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Biomedical subjects

F Jiang

Publications and source records attributed to F Jiang.

At least 55 records · Page 3Linked to original sources

Beneficial effect of ginseng root in SOD-1 (G93A) transgenic mice.

Many patients with amyotrophic lateral sclerosis (ALS; motor neuron disease) use natural or traditional therapies of unproven benefit. One such therapy is ginseng root. However, in some other disease models, ginseng has proven efficacious. Ginseng improves learning and memory in rats, and reduces neuronal death following transient cerebral ischemia. These effects of ginseng have been related to increases in the expression of nerve growth factor and its high affinity receptor in the rat brain, and antioxidant actions, inter alia. Since such actions could be beneficial in ALS as well, we studied the effect of ginseng (Panax quinquefolium), 40 and 80 mg/Kg, in B6SJL-TgN(SOD1-G93A)1Gur transgenic mice. The ginseng was given in drinking water, from age 30d onwards. We measured the time to onset of signs of motor impairment, and survival. There was no difference between the two ginseng groups (n=6, 6) in either measure. However, compared to controls (n=13), there was a prolongation in onset of signs (116d vs. 94d, P<0.001), and survival (139d vs. 132d, P<0.05). These experiments lend support to the use of ginseng root in ALS. Future experiments using this model could examine for symptomatic effects of ginseng, measure the effect of specific ginsenosides (which differ between ginseng species), and elucidate their mechanisms of action.

Amyotrophic Lateral Sclerosis↗

Examination of the transcription factor NtcA-binding motif by in vitro selection of DNA sequences from a random library.

A recursive in vitro selection among random DNA sequences was used for analysis of the cyanobacterial transcription factor NtcA-binding motifs. An eight-base palindromic sequence, TGTA-(N(8))-TACA, was found to be the optimal NtcA-binding sequence. The more divergent the binding sequences, compared to this consensus sequence, the lower the NtcA affinity. The second and third bases in each four-nucleotide half of the consensus sequence were crucial for NtcA binding, and they were in general highly conserved. The most frequently occurring sequence in the middle weakly conserved region was similar to that of the NtcA-binding motif of the Anabaena sp. strain PCC 7120 glnA gene, previously known to have high affinity for NtcA. This indicates that the middle sequences were selected for high NtcA affinity. Analysis of natural NtcA-binding motifs showed that these could be classified into two groups based on differences in recognition consensus sequences. It is suggested that NtcA naturally recognizes different DNA-binding motifs, or has differential affinities to these sequences under different physiological conditions.

Bacterial Proteins↗

YidC mediates membrane protein insertion in bacteria.

The basic machinery for the translocation of proteins into or across membranes is remarkably conserved from Escherichia coli to humans. In eukaryotes, proteins are inserted into the endoplasmic reticulum using the signal recognition particle (SRP) and the SRP receptor, as well as the integral membrane Sec61 trimeric complex (composed of alpha, beta and gamma subunits). In bacteria, most proteins are inserted by a related pathway that includes the SRP homologue Ffh, the SRP receptor FtsY, and the SecYEG trimeric complex, where Y and E are related to the Sec61 alpha and gamma subunits, respectively. Proteins in bacteria that exhibit no dependence on the Sec translocase were previously thought to insert into the membrane directly without the aid of a protein machinery. Here we show that membrane insertion of two Sec-independent proteins requires YidC. YidC is essential for E. coli viability and homologues are present in mitochondria and chloroplasts. Depletion of YidC also interferes with insertion of Sec-dependent membrane proteins, but it has only a minor effect on the export of secretory proteins. These results provide evidence for an additional component of the translocation machinery that is specialized for the integration of membrane proteins.

ATP-Binding Cassette Transporters↗

Absence of cardiolipin in the crd1 null mutant results in decreased mitochondrial membrane potential and reduced mitochondrial function.

Cardiolipin (CL) is a unique phospholipid which is present throughout the eukaryotic kingdom and is localized in mitochondrial membranes. Saccharomyces cerevisiae cells containing a disruption of CRD1, the structural gene encoding CL synthase, have no CL in mitochondrial membranes. To elucidate the physiological role of CL, we compared mitochondrial functions in the crd1Delta mutant and isogenic wild type. The crd1Delta mutant loses viability at elevated temperature, and prolonged culture at 37 degrees C leads to loss of the mitochondrial genome. Mutant membranes have increased phosphatidylglycerol (PG) when grown in a nonfermentable carbon source but have almost no detectable PG in medium containing glucose. In glucose-grown cells, maximum respiratory rate, ATPase and cytochrome oxidase activities, and protein import are deficient in the mutant. The ADP/ATP carrier is defective even during growth in a nonfermentable carbon source. The mitochondrial membrane potential is decreased in mutant cells. The decrease is more pronounced in glucose-grown cells, which lack PG, but is also apparent in membranes containing PG (i.e. in nonfermentable carbon sources). We propose that CL is required for maintaining the mitochondrial membrane potential and that reduced membrane potential in the absence of CL leads to defects in protein import and other mitochondrial functions.

Cardiolipins↗

Understanding the insertion of transporters and other membrane proteins.

Recent studies show that transporters integrate into the lipid bilayer using topogenic sequences present throughout the entire polypeptide chain. These topogenic sequences can act in unpredictable ways with new translocation/stop transfer activities. In addition, a new membrane-insertion pathway has been identified in bacteria with homologs in mitochondria and chloroplasts.

Biological Transport↗

The multifocal electroretinogram in age-related maculopathies.

To measure and compare the multifocal electroretinogram in control group and patients with age-related maculopathies, 17 eyes of control subjects, 9 eyes of wet-form ARMD, 8 eyes of dry-form ARMD and 14 eyes of idiopathic macular hole were tested with VERIS Sciences 4.0. The latencies and average response densities of 6 ring retinal regions in control eyes were compared with those in ARMD and macular hole. The amplitude depression and latency prolongation were found in age-related maculopathies. The changes of multifocal ERG were dramatic in wet-form ARMD and moderate in dry-form ARMD and IMH, which were correspondent with the pathological changes of the diseases. Our results suggest that the multifocal electroretinogram can be used to quantity the visual function in age-related maculopathies.

Aged↗

A syndrome of tricuspid atresia in mice with a targeted mutation of the gene encoding Fog-2.

Tricuspid atresia (TA) is a common form of congenital heart disease, accounting for 1-3% of congenital cardiac disorders. TA is characterized by the congenital agenesis of the tricuspid valve connecting the right atrium to the right ventricle and both an atrial septal defect (ASD) and a ventricular septal defect (VSD). Some patients also have pulmonic stenosis, persistence of a left-sided superior vena cava or transposition of the great arteries. Most cases of TA are sporadic, but familial occurrences with disease in multiple siblings have been reported. Gata4 is a zinc-finger transcription factor with a role in early cardiac development. Gata4-deficient mice fail to form a ventral heart tube and die of circulatory failure at embryonic day (E) 8.5 (refs 6,7). Zfpm2 (also known as Fog-2) is a multi-zinc-finger protein that is co-expressed with Gata4 in the developing heart beginning at E8.5 (refs 8-10). Zfpm2 interacts specifically with the N-terminal zinc finger of Gata4 and represses Gata4-dependent transcription. Here we use targeted mutagenesis to explore the role of Zfpm2 in normal cardiac development. Zfpm2-deficient mice died of congestive heart failure at E13 with a syndrome of tricuspid atresia that includes an absent tricuspid valve, a large ASD, a VSD, an elongated left ventricular outflow tract, rightward displacement of the aortic valve and pulmonic stenosis. These mice also display hypoplasia of the compact zone of the left ventricle. Our findings indicate the importance of Zfpm2 in the normal looping and septation of the heart and suggest a genetic basis for the syndrome of tricuspid atresia.

Animals↗

Mechanisms of nitric oxide-independent relaxations induced by carbachol and acetylcholine in rat isolated renal arteries.

1. In rat isolated renal artery segments contracted with 0.1 microM phenylephrine and in the presence of the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME), carbachol and acetylcholine produced endothelium-dependent relaxations. The mechanisms underlying these relaxations were studied. 2. These relaxations were not affected by ODQ (1H-[1,2,4]oxadiazolo[4,3, -a]quinoxalin-1-one) or indomethacin. In arteries contracted with 20 - 30 mM K(+), L-NAME-resistant relaxations induced by carbachol and acetylcholine were virtually absent. 3. The Na(+)-K(+) ATPase inhibitor ouabain reduced these relaxations in a concentration-dependent manner. 4. In K(+)-free media, addition of K(+) (5 mM) produced 90. 5+/-3.9% (n=3) relaxation of phenylephrine-induced tone. This relaxation was endothelium-independent and ouabain-sensitive. 5. Tetraethylammonium (TEA), charybdotoxin (ChTX) and iberiotoxin (IbTX) reduced the sensitivity of carbachol-induced relaxations, but did not change the maximal response. These relaxations were not altered by 4-aminopyridine (4-AP), glibenclamide or apamin. Acetylcholine (1 microM)-induced relaxation was reduced by ChTX, but not by TEA or IbTX. 6. The cytochrome P450 inhibitor miconazole, but not 17-octadecynoic acid, reduced the sensitivity of carbachol-induced relaxations, without changing the maximal response. 7. In conclusion, in rat isolated renal arteries, acetylcholine and carbachol produced a non-NO/non-PGI(2) relaxation which is mediated by an endothelium-derived hyperpolarizing factor (EDHF). This factor does not appear to be a cytochrome P450 metabolite. The inhibition by ouabain of these relaxations suggests the possible involvement of Na(+)-K(+) ATPase activation in EDHF responses, although other mechanisms cannot be totally ruled out.

Acetylcholine↗

Distance-based reconstruction of tree models for oncogenesis.

Comparative genomic hybridization (CGH) is a laboratory method to measure gains and losses in the copy number of chromosomal regions in tumor cells. It is hypothesized that certain DNA gains and losses are related to cancer progression and that the patterns of these changes are relevant to the clinical consequences of the cancer. It is therefore of interest to develop models which predict the occurrence of these events, as well as techniques for learning such models from CGH data. We continue our study of the mathematical foundations for inferring a model of tumor progression from a CGH data set that we started in Desper et al. (1999). In that paper, we proposed a class of probabilistic tree models and showed that an algorithm based on maximum-weight branching in a graph correctly infers the topology of the tree, under plausible assumptions. In this paper, we extend that work in the direction of the so-called distance-based trees, in which events are leaves of the tree, in the style of models common in phylogenetics. Then we show how to reconstruct the distance-based trees using tree-fitting algorithms developed by researchers in phylogenetics. The main advantages of the distance-based models are that 1) they represent information about co-occurrences of all pairs of events, instead of just some pairs, 2) they allow quantitative predictions about which events occur early in tumor progression, and 3) they bring into play the extensive methodology and software developed in the context of phylogenetics. We illustrate the distance-based tree method and how it complements the branching tree method, with a CGH data set for renal cancer.

Algorithms↗

MEKK1 activation of human estrogen receptor alpha and stimulation of the agonistic activity of 4-hydroxytamoxifen in endometrial and ovarian cancer cells.

Estrogens are mitogens that stimulate the growth of both normal and transformed epithelial cells of the female reproductive system. The effect of estrogens is mediated through the estrogen receptors, which are ligand-regulated transcription factors. Tamoxifen, a selective estrogen receptor modulator, functions as an estrogen receptor antagonist in breast but an agonist in uterus. In the current study, we show that coexpression of a constitutively active MEKK1, but not RAF or MEKK2, significantly increases the transcriptional activity of the receptor in endometrial and ovarian cancer cells. The expression of wild-type MEKK1 and an active Rac1, which functions upstream of MEKK1, also increased the activity of the receptor while coexpression of dominant negative MEKK1 blocked the Rac1 induction, indicating that endogenous MEKK1 is capable of activating the receptor. Additional experiments demonstrated that the MEKK1-induced activation was mediated through both Jun N-terminal kinases and p38/Hog1 and was independent of the known phosphorylation sites on the receptor. p38, but not Jun N-terminal kinases, efficiently phosphorylated the receptor in immunocomplex kinase assays, suggesting a differential involvement of the two kinases in the receptor activation. More importantly, the expression of the constitutively active MEKK1 increased the agonistic activity of 4-hydroxytamoxifen to a level comparable to that of 17beta-estradiol and fully blocked its antagonistic activity. These findings suggest that the uterine-specific agonistic activity of the tamoxifen compound may be determined by the status of kinases acting downstream of MEKK1.

Endometrial Neoplasms↗

Detection of chromosome 11q13 breakpoints by interphase fluorescence in situ hybridization. A useful ancillary method for the diagnosis of mantle cell lymphoma.

We assessed cytologic specimens from 11 mantle cell lymphomas (MCLs) and 32 other B-cell non-Hodgkin lymphomas (NHLs) for 11q13 breakpoints using a 2-color fluorescence in situ hybridization (FISH) assay that uses an 11q13 probe centered on the CCND1 gene and a centromeric chromosome 11 probe (CEP11). The number of nuclei in 200 cells were counted, and results were expressed as an 11q13/CEP11 ratio. All MCLs showed a high percentage of interphase nuclei with 3 or more 11q13 signals (mean, 74.8%; range 57%-90%). In contrast, in other B-cell NHLs the mean percentage of cells with 3 or more 11q13 signals was 9.2%. All MCLs had an elevated 11q13/CEP11 ratio (mean, 1.38). The mean ratio for other B-cell NHLs was 0.99. Two non-MCL cases, 1 large B-cell and 1 B-cell unclassified NHL, had high 11q13/CEP11 ratios of 1.15 and 1.30, respectively. Conventional cytogenetic analysis performed on the former case revealed a t(5;11)(q31;q13). Interphase FISH analysis using 11q13 and CEP11 probes is a convenient ancillary method for assisting in the diagnosis of MCL. This commercially available assay is simple to use on cytology or imprint specimens, and results can be obtained within 24 hours.

Adult↗

Suppressive effect of rebamipide, an antiulcer agent, against activation of human neutrophils exposed to formyl-methionyl-leucyl-phenylalanine.

Rebamipide, an antiulcer agent, has been shown to be able to prevent gastric mucosal injury resulting in part from activation of neutrophils. The mechanism of its suppressive action, however, remains to be established. The present study aimed to determine the effect of rebamipide on activation of isolated human neutrophils and to identify the signal transduction pathway involved in its regulation. In unstimulated cells, alkaline phosphatase activity was found residing in short rod-shaped intracellular granules. Upon stimulation with a chemotactic peptide formyl-methionyl-leucyl-phenylalanine, the granules fused to form elongated tubular structures and spherical vacuoles. Rebamipide inhibited reorganization of alkaline phosphatase-containing granules along with upregulation of alkaline phosphatase activity and CD16, a marker of the granules. It also suppressed chemotaxis, an increase in intracellular calcium ion concentration, and NADPH oxidase activation in cells stimulated with formyl-methionyl-leucyl-phenylalanine. In contrast, the drug showed no inhibitory action toward upregulation of alkaline phosphatase activity and CD16, and activation of NADPH oxidase in cells stimulated with phorbol myristate acetate, an activator of protein kinase C. These findings demonstrate that rebamipide exerts a broad spectrum of suppressive actions toward biological functions of human neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine, but not with phorbol myristate acetate, and suggest that the upstream point of protein kinase C is the signal transduction pathway involved in its regulation.

Alanine↗

[Cytogenetics and clinical studies of hematologic malignancies with 11q23 abnormalities in China].

OBJECTIVE: To evaluate the association between 11q23 abnormalities and the clinical, hematologic, prognostic aspects of hematologic malignancies. METHODS: A total of 6000 cases of hematologic malignancies from our hospital and near regions in China were investigated between October 1985 and November 1998. Chromosome preparations were made on bone marrow cells by using direct method and/or unstimulated short-term cultures. Karyotypes were analyzed by R-banding technique and expressed according to ISCN(1995). RESULTS: 11q23 abnormalities were found in 28 of 6000 cases with hematologic malignancies(0.47%). It may be separated into seven cytonetic categories: t(4;11)(q21;q23)(ten cases), t(11;19)(q23;p13)(five cases), t(9;11)(p12;q23)(two cases), t(10;11)(p15;q23)(two cases), t(6;11)(q27;q23) (one case), del(11)(q23)(seven cases), and t(11;?)(q23;?)(one case). The diagnoses included acute myeloid leukemia in 14 cases (M(2a), three; M(4), two; M(5a), one; M(5b), eight), acute lymphoblastic leukemia(ALL) in 10 cases, myelodysplastic syndrome in three cases and malignant histiocytosis in one case. All 10 cases with t(4;11) anomaly were ALL. Follow-up data were available for 22 of them. Their median survival was 113 days. The patients may be grouped according to the presence or absence of additional abnormalities and/or normal karyotype. The median survival was 75 days for five patients with 11q23 anomaly only, 18 days for two patients with 11q23 and additional abnormalities, 135 days for 10 patients with 11q23 anomaly, additional abnormalities and normal karyotype, and 150 days for 5 patients with 11q23 anomaly and normal karyotype. CONCLUSION: 11q23 abnormalities were mainly seen in ALL and acute monocytic leukemia. Their prognosis was very poor. Both additional abnormalities and lack of normal karyotype had adverse effects on the survival of patients. Thus, they represent a unique clinical-cytogenetic association. 11q23 abnormality; hematologic malignancy; acute monocytic leukemia; acute lymphoblastic leukemia; prognosis

Adolescent↗

The value of serum GPDA-F for the diagnosis of primary hepatocellular carcinoma.

OBJECTIVE: To investigate the role of glycylproline dipeptidyl aminopeptidase isoenzymes in the diagnosis of primary hepatocellular carcinoma (PHC). METHODS: We developed a stage gradient polyacrylamide gel electrophoresis system to separate serum GPDA isoenzymes. Total GPDA activities, alpha-fetoprotein, the sizes of tumors and alanine aminotransferase (ALT) activities were also measured simultaneously and the correlation between GPDA-F and these indices was analyzed. RESULTS: Serum GPDA was separated into two bands, namely fast band (GPDA-F) and slow band (GPDA-S). GPDA-F was negative in all healthy persons as well as in the patients with benign liver filling defects, while it was positive in 85.3% cases of PHC. Liver cirrhosis, chronic hepatitis, extrahepatic carcinoma and metastatic liver carcinoma had low positive rates. GPDA-F was positively correlated with serum total GPDA activities, but had no correlation with AFP and size of the tumors. There was the correlation between GPDA-F and ALT in benign liver diseases, but no correlation between GPDA-F and ALT in PHC. Serial measurements of serum GPDA-F showed that GPDA-F was persistently positive in PHC but might change into negative in benign liver diseases. Dynamic determination of GPDA-F might be helpful to differentiate true positive of PHC from false positive of benign liver diseases. CONCLUSION: GPDA-F is a new serum marker of PHC. Measurement of serum GPDA-F is of value for the diagnosis of PHC, especially for those at early stage or with negative AFP.

Alanine Transaminase↗

[The association and linkage analysis between the FcgammaR II a-131 and system lupus erythematosus].

OBJECTIVE: To shed light on the relationship between FcgammaR II a-131 and systemic lupus erythematosus(SLE) in southern Chinese Han population. METHODS: A population-based and family-based study was carried out. FcgammaR II a-131 of each subject was measured by using PCR-allele specific oligonucleotide hybridization(ASO) method. RESULTS: (1) The distribution of FcgammaR II A-131 genotype in cases is significantly different from that in controls (P<0.05). So is the frequency of FcgammaR II aR-131 allele (P < 0.01) which suggests that subjects who have R131 allele tend to be more susceptible to SLE. The subjects with R/R131 homozygous genotype have a higher risk of suffering from SLE. (2) The distribution of FcgammaR II a-131 varies in different races, with identical distribution type among Chinese and Japanese. (3) The results of family-based association analysis and transmitted/disequilibrium test(TDT) suggest that there is not any linkage evidence between FcgammaR II a-131 and SLE. Possibly, the sample size was too small to get positive result. CONCLUSION: This study suggests that FcgammaR II a-131 is a major factor predisposing to the development of SLE in southern Chinese Han population.

Alleles↗

[Ecological study on relationship between desertification process and vegetation dynamics in west of northeast China: vegetation classification].

Based on the data obtained from 72 plant community plots and 276 plant species in Hulunbeier Sandy Land and Kerqin Sandy Land in the northeast desertification region of China, TWINSPAN analysis was carried out. Meanwhile the practical classification result was obtained by Detrended correspondence Analysis (DCA). Under the vegetation classification principles of China, the vegetation classification system of the desertification regions in northeast China was preliminarily established, which includes 6 vegetation types, 11 subtypes, 40 formations, and 55 associations.

China↗

[Evaluation on soil anti-erodibility of soil and water conservation forest].

Indexes including organic matter content, water stable aggregate content, mean weight diameter of water stable aggregate, aggregate degree and disperse coefficient were selected to evaluate soil anti-erodibility of soil and water conservation forests component of different tree species at different ages. The results showed that soil and water conservation forest played an important role in improving soil anti-erodibility, especially to the topsoil. Compared with that of Chinese pine pure forests, Chinese pine-broadleaved mixed forests had higher soil organic matter content, and water stable aggregate content increased by 1.71%-38.53%, and soil anti-erodibility was also increased with increasing stand age.

China↗

[Morphological changes in canine heart after electrical injury].

OBJECTIVE: To observe the histomorphological changes in canine heart after electrical injury. METHODS: Light and electronic microscopes (LM, EM) were employed to observe the histomorphological changes in canine heart after electrical injury. RESULTS: There were swelling and deformation of pacemaker cells (p cells) and mitochondrial swelling and vacuolization in cardiac conduct system. The cardiac muscle cells in the atrial and the ventricular walls exhibited obvious swelling and deformation, blurred cross striation, intracytoplasmic structural destruction of myofibrils, messy microfilaments, mitochondrial swelling, vacuolization and even dissolution. Furthermore, there was also breaking and expanding of the intercalated disk between adjacent cardiac muscle cells. The gap junctions at sites of intercalated disk were disrupted. CONCLUSION: The pathomorphological characteristics of cardiac histological changes after electrical injury were similar to those of acute myocardial infarction.

Animals↗