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Biomedical subjects

Q Lin

Publications and source records attributed to Q Lin.

At least 181 records · Page 10Linked to original sources

Effects of configuration on the myocardial uptake of radioiodinated 3(R)-BMIPP and 3(S)-BMIPP in rats.

UNLABELLED: Radioiodinated 3(R)-(+)- and 3(S)-(-)-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) were prepared and evaluated in rats to investigate the effects of absolute configuration of the 3(beta)-methyl group on myocardial uptake and release kinetics. METHODS: The 3(R)-(+)-BMIPP analog was synthesized by initial acylation of a thiophene template with the acid chloride of ethyl 3(R)-methylglutarate. 3(S)-(-)-BMIPP was obtained by separation from the mixture of diastereomeric amides prepared from reaction of the acid chloride of racemic BMIPP with the S-(-)-alpha-methylbenzylamine. The amide of synthetic 3(R)-BMIPP prepared from S-(-)-alpha-methylbenzylamine was identical to the chromatographically more polar isomer. Free acids were obtained by acid hydrolysis of the amides, fully characterized and then converted to the radioiodinated BMIPP isomers. RESULTS: Biodistribution studies in rats with the dual-labeled [(131)I]-3(S)-BMIPP/[(125)I]-3(R)-BMIPP mixture demonstrated greater myocardial uptake of 3(R)-BMIPP compared with the 3(S)-BMIPP isomer [60 min: 3(R)-BMIPP = 4.37 %ID/g; 3(S)-BMIPP = 3.44; p < 0.05; 180 min, 2.31 and 1.78 %ID/G, respectively, p < 0.01], although both isomers had similar myocardial washout curves (5-180 min). Percent ID/g values for other tissues which were examined (blood, lungs, thyroid) were similar. CONCLUSION: Higher myocardial uptake of the 3(R)-BMIPP isomer observed in these animal studies may suggest differences in carrier-mediated myocyte uptake of the two isomers. These studies suggest that [(123)I]-3(R)-BMIPP is a candidate for clinical evaluation and may show greater myocardial uptake than the 3(S)-BMIPP isomer and may thus require reduced injected dose.

Animals↗

[Clinical observation of cardiac pacemaker in pregnant women].

OBJECTIVE: To study the clinical results in pregnant women with bradycardia implanted with cardiac pacemakers. METHOD: Five pregnant women with bradycardia were retrospectively studied in our hospital from 1980 to 1996. RESULTS: Four of the patients had A-V block, and the other one sinus bradycardia. Classification of cardiac function, showed 1 case of class IV, 3 cases of class III, and 1 case of class II before implantation of cardiac pacemaker. One case had the pacemaker implanted before pregnancy and 4 cases during pregnancy. Cardiac function improved significantly after implantation and pregnancies went uneventfully. Three women had term living birth by cesarean section, and 2 ended by therapeutic abortions safely. CONCLUSION: Bradycardia is a rare and serious complication in pregnancy, especially due to A-V block of III degree. Cardiac pacemaker should be implanted before pregnancy or at early stage of pregnancy in order to maintain adequate heart function. These patients should receive cesarean section.

Adult↗

[Immunohistochemical study on the decidua vessels in recurrent spontaneous abortion].

OBJECTIVE: To investigate the effects of uterine local immunological factors in recurrent spontaneous abortion (RSA). METHODS: The decidua vessels were studied by immunohistochemical ABC method in 26 cases of RSA and 10 cases of normal pregnant women (control group). Meanwhile, serum IgG, IgM, IgA, C3 and CH50 were determined in RSA group and in control group. RESULTS: In RSA cases, the depositions of IgM (17 cases, 80.8%) were significantly increased (P < 0.001, respectively) as compared with the control group, the depositions of IgG (2 cases, 7.8%) were significantly decreased (P < 0.001); the levels of serum C3, CH50 were significantly decreased (P < 0.01 respectively), but the level of serum IgA was increased significantly (P < 0.05) as compared with the control group. The depositions of C3 were significantly increased in RSA who had autoantibodies (P < 0.01), as compared with those without autoantibodies. In addition, the positive stain of IGM and C3 in the cytoplasm and nuclei of decidua cells and in the cytoplasm of gland cells of some RSA patients were also observed. CONCLUSION: The results suggest that the immunological damage of decidua vessels is a very important factor in immunopathogenesis for RSA. Decidua cells and gland cells may have potential immunological function.

Abortion, Habitual↗

Effects of GABA and glycine receptor antagonists on the activity and PAG-induced inhibition of rat dorsal horn neurons.

The effects of bicuculline and strychnine on the activity and periaqueductal gray (PAG)-induced inhibition of rat dorsal horn neurons of the lumbar spinal cord were tested. Extracellular single unit recordings were from 36 dorsal horn neurons near a microdialysis fiber passed through the spinal cord for drug application. The GABAA receptor antagonist, bicuculline, was tested on 19 cells, whereas the glycine receptor antagonist, strychnine, was tested on 17 cells. Both bicuculline and strychnine increased the background activity and responses to mechanical stimulation (BRUSH, PRESS, and PINCH) of the skin.06 They also significantly blocked the PAG-induced inhibition of responses to peripheral mechanical stimuli. This experiment suggests that the mechanism of PAG-induced descending inhibition of dorsal horn neuron activity involves GABA and/or glycine release in the spinal cord and that there is tonic release of these inhibitory neurotransmitters.

Analysis of Variance↗

Possible role of protein kinase C in the sensitization of primate spinothalamic tract neurons.

The responsiveness of spinal cord nociceptive neurons to innocuous mechanical stimuli can be increased by the release of excitatory amino acids (EAAs) and peptides attributable to an injury-induced barrage of impulses. This sensitization of spinal dorsal horn neurons can also result from administration of phorbol ester by microdialysis, presumably by direct activation of protein kinase C (PKC). This study was designed to examine the effects of central sensitization of spinothalamic tract (STT) neurons produced by intradermal injection of capsaicin on the descending inhibition driven from the periaqueductal gray (PAG) and the possible role of PKC in this process in anesthetized monkeys. Sensitization of responses of STT cells to mechanical stimuli was induced by intradermal injection of capsaicin. PAG inhibition was significantly attenuated when sensitization of responses to mechanical stimuli occurred. However, perfusion of the spinal cord with NPC15437 (a selective PKC inhibitor) by microdialysis could prevent the sensitization of the responses to mechanical stimuli and the reduction in PAG inhibition of these responses induced by capsaicin injection. Results similar to those produced by capsaicin injection were observed when a PKC activator, phorbol ester (12-O-tetradecanoylphorbol-13-acetate), was infused within the dorsal horn by microdialysis. An inactive phorbol ester (4 alpha-phorbol 12,13-didecanoate) had no effect. These results provide evidence that the activation of PKC contributes to the development of central sensitization in dorsal horn neurons produced by chemical stimulation with capsaicin. Attenuation of the effectiveness of PAG inhibition takes place when the sensitization of dorsal horn cells develops, and PKC may play a significant role in this process.

Animals↗

The mouse BP-1 gene: structure, chromosomal localization, and regulation of expression by type I interferons and interleukin-7.

The BP-1/6C3 antigen is a homodimeric, phosphorylated type II membrane integral glycoprotein expressed on immature B-lineage cells, bone marrow stromal cells, thymic cortical epithelial cells, endothelial cells, enterocytes, and renal proximal tubular cells. Biochemical and molecular analysis identified BP-1 as glutamyl aminopeptidase, an ectoenzyme that catalyzes the hydrolysis of acidic amino acid residues from the amino termini of regulatory peptides. We have isolated genomic clones that encode the BP-1 gene (gene symbol Enpep). The gene spans more than 110 kb and contains 20 exons. Except for the first and the last exons, it is composed of small exons ranging from 56 to 171 bp that are separated by introns ranging from less than 100 bp to approximately 10 kb. The zinc binding motif HEXXH and the glutamic acid residue 19 amino acids downstream, which also binds zinc, are encoded in exons 5 and 6. Primer extension analysis revealed a common major transcriptional start site in a pre-B cell line, in a bone marrow stromal cell line, and in kidney cells. The promoter region contains a TATA-like element and potential DNA-binding motifs for lymphocyte-specific transcription factors including Ikaros, BSAP, PU.1, and octamer binding proteins, as well as DNA binding motifs for several ubiquitous transcription factors. An interferon responsive element also located in the promoter region appeared to be functional, since type I interferons (IFN-alpha/IFN-beta) upregulated BP-1 expression in pre-B cell lines. A 2.1-kb promoter fragment, when fused to a luciferase reporter gene, was able to drive luciferase expression in pre-B cells, which normally express BP-1, and the Ag8 cells, in which BP-1 expression is extinguished. The BP-1/ Enpep gene was localized to a distal region of mouse chromosome 3 in a region homologous to human chromosome 4q25. Interestingly, while interleukin-7 (IL-7) induced both cell growth and increased BP-1 expression, IFN-alpha/IFN-beta upregulated BP-1 expression but inhibited IL-7 induced proliferation. This finding indicates that the upregulated BP-1 expression can be disassociated from the cell growth signal.

Amino Acid Sequence↗

A single strand conformation polymorphism study of CD40 ligand. Efficient mutation analysis and carrier detection for X-linked hyper IgM syndrome.

Mutations in the gene for CD40 ligand are responsible for the X-linked form of hyper IgM syndrome. However, no clinical or laboratory findings that reliably distinguish X-linked disease from other forms of hyper IgM syndrome have been reported, nor are there tests available that can be used to confidently provide carrier detection. To identify efficiently mutations in the gene for CD40 ligand, eight pairs of PCR primers that could be used to screen genomic DNA by single strand conformation polymorphism (SSCP) were designed. 11 different mutations were found in DNA from all 13 patients whose activated T cells failed to bind a recombinant CD40 construct. The exact nature of four of these mutations, a deletion and three splice defects, could not be determined by cDNA sequencing. In addition, SSCP analysis permitted rapid carrier detection in two families in whom the source of the mutation was most likely a male with gonadal chimerism who passed the disorder on to some but not all of his daughters. These studies document the utility of SSCP analysis for both mutation detection and carrier detection in X-linked hyper IgM syndrome.

Base Sequence↗

CD38 signal transduction in human B cell precursors. Rapid induction of tyrosine phosphorylation, activation of syk tyrosine kinase, and phosphorylation of phospholipase C-gamma and phosphatidylinositol 3-kinase.

Ligation of CD38 inhibits proliferation and induces apoptosis of human immature B cells, but the molecular mechanisms underlying this function are unknown. We found that CD38 dimerization with the specific mAbs T16 and IB4 induces rapid and transient tyrosine phosphorylation of several intracellular proteins in the immature B cell lines RS4;11, REH, 380, Nalm6, and OP-1. This effect could be markedly reduced by incubating cells with the tyrosine kinase inhibitors genistein, staurosporine, and herbimycin A. CD38 dimerization induced tyrosine phosphorylation of the protein kinase syk and increased syk kinase activity. CD38 dimerization also induced tyrosine phosphorylation of phospholipase C-gamma and of the p85 subunit of phosphatidylinositol 3-kinase (PI 3-K). The latter was accompanied by a distinct increase in PI 3-kinase activity in the immunoprecipitates obtained with an anti-phosphotyrosine Ab. In contrast to the signaling triggered by surface Ig engagement in B lymphocytes, CD38 ligation did not appear to induce tyrosine phosphorylation of the src-like protein tyrosine kinases lyn, fyn, and btk, or of vav- and ras-GTPase-activating protein, nor did it induce detectable changes in cytosolic CA2+ concentrations. CD38 signaling also differed from cytokine-induced signaling in that it did not cause tyrosine phosphorylation of Jak1 and Jak2. Finally, CD38 ligation did not inhibit IL-3-induced tyrosine phosphorylation of Jak2. These results identify CD38 as a cell surface receptor with signal transduction properties activated by dimerization. Induction of signal transduction by CD38 ligation implies the existence of a yet unidentified natural ligand of CD38.

ADP-ribosyl Cyclase↗

Expression and functional analysis of Euglena Gracilis chloroplast initiation factor 3.

A portion of a cDNA predicted to encode the mature form of Euglena gracilis chloroplast translational initiation factor 3 (IF-3chlM, molecular mass, 46 402) and the portion of this factor homologous to bacterial IF-3 (IF-3chlH, molecular mass 22 829) have been cloned and expressed in Escherichia coli as histidine-tagged proteins. The homology domain can be expressed in reasonable levels in E. coli. However, IF-3chlM is quite toxic and can only be produced in small amounts. Both forms of the chloroplast factor are associated with E. coli ribosomes. Purification procedures have been developed for both IF-3chlM and IF-3chlH using Ni-NTA affinity chromatography followed by ion exchange chromatography. IF-3chlM and IF-3chlH are active in promoting ribosome dissociation and in promoting the binding of fMet-tRNA to E. coli ribosomes. However, IF-3chlH has at least 5-fold more activity than either native IF-3chl or IF-3chlM in promoting initiation complex formation on chloroplast 30S ribosomal subunits in the presence of a mRNA carrying a natural translational initiation signal. This observation suggests that regions of IF-3chl lying outside of the homology domain may down-regulate the activity of this factor.

Animals↗

Cloning and initial characterization of 14 myb-related cDNAs from tomato (Lycopersicon esculentum cv. Ailsa Craig).

myb-related transcription factors contain highly conserved DNA-binding domains. Using a mixture of degenerate oligonucleotides derived from the highly conserved region as probe, 14 myb-related clones were isolated from a cDNA library constructed using tomato hypocoyl mRNA. The expression of these clones was studied by northern blot analysis using poly(A)+ RNA from 7 tissue types (hypocotyl, leaf, root, green and red fruit, immature and mature flower). This study has revealed a wide range of expression patterns which include multiple and single transcripts, some of which show marked tissue specificity. Two clones showing different expression patterns have been fully sequenced. The DNA-binding domains of these two tomato myb clones are compared with myb genes from other plant species and organisms. Of the three clones analysed so far by Southern hybridization, two are single-copy genes and one has multiple genomic copies.

Amino Acid Sequence↗

Role of GABA receptor subtypes in inhibition of primate spinothalamic tract neurons: difference between spinal and periaqueductal gray inhibition.

1. gamma-Aminobutyric acid (GABA) is thought to inhibit both pre- and postsynaptically the transfer of nociceptive signals from primary afferent fibers to spinal dorsal horn sensory cells, including spinothalamic tract (STT) neurons. The inhibition can be mediated by both GABAA and GABAB receptors. We now attempt to characterize the synaptic inhibition of STT cells by spinal GABAA and GABAB receptors in anesthetized monkeys and to analyze the roles of these two receptor subtypes in the inhibition of STT cellular activity produced by stimulation in the periaqueductal gray (PAG). 2. Iontophoretic release of GABA or muscimol (a selective GABAA receptor agonist) onto STT cells elicited a profound and dose-related inhibition of the responses of all cells tested to noxious cutaneous stimuli. Only four cells (16.7%) were found to be inhibited when baclofen (a selective GABAB receptor agonist) was applied iontophoretically. However, a strong and dose-dependent inhibition of the responses to cutaneous mechanical and thermal stimuli was obtained in all cells examined when baclofen was administered into the dorsal horn through a microdialysis fiber. The inhibitory effects were mainly on nociceptive inputs. 3. The inhibition of cellular activity by GABAA and GABAB agonists could be selectively antagonized by specific antagonists applied through a microdialysis fiber. 4. The excitatory responses evoked by pulsed release of glutamic acid (GLUT) were also inhibited in a dose-related manner by iontophoretic application of GABA and muscimol, but not by baclofen. A high dose of baclofen administered by microdialysis resulted in only a small decrease in GLUT-evoked excitatory responses. 5. Infusion of GABAA and GABAB antagonists into the dorsal horn by microdialysis caused an increase in both background activity and responses to cutaneous stimuli, suggesting that there is a tonic GABAergic inhibition of STT cells. 6. The inhibition of responses to mechanical and thermal stimulation of the cutaneous excitatory receptive field resulting from stimulation in PAG was significantly antagonized in most of the STT cells tested when the GABAA antagonist bicuculline was infused into the spinal dorsal horn through a microdialysis fiber. In contrast, the inhibition produced by PAG stimulation in most of the cells examined was not significantly antagonized by the GABAB antagonists phaclofen or 3-amino-propyl(diethoxymethyl)phophinic acid (CGP35348) administered into the spinal dorsal horn by microdialysis. 7. Our results support the contention that GABAergic mechanisms in the spinal dorsal horn normally exert a tonic modulation of nociceptive inputs through both GABAA and GABAB receptors. The evidence provided here indicates that GABAA receptors located on primate STT neurons contribute to a postsynaptic inhibitory effect on the transmission of peripheral nociceptive inputs. A possible presynaptic GABAA action was not investigated. Our finding of a GABAB-receptor-mediated inhibition is consistent with the view that both pre- and postsynaptic GABAB receptors are involved in inhibitory modulation of spinal nociceptive transmission. Finally, it is suggested from this study that primate spinal GABAA, but not GABAB receptors, are involved in mediating the descending inhibition induced by PAG stimulation.

Animals↗

Inhibition of primate spinothalamic tract neurons by spinal glycine and GABA is reduced during central sensitization.

1. In our previous work, we demonstrated that the glycinergic and GABAergic mechanisms that help mediate the descending inhibition from the periaqueductal gray exert a tonic modulation of nociceptive inputs through spinal glycine and gamma-aminobutyric acid (GABA) receptors. This study was designed to examine further possible changes in the inhibition of the activity of spinothalamic tract (STT) neurons mediated by spinal glycine and GABA receptors when STT cells are sensitized by intradermal injection of capsaicin, and to investigate the role of the protein kinase C (PKC) system in the functional modulation of these receptors. 2. Although the responses of STT cells to cutaneous mechanical stimuli were sensitized by intradermal injection of capsaicin, the inhibition of the responses of all STT cells tested to noxious cutaneous stimuli produced by iontophoretic release of glycine and GABA was significantly attenuated. The inhibition elicited by iontophoretic application of a GABAA agonist, muscimol, was reduced in some of the cells tested. 3. When the spinal cord dorsal horn was pretreated with a selective PKC inhibitor, 2,6-diamino-N-([1-oxotridecyl-2-piperidinyl]- methyl)hexanamide, by microdialysis, sensitization of STT cells by capsaicin injection and the accompanying attenuation of glycine- and GABA-induced inhibition were prevented. 4. Sensitization of STT cells to cutaneous mechanical stimuli was also induced by administration of the PKC activator, 12-O-tetradecanoylphorbol-13-acetate, into the spinal dorsal horn. The inhibition produced by iontophoretic release of glycine, GABA, and muscimol was found to be reduced in most cells examined when this phorbol ester was used. An inactive phorbol ester, 4 alpha-phorbol 12,13-didecanoate, did not produce significant effects on cellular activity. 5. These results suggest that there is an activation of PKC in the spinal cord when STT neurons are sensitized after intradermal injection of capsaicin or administration of phorbol ester. This sensitization is likely to be involved in the development of allodynia and secondary hyperalgesia not only by enhancing the responses of excitatory amino acid receptors but also by desensitizing glycine and GABA receptors.

Animals↗

The role of 5-HT3 receptors in periaqueductal gray-induced inhibition of nociceptive dorsal horn neurons in rats.

Electrical stimulation in the periaqueductal gray (PAG) can inhibit dorsal horn cell responses to both innocuous and noxious cutaneous stimuli. This inhibition is believed to be due to the release of serotonin (5-HT) into the dorsal horn of the spinal cord from descending axons of the nucleus raphe magnus and the adjacent reticular formation. It is still not clearly known which subtypes of 5-HT receptors are involved in the PAG-induced inhibition. Extracellular single-unit recordings of dorsal horn cell activity, in combination with drug administration through a microdialysis fiber, were used to test the role of 5-HT3 receptors in PAG-induced inhibition. The responses of the cells to mechanical stimulation of the skin (BRUSH, PRESS and PINCH) and to the same stimuli while stimulating PAG were recorded. When the 5-HT3 antagonist, ondansetron, was perfused through the microdialysis fiber, not only was the background activity of the cell increased, but also the responses to BRUSH, PRESS and PINCH stimuli. The PAG-induced inhibition of responses to the same stimuli was partially or completely blocked by ondansetron. Another 5-HT3 antagonist, zacopride, did not increase the background activity or responses to PRESS and PINCH, yet this agent, like ondansetron, blocked PAG inhibition. The 5-HT3 agonist, phenylbiguanide, inhibited the background activity and the responses to mechanical stimuli. These results suggest that 5-HT released in the dorsal horn by stimulation in the PAG excites inhibitory interneurons through 5-HT3 receptors, resulting in inhibition of dorsal horn neurons.

Animals↗

[Cloning and sequencing of VH and VL genes of an anti-human lung adenocarcinoma monoclonal antibody].

By comparing the conserved regions at each end of the nucleotide sequences of murine germ-line genes encoding FR1 and FR4 regions of immunoglobulin heavy and light chain variable regions, we designed two sets of primer for amplification of VH and VL genes. Hybridoma cell WLA-2C4, secreting an antihuman lung adenocarcinoma McAb, was cultured and the genome DNA was extracted and used as template for PCR. After PCR the desired VH and VL fragments were amplified. The PCR products were then cloned into pUC19 vector. By screening and identification, several recombinants that had been inserted with the target fragments were obtained. Then they were sequenced with Sanger's method. It was confirmed by computer-assisted comparative sequence analysis that clones of full-length and potentially functional VH and VL genes from the hybridoma cell line WLA-2C4 were ob-tained.

Adenocarcinoma↗

Adsorption of mixtures of bile salt taurine conjugates to lecithin-cholesterol membranes: implications for bile salt toxicity and cytoprotection.

Tauroursodeoxycholate (TUDC), a relatively hydrophilic bile salt, reduces disruption of cholesterol-rich membranes by more hydrophobic bile salts such as taurocholate (TC), taurochenodeoxycholate (TCDC), or taurodeoxycholate (TDC). We examined the interactions of these bile salts in adsorption to large unilamellar vesicles to determine whether TUDC may stabilize membranes by preventing adsorption of more toxic bile salts. Fractional adsorption was quantified by rapid ultrafiltration. Adsorption coefficient Ai was defined for each bile salt i as ([bound i]/[free i])/[lecithin]. Affinity of different bile salts for lecithin vesicles varied with their relative hydrophobicity, increasing in the order TUDC < TC << TCDC < or = TDC. Ai of each bile salt fell with its accumulation on membranes, reaching a minimum at bound bile salt/lecithin mole ratio (B:L) between 0.05 and 0.1, then increasing with formation of higher-affinity mixed micelles. Inclusion of cholesterol in vesicles reduced Ai of all bile salts. In heterologous binding studies at submicellar concentrations, Ai of each bile salt varied with total B:L but was independent of the specific bile salts present on the membrane. Addition of TUDC to TDC reduced binding of TDC to membranes only slightly and lowered the threshold TDC concentration associated with transition to mixed micelles. However, above this threshold, TUDC markedly altered the adsorption of TDC to lecithin-containing phases. We conclude that TUDC does not directly stabilize membranes; rather, reduced permeabilization and dissolution of cholesterol-rich membranes after addition of TUDC to TDC may result from effects on the formation and structure of simple and mixed micelles.

Adsorption↗