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Biomedical subjects

Yan Yu

Publications and source records attributed to Yan Yu.

At least 37 records · Page 2Linked to original sources

In vivo cancer diagnosis with optical spectroscopy and acoustically induced blood stasis using a murine MCa35 model.

Ultrasound-induced blood stasis has been observed for more than 30 years. Most of the literature has been focused on the health risks associated with this phenomenon and methods employed to prevent stasis from occurring during ultrasound imaging. To date, experimental observations have been either in vitro or invasive. The current work demonstrates ultrasound-induced blood stasis in murine normal leg muscle versus tumor-bearing legs, observed through noninvasive measurements of optical spectroscopy, and discusses possible diagnostic uses for this previously undesirable effect of ultrasound. We demonstrate that, using optical spectroscopy, effects of ultrasound can be used to differentiate tumor from normal leg muscle tissue in mice. Finally, we propose a novel diagnostic algorithm that quantitatively differentiates tumor from nontumor with maximum specificity 0.83, maximum sensitivity 0.79, and area under receiver-operating-characteristics curve 0.90.

Animals↗

Vivo motion and force measurement of surgical needle intervention during prostate brachytherapy.

In this paper, we present needle insertion forces and motion trajectories measured during actual brachytherapy needle insertion while implanting radioactive seeds in the prostate glands of 20 different patients. The needle motion was captured using ultrasound images and a 6 degree-of-freedom electromagnetic-based position sensor. Needle velocity was computed from the position information and the corresponding time stamps. From in vivo data we found the maximum needle insertion forces to be about 15.6 and 8.9 N for 17 gauge (1.47 mm) and 18 gauge (1.27 mm) needles, respectively. Part of this difference in insertion forces is due to the needle size difference (17G and 18G) and the other part is due to the difference in tissue properties that are specific to the individual patient. Some transverse forces were observed, which are attributed to several factors such as tissue heterogeneity, organ movement, human factors in surgery, and the interaction between the template and the needle. However, theses insertion forces are significantly responsible for needle deviation from the desired trajectory and target movement. Therefore, a proper selection of needle and modulated velocity (translational and rotational) may reduce the tissue deformation and target movement by reducing insertion forces and thereby improve the seed delivery accuracy. The knowledge gleaned from this study promises to be useful for not only designing mechanical/robotic systems but also developing a predictive deformation model of the prostate and real-time adaptive controlling of the needle.

Brachytherapy↗

[Effect of treatment with ethyl pyruvate on multiple organ dysfunction and mortality following delayed resuscitation after burn injury in rat].

OBJECTIVE: To observe the effects of ethyl pyruvate (EP) treatment on multiple organ dysfunction and mortality following delayed resuscitation after burn injury in rat, and investigate the mechanisms of its protective effect. METHODS: Male Wistar rats were subjected to 30% full-thickness scald injury followed with delayed resuscitation (6 hours postburn). (1) One hundred and thirty male Wistar rats were randomly divided into sham scald group (n=10), scald group (n=60) and EP-treatment group (n=60). In the scald group, 40 ml/kg normal saline was injected intraperitoneally 6 hours after scald injury for resuscitation, and it was repeated periodically. Following delayed resuscitation after burn injury, EP was injected at a dose of 40 mg/kg every 12 hours in EP-treatment group for 3 days. According to the interventional time points, rats of scald and EP-treatment groups were respectively divided in three subgroups: 2 hours prior to scald (n=20), 2 hours after scald (n=20), and 12 hours after scald (n=20). The mortality of animals was observed with 7 days as the cut point. (2) Seventy male rats were randomly divided into sham scald group (n=10), scald group (n=30), and EP-treatment group (n=30). In EP-treatment group, 40 mg/kg EP was injected intraperitoneally 2 hours after scald. Animals were sacrificed at 12, 24, and 72 hours postburn, and serum samples were collected to determine the organ functional parameters, and lung tissue was obtained for measurement of myeloperoxidase (MPO) activity. RESULT: The 7-day mortality in scald and EP-treatment groups (EP given 12 hours postburn) was 75.0% and 35.0% respectively (P<0.05). Compared with scald group, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine (Cr) and creatine kinase (CK) levels were markedly decreased in EP-treatment group at 12 to 24 hours postburn (P<0.05 or P<0.01), and pulmonary MPO activities were also significantly declined at 12 to 72 hours following burns (P<0.05 or P<0.01). CONCLUSION: EP can obviously improve the outcome in rats with delayed resuscitation after burn injury, and prevent the development of multiple organ dysfunction secondary to major burns.

Animals↗

[Expression of NF-kappaB/IkappaB signal pathway in renal tissues of hepatitis B virus-associated nephritis].

AIM: To investigate the expression of nuclear transcription factor-kappa B (NF-kappaB)/IkappaB in renal tissues of hepatitis B virus-associated nephritis (HBVGN) and to study its role in the pathogenesis of HBVGN. METHODS: The expression of NF-kappaB p65 and IkappaB-alpha in renal tissues was examined in biopsy specimens from 42 HBVGN patients, 20 patients with primary membranous nephropathy and 5 normal subjects by immunohistochemical staining. RESULTS: The NF-kappaB p65 expression in glomerular and tubular of HBVGN tissues was notably higher than that in normal control tissues (P<0.05) and in primary membranous nephropathy tissues (P<0.01). The IkappaB-alpha expression in glomerular and tubular of HBVGN tissues was lower than that in primary membranous nephropathy tissues (P<0.05). CONCLUSION: There might be protein degradation of IkappaB-alpha and nuclear translocation of NF-kappaB in renal tissues of HBVGN, which suggests that NF-kappaB/IkappaB signal pathway may play an important role in the pathogenesis of HBVGN.

Adolescent↗

[Allelic loss of 6q16.3 microsatellite DNA in childhood acute lymphoblastic leukemia and bioinformatics analysis].

OBJECTIVE: To locate the cluster region of loss of heterozygosity (LOH) in children with acute lymphoblastic leukemia (ALL), and explore the new tumor suppressor gene. METHODS: Allelic loss was analyzed by PCR with 15 microsatellite markers mapping on 6q16.3. The LOH was analyzed by bioinformatics. The relationship between LOH and clinical factors was further analyzed. RESULTS: The frequency of LOH at least at one loci on 6q16.3 was 32.7%. The LOH in relapsed patients was higher than those in not relapsed. The higher frequency of LOH was observed in two regions of D6S1709-D6S1028 and D6S2160-D6S1580 at 6q16.3. GRIK2 may be a candidate of tumor suppressor gene. There are 12 ESTs may carry out new anti-oncogene. Patients with 6q LOH had higher WBC counts (P < 0.01), blast cells percentage (P < 0.01), relapse rate (P < 0.05) and chromosomal aberration (P < 0.05). CONCLUSION: D6S1709-D6S1028 and D6S2160-D6S1580 are two regions of minimus deletion on 6q16.3 in which tumor suppressor gene may exist. The LOH on 6q16.3 may be a prognostic index of children with ALL.

Adolescent↗

Bacterial genome adaptation to niches: divergence of the potential virulence genes in three Burkholderia species of different survival strategies.

BACKGROUND: Two closely related species Burkholderia mallei (Bm) and Burkholderia pseudomallei (Bp) are serious human health hazards and are potential bio-warfare agents, whereas another closely related species Burkholderia thailandensis (Bt) is a non-pathogenic saprophyte. To investigate the genomic factors resulting in such a dramatic difference, we first identified the Bm genes responsive to the mouse environment, and then examined the divergence of these genes in Bp and Bt. RESULTS: The genes down-expressed, which largely encode cell growth-related proteins, are conserved well in all three species, whereas those up-expressed, which include potential virulence genes, are less well conserved or absent notably in Bt. However, a substantial number of up-expressed genes is still conserved in Bt. Bm and Bp further diverged from each other in a small number of genes resulting from unit number changes in simple sequence repeats (ssr) in the homologs. CONCLUSION: Our data suggest that divergent evolution of a small set of genes, rather than acquisition or loss of pathogenic islands, is associated with the development of different life styles in these bacteria of similar genomic contents. Further divergence between Bm and Bp mediated by ssr changes may reflect different adaptive processes of Bm and Bp fine-tuning into their host environments.

Animals↗

Downregulation of MDM2 expression by RNAi inhibits LoVo human colorectal adenocarcinoma cells growth and the treatment of LoVo cells with mdm2siRNA3 enhances the sensitivity to cisplatin.

To investigate the biological effect of mdm2 in human colorectal adenocarcinoma LoVo cells, three mdm2siRNA constructions were recombined and transient transfected into human colorectal adenocarcinoma LoVo cells with low differentiation character in vitro. The results showed that mdm2siRNA3 reduced mRNA level of mdm2 and protein level of mdm2, leading to proliferation inhibition on LoVo cells, and reduced tumor growth in nude mice. It was found that depletion of MDM2 in this pattern promoted apoptosis of LoVo cells and Cisplatin (DDP) treated in the mdm2siRNA3 transfected cell population would result in a substantial decrease by MTT colorimetry. Decreasing the MDM2 protein level in LoVo cells by RNAi could significantly inhibit tumor growth both in vitro and in vivo, which indicated that mdm2 gene played a definite role in the development and aggressiveness of human colon carcinoma. It also could be a therapeutic target in colorectal carcinoma. The synergistic activation of RNAi and cell toxicity agents indicated that the combination of chemotherapy and gene therapy will be a promising approach in the future.

Adenocarcinoma↗

Growth factor expression following clinical mandibular distraction osteogenesis in humans and its comparison with existing animal studies.

AIM: Lengthening the mandible by distraction osteogenesis (DO) is nowadays a well recognized technique in maxillofacial surgery. In this study growth factor expression profiles were examined in biopsies taken from six patients undergoing mandibular DO and compared with findings from a sheep model for mandibular DO. STUDY DESIGN: In all patients (and sheep), the ascending ramus was distracted 10-15 mm at a rate of 1mm/day using an intraoral device. Biopsies were taken from the centre of the distraction zone 21 days after completion of distraction. Using standard immunohistochemical techniques, samples were stained for platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-beta), basic fibroblast growth factor (bFGF) and bone morphogenetic proteins-2, -4 and -7 (BMP-2, -4, -7), matrix metalloproteinases-1 and -3 (MMP-1, -3), the vascular endothelial growth factor (VEGF), a marker for endothelial cells (CD-31) and type IV collagen (Col IV). RESULTS: Positive staining for PDGF, bFGF, TGF-beta, BMP-2, -4, and -7 was noted in cells and matrix components. There was intense staining for MMP-1. Strong staining for CD-31 and COL IV was observed adjacent to vessels. VEGF staining was less specific. Similar findings were noted in the sheep model. CONCLUSION: Growth factor expression in the human distraction site is similar to that in the sheep model.

Adolescent↗

Genome-wide expression analysis of iron regulation in Burkholderia pseudomallei and Burkholderia mallei using DNA microarrays.

Burkholderia pseudomallei and B. mallei are the causative agents of melioidosis and glanders, respectively. As iron regulation of gene expression is common in bacteria, in the present studies, we have used microarray analysis to examine the effects of growth in different iron concentrations on the regulation of gene expression in B. pseudomallei and B. mallei. Gene expression profiles for these two bacterial species were similar under high and low iron growth conditions irrespective of growth phase. Growth in low iron led to reduced expression of genes encoding most respiratory metabolic systems and proteins of putative function, such as NADH-dehydrogenases, cytochrome oxidases, and ATP-synthases. In contrast, genes encoding siderophore-mediated iron transport, heme-hemin receptors, and a variety of metabolic enzymes for alternative metabolism were induced under low iron conditions. The overall gene expression profiles suggest that B. pseudomallei and B. mallei are able to adapt to the iron-restricted conditions in the host environment by up-regulating an iron-acquisition system and by using alternative metabolic pathways for energy production. The observations relative to the induction of specific metabolic enzymes during bacterial growth under low iron conditions warrants further experimentation.

Adaptation, Physiological↗

[The mechanisms of extracellular-signal regulated protein kinase pathway in biopterin induction in rats with endotoxic shock].

OBJECTIVE: To observe the influence of treatment with the inhibitor of extracellular-signal regulated protein kinase (ERK) signal transduction pathway on the expression of biopterin/nitric oxide (NO) as well as the activation of nuclear factor-kappaB (NF-kappaB), and to clarify the potential cross-talk regulation mechanisms between ERK and NF-kappaB pathway in biopterin-mediated NO induction in rats with endotoxic shock. METHODS: Using an endotoxic shock model, 60 male Wistar rats were randomly divided into normal controls (n = 8), endotoxic shock group (n = 32) and PD98059 treatment group (n = 20). At serial time points animals in each group were sacrificed, and tissue samples from liver, lungs as well as kidneys were harvested to detect NF-kappaB activity, guanosine triphosphate-cyclohydrolase (GTP-CHI) and inducible nitric oxide synthase (iNOS) mRNA expression. Biopterin and NO levels in plasma and tissues were also assayed. RESULTS: It was found that after lipopolysaccharide (LPS) challenge, GTP-CHI mRNA expression and biopterin levels significantly elevated in liver, lungs and kidneys, keeping at high values up to 24 h, so did the values of iNOS mRNA expression and NO levels. NF-kappaB DNA binding activity was enhanced rapidly in various tissues, peaking at 2 h after LPS challenge. Treatment with PD98059, an inhibitor of ERK signal transduction pathway, could significantly inhibit GTP-CHI mRNA expression in kidneys, and GTP-CHI mRNA expression in liver and lungs showed certain down-regulation tendency. At the same time, biopterin level was significantly decreased in plasma, liver and kidneys at 12 h. Similarly, iNOS/NO induction at early stage markedly decreased in various tissues. In addition, treatment with PD98059 reduced NF-kappaB DNA binding activity in liver, lungs, as well as kidneys at 2-6 h, 2 h, 24 h and 24 h after LPS challenge, respectively. CONCLUSIONS: Inhibition of ERK pathway could partially inhibit the production of biopterin/NO as well as the activation of NF-kappaB pathway, which indicated that cross-talk regulation seems to be existed between ERK and NF-kappaB pathway, and they might be involved in the regulatory process of biopterin-mediated nitric oxide induction in rats with endotoxic shock.

Animals↗

[CD14 genomic polymorphism influences CD14 expression in whole blood culture].

OBJECTIVE: To investigate whether -159C/T promoter polymorphism of the CD14 gene influences the CD14 expression as well as release in whole blood culture. METHODS: One hundred and eighteen healthy human blood donors were included in the present study. CD14 mRNA expression and soluble CD14 levels were measured using a whole blood cell culture model with or without lipopolysaccharide (LPS) stimulation. The CD14 gene polymorphism was determined by polymerase chain reaction and subsequent HaeIII restriction enzyme digestion of the polymerase chain reaction products. TNF-alpha production in the whole blood culture was also measured. RESULTS: Among the 118 individuals, there were 40 subjects homozygous for the T allele (TT), 62 were heterozygous (CT), and 16 had the genotype CC. The CD14 mRNA expression in leukocytes and soluble CD14 levels in supernatant were higher in TT homozygotes and carriers of the genotype TC compared with individuals homozygous for the C allele (P < 0.05 or 0.01). In addition, the highest values of TNF-alpha production were found in TT homozygote [(352 +/- 215) pg/ml] compared with both genotype TC and CC [(261 +/- 163) pg/ml, (198 +/- 122) pg/ml, both P < 0.05]. CONCLUSION: The -159C/T promoter polymorphism of the LPS receptor CD14 may influence the CD14 expression as well as release in whole blood culture, and it might be associated with TNF-alpha response to LPS stimulation.

Adolescent↗

Genetic diversity and geographic differentiation in endangered Ammopiptanthus (Leguminosae) populations in desert regions of northwest China as revealed by ISSR analysis.

BACKGROUND AND AIMS: The desert legume genus Ammopiptanthus comprises two currently endangered species, A. mongolicus and A. nanus. Genetic variability and genetic differentiation between the two species and within each species were examined. METHODS: Inter-simple sequence repeat (ISSR) marker data were obtained and analysed with respect to genetic diversity, structure and gene flow. KEY RESULTS: Despite the morphological similarity between A. mongolicus and A. nanus, the two species are genetically distinct from each other, indicated by 63 % species-specific bands. Low genetic variability was detected for both population level (Shannon indices of diversity Hpop = 0.106, percentage of polymorphic loci P = 18.55 % for A. mongolicus; Hpop = 0.070, P = 12.24 % for A. nanus) and species level (Hsp = 0.1832, P = 39.39 % for A. mongolicus; Hsp = 0.1026, P = 25.89 % for A. nanus). Moderate genetic differentiation was found based on different measures (AMOVA PhiST and Hickory B) in both A. mongolicus (0.3743-0.3744) and A. nanus (0.2162-0.2369). CONCLUSIONS: The significant genetic difference between the two species might be due to a possible vicariant evolutionary event from a single common ancestor through the fragmentation of their common ancestor's range. Conservation strategies for these two endangered species are proposed.

Analysis of Variance↗

A model for CD2/CD58-mediated adhesion strengthening.

Stable cell adhesion is vital for structural integrity and functional efficacy. Yet how low affinity adhesion molecules such as CD2 and CD58 can produce stable cell adhesion is still not completely understood. In this paper, we present a theoretical model that simulates the accumulation of CD2 and CD58 in the contact area of a Jurkat T lymphoblast and a CD58-containing substrate. The cell is assumed to have a spherical shape initially and it is allowed to spread gradually on a circular substrate. Mobile CD2 and CD58 can diffuse freely on both the cell and substrate. Their binding in the contact area is controlled by first-order kinetics. The contact area grows linearly with the total number of CD2/CD58 bonds. Cellular deformation and cytoskeleton involvement were not considered. This time-dependent moving-boundary problem was solved with the Crank-Nicolson finite difference scheme and the variable space grid method. Our simulated results are in reasonable agreement with the experimental observations. The role of diffusion becomes more and more prominent during the contact area increase, which is not sensitive to the kinetic rate constants tested in this study. However, it is very sensitive to the dissociation equilibrium constant and the concentrations of CD2 and CD58.

Adhesiveness↗

Bouquet brachytherapy: feasibility and optimization of conically spaced implants.

PURPOSE: To examine the dosimetric feasibility of a conical implantation approach to robotic-assisted prostate brachytherapy. METHODS AND MATERIALS: An in-house inverse planning software based on the genetic algorithm (GA) was used to optimize the needle angulations and the seed positions along needles that form one or two bouquets. Volume data from 20 prostate seed implant patients (six 125I and 14 103Pd) previously treated using the conventional rectilinear template approach were used. The dosimetry outcomes of the optimized treatment plan in the conical approach were compared with those from the original treatment plans based on the conventional rectilinear template approach. RESULTS: When seed spacing is restricted to nominal 1 cm center-to-center spacing, dosimetry results in the conical approach suffer from a higher urethra dose and higher dose heterogeneity compared with the original rectilinear template plans. When the seed loading patterns are optimized as part of inverse planning, the resulting dosimetry plans exhibit adequate dose coverage and uniformity through the target volume, as well as satisfactory sparing of the urethra and rectum. CONCLUSIONS: Conically spaced implantation for prostate brachytherapy with 125I and 103Pd seeds is feasible in terms of dosimetry outcomes. Techniques for optimized inverse planning for this approach have been developed.

Brachytherapy↗

Transcriptional divergence of the duplicated oxidative stress-responsive genes in the Arabidopsis genome.

Previous studies have indicated that Arabidopsis thaliana experienced a genome-wide duplication event shortly before its divergence from Brassica followed by extensive chromosomal rearrangements and deletions. While a large number of the duplicated genes have significantly diverged or lost their sister genes, we found 4222 pairs that are still highly conserved, and as a result had similar functional assignments during the annotation of the genome sequence. Using whole-genome DNA microarrays, we identified 906 duplicated gene pairs in which at least one member exhibited a significant response to oxidative stress. Among these, only 117 pairs were up- or down-regulated in both pairs and many of these exhibited dissimilar patterns of expression. Examination of the expression patterns of PAL1 and PAL2, ACD1 and ACD2, genes coding for two Hsp20s, various P450s, and electron transfer flavoproteins suggests Arabidopsis evolved a number of distinct oxidative stress response mechanisms using similar gene sets following the duplication of its genome.

Arabidopsis↗

[Effects of ethyl pyruvate on cell-mediated immune function in rats with delayed resuscitation after burn injury].

OBJECTIVE: To investigate the effects of ethyl pyruvate (EP) on cell-mediated immune function in rats with delayed resuscitation after burn injury, and its potential regulatory mechanism. METHODS: Wistar rats were subjected to 30% full-thickness scald injury with delayed resuscitation. One hundred and three male rats were randomly divided into normal controls (n=7), sham scald group (n=32), scald group (n=32) in which 40 ml/kg normal saline was infused peritoneally 6 hours after scald, and EP treatment group (n=32) in which 40 mg/kg EP was injected peritoneally 6 hours after scald. Animals were sacrificed on postburn day 1, 3, 5, and 7, and spleen was collected to determine splenocyte proliferation, IL-2 production and cell-surface IL-2 receptor (IL-2R) expression. RESULTS: Splenic lymphocyte proliferation responses to T cell mitogen, concanavalin A (Con A), were depressed from 1 to 7 days after scald injury (all P<0.05). Meanwhile, in comparison with sham scald group, burn injury resulted in a significant decrease in splenic production of IL-2 on postburn day 1, 3, as well as 5, and a marked suppression of IL-2R expression on days 1 and 3 postburn (all P<0.05). Treatment with EP after burn injury showed a dramatic restoration of lymphocyte proliferation rate and increased production of IL-2 at various time points (all P<0.05). However, treatment with EP did not affect IL-2R expression compared with scalded rats (all P>0.05). CONCLUSION: Treatment with EP could markedly elevate splenic T lymphocyte proliferation response and increase production of IL-2 following burn injury, thereby improving cell-mediated immunity in thermally injured rats with delayed resuscitation.

Animals↗