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Biomedical subjects

M Yan

Publications and source records attributed to M Yan.

At least 55 records · Page 3Linked to original sources

Identification of a receptor for BLyS demonstrates a crucial role in humoral immunity.

B lymphocyte stimulator (BLyS) is a member of the tumor necrosis factor (TNF) superfamily. BLyS stimulates proliferation of, and immunoglobulin production by, B cells. However, the relative importance of BLyS in physiological B cell activation is unclear. We identified a B cell receptor for BLyS through expression cloning as TACI, an orphan TNF receptor homologue of unknown function. Binding of BLyS to TACI activated signaling by nuclear factor-kappa B (NF-kappa B). In vitro soluble TACI-Fc fusion protein blocked BLyS-induced NF-kappa B activation in B lymphoma cells and IgM production in peripheral blood B cells. In vivo treatment of immunized mice with TACI-Fc inhibited production of antigen-specific IgM and IgGI antibodies and abolished splenic germinal center (GC) formation. Thus, BLyS activity must play a critical role in the humoral immune response.

Animals↗

[A mechanistic model of phasic and phenological development of wheat. I. Assumption and description of the model].

The temperature effectiveness for wheat development was non-linearized and the apical and phenological development stages were systematically predicted by the scale of physiological development time which was based on the ecophysiological development process. The predicted apical development stages included single ridge stage, double ridge stage, floral initiation stage, stamen and pistil initiation stage, anther seperation stage, tetrad stage, and heading stage, while the predicted phenological development stages included germination stage, emergence stage, tillering stage, winterovering stage, green-turning stage, jointing stage, booting stage, heading stage, flowering stage, grain filling stage, and maturity stage. Four cultivar specific parameters were used to describe the genotypic differences of wheat development. They were temperature sensitivity, physiological vernalization time, photoperiod sensitivity, and intrinsic earliness, reflecting the genetic properties of different cultivars in thermal effectiveness, vernalization, photoperiod response and shortest time required for reaching flowering, respectively. The four parameters determined the physiological development time required for each development stage of different cultivars.

Models, Biological↗

[Two-phase linear models of leaf emergence at different tillering positions in wheat and effects of different varieties and sowing dates].

Dynamics of leaf emergence shows the development progress and its relationship with growth in wheat. It was found that two-phase linear model equations (phase I faster than phase II) divided by glum differentiation stage could describe leaf emergence progress in relation to growing degree days (GDD) after sowing in wheat. This pattern was consistent in main stems and tillers of normal development with both winter-and-spring type varieties. The beginning of phase II shifted to an earlier development stage on main stems of winter type varieties of early planting (EP, September 30) and late planting (LP, March 2), and on T3 of both varieties of EP, MP (middle planting, on October 30) and LP due to their abnormal development. The thermal rate of leaf emergence on main stem was relatively high and steady during development for winter type variety of MP, and quickened with the postponing of sowing for spring type variety. The above results illustrated the difference of leaf emergence at different tillering positions, and the biological characteristics affected by different varieties and sowing dates.

Germination↗

[The study of RDS gene mutation and clinical phenotype in a family with primary retinitis pigmentosa].

OBJECTIVE: To investigate retinal degeneration slow (RDS) gene mutation in a Chinese family with primary retinitis pigmentosa (RP) and the association of the mutation with clinical phenotypes and to explore the pathogenesis of RP. METHODS: Blood DNA from 2 patients in the same family with RP and 2 normal persons was analyzed by molecular genetic methods. RDS gene mutation was screened out by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. The mutant RDS gene fragment was cloned, then sequenced with an automatic DNA sequencer using a dideoxy chain termination protocol. The phenotype of the patients with the gene mutation were examined and determined by clinical ophthalmologic examinations. RESULTS: The PCR-RFLP analysis of the RDS gene in 2 patients with RP revealed codon 216 mutation of RDS gene. The mutation was heterozygous, and not found in 2 normal persons as controls. The alteration in the DNA sequence was identified as a heterozygous transversional change of C to T at the second nucleotide in codon 216 of RDS gene, resulting in the amino acid replacement of proline residue with leucine residue (Pro216Leu). The ocular finding of the patients with Pro216Leu mutation of RDS gene included severe visual loss and diffuse distribution of pigmentary changes with macular degeneration. CONCLUSIONS: The Pro216Leu mutation of RDS gene is found in Chinese patients with RP. The gene mutation is associated with the ocular phenotype, diffuse RP with macular degeneration.

Adult↗

[The detection of disparity evoked potentials in anisometropes].

OBJECTIVE: To investigate the affection of anisometropia on stereopsis and its mechanism. METHODS: A new set of static random-dot stereograms was utilized as a stimulus to elicit evoked potentials in 20 anisometropes and 40 normal subjects. RESULTS: Under the stimulus of different degrees of disparity in anisometropes, the P(250) waves related to stereopsis could be recorded. However, the percentage of their P(250) wave amplitude over the plane figure was significantly lower than that of normal persons (P < 0.05). The P(250) wave mean amplitude of severe anisometropes (aniseikonia >or= 5%) in fine disparity (14' and 23') was lower than that in mild anisometropes (aniseikonia < 5%, P < 0.05). CONCLUSIONS: Anisometropia may affect and disturb the stereopsis. The degree of disturbance is related to the degree of anisometropia. The higher the degree of anisometropia, the lower the amplitude of the P(250) potential, and the main defect is at the part of fine disparity.

Adolescent↗

[Cytochrome P450IA1 and the genetic susceptibility to esophageal carcinoma].

OBJECTIVES: To explore the susceptibility to esophageal carcinoma (EC) in different population with different cytochrome P450 IA1 (CYPIA1) genotype, and study the synergistic effects between CYPIA1 and smoking. METHODS: A case-control study (case = 111, control = 114) was used to compare the frequency of CYPIA1 genotype between EC and controls with a PCR method. RESULTS: The distribution of three genotypes of CYPIA1 in EC and controls was significantly different (chi(2) = 19.35, P < 0.01). There was a synergistic effect between the mutation of CYPIA1 4,889 site and smoking (SIA = 1.56), and a significant dose-response effect was observed. The risk of individual whose CYPIA1 4,889 site is mutated was 3 times higher than those not mutated. CONCLUSIONS: The mutation of CYPIA1 ,89 site maybe one of important host susceptible factors of EC, and the risk would increase significantly in smokers.

Aged↗

[Audiological findings and mitochondrial DNA mutation in a large family with matrilineal sensorineural hearing loss].

OBJECTIVE: To explore audiological features of matrilineal non-syndromic deafness and its molecular mechanism. METHODS: A large family with 41 members having inherited deafness was studied. Complete history and the data of general and otolaryngological examinations were collected. All subjects were screened for mitochondrial DNA A1555G mutation by molecular analysis. Audiological evaluation included puretone audiometry, auditory brainstem responses and transiently evoked otoacoustic emissions. RESULTS: All subjects were in good health generally. Molecular analysis showed that all maternal relatives with or without hearing loss harbored the A1555G mitochondrial mutation. No mutation was found among spouses and paternal relatives. Audiological results showed notable symmetric bilateral sensorineural hearing loss in 17 of 20 maternal relatives, in which 5 cases had a progressive hearing loss in the recent 11 years. The age of appearance of hearing loss ranged from 1 to 50 years. CONCLUSION: All hearing-impaired subjects of this family had late-onset sensorineural hearing loss. Most of which were progressive. The A1555G mitochondrial mutation in the 12S rRNA gene is responsible for the disorder. Other factors, such as nuclear genes or environmental determinants, may influence the clinical expression of mutant mtDNA.

Acoustic Impedance Tests↗

[Whole genome-wide scanning for a large pedigree with matrilineal deafness].

OBJECTIVE: To search responsible nuclear genes for matrilineal non-syndromic deafness. METHODS: Whole genome-wide scanning was performed to analyze the 365 short tandem repeats in a deaf pedigree with maternal inheritance using DNA pooling strategy. Frequencies of allele in one patient pool were compared with that in one unaffected relative pool as well as in one normal control pool. Linkage analysis was also conducted in some positive loci. RESULTS: Allele from 45 loci occurred more frequently in the patient pool than that in the unaffected relative pool and the control pool. No linkage was found from any candidate locus investigated. CONCLUSION: 45 positive loci obtained from this family may be as the candidate positions for matrilineal non-syndromic deafness.

Deafness↗

The use of ATP and initiating nucleotides during postrecruitment steps at the activated adenovirus E4 promoter.

Permanganate probing has been used to follow the progress and ATP dependence of promoter opening during activated adenovirus E4 initiation and clearance. Using templates designed to restrict synthesis to defined positions, formation of a 3-nucleotide-long RNA was found to be sufficient to trigger expansion of the initial transcription bubble. This occurred by a discrete transition that expanded the downstream limit of melting from position 1 to 15. Subsequent clearance of the bubble from the promoter region also occurred without detectable intermediates. Thus, initial opening, extension, and the clearance of the promoter bubble appear to occur as discrete, unique transitions. The apparent K(m) values for these three steps were determined to be near 5, 9, and 50 microM, respectively. Comparison of these values with ATPase activities within known transcription factors raises the possibility that different activities could be responsible for each step.

Adenosine Triphosphate↗

Sex differences in brain gray and white matter in healthy young adults: correlations with cognitive performance.

Sex-related differences in behavior are extensive, but their neuroanatomic substrate is unclear. Indirect perfusion data have suggested a higher percentage of gray matter (GM) in left hemisphere cortex and in women, but differences in volumes of the major cranial compartments have not been examined for the entire brain in association with cognitive performance. We used volumetric segmentation of dual echo (proton density and T2-weighted) magnetic resonance imaging (MRI) scans in healthy volunteers (40 men, 40 women) age 18-45. Supertentorial volume was segmented into GM, white matter (WM), and CSF. We confirmed that women have a higher percentage of GM, whereas men have a higher percentage of WM and of CSF. These differences sustained a correction for total intracranial volume. In men the slope of the relation between cranial volume and GM paralleled that for WM, whereas in women the increase in WM as a function of cranial volume was at a lower rate. In men the percentage of GM was higher in the left hemisphere, the percentage of WM was symmetric, and the percentage of CSF was higher in the right. Women showed no asymmetries. Both GM and WM volumes correlated moderately with global, verbal, and spatial performance across groups. However, the regression of cognitive performance and WM volume was significantly steeper in women. Because GM consists of the somatodendritic tissue of neurons whereas WM comprises myelinated connecting axons, the higher percentage of GM makes more tissue available for computation relative to transfer across distant regions. This could compensate for smaller intracranial space in women. Sex difference in the percentage and asymmetry of the principal cranial tissue volumes may contribute to differences in cognitive functioning.

Adolescent↗

mE10, a novel caspase recruitment domain-containing proapoptotic molecule.

Apoptotic signaling is mediated by homophilic interactions between conserved domains present in components of the death pathway. The death domain, death effector domain, and caspase recruitment domain (CARD) are examples of such interaction motifs. We have identified a novel mammalian CARD-containing adaptor molecule termed mE10 (mammalian E10). The N-terminal CARD of mE10 exhibits significant homology (47% identity and 64% similarity) to the CARD of a gene from Equine Herpesvirus type 2. The C-terminal region is unique. Overexpression of mE10 in MCF-7 human breast carcinoma cells induces apoptosis. Mutational analysis indicates that CARD-mediated mE10 oligomerization is essential for killing activity. The C terminus of mE10 bound to the zymogen form of caspase-9 and promoted its processing to the active dimeric species. Taken together, these data suggest a model where autoproteolytic activation of pro-caspase-9 is mediated by mE10-induced oligomerization.

Adaptor Proteins, Signal Transducing↗

Altered trafficking and turnover of LAMP-1 in Pompe disease-affected cells.

The lysosome-associated membrane protein (LAMP-1) is elevated in the cells and plasma from lysosomal storage disorder-affected individuals; however, the mechanism of this elevation is not well defined. In this study we have investigated the synthesis, glycoprocessing, trafficking, and turnover of LAMP-1 in human skin fibroblasts from Pompe disease patients and control individuals. There were similar levels of LAMP-1 synthesis in both cell types, but glycoprocessing was retarded in Pompe (T1/2 = 25 min) compared to control (T1/2 = 17 min) fibroblasts. There was also a marked delay in trafficking of LAMP-1 to lysosomes of Pompe (T1/2 = 200 min) compared to control (T1/2 = 100 min) cells. A proportion of newly synthesized LAMP-1 (5.4% in Pompe and 8.5% in controls) was trafficked out of the cell (T1/2 = 3.5 h in controls) and, although significantly smaller than the lysosomal form, still had a transmembrane domain and cytoplasmic tail. In contrast, a soluble lysosomal pool of LAMP-1 had no tail sequence, suggesting that it had been clipped from the membrane. In turnover studies, LAMP-1 was more stable in Pompe (T1/2 = 4.9 days) compared to control (T1/2 = 1. 6 days) cells, implying either reduced proteolysis or lysosomal function, in Pompe cells. These results indicate altered traffic and turnover of LAMP-1 in storage disorders and identify different intracellular and extracellular pools of soluble LAMP-1, suggesting alternative trafficking pathways.

Amino Acid Sequence↗

Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32).

Mucosa-associated lymphoid tissue (MALT) lymphomas most frequently involve the gastrointestinal tract and are the most common subset of extranodal non-Hodgkin lymphoma (NHL). Here we describe overexpression of BCL10, a novel apoptotic signalling gene that encodes an amino-terminal caspase recruitment domain (CARD), in MALT lymphomas due to the recurrent t(1;14)(p22;q32). BCL10 cDNAs from t(1;14)-positive MALT tumours contained a variety of mutations, most resulting in truncations either in or carboxy terminal to the CARD. Wild-type BCL10 activated NF-kappaB but induced apoptosis of MCF7 and 293 cells. CARD-truncation mutants were unable to induce cell death or activate NF-kappaB, whereas mutants with C-terminal truncations retained NF-kappaB activation but did not induce apoptosis. Mutant BCL10 overexpression might have a twofold lymphomagenic effect: loss of BCL10 pro-apoptosis may confer a survival advantage to MALT B-cells, and constitutive NF-kappaB activation may provide both anti-apoptotic and proliferative signals mediated via its transcriptional targets.

Adaptor Proteins, Signal Transducing↗

Multiple functional P2X and P2Y receptors in the luminal and basolateral membranes of pancreatic duct cells.

Purinergic receptors in the basolateral and luminal membranes of the pancreatic duct can act by a feedback mechanism to coordinate transport activity in the two membranes during ductal secretion. The goal of the present work was to identify and localize the functional P2 receptors (P2R) in the rat pancreatic duct. The lack of selective agonists and/or antagonists for any of the cloned P2R dictated the use of molecular and functional approaches to the characterization of ductal P2R. For the molecular studies, RNA was prepared from microdissected pancreatic intralobular ducts and was shown to be free of mRNA for amylase and endothelial nitric oxide synthase (markers for acinar and endothelial cells, respectively). A new procedure is described to obtain an enriched preparation of single duct cells suitable for electrophysiological studies. Localization of P2R was achieved by testing the effect of various P2R agonists on intracellular Ca(2+) concentration ([Ca(2+)](i)) of microperfused intralobular ducts. RT-PCR analysis suggested the expression of six subtypes of P2R in the pancreatic duct: three P2YR and three P2XR. Activation of Cl(-) current by various nucleotides and coupling of the receptors activated by these nucleotides to G proteins confirmed the expression of multiple P2R in duct cells. Measurement of [Ca(2+)](i) in microperfused intralobular ducts suggested the expression of P2X(1)R, P2X(4)R, probably P2X(7)R, and as yet unidentified P2YR, possibly P2Y(1)R, in the basolateral membrane. Expression of P2Y(2)R, P2Y(4)R, and P2X(7)R was found in the luminal membrane. The unprecedented expression of such a variety of P2R in one cell type, many capable of activating Cl(-) channels, suggests that these receptors may have an important role in pancreatic duct cell function.

Animals↗

[An extensive matrilineal nonsyndromic sensorineural deafness family and mtDNA 12SrRNA gene mutation].

OBJECTIVE: To investigate the possible cause and molecular genetic mechanism of matrilineal nonsyndromic sensorineural deafness, the authors analyzed an extensive matrilineal nonsyndromic sensorineural deafness family. METHODS: PCR amplification of the nt1555 and nt7445 of the mitochondrial DNA, combined with PCR-SSCP, PCR-RFLP and sequence to analyze the family. RESULTS: The authors found a homoplasmic A to G transition at position 1555(A1555G) of the mitochondrial 12SrRNA gene from all the patients, and four matrilineal relatives of this family, but the mutation was not found in the normal spouses of the family and controls (100 normal persons). CONCLUSION: The A1555G mutation may be one of the major factors that cause deafness in this family.

DNA, Mitochondrial↗

Amplified fragment length polymorphism analysis on D5S436 locus and its application to linkage analysis in gene diagnosis of asthma.

OBJECTIVES: To detect the polymorphism of D5S436 locus, and to carry out an amplified fragment length polymorphism (Amp-FLP) genotyping linkage analysis in asthma families. METHODS: Allele and genotype frequencies of the high polymorphic D5S436 locus were determined in 92 unrelated Chinese individuals by using polymerase chain reaction (PCR). The amplified fragments were separated by denaturing polyacrylamide gel electrophoresis and silver staining techniques. RESULTS: Eight alleles and 22 genotypes were observed in this population. The heterozygosity was 78.26%. The polymorphism information content (PIC) was 0.76. Amp-FLP genotyping linkage analyses were carried out in four asthma families, demonstrating that the locus was inherited according to Mendel's law and had a clear result. CONCLUSION: The PIC of D5S436 is high in Chinese individuals, so it could be used as a genetic marker of asthma in Chinese and might be useful in the gene diagnosis of asthma.

Alleles↗

[Effect of alum on intestinal microecological balance in mice].

OBJECTIVE: To observe the degree of microecological imbalance induced by alum in normal intestine of mice, and the bacterial adherence activity in the intestine of the mice administered orally with alum. METHODS: The mice were medicated orally with alum of small and large doses (0.25 g/kg and 1 g/kg) for 8 weeks, then 5 weeks after stopping administration of alum, microflora analysis and bacterial adherence to intestinal mucosal epithelial cells were carried out respectively. RESULTS: Eight weeks after administration with alum, the counts of Bifidobacteria and Lactobacilli decreased significantly, but the numbers of pathogenetic E. Coli increased significantly. The adherence rate of Bifidobacteria to the enterocytes of mice reduced markedly, but E. Coli was on the contrary of Bifidobacteria. Five weeks after the ceasing of medication, the intestinal flora were balanced, the adherence rate of both strains as mentioned above recovered to normal level. CONCLUSION: The imbalance of intestinal flora of mice administered with alum for a long time were only the transient change of bacterial counts. The imbalance of intestinal flora and the adherence rate of bacteria regained normal status five weeks after cancelling action factor.

Alum Compounds↗