Biomedical subjects

M Yan

Publications and source records attributed to M Yan.

At least 55 records · Page 3Linked to original sources

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

[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↗

PubMed1999

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↗

PubMed1999

[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↗

PubMed1999

[Construction of porous hydroxyapatite (HA) block loaded with cultured chondrocytes].

OBJECTIVE: To construct a kind of bone healing enhancing implant with cultured chondrocytes bound to hydroxyapatite (HA). METHODS: Chondrocytes were obtained from the costicartilage of rat and were cultured on the porous HA blocks, 3 mm x 3 mm x 4 mm size, for three and seven days. Scanning electron micrograph was taken to show whether the cells grew outside and inside the pore of HA block. The cells cultured on tiny glass sheet for 2 days were used to prove where the cells come from by in situ hybridization technique with alpha1 (II) cDNA probe. RESULTS: Scanning electron micrographs showed that the pores of the HA surface and inside of the blocks are filled with cultured cells, especially the longer cultured block. The cells were chondrocytes confirmed by in situ hybridization. CONCLUSION: The porous HA can be used as cell cultured substrate and chondrocyte can adhere and proliferate inside the porous HA block.

Animals↗

PubMed1998

Membrane-limited expression and regulation of Na+-H+ exchanger isoforms by P2 receptors in the rat submandibular gland duct.

1. Cell-specific reverse transcriptase-polymerase chain reaction (RT-PCR), immunolocalization and microspectrofluorometry were used to identify and localize the Na+-H+ exchanger (NHE) isoforms expressed in the submandibular gland (SMG) acinar and duct cells and their regulation by basolateral and luminal P2 receptors in the duct. 2. The molecular and immunofluorescence analysis showed that SMG acinar and duct cells expressed NHE1 in the basolateral membrane (BLM). Duct cells also expressed NHE2 and NHE3 in the luminal membrane (LM). 3. Expression of NHE3 was unequivocally established by the absence of staining in SMG from NHE3 knockout mice. NHE3 was expressed in the LM and in subluminal regions of the duct. 4. Measurement of the inhibition of NHE activity by the amiloride analogue HOE 694 (HOE) suggested expression of NHE1-like activity in the BLM and NHE2-like activity in the LM of the SMG duct. Several acute and chronic treatments tested failed to activate NHE activity with low affinity for HOE as expected for NHE3. Hence, the physiological function and role of NHE3 in the SMG duct is not clear at present. 5. Activation of P2 receptors resulted in activation of an NHE-independent, luminal H+ transport pathway that markedly and rapidly acidified the cells. This pathway could be blocked by luminal but not basolateral Ba2+. 6. Stimulation of P2U receptors expressed in the BLM activated largely NHE1-like activity, and stimulation of P2Z receptors expressed in the LM activated largely NHE2-like activity. 7. The interrelation between basolateral and luminal NHE activities and their respective regulation by P2U and P2Z receptors can be used to co-ordinate membrane transport events in the LM and BLM during active Na+ reabsorption by the SMG duct.

Adenosine Triphosphate↗

PubMed1998

Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation.

Vascular endothelial growth factor (VEGF) has been found to have various functions on endothelial cells, the most prominent of which is the induction of proliferation and differentiation. In this report we demonstrate that VEGF or a mutant, selectively binding to the Flk-1/KDR receptor, displayed high levels of survival activity, whereas Flt-1-specific ligands failed to promote survival of serum-starved primary human endothelial cells. This activity was blocked by the phosphatidylinositol 3'-kinase (PI3-kinase)-specific inhibitors wortmannin and LY294002. Endothelial cells cultured in the presence of VEGF and the Flk-1/KDR-selective VEGF mutant induced phosphorylation of the serine-threonine kinase Akt in a PI3-kinase-dependent manner. Akt activation was not detected in response to stimulation with placenta growth factor or an Flt-1-selective VEGF mutant. Furthermore, a constitutively active Akt was sufficient to promote survival of serum-starved endothelial cells in transient transfection experiments. In contrast, overexpression of a dominant-negative form of Akt blocked the survival effect of VEGF. These findings identify the Flk-1/KDR receptor and the PI3-kinase/Akt signal transduction pathway as crucial elements in the processes leading to endothelial cell survival induced by VEGF. Inhibition of apoptosis may represent a major aspect of the regulatory activity of VEGF on the vascular endothelium.

Amino Acid Chloromethyl Ketones↗

PubMed1998

An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits.

Patients with abetalipoproteinemia, a disease caused by defects in the microsomal triglyceride transfer protein (MTP), do not produce apolipoprotein B-containing lipoproteins. It was hypothesized that small molecule inhibitors of MTP would prevent the assembly and secretion of these atherogenic lipoproteins. To test this hypothesis, two compounds identified in a high-throughput screen for MTP inhibitors were used to direct the synthesis of a highly potent MTP inhibitor. This molecule (compound 9) inhibited the production of lipoprotein particles in rodent models and normalized plasma lipoprotein levels in Watanabe-heritable hyperlipidemic (WHHL) rabbits, which are a model for human homozygous familial hypercholesterolemia. These results suggest that compound 9, or derivatives thereof, has potential applications for the therapeutic lowering of atherogenic lipoprotein levels in humans.

Alanine Transaminase↗

PubMed1998

A novel approach to distinguish between intron-containing and intronless genes based on the format of Z curves.

A novel method to distinguish between intron-containing and intronless DNA sequences has been proposed, based on different statistic behaviors between them. In this method, DNA sequences are first represented as Z curves. Three exponents alpha, beta and gamma for each given sequence are calculated based on the format of the Z curve for the DNA sequence. A three-dimensional space is spanned by the three exponents. Each DNA sequence may be represented by a point in this space. One hundred intronless and intron-containing genes, respectively, were selected randomly from the GenBank or EMBL database. It is shown that the 200 points are roughly distributed in different regions. The best separating plane to separate the two regions is obtained by using Fisher's discriminant algorithm. For any given sequence to be discriminated, calculate three exponents alpha, beta and gamma, corresponding to a point in the three-dimensional space. If the point is situated at the upper region of the separating plane, the sequence is discriminated as an intronless one; otherwise, the sequence is an intron-containing one. A test of the method for the sequences in an independent test set shows that the discriminant accuracy reaches as high as 89.0%.

Animals↗

PubMed1998

Regional gray matter, white matter, and cerebrospinal fluid distributions in schizophrenic patients, their siblings, and controls.

BACKGROUND: Cortical gray matter volume reductions and cerebrospinal fluid (CSF) volume increases are robust correlates of schizophrenia, but their sources have not been established conclusively. METHODS: Structured diagnostic interviews and magnetic resonance imaging scans of the brain were obtained on 75 psychotic probands (63 with schizophrenia and 12 with schizoaffective disorder), ascertained so as to be representative of all such probands in a Helsinki, Finland, birth cohort; 60 of their nonpsychotic full siblings; and 56 demographically similar control subjects without a personal or family history of treated psychiatric morbidity. RESULTS: Patients with schizophrenia and their siblings exhibited significant reductions in cortical gray matter volume and significant increases in sulcal CSF volume compared with controls. The patients, but not their siblings, also exhibited significant reductions in white matter volume and significant increases in ventricular CSF volume. Regional effects were most robust when component volumes were expressed as percentages of overall regional volumes; in this case, for patient and sibling groups, gray matter volume reductions and sulcal CSF volume increases were significantly more pronounced in the frontal and temporal lobes than in the remainder of the brain. None of the group differences varied significantly by sex or hemisphere. CONCLUSIONS: Structural alterations of the cerebral cortex, particularly in the frontal and temporal lobes, are present in patients with schizophrenia and in some of their siblings without schizophrenia; such changes are thus likely to reflect genetic (or shared environmental) effects. Ventricular enlargement is unique to the clinical phenotype and is thus likely to be affected primarily by nonshared causative factors.

Adult↗

PubMed1998

Jak-STAT pathway is involved in the induction of TNF-beta gene during stimulation by IL-2.

IL-2 is the major regulatory cytokine of the immune system. It plays a key role in T cell survival, growth and activation. IL-2 may induce the expression of multiple genes including some cytokine genes. The induction of these genes is triggered by different signal pathways, one of them being the Jak-STAT signal pathway. The genes regulated by this pathway remain to be determined. By studying IL-2-inducible genes, we have confirmed that the TNF-beta gene is one of the immediate early genes activated by IL-2. By analysis of the DNA sequences around 180-300 bases upstream of the transcription initiation point of the mouse TNF-beta gene, we demonstrate that there is a STAT5 binding site which is essential to the inducibility of the TNF-beta gene. Furthermore, in BA/F3 cells co-transfected with the STAT5A gene and IL-2R beta gene, the activation of the TNF-beta gene promoter by IL-2 was greatly promoted, whereas the TNF-beta gene promoter became IL-2-non-inducible if the STAT5A gene was substituted with a dominant negative STAT5A, i.e. a C-terminally truncated mutant. Taken together, our results show that the Jak-STAT signal pathway is involved in induction of the TNF-beta gene in cells stimulated by IL-2.

Animals↗

PubMed1998

Effects of micromolar concentrations of Mn, Mo, and Si on alpha1-adrenoceptor-mediated contraction in porcine coronary artery.

We studied the effects of trace elements, Mn, Mo, and Si, on vasoconstriction induced by norepinephrine (NE) or electrical field stimulation in isolated porcine right coronary arteries. Alpha1-adrenoceptor (AR) antagonist prazosin dose-despondently suppressed vasoconstriction in response to NE or field stimulation indicating an alpha1-AR mediated response. Mn, Mo, and Si at 0.3-3 micromol/L dose-despondently inhibited NE mediated contraction (all p < 0.05). In contrast, Mn, Mo, and Si at the same concentrations (0.3-3 micromol/L) enhanced the maximal contractile response to field stimulation in a dose-dependent manner (all p < 0.05), but these elements at 10 micromol/L suppressed the vasoconstrictive response. The results indicate that in porcine right coronary arteries, the alpha1-AR-mediated vasoconstriction by NE or electrical field stimulation was affected differently by micromolar concentrations of Mn, Mo, and Si and that the elements might facilitate NE release presynaptically but inhibit the contractile response postsynaptically.

Adrenergic alpha-Antagonists↗

PubMed1998

A new fourier transform approach for protein coding measure based on the format of the Z curve.

MOTIVATION: At the core of most protein gene-finding algorithms are the coding measures used to make a decision on coding/non-coding. Of the protein coding measures, the Fourier measure is one of the most important. However, due to the limited length of the windows usually used, the accuracy of the measure is not satisfactory. This paper is devoted to improving the accuracy by lengthening the sequence to amplify the periodicity of 3 in the coding regions. RESULTS: A new algorithm is presented called the lengthen-shuffle Fourier transform algorithm. For the same window length, the percentage accuracy of the new algorithm is 6-7% higher than that of the ordinary Fourier transform algorithm. The resulting percentage accuracy (average of specificity and sensitivity) of the new measure is 84.9% for the window length 162 bp. AVAILABILITY: The program is available on request fromC.-T. Zhang. CONTACT: ctzhang@tju.edu.cn

Algorithms↗

PubMed1998

Prediction of the helix/strand content of globular proteins based on their primary sequences.

An improved multiple linear regression method has been proposed to predict the content of alpha-helix and beta-strand of a globular protein based on its primary sequence. The amino acid composition and the auto-correlation functions based on the hydrophobicity profile of the primary sequence have been taken into account in the algorithm. The resubstitution test shows that the average absolute errors are 0.077 and 0.073 with the standard deviations 0.059 and 0.057 for the prediction of the content of alpha-helix and beta-strand, respectively. A stringent cross-validation test, i.e., the jackknife test, shows that the average absolute errors are 0.087 and 0.081 with the standard deviations 0.067 and 0.065 for the prediction of the content of alpha-helix and beta-strand, respectively. Both tests indicate the self-consistency and the extrapolating effectiveness of the new algorithm. This greatly improves on previous results (Eisenhaber,F., Imperiale,F., Argos,P. and Frommel,C., 1996, Proteins, 25, 157-168). Compared with other methods currently available, our method has the merits of simplicity and ease-of-use as well as a higher prediction accuracy. The only input of the method is the primary sequence of the query protein to be predicted. The program is available on request via e-mail: ctzhang@tju.edu.cn.

Amino Acid Sequence↗