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Biomedical subjects

G Liu

Publications and source records attributed to G Liu.

At least 127 records · Page 7Linked to original sources

Transcription of essential cell division genes is linked to chromosome replication in Escherichia coli.

Cell division normally follows the completion of each round of chromosome replication in Escherichia coli. Transcription of the essential cell division genes clustered at the mra region is shown here to depend on continuing chromosomal DNA replication. After chromosome replication was blocked by either nalidixic acid treatment or thymine starvation, the transcription of these cell division genes was repressed significantly. This suggests a way in which cell division is controlled by chromosome replication.

Bacterial Proteins↗

Evaluation of a single stage nitroglycerin tilt table test for diagnosis of neurally mediated syncope.

The purpose of this study was to compare clinical outcomes between a single stage head-up tilt table test (HUT) with infusion of 3.44 microg/kg per hour of nitroglycerin and a conventional multistage test with infusion of nitroglycerin from 1.72 microg/kg per hour to 5.16 microg/kg per hour in five successive stages. Thirty-seven patients with recurrent syncope underwent both tests in a prospective, randomized, crossoverfashion. During single stage HUT, a positive response occurred in 24 (64.9%) patients with unexplained syncope, an exaggerated response occurred in 3 (8.1%), a negative response in 7 (18.9%), and drug intolerance in 3 (8.1%). During the multistage HUT, these percentages were 62.2%, 16.2%, 13.5%, and 8.1%, respectively. Twenty healthy control subjects were involved in both tests, One of the control subjects had a positive response to single stage HUT, and two (10%) patients to multistage HUT. The duration of the test in single stage HUT was shorter than that in multistage HUT (8.6 +/- 10.3 vs 38.6 +/- 32.1 minutes, P < 0.01). The results showed that the single stage HUT was a fairly sensitive, specific, and a time-efficient test for provoking neurally mediated syncope.

Adolescent↗

Changes in plasma creatinine concentration after cardiac anesthesia with isoflurane, propofol, or sevoflurane: a randomized clinical trial.

BACKGROUND: Renal impairment often follows cardiac surgery. The authors investigated whether sevoflurane produces greater increases in plasma creatinine concentration than isoflurane or propofol after elective coronary artery surgery. METHODS: As part of maintenance anesthesia, including during cardiopulmonary bypass, patients were randomly allocated to receive one of three agents: isoflurane (n = 118), sevoflurane (n = 118), or propofol (n = 118). Fresh gas flows were 3 l/min. The preoperative plasma creatinine concentration was subtracted from the highest creatinine concentration in the first 3 postoperative days. A median maximum increase greater than 44 microM (0.5 mg/dl) was regarded as clinically important. Data were analyzed on an intention-to-treat basis. Subgroup analyses were performed on per-protocol patients and those with preoperative renal impairment (creatinine concentration > 130 microM [1.47 mg/dl] or urea > 7.7 mM [blood urea nitrogen, 21.6 mg/dl]). RESULTS: The differences between the groups were small, clinically unimportant, and not statistically significant for the primary analysis and subgroups. The proportions of patients with creatinine increases greater than 44 microM were 15% in the isoflurane group, 17% in the sevoflurane group, and 11% in the propofol group (P = 0.45). The median increases were 8 microM in the isoflurane group, 4 microM in the sevoflurane group, and 6 microM in the propofol group. The differences between the three median maximum increases were 1-4 microM (P > 0.45). In the subgroup with preoperative renal impairment, the median increases were 10 microM in the isoflurane group, 15 microM in the sevoflurane group, and 5 microM in the propofol group (P = 0.72). CONCLUSIONS: Sevoflurane did not produce greater increases in creatinine than isoflurane or propofol after elective coronary artery surgery.

Aged↗

The G to C polymorphism at -174 of the interleukin-6 gene is rare in a Southern Chinese population.

Interleukin-6 is thought to be involved in the pathogenesis of coal workers' pneumoconiosis. Recently, a functional G to C polymorphism at position -174 of the promoter of the IL-6 gene has been described. We examined the -174 polymorphisms in 259 retired Chinese men from Guangxi province (all retired coal miners). Only one GC heterozygous and no CC homozygous variants were found. Our results suggest that the frequency of the C allele in this Chinese population is lower than in Caucasian and east Indian populations.

5' Untranslated Regions↗

Targeted inactivation of the mecB gene, encoding cystathionine-gamma-lyase, shows that the reverse transsulfuration pathway is required for high-level cephalosporin biosynthesis in Acremonium chrysogenum C10 but not for methionine induction of the cephalosporin genes.

Targeted gene disruption efficiency in Acremonium chrysogenum was increased 10-fold by applying the double-marker enrichment technique to this filamentous fungus. Disruption of the mecB gene by the double-marker technique was achieved in 5% of the transformants screened. Mutants T6 and T24, obtained by gene replacement, showed an inactive mecB gene by Southern blot analysis and no cystathionine-gamma-lyase activity. These mutants exhibited lower cephalosporin production than that of the control strain, A. chrysogenum C10, in MDFA medium supplemented with methionine. However, there was no difference in cephalosporin production between parental strain A. chrysogenum C10 and the mutants T6 and T24 in Shen's defined fermentation medium (MDFA) without methionine. These results indicate that the supply of cysteine through the transsulfuration pathway is required for high-level cephalosporin biosynthesis but not for low-level production of this antibiotic in methionine-unsupplemented medium. Therefore, cysteine for cephalosporin biosynthesis in A. chrysogenum derives from the autotrophic (SH(2)) and the reverse transsulfuration pathways. Levels of methionine induction of the cephalosporin biosynthesis gene pcbC were identical in the parental strain and the mecB mutants, indicating that the induction effect is not mediated by cystathionine-gamma-lyase.

Acremonium↗

Notch1IC partially replaces EBNA2 function in B cells immortalized by Epstein-Barr virus.

Immortalization of B cells by Epstein-Barr virus (EBV) depends on the virally encoded EBNA2 protein. Although not related by sequence, the cellular Notch protein and EBNA2 share several biochemical and functional properties, such as interaction with CBF1 and the ability to activate transcription of a number of cellular and viral genes. Whether these similarities are coincidental or exemplify EBNA2 mimicry of evolutionarily conserved cellular signaling pathways is unclear. We therefore investigated whether activated forms of Notch could substitute for EBNA2 in maintaining the immortalized phenotype of EBV-infected B cells. To address this question, we devised a transcomplementation system using EREB2.5 cells. EREB2.5 cells are immortalized by EBV expressing a conditional estrogen receptor EBNA2 fusion protein (EREBNA2), and cellular proliferation is dependent on the availability of estrogen. Withdrawal of estrogen results in inactivation of EREBNA2, leading to growth arrest and eventually to cell death. Transduction of EREB2.5 cells with a lentiviral vector expressing wild-type EBNA2 rescued EREB2.5 cells from the growth-inhibitory effects of estrogen deprivation, in contrast to transduction with the lentivirus vector alone. EREB2.5 cells were also rescued by enforced expression of human Notch1IC after estrogen starvation, but this effect was restricted to cells expressing high levels of the transcription factor. Compared to wild-type EBNA2-expressing EREB2.5 cells, the Notch-expressing cells expanded more slowly after estrogen starvation, and once established, they continued to display a lower proliferation rate. Analysis of viral and cellular gene expression from transduced EREB2.5 cells after estrogen withdrawal indicated that both wild-type EBNA2- and Notch1IC-positive cells expressed c-Myc at levels similar to those found in parental EREB2.5 cells. However, the latter cells expressed LMP-1 far less efficiently than cells transduced with the wild-type EBNA2 gene. Cells rescued by either wild-type EBNA2 or Notch1IC expressed surface CD21 and CD23 proteins, but not CD10, indicating that induction of relevant type III latency markers was maintained. The data imply that both Notch and EBNA2 activate an important subset of cellular genes associated with type III latency and B-cell growth, while EBNA2 more efficiently induces important viral genes, such as LMP-1. Thus, exploitation of conserved Notch-related signaling pathways may represent a key mechanism by which EBNA2 contributes to EBV-induced cell immortalization.

B-Lymphocytes↗

Spectral karyotyping (SKY) of mouse meiotic chromosomes.

The spectral karyotyping procedure of in situ hybridization with chromosome-specific probes assigns a unique colour code to each of the 21 mouse mitotic chromosomes. We have adapted this procedure to meiotic prophase chromosomes, and the results show that each of the pachytene or metaphase I bivalents can be identified. This technique has the potential to recognize synaptic anomalies and chromosome-specific structural and behavioural characteristics. We confirm these potentials by the recognition of the heterologous synapsis of the X and Y chromosomes and by the variances of synaptonemal complex lengths for each of the colour-coded bivalents in eight prophase nuclei.

Animals↗

Characterization of euploid backcross progenies derived from interspecific hybrids between Oryza sativa and O. eichingeri by restriction fragment length polymorphism (RFLP) analysis and genomic in situ hybridization (GISH).

Restriction fragment length polymorphism (RFLP) analysis and GISH (genomic in situ hybridization) were performed on euploid plants derived from crosses between Oryza sativa (2n = 24, AA) and two brown planthopper-resistant accessions of O. eichingeri (2n = 24, CC). After screening with 164 RFLP markers, 60 of the 67 euploid plants were identified as introgression lines, each carrying 1-6 small O. eichingeri segments integrated on chromosomes 1, 2, 6, or 10. In the somatic chromosome preparations of F1 hybrid, O. eichingeri chromosomes, fluorescing greenish-yellow in the sequential GISH, appeared to be longer and to contain more heterochromatin than O. sativa ones, and this karyotypic polymorphism can be used to detect some introgressed O. eichingeri segments in euploid plants. In addition, GISH identification presented direct evidence for the transfer of small segments from O. eichingeri to O. sativa chromosome(s) which were subsequently recognized according to their condensation pattern, arm ratio, and chromosome length. The present results would contribute to the molecular mapping and selection of O. eichingeri--derived brown planthopper-resistant gene and positive yield QTLs.

Chromosome Mapping↗

Re-defining the chromatin loop domain.

It is commonly accepted that the loop domain represents the basic structural unit of eukaryotic chromatin associated with DNA replication, gene expression and higher order packaging. However, molecular-cytological information defining the loop domain is lacking. There are gaps in our knowledge of the loop structure and how it regulates gene expression. The combination of new data/reagents from the Human Genome Project plus the use of novel molecular cytological technology will provide answers. Here we briefly review the status of chromatin loop research and pose questions that need to be addressed. New experimental systems are also presented to target some long-standing issues regarding the structure and function of the chromatin loop domain and its relationship with the nuclear matrix. This new knowledge will have a profound impact for modern genetics and molecular medicine.

Animals↗

The combination of SKY and specific loci detection with FISH or immunostaining.

Spectral karyotyping (SKY) represents an effective tool to detect individual chromosomes and analyze major karyotype abnormalities within an entire genome. We have tested the feasibility of combining SKY and FISH/protein detection in order to combine SKY's unique abilities with specific loci detection. Our experimental results demonstrate that various combined protocols involving SKY, FISH and immunostaining work well when proper procedures are used. This combined approach allows the tracking of key genes or targeted chromosome regions while monitoring changes throughout the whole genome. It is particularly useful when simultaneously monitoring the behavior of both protein complexes and DNA loci within the genome. The details of this methodology are described and systematically tested in this communication.

Animals↗

Complete heart block and sudden death in mice overexpressing calreticulin.

The expression of calreticulin, a Ca(2+)-binding chaperone of the endoplasmic reticulum, is elevated in the embryonic heart, and because of impaired cardiac development, knockout of the Calreticulin gene is lethal during embryogenesis. The elevated expression is downregulated after birth. Here we have investigated the physiological consequences of continued high expression of calreticulin in the postnatal heart, by producing transgenic mice that overexpress the protein in the heart. These transgenic animals exhibit decreased systolic function and inward I(Ca,L), low levels of connexin43 and connexin40, sinus bradycardia, and prolonged atrioventricular (AV) node conduction followed by complete heart block and sudden death. We conclude that postnatal downregulation of calreticulin is essential in the development of the cardiac conductive system, in particular in the sinus and AV nodes, when an inward Ca(2+) current is required for activation. This work identifies a novel pathway of events, leading to complete heart block and sudden cardiac death, which involves high expression of calreticulin in the heart.

Animals↗

Adenovirus-directed expression of functional luteinizing hormone (LH) receptors in undifferentiated rat granulosa cells: evidence for differential signaling through follicle-stimulating hormone and LH receptors.

This study was conducted to determine the feasibility of using replication-defective adenovirus vectors to express receptors for LH. Two vectors were constructed, one that directs the expression of wild-type human LH receptor (LHr; AdRSVLHrwt) and another that directs the expression of the constitutively activated D578H mutant human LH receptor (AdRSVD578HLHr). When infected with AdRSVwtLHr and AdRSVD578HLHr, COS-1 cells expressed LH/hCG-binding sites as reflected by specific binding of [(125)I]hCG. To determine the ability of the vectors to confer LH responsiveness, undifferentiated rat granulosa cells, which possess only FSH receptors, were infected with AdRSVwtLHr and AdRSVD578HLHR: Expression of the constitutively activated D578H LHr increased basal (gonadotropin-independent) estrogen and progesterone production. Expression of the wild-type LHr in granulosa cells did not stimulate basal steroid production, but conferred responsiveness to exogenous LH. For both wild-type LHr and D578HLHr, the absolute levels of steroid production were dependent upon the input of viral titers. Using these vectors, we compared effects of FSH and LH receptor activation in undifferentiated granulosa cells. Stimulation of undifferentiated granulosa cells by FSH and D578HLHr, as well as activation of wild-type LHr with LH resulted in comparable production of progesterone. In contrast, estradiol production in cells stimulated with FSH was greater than that in cells that expressed either D578H receptors or wild-type LHr in the presence of LH. Analysis of messenger RNAs (mRNAs) revealed that activations of FSH and the LH receptors were comparable in the induction of alpha-inhibin and 3betahydroxysteroid dehydrogenase mRNAS: However, activation of FSH receptor led to significantly greater expression of P450 aromatase and LHr mRNAs than did activation of LHR: These results suggest that activation of FSH and LH receptors in granulosa cells may differ with respect to activating intracellular signaling pathways and stimulating gene expression.

8-Bromo Cyclic Adenosine Monophosphate↗

Genetic variation in the promoter region of the beta2 bradykinin receptor gene is associated with essential hypertension in a Chinese Han population.

The present study examined whether a genetic variant (-58T/C) in the promoter region of the human beta2 bradykinin receptor gene was genetically involved in essential hypertension. Chinese hypertensive subjects (n = 120) and normotensive controls (n = 98; sex- and age-matched with hypertensives) were recruited from the outpatients of Fu Wai hospital. Distribution of the -58T/C polymorphism was determined in patients and controls by means of PCR, SSCP, cloning and sequencing. The allelic frequencies were 0.56 for the C allele and 0.44 for the T allele in hypertensive subjects, and 0.46 for the C allele and 0.54 for the T allele in normotensive subjects. The allelic frequencies were in Hardy-Weinberg equilibrium. Significant differences between hypertensive and normotensive subjects were seen in the genotypes distribution (p = 0.045) and allelic frequencies (p = 0.033). These results suggested that -58C allele of the human beta2 bradykinin receptor gene may be an independent risk factor for essential hypertension in the Chinese Han population.

Aged↗

Clinical trial of arotinolol in the treatment of hypertension: dippers vs. non-dippers.

To compare the effects of an alpha, beta blocker, arotinolol, in the treatment of essential hypertension between patients with a dipper and those with a non-dipper profile by means of 24-h ambulatory blood pressure monitoring (ABPM), a multicenter single blind parallel trial was carried out in five clinical centers. After a one-week single blind placebo run-in period, the patients underwent ABPM if their clinic diastolic blood pressure (DBP) ranged from 90-109 mmHg and their clinic systolic blood pressure (SBP) was <180 mmHg. They were divided into two groups according to the absence (non-dipper group, 24 cases) or presence (dipper group, 23 cases) of nocturnal BP reduction > or =10% of daytime BP. ABPM was measured again at the end of the active treatment phase. All patients were given Arotinolol 10-20 mg twice daily for 4 weeks. Twenty four-hour systolic and diastolic average BPs (MSBP, MDBP), 24-h systolic and diastolic blood pressure load (LS BP, LDBP), daytime systolic and diastolic average BPs (dMSBP, dMDBP), daytime systolic and diastolic blood pressure load (dLSBP, dLDBP), nighttime systolic and diastolic average BPs (nMSBP, nMDBP) and nighttime systolic and diastolic blood pressure load (nLSBP, nLDBP) were calculated. Arotinolol was effective in 78.2% of dippers and 54.2% of non-dippers, but the difference in effectiveness between these groups was not statistically significant. After treatment, SBP and DBP-including 24-h, daytime and nighttime systolic and diastolic BPs- were significantly reduced in both groups. During the daytime period, the systolic and diastolic blood pressures were significantly reduced in both dippers and non-dippers, while nighttime systolic and diastolic blood pressures were significantly reduced only in the non-dipper group. No significant changes were found in the dipper group over this period. In conclusion, Arotinolol, which can be dosed twice daily, is an effective antihypertensive agent which effectively lowers blood pressure during the day while reducing nighttime blood pressure more in non-dippers than in dippers, without excessive lowering blood pressure in the latter.

Adrenergic beta-Antagonists↗

Genome screen for quantitative trait loci underlying normal variation in femoral structure.

Femoral structure contributes to bone strength at the proximal femur and predicts hip fracture risk independently of bone mass. Quantitative components of femoral structure are highly heritable traits. To identify genetic loci underlying variation in these structural phenotypes, we conducted an autosomal genome screen in 309 white sister pairs. Seven structural variables were measured from femoral radiographs and used in multipoint sib-pair linkage analyses. Three chromosomal regions were identified with significant evidence of linkage (log10 of the odds ratio [LOD] > 3.6) to at least one femoral structure phenotype. The maximum LOD score of 4.3 was obtained for femur neck axis length on chromosome 5q. Evidence of linkage to chromosome 4q was found with both femur neck axis length (LOD = 3.9) and midfemur width (LOD = 3.5). Significant evidence of linkage also was found to chromosome 17q, with a LOD score of 3.6 for femur head width. Two additional chromosomal regions 3q and 19p gave suggestive (LOD > 2.2) evidence of linkage with at least two of the structure phenotypes. Chromosome 3 showed evidence of linkage with pelvic axis length (LOD = 3.1), midfemur width (LOD = 2.8), and femur head width (LOD = 2.3), spanning a broad (60 cm) region of chromosome 3q. Linkage to chromosome 19 was supported by two phenotypes, femur neck axis length (LOD = 2.8) and femur head width (LOD = 2.8). This study is the first genome screen for loci underlying variation in femoral structure and represents an important step toward identifying genes contributing to the risk of osteoporotic hip fracture in the general population.

Adult↗

Variability in skeletal mass, structure, and biomechanical properties among inbred strains of rats.

The aim of this study was to assess the usefulness of the inbred rat model for studies of genetic influences on skeletal fragility. We characterized bone mass, geometry, and skeletal biomechanics in 11 inbred strains of rats. This study showed that considerable variation exists in bone structure, areal bone mineral density (aBMD), and fragility phenotypes among inbred strains of rats. Interestingly, the variability in skeletal phenotypes in rats was site specific, suggesting that no single gene regulates skeletal fragility at all sites. For instance, the Copenhagen 2331 (COP) strain had the greatest biomechanical properties in the femoral neck but only modest bone strength at the femoral midshaft, compared with other strains. Consequently, COP rats appear to have alleles that specifically enhance femoral neck biomechanical properties and may serve as a model for studying genetic influences on hip strength. The Brown Norway (BN) and Fischer 344 (F344) strains may provide models for vertebral fragility because each has relatively fragile lumbar vertebrae. The F344 rats also had the most fragile femora and, thus, appear to carry alleles that cause overall skeletal fragility. We identified two inbred rat crosses that will facilitate the study of genetic influences on skeletal fragility at clinically relevant skeletal sites: Lewis (LEW) with F344 (primarily for vertebral fragility) and COP with DA (primarily for femoral neck fragility). The results strongly suggest that selected crosses of inbred strains of rats will provide useful models for studying genetic influences on bone strength and structure.

Animals↗

Cholecystokinin expression in the developing and regenerating pancreas and intestine.

In developmental terms, the endocrine system of neither the gut nor the pancreatic islets has been characterized fully. Little is known about the involvement of cholecystokinin (CCK), a gut hormone, involved in regulating the secretion of pancreatic hormones, and pancreatic growth. Here, we tracked CCK-expressing cells in the intestines and pancreata of normal mice (BALB/c), Non Obese Diabetic (NOD) mice and interferon (IFN)-gamma transgenic mice, which exhibit pancreatic regeneration, during embryonic development, the postnatal period and adulthood. We also questioned whether IFN-gamma influences the expression of CCK. The results from embryonic day 16 showed that all three strains had CCK in the acinar region of pancreata, and specifically in alpha cells that also expressed glucagon. However, in adulthood only BALB/c and NOD mice continued this pattern. By contrast, in IFN-gamma transgenic mice, CCK expression was suppressed from birth to 3 months of age in the pancreata but not intestines. However, by 5 months of age, CCK expression appeared in the regenerating pancreatic ductal region of IFN-gamma transgenic mice. In the intestine, CCK expression persisted from fetus to adulthood and was not influenced by IFN-gamma. Intestinal cells expressing CCK did not co-express glucagon, suggesting that these cells are phenotypically distinct from CCK-expressing cells in the pancreatic islets, and the effect of IFN-gamma on CCK varies depending upon the cytokine's specific microenvironment.

Animals↗

Hepatitis B virus transgenic mice for the model of anti-hepatitis B virus drug study.

OBJECTIVE: To establish hepatitis B virus (HBV) transgenic mice models and to investigate if the model can be used for the evaluation of anti-HBV drugs. METHODS: HBV transgenic mice models were produced by microinjection to analyze the integration, expression of HBV in the transgenic mice by nested PCR, southern blot, immunohistochemistry, and ELISA. Sixty mice whose HBV DNA, HBsAg were positive were divided into 6 groups randomly, in which 3 groups were given drugs: lamivudine administrated by perfusion of stomach tube (100mg x kg(-1) x day(-1) for 21 days); thymosine administrated by abdomen injection (3mg x day(-1) for 90 days); and DNA vaccine of 100 microg by muscle injection. The other 3 groups were negative control. RESULTS: Lamivudine, thymosine and DNA vaccine made HBV DNA become negative in the serum of HBV transgenic mice. The negative ratio was highest in lamivudine treatment group. HBV DNA became positive again when lamivudine terminated. CONCLUSION: Limvudine, thymosine, and DNA vaccine can inhibit HBV replication. Transgenic mice might be used as the model for anti-HBV drug screening and evaluation.

Animals↗