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Biomedical subjects

L Wang

Publications and source records attributed to L Wang.

At least 1,261 records · Page 70Linked to original sources

Production of emotional facial expressions in European American, Japanese, and Chinese infants.

European American, Japanese, and Chinese 11-month-olds participated in emotion-inducing laboratory procedures. Facial responses were scored with BabyFACS, an anatomically based coding system. Overall, Chinese infants were less expressive than European American and Japanese infants. On measures of smiling and crying, Chinese infants scored lower than European American infants, whereas Japanese infants were similar to the European American infants or fell between the two other groups. Results suggest that differences in expressivity between European American and Chinese infants are more robust than those between European American and Japanese infants and that Chinese and Japanese infants can differ significantly. Cross-cultural differences were also found for some specific brow, cheek, and midface facial actions (e.g., brows lowered). These are discussed in terms of current controversies about infant affective facial expressions.

Child, Preschool↗

Tumour induction by methyl-nitroso-urea following preconceptional paternal contamination with plutonium-239.

We have investigated the possibility that transgenerational effects from preconceptional paternal irradiation (PPI) may render offspring more vulnerable to secondary exposure to an unrelated carcinogen. 239Pu (0, 128 or 256 Bq g(-1)) was administered by intravenous injection to male mice, 12 weeks before mating with normal females. Two strains of mouse were used -- CBA/H and BDF1. Haemopoietic spleen colony-forming units (CFU-S) and fibroblastoid colony-forming units (CFU-F), a component of their regulatory microenvironment, were assayed independently in individual offspring at 6, 12 and 19 weeks of age. Bone marrow and spleen from each of these mice were grown in suspension culture for 2 or 7 days for assessment of chromosomal aberrations. Female BDF1 were injected with methyl-nitroso-urea (MNU) as a secondary carcinogen at 10 weeks of age and monitored for onset of leukaemia/lymphoma. Mean values of CFU-S and CFU-F were unaffected by preconceptional paternal plutonium-239 (PP-239Pu), although for CFU-F in particular there was an apparent increase in variation between individual animals. There was significant evidence of an increase in chromosomal aberrations with dose in bone marrow but not in spleen. By 250 days, 68% of MNU-treated control animals (no PPI) had developed thymic lymphoma (62%) or leukaemia (38%). The first case arose 89 days after MNU administration. In the groups with PPI, leukaemia/lymphoma developed from 28 days earlier, rising to 90% by 250 days. Leukaemia (65%) now predominated over lymphoma (35%). This second generation excess of leukaemia appears to be the result of PPI and may be related to inherited changes that affect the development of haemopoietic stem cells.

Animals↗

Potentiation of E7 antisense RNA-induced antitumor immunity by co-delivery of IL-12 gene in HPV16 DNA-positive mouse tumor.

Down-regulation of oncogene expression by antisense-based gene therapy has been extensively studied, and in some cases, therapeutic effects have been demonstrated. We have previously shown that down-regulation of HPV16 E6 and E7 gene expression inhibited HPV DNA-positive C3 mouse tumor growth. Although not all of the tumor cells were transfected by pU6E7AS plasmid, complete tumor regression was achieved if the tumor size was small at the start of therapy in a syngeneic host. This suggests that some other antitumor mechanisms may be involved in addition to the direct down-regulation of HPV16 E7 oncogene expression by the antisense effect of E7AS. In the current study, we demonstrated that E7AS induces tumor cell apoptosis. More importantly, a strong antitumor immune response was elicited in the pU6E7AS-treated and tumor-regressed mice. There was no tumor growth after rechallenging the tumor-regressed mice with 1 million C3 cells. This E7AS-induced antitumor immune response was augmented by co-delivery of mIL-12 cytokine gene. The combination therapy strategy resulted in complete regression of 26 of 28 (93%) tumors. Only 12 of 31 (38%) tumors from the group treated with pU6E7AS alone and 14 of 28 (50%) tumors from the group treated with pCMVmIL-12 alone had completely regressed. Complete regression was also demonstrated in tumors located 1 cm from the treated tumors, which indicates that a systemic antitumor effect was induced by E7AS and mIL-12. Immunohistochemistry demonstrated that a significant amount of CD4+ and CD8+ cells infiltrated into tumors treated with pU6E7AS, pCMVmIL-12 and pU6E7AS+pCMVmIL-12. These data indicate that host immunity is an important factor for antisense-based gene therapy approach which can be further enhanced by combination with cytokine gene therapy.

Animals↗

Linkage and physical mapping of prolactin to porcine chromosome 7.

Comparative mapping studies between human and pig have shown that there is conserved synteny between human chromosome 6 and pig chromosomes 1 and 7, but some gene locations are not well established. Prolactin (PRL), an anterior pituitary hormone, has been mapped to human chromosome 6, and has tentatively mapped to pig chromosome 7 using Southern-RFLP analysis with a limited number of meioses. To confirm the assignment of prolactin to porcine chromosome 7 by physical and linkage analysis, pig cDNA and human genomic DNA sequences were used to design pig-specific PCR primers. The primers amplified a fragment of approximately 2.8 kb. Two polymorphic restriction sites were identified within this fragment with the restriction endonuclease BstUI. Prolactin was significantly linked to six markers on the published PiGMaP map of pig chromosome 7. Prolactin was physically mapped using a pig x rodent somatic cell hybrid panel. An analysis of these data placed PRL on pig 7p1.1-p1.2 with 100% concordance and was in complete agreement with the linkage data. Both mapping techniques placed PRL in a conserved order with the loci in the syntenic region of human chromosome 6.

Animals↗

Mapping of the natural resistance-associated macrophage protein 1 (NRAMP1) gene to pig chromosome 15.

The natural resistance-associated macrophage protein 1 (NRAMP1) was mapped in the pig for study as a potential candidate gene in controlling pig resistance to Salmonella infection. Primers were designed from the pig cDNA to amplify a 1.6 kb fragment between exons 1 and 3. By using a pig-rodent somatic cell hybrid panel, NRAMP1 was mapped to pig chromosome 15 (SSC15) with 100% probability, and the regional assignment was SSC15q23-26 with 87% concordance. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) marker was developed by using the HinfI enzyme and three alleles were identified from a population including 11 breeds. Linkage analysis confirmed the physical assignment by using the PiGMaP reference families. Pig NRAMP1 was linked to SSC15 markers S0088, S0149 and S0284 (LOD > 3). A small population study revealed large allele frequency differences among tested breeds. An A allele is only observed in dam (white) lines whereas a similar exclusivity of the C allele was seen in sire (colored) breeds.

Alleles↗

Mapping of calpastatin and three microsatellites to porcine chromosome 2q2.1-q2.4.

Three polymorphisms were identified in a 1.6-kb fragment of the porcine calpastatin (CAST) gene and these polymorphisms were used for genetic linkage mapping. Linkage analysis revealed significant linkage of CAST to five microsatellites previously mapped to porcine chromosome 2; these microsatellites were S0010, S0226, SWI4, Sw395 and Sw776. A somatic cell hybrid panel was used to determine the chromosomal localization of CAST and the microsatellites S0091, S0226 and Sw395. All of these were localized to the region 2q2.1-q2.4.

Animals↗

FtsK is an essential cell division protein that is localized to the septum and induced as part of the SOS response.

The role of ftsK in the growth of Escherichia coli was examined by turning off its expression. This resulted in smooth filaments without constrictions, indicating that FtsK was required at an early step in septation. Consistent with this, FtsK was found to localize to the septum in 70% of the cells, indicating that it was recruited relatively early in this process. FtsK localization required the function of FtsZ and FtsA but not FtsI and FtsQ. Consistent with this, Z rings were present in FtsK-depleted filaments. Subcellular localization of FtsK confirmed that it was a membrane protein. Only the first 202 amino acids of FtsK were essential for its role in membrane localization, cell division and viability. The expression of ftsK increased as part of the SOS response, and increased expression of ftsK conferred increased resistance to DNA damage.

Bacterial Proteins↗

Ssa1p chaperone interacts with the guanine nucleotide exchange factor of ras Cdc25p and controls the cAMP pathway in Saccharomyces cerevisiae.

We have found that the guanine nucleotide exchange factor for ras, Cdc25p, interacts with Ssa1p in Saccharomyces cerevisiae. This interaction was observed with GST-fused Cdc25p polypeptides and confirmed by coimmunoprecipitation with the endogenous Cdc25p. Hsp82 appeared also to be co-immunoprecipitated with Cdc25p, albeit to a lower level than Hsp70. In a strain deleted for SSA1 and SSA2, we observed a reduced cellular content of Cdc25p. Consistent with a reduced activity of the cAMP-dependent PKA pathway, the rate of accumulation of both trehalose and glycogen was stimulated in the ssa-deleted strain. Expression of SSA1 reversed these effects, whereas co-expression of SSA1 and PDE2 restored high accumulation. The expression of genes repressed by cAMP, GAC1 and TPS1, fused to beta-galactosidase, was also stimulated by deletion of SSA genes. The effect of ssa deletion on glycogen accumulation was lost in a strain deleted for CDC25 rescued by the RAS2ile152 allele. Altogether, these results lead to the conclusion that Ssa1p positively controls the cAMP pathway through Cdc25p. We propose that this connection plays a critical role in the adaptation of cells to stress conditions.

Adenosine Triphosphatases↗

Transposase binding site methylation in the epigenetically inactivated Ac derivative Ds-cy.

The authors have determined the C-methylation pattern of the non-autonomous transposable element Ds-cy, which is an epigenetically inactivated, transcriptionally silent derivative of the maize Activator (Ac) element. Like Ac, Ds-cy is hypermethylated at the 3-end. However, in Ds-cy the 5-end is also hypermethylated, including all subterminal binding sites for the Ac-encoded transposase protein. As Ds-cy transposes in the presence of an active Ac in the genome, the authors conclude that methylation of the 5-end TPase binding sites does not interfere with transposition, but correlates with inactivity of the Ac promoter. the authors discuss the implications of these results for the chromatid selectivity of Ac/Ds transposition and the mechanism of Ac-induced chromosome breakage events.

Base Sequence↗

Quantitative techniques for lesion load measurement in multiple sclerosis: an assessment of the global threshold technique after non uniformity and histogram matching corrections.

The quantitative assessment of abnormalities on brain MRI (magnetic resonance imaging) in multiple sclerosis (MS) provides a widely used endpoint in monitoring treatment efficacy. Semi-automated intensity thresholding (global thresholding) is an established method of lesion segmentation, but it is limited by the heavy dependence of derived volumes on the chosen intensity threshold. Inconsistency in threshold choice substantially contributes to its suboptimal reproducibility. A potential improvement to global thresholding is to utilize the histogram matching algorithm to correct for variations in scanner sensitivity. This study evaluated whether or not a single intensity threshold could then be applied across multiple histogram matched images. Eight MS patients were scanned at baseline and after nine months. After non-uniformity correction, the histogram matching correction was applied, reducing the mean absolute percentage variation in normal appearing white matter signal intensity from 15.2 to 3.8% for baseline scans and from 11.9 to 2.1% across serial studies. Lesion volumes were measured with the global threshold technique using a single threshold selected from one scan. A local thresholding technique (contouring) was also performed as a gold standard measure. Agreement between techniques for baseline lesion volumes was only moderate with an intra-class correlation coefficient (ICC) of 0.46 and there was little agreement for change in lesion volume (ICC = 0.17), reflecting inconsistencies in the volume of non-lesion regions included by the threshold. Agreement was improved by deleting non-lesion regions, but this was time consuming and less reproducible than contouring method. At present, the contour technique remains a more appropriate method for lesion load quantification.

Journal Article↗

Epidermal expression of collagenase delays wound-healing in transgenic mice.

A vital characteristic of skin is its ability for wound repair in response to injury. A transient elevation of matrix metalloproteinases (MMP) in the epidermal and dermal compartments of healing wounds implicates the MMP family of enzymes in the regulation of events important to injury repair. Transgenic mice expressing human interstitial collagenase (MMP-1) in the epidermis were used to perturb the regulation of this proteinase in order to examine the role of epidermal collagenase during wound healing. The relative healing potential of collagenase transgenic mice and wild-type littermates was assessed by measurements of the wound area during closure of full-thickness wounds. Transgenic mice exhibited a 2-3 d delay in the time required to reach 50% closure of 6 mm wounds. Histologic analysis of the transgenic wound bed revealed the retarded migration of the epithelium across the open wound. The results are consistent with the hypothesis that control of collagenase (MMP-1) expression is important for re-epithelialization during wound healing and indicate that collagenase regulation is critical to the kinetics of normal wound closure.

Animals↗

Synergistic effect of dexamethasone and isoproterenol on the expression of angiotensinogen in immortalized rat proximal tubular cells.

To investigate whether the expression of angiotensinogen (ANG) in rat kidney proximal tubules is stimulated by dexamethasone and isoproterenol, immortalized rat proximal tubular cells (IRPTC) were cultured in a monolayer. Immunoreactive rat ANG (IR-rANG) in the culture medium was measured by a specific radioimmunoassay (RIA) for rANG. This RIA was developed by employing rabbit antiserum against the purified recombinant rat ANG (rANG). The purified rANG from plasma and the iodinated rANG were used as the hormone standard and tracer, respectively. The RIA is specific for rat ANG and it has no cross-reactivity with other pituitary hormone preparations or other rat plasma proteins. The sensitivity of detection of the RIA is approximately 2 ng of rANG. The levels of IR-rANG in the culture media of IRPTC ranged from 2 to 5 ng/ml/24 hr/10(6) cells. The addition of dexamethasone (10(-13) to 10(-5) M) stimulated the expression and secretion of rANG from IRPTC in a dose-dependent manner, whereas the addition of isoproterenol alone had no effect. However, a combination of both dexamethasone and isoproterenol synergistically stimulated the expression and secretion of rANG by IRPTC. The synergistic effect of dexamethasone and isoproterenol was blocked by the presence of RU 486 (a glucocorticoid receptor antagonist) or propranolol (beta-adrenoceptor blocker). These studies suggest that the addition of dexamethasone and isoproterenol acts synergistically to stimulate the expression and secretion of ANG protein in rat proximal tubules in vivo.

Adrenergic beta-Agonists↗

Exposure to GB virus type C or hepatitis G virus in selected Australian adult and children populations.

BACKGROUND: The epidemiology and disease association for the GB virus type C (GBV-C) or hepatitis G virus (HGV) are poorly understood. STUDY DESIGN AND METHODS: This study describes the exposure rates to GBV-C/HGV in diverse Australian population groups by testing for current infection and evidence of past infection with a reverse transcriptase polymerase chain reaction and an anti-E2 enzyme-linked immunosorbent assay, respectively. Subjects included volunteer blood donors, hepatitis C antibody (anti-HCV)-positive donors, children, hemodialysis patients, pregnant women attending a prenatal clinic, injecting drug users (IVDUs), and adult hemophiliacs. RESULTS: Combined GBV-C RNA and E2 antibody prevalence was 6.5 percent (6/93) in children, 13.3 percent (75/565) in blood donors, 14 percent (14/99) in pregnant women, 22.5 percent (18/80) in hemodialysis patients, 80 percent (56/70) in anti-HCV-positive donors, 88.6 percent (31/35) in IVDUs, and 85.7 percent (54/63) in adult hemophiliacs. Children had the lowest antibody rate, 1.1 percent, whereas the rate was 10.8 percent for blood donors and rose to 45.7 percent for IVDUs, 57.1 percent for anti-HCV-positive donors, and 74.6 percent for hemophiliacs. In contrast, current infection rates were comparable for children, blood donors, and pregnant women (5.4, 2.6, and 6%, respectively), rising to 11.1 percent for hemophiliacs, 24.3 percent for anti-HCV-positive donors, and 48.6 percent for IVDUs. Ten of 12 blood donors had persistent viremia, while 2 had recent infections, 1 with apparent resolution. CONCLUSION: Exposure to GBV-C can commence at an early age, although ongoing exposure may also occur among adults with no apparent risk factors. GBV-C RNA positivity was not associated with abnormal plasma alanine aminotransferase levels among blood donors.

Adult↗

Glissadic saccades: a possible measure of vigilance.

Eight males and eight females participated in a 60-min visual signal detection task requiring saccadic eye movements. The waveforms of saccades were evaluated in terms of glissades, slow eye movements in saccade initiation and termination, as a function of time-on-task. Saccades were categorized as anticipatory, stimulus-elicited, and return saccades; as well as blink-concurrent versus blink-free. The results showed that, for blink-free saccades, the occurrence of glissadic saccades increased with time-on-task for anticipatory and return saccades, but not for stimulus-elicited saccades. Likelihood of blink-concurrent glissadic saccades did not change over time-on-task. The results suggest that an increase in anticipatory and return glissadic saccades over time-on-task may be an index of vigilance decrement.

Adult↗

Induction of lympho-haemopoietic malignancy: impact of preconception paternal irradiation.

PURPOSE: To investigate the effects of preconception paternal irradiation (PPI) from injected 239Pu on the susceptibility to induction of lympho-haemopoietic malignancy by subsequent irradiation or exposure to a chemical carcinogen. MATERIALS AND METHODS: The male CBA/H and DBA2 mouse was injected with 0, 128 or 256 Bqg(-1) 239Pu 12 weeks before mating with the normal CBA/H and C57B1 female respectively. CBA/H offspring were exposed to 3.3 Gy gamma-rays total body irradiation: BDF1 offspring were injected with 50 mg kg(-1) methyl nitrosourea (MNU). The offspring were assayed for changes in bone marrow progenitor cell numbers and chromosome aberrations and were followed up for subsequent induction of neoplasia. RESULTS: While the untreated mouse showed a normal distribution for cellularity, spleen colony-forming units (CFU-S) and fibroblastoid colony-forming units (CFU-F), significant numbers of PPI offspring presented levels outside the normal range. There was a tendency for them also to show increased, dose-related, levels of chromosomal aberrations. Offspring treated with irradiation or MNU developed an increased incidence of lympho-haemopoietic malignancies. CONCLUSIONS: These studies have shown that PPI results in offspring that are more susceptible to the induction of lymphohaemopoietic malignancy on encountering a secondary carcinogenic insult. This may be linked to inherited chromosomal instability and abnormal kinetics of haemopoiesis. The experiments indicate a potential mechanism by which an increased incidence of leukaemia may be linked to PPI.

Animals↗

A human B cell line AF10 expressing HIL-17.

AF10, a human B cell line, is a mycoplasma-free variant cloned from the human IgE myeloma cell line U266. Total RNA isolated from the AF10 cells was used as template for RT-PCR, and a specific product of about 411bp corresponding to the coding region of hIL-17 lack of a leading sequence obtained. The sequence of the RT-PCR product is the same to that reported in the literature. The expressed rhIL-17 in E. coli can induce 10- to 15-fold increase of IL-6 secretion by mouse fibroblast 3T3 cells. It is for the first time until now that hIL-17 messager has been detected in B cell. There may exist some potential relationship between hIL-17 and myeloma cells.

3T3 Cells↗

Constructing additive trees when the error is small.

We consider the problem of constructing an additive tree from a given matrix of pairwise distances, when observation errors are allowed. We give conditions under which the tree topology is unique and semi-unique. We also design an efficient algorithm to construct a tree when the error is relatively small.

Algorithms↗