimer's disease.

Alzheimer Disease↗
PubMed1998

[Influence of compensatory hepatocyte proliferation on the carcinogenesis of N-nitrosodimethylamine].

OBJECTIVE: To study the influence of compensatory hepatocyte proliferation on the N-nitrosodimethylamine (NDMA) carcinogenesis in rats. METHODS: NDMA was given to animals of the experimental group 24 hours after partial hepatectomy, and the control group was only treated with NDMA. Expression of gamma-glutamyltransferase (GGT), glutathione S-transferase placental form (GSTP), proliferating cell nuclear antigen (PCNA), insulin-like growth factor-II (IGF-II) and oncogenes was detected. RESULTS: The numbers and areas of GGT- and GSTP-foci in the experimental group were significantly increased in comparing with the control groups. The expression of GSTP was higher than that of GGT. The total tumor incidence of the experimental group was higher than that of the control by the end of the 56th week. Up to week 71, the incidences of liver and other tumors were higher respectively in the experimental group. The amount of PCNA positive cells were corresponding with proliferative condition of the hepatic lesions. The expression of IGF-II, c-myc and H-ras mRNA increased in the altered hepatocyte foci and nodules, but markedly decreased in hepatocellular carcinoma and adenoma. No c-jun mRNA expression was detected in all the normal and abnormal tissues of liver. CONCLUSIONS: The results suggest that compensatory hepatocyte proliferation enhances the carcinogenesis induced by multiple doses of NDMA, and the over expression of IGF-II, c-myc, H-ras may play a synergetic role in NDMA-induced hepatocarcinogenesis.

Animals↗
PubMed1998

[The relationship between severe burn injury and systemic inflammatory response syndrome].

OBJECTIVE: To study course of systemic inflammatory response syndrome (SIRS). METHODS: The relationship was observed between SIRS and the effect of burn injury on cellular and humoral immunity between survivors. Nonsurvivors were also compared. The gastric mucosal pHi was measured. RESULTS: The SIRS initiated 22 hours after burn injury and peaked 3 days to 7 days postburn. Compared to the survivors significan increase of content of TNF and decrease of content of G-CSF were detected in the nonsurvivors serum. Obvious immunosuppression could be found. In patients with SIRS accompanied with infection or organ failure, marked increase of mortality was seen. The value of pHi was very low. CONCLUSION: Severe burn injury can lead to the release of massive inflammatory mediators. The second insult such as infection can further amplify the process leading to a vicious cycle of inflammation which cause tissue damage and immunosuppression. To prevent MODS, early diagnosis and treatment including organ supply, use of antibacterial agents, oxygen supply and immunity therapy were necesary.

Adolescent↗
PubMed1997

[Levels of serum G-CSF and supplement of GM-CSF in rats sustaining delayed resuscitation after major burn].

UNLABELLED: Delayed fluid resuscitation of burn shock may lead to infection in early period following major burn injury, resulting in multiple organ failure with high mortality. The change in colony stimulation factors (CSFs) may play a role in developing infection. We assessed the levels of serum granulocyte colony stimulation factor (G-CSF), tumor necrosis factor-alpha (TNF-alpha), phagocytosis of neutrophil and counts of peripheral blood cells of rats with 30% TBSA full thickness burn having either immediate or delayed fluid replacement. We also evaluated the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) in improving survival of rats following burn injury with a superimposed burn wound infection. THE RESULTS: 1. A delayed rise in serum G-CSF was found in delayed resuscitation group, and the levels of serum G-CSF and phagocytosis of neutrophil were lower compared with immediate resuscitation group. 2. Nonsurvival group had lower levels of serum G-CSF and higher content of TNF-alpha compared with survival. 3. Supplement of GM-CSF could significantly improve animal survival with burn wound infection following severe burn shock. CONCLUSION: Decrease in G-CSF production plays a role in developing fatal wound infection after severe burn shock; supplement of GM-CSF is beneficial in improving survival.

Animals↗
PubMed1997

[Immunoblots of hydrophobic OmpL39 of Leptospiral interrogans with immunoprotective Mb E4B7G5].

The immunoprotective Mb E4B7G5 against outer membrane antigens from L. interrogans serovar Lai strain 017 were produced and used in immunoblots of the OMP of six strains of L. interrogans (017, 601, 603, 609, 620 and 245). The OMP from the six strains, which partitioned into the hydrophobic detergent phase, contained four-seven major proteins bands of 66 kd-16 kd. It was found that Mb E4B7G5 recognized only specifically the 39 kd antigenic band of strain 017, 601, 603 and 609, and did not recognize apparently any bands of strains 620 and 245. The findings suggest that Mb E4B7G5 be valuable for separating protective antigen of OMP and studying genetic vaccines.

Animals↗
PubMed1997

[Construction of genomic library of L. interrogans serovar lai using lambda gt11 as the vector and a study of recombiant plasmid pDL121].

A genomic library of L. interrogans serovar lai strain 017 has been constructed using lambda gt11 as the vector. DNA was partially digested by two blunt-end restriction enzymes, then methylated with EcoR I methylase; after EcoR I linker was added to the DNA, the linker-ended DNA was ligated to the dephosphorylated EcoR I digested lambda gt11 arms. The recombined DNA was packaged in vitro, and used to transduct E. coli Y1090 for amplification. There were 2.1 x 10(6) recombinant bacteriophages as recognized by their ability to form white plaques plated on Lac host in the presence of both IPTG and X-Ga1. A positive clone, designated lambda DL12, was screened with a rabbit anti-serum against L. interrogans serovar lai from the genomic library. The DNA from lambda DL12 was subcloned into plasmid pUC18. A recombinant (designated as pDL121) was obtained. SDS-PAGE analysis indicated that a 23 kd was expressed in E. coli JM 103 harboring pDL121. Western blotting analysis showed that a specific protein band molecular weight of 23 kd could be recognized by the rabbit antiserum against L. interrogans serovar lai strain 017.

Cloning, Molecular↗
PubMed1997

[GS-MS analysis of essential oils from five species of Asarum].

This paper reports the result of GS-MS analysis of the essential oils from five species of Asarum, namely, A. heterotropoides var. mandshuricum (cultivated), A. sieboldii (cultivated), A. caudigerellum (from Sichuan), A. sieboldii(from Shandong) and A. sieboldii(wild). Ninety-two constituents were detected, of which 73 compounds were identified.

Drugs, Chinese Herbal↗
PubMed1997

[Studies on bone density in healthy girls during their period of growth spurt].

Bone mass in 69 healthy girls in their period of growth spurt was measured twice, with an interval of one year, by dual energy X-ray bone densitometer to study the relationship between changes in bone density and the speed of height growth, development of secondary sex characteristics and nutritional status. Results showed that bone density in the different sites in the period of growth spurt increased significantly with their age, but with difference in the magnitude of its increase and in the time. Their nutritional status (overweight or underweight) correlated closely with sex development and increase in bone density. It suggests that it is necessary to strengthen nutrient intake during their puberty for preventing from osteoporosis. In addition, early puberty is an important period for the increase in female bone density, as a result of comparison of bone mass between prepuberty girls and young women. The results in this study can provide reference for further studies on bone mass in girls during their puberty.

Bone Density↗
PubMed1996

Unique signal transduction of Eyk: constitutive stimulation of the JAK-STAT pathway by an oncogenic receptor-type tyrosine kinase.

The proto-oncogene c-eyk, the cellular counterpart of a transforming oncogene, v-eyk, encodes a receptor protein tyrosine kinase with a distinctive extracellular region. We now demonstrate that c-Eyk can be constitutively activated through dimerization, and that the active Eyk displays a unique signaling pattern. When the kinase domain of c-Eyk was fused to the extracellular and transmembrane domains of CD8, the resulting chimera showed elevated kinase activity and caused cellular transformation. We found that the activated Eyk kinases, both v- and c-Eyk, constitutively stimulate the JAK-STAT pathway, while exerting little effect on other signaling routes such as the Ras-MAP kinase and the JNK pathways. The activated Eyk kinases specifically stimulate tyrosine phosphorylation of STAT1, STAT3 and JAK1. These downstream molecules also co-immunoprecipitate with the constitutively dimerized form of Eyk. The Eyk kinase activity is required for STAT1 stimulation. We found that the activation of STAT1 but not STAT3 correlates well with cellular transformation. In constitutively stimulating the JAK-STAT pathway, particularly STAT1, Eyk is unique in its downstream signaling and may be dependent on this pathway for cellular transformation.

Animals↗
PubMed1996

A JAK-STAT pathway regulates wing vein formation in Drosophila.

We present evidence that the JAK-STAT signal transduction pathway regulates multiple developmental processes in Drosophila. We screened for second-site mutations that suppress the phenotype of the hyperactive hopTum-1 Jak kinase, and recovered a mutation that meiotically maps to the known chromosomal position of D-Stat, a Drosophila stat gene. This hypomorphic mutation, termed statHJ contains a nucleotide substitution in the first D-Stat intron, resulting in a reduction in the number of correctly processed transcripts. Further, the abnormally processed mRNA encodes a truncated protein that has a dominant negative effect on transcriptional activation by the wild-type cDNA in cell culture. statHJ mutants exhibit patterning defects that include the formation of ectopic wing veins, similar to those seen in mutants of the epidermal growth factor/receptor pathway. Abnormalities in embryonic and adult segmentation and in tracheal development were also observed. The hopTum-1 and statHJ mutations can partially compensate for each other genetically, and Hop overexpression can increase D-Stat transcriptional activity in vitro, indicating that the gene products interact in a common regulatory pathway.

Animals↗
PubMed1996

Identification of a Stat gene that functions in Drosophila development.

A Drosophila Stat gene (D-Stat) with a zygotic segmental expression pattern was identified. This protein becomes phosphorylated on Tyr-704 when coexpressed in Schneider cells with a Drosophila janus kinase (JAK), Hopscotch (HOP). The phosphorylated protein binds specifically to the consensus sequence TTCCCGGAA. Suppressor mutations of hopTum-I, a dominant hyperactive allele of hop whose phenotype is hematocyte overproduction and tumor formation, were selected. One of these mutants, statHJ, mapped to the same chromosomal region (92E) as does D-Stat, had an incompletely penetrant pair rule phenotype, and exhibited aberrant expression of the pair rule gene even skipped (eve) at the cellular blastoderm stage. Two D-STAT-binding sites were identified within the eve stripe 3 enhancer region. Mutations in either of the STAT-binding sites greatly decreased the stripe 3 expression in transgenic flies. Clearly, the JAK-STAT pathway is connected to Drosophila early development.

Amino Acid Sequence↗
PubMed1996

[Basic research and clinical applications of the human hair suture].

An atraumatic suture was manufactured from human hair, which has been tested and used in 817 clinical cases with satisfactory results. The authors found that the suture has the following characteristics: smooth, thin, strong and elastic, structurally steady, histocompatible, atoxic, aseptic, atraumatic, with endurance of more than one thousand times of bending. It does not swell in water or blood nor it causes reaction after being buried in tissue for 150 days. It definitely has an advantage over the silk and nylon. The rich resources of hair favor its wide applications.

Adolescent↗
PubMed1996

[Research on the recombinant plasmid pDJH2 of L. interrogans serovar lai: sequencing and alignment with other known bacterial Omp sequence].

The Leptospira whole cell vaccine (LWCV) currently used in China is safe and effective, out the immunity following vaccination with two doses of the fluid medium vaccine is of low order. The duration of immunity conferred by this vaccine is rather short, six months or at most one year. Therefore, it is necessary to develop new generation vaccines against Leptospirosis for the developing world. In this paper we report the sequencing of the insert fragment of pDJH2 from genomic DNA of L. interrogans sevovar lai strain 017 and its alignment with other bacterial omp sequences. A genomic library of Leptospira interrogaans serovar lai strain 017 was constructed with the plasmid vector pUC18. A recombinant plasmid designated pJDH2 was screened from the genomic library. Inserted fragment of pDH2 is 1.9 kb by gel electrophoresis. Immunization/protection was studied in BALB/c mice model. The results showed highly significant difference between pDJH2 and pUC18 (control). Inserted fragment of pDJH2 DNA sequencing was performed by Dr Yan Zhengxin (Max-Planck-Institut for Biology. Tubingen, Germany). Insert fragment was cloned into pBluescript II KS-(stratagene) and sequenced by using AB1 (Applied Bio Systems, Model 373A). Two open reading frames of 565 and 662 nucleotides were identified. There were identifiable initiation codons, terminators, Shine-Dalgano ribosome combining site, Pribnow boxes and Sextama boxes within the 2 sequenced regions. Nucleotide sequences were analysed using Gene Work, a suit of computer program developed by Department of Biochemistry St. Jude Children's Research Hospital Memphis. U.S.A. The results of formatted alignment showed the predicted nucleotide sequence of ORF1 of the serovar lai had significant similarity with ORF2 (49.36%). L. kirschneri ompL1 (49.26%), Borrelia burgdoferi omp (48.97%), Treponema phagedenis omp (47.3%); Salmonella typhimurium ompC(46.87%), Yersinia enterocolitica ompH (46.7%), Leptospira borgpeterseni pfap (46.3%), and Serratia marcescens omp (43.3%). The close relationship of the pDJH2 ORF1 and ORF2 nucleotide sequences from Leptospira kirschneri ompL 1 is apparent. Whether the recombinant pDJH2 will prove useful for vaccine development remains to be tested.

Animals↗
PubMed1995

Human protein synthesis initiation factor eIF-4 gamma is encoded by a single gene (EIF4G) that maps to chromosome 3q27-qter.

Messenger RNA binding to the ribosome, the rate-limiting step in eukaryotic protein synthesis, is catalyzed by the eIF-4 group of initiation factors. These factors collectively bind to the m7GTP-containing cap of mRNA and unwind mRNA secondary structure at the expense of ATP. One member of the group, eIF-4 gamma, is the target for proteolytic cleavage during picornavirus infection, an event that is thought to be responsible for the inhibition of host cellular mRNA translation. Human eIF-4 gamma migrates as a cluster of polypeptides in the range of 200-220 kDa during SDS-PAGE, raising the possibility that it is a family of proteins encoded by separate genes. In this study, we present genomic Southern blotting results which indicate that there is only a single gene, here designated EIF4G. Furthermore, we have employed a PCR approach to map EIF4G to chromosome 3q27-qter.

Animals↗