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Biomedical subjects

Y Yu

Publications and source records attributed to Y Yu.

At least 181 records · Page 10Linked to original sources

Artery and vein separation using susceptibility-dependent phase in contrast-enhanced MRA.

In magnetic resonance angiography, contrast agents are frequently used to help highlight arteries over background tissue. Unfortunately, enhancing veins hamper the visualization of arteries when data are collected over a long period of time after the arterial phase of the contrast agent. To overcome this problem, we have developed a novel imaging and postprocessing method that is capable of eliminating veins by utilizing the susceptibility difference between veins and surrounding tissue. This method was applied in the peripheral vasculature where the vessels are predominantly parallel to the main field and where the blood oxygen level-dependent effect is most pronounced. Results are presented for both long (15.8 msec) and short echo times (7.8 msec) and for sequential and centrally reordered acquisition schemes. The short echo scan approach appears to be the most promising, making it possible to obtain good suppression of the venous signal even when the timing is not perfect or when repeat scans are necessary.

Arteries↗

Human papillomavirus type 33 DNA in breast cancer in Chinese.

BACKGROUND: The association between human papillomavirus (HPV) and anogenital tumors, especially cervical cancer, is well documented. However, it remains unclear whether there is also a correlation between HPV infection and human breast cancer. METHODS: We used PCR and Southern blot hybridization to analyze HPV-related DNA specimens from 32 cases of invasive ductal carcinoma operated upon in the Shanghai region of China. RESULTS: DNA derived from HPV33 was detected in 14 cases (43.8%). No HPV16 or HPV18 DNA was detected in any of the cases in this study. This is the first report demonstrating a correlation between HPV33 infection and breast cancer. CONCLUSIONS: Our results suggest that HPV33 infection may be involved in the pathogenesis of breast cancer in Chinese.

Adult↗

In-vitro antibacterial activities of cefpiramide and other broad-spectrum antibiotics against 440 clinical isolates in China.

The in-vitro antibacterial activity of cefpiramide was compared with those of 15 other broad-spectrum cephalosporins. A total of 440 clinical strains of bacteria, including 9 bacterial species, were isolated from our hospital in 1998. The minimum inhibitory concentrations (MICs) of cefpiramide and five other antibiotics were determined for each species, using the agar-dilution method. The MIC of cefpiramide for Escherichia coli and Klebsiella pneumoniae was higher than those of three other third-generation cephalosporins, (ie, cefoperazone, ceftazidime, and ceftriaxone). Fifty-one percent (26/51) of Enterobacter cloacae isolates were resistant to cefpiramide. Cefoperazone/sulbactam and cefepime had greater activity against E. cloacae (resistance, 3.9% and 19.6%, respectively) than cefpiramide. Cefpiramide was more active against Pseudomonas aeruginosa (resistance rates, 12%) than cefoperazone, ceftazidime, ceftriaxone, aztreonam, and cefepime. Cefpiramide-resistant P. aeruginosa strains were resistant to ceftazidime, but 27% of ceftazidime-resistant strains were susceptible to cefpiramide; 15.3% of cefpiramide-resistant S. maltophilia strains were also susceptible to ceftazidime, but 50% of ceftazidime-resistant strains were still susceptible to cefpiramide. Cefoperazone/sulbactam was the most active agent against Acinetobacter baumannii, showing a resistance rate of 2%. Ampicillin/sulbactam, ceftazidime, and cefpiramide were the second most active agents, and about 50% of the tested strains were susceptible to these three antibiotics. Cefpiramide had an activity comparable to that of all tested beta-lactams against oxacillin-susceptible Staphylococcus aureus (MIC90, 2 microg/ml). Against Streptococcus pneumoniae and Haemophilus influenzae, cefpiramide had good activity, with an MIC90 concentration at which 90% of the strain was inhibited of 1 microg/ml and 0.5 microg/ml, respectively. These results indicated that cefpiramide was more active against glucose non-fermenting bacteria than against Enterobacteriaceae, and was very active against oxacillin-susceptible Staphylo-coccus aureus, S. pneumoniae, and H. influenzae. Thus, cefpiramide may be a good choice of drug for the treatment of patients with infections with glucose non-fermenting bacteria and community acquired infections.

Cefazolin↗

Role of nitric oxide in maintenance of basal oral tissue blood flow in anesthetized cats.

Experiments were undertaken to determine if nitric oxide (NO) plays a role in regulation of basal blood flow in the oral cavity of pentobarbital anesthetized cats and, if so, to quantify this effect using dose-response relationships. Blood flow was continuously measured from the surface of the tongue and mandibular gingiva (laser-Doppler flowmetry) and from the lingual artery (ultrasonic flowmetry). Cardiovascular parameters also were recorded. Administration of the nonselective inhibitor of nitric oxide synthase (NOS), L-NAME (0.08-20 mg/kg i.v.), produced a dose-related increase of blood pressure associated with decreases of blood flow at all three measurement sites. Maximal blood flow depression of 50-60% was seen 30-60 min after administration of 1.25 mg/kg of L-NAME. D-NAME (1.25 mg/kg i.v.) was inactive at all sites. Subsequent administration of L-arginine partially reversed effects of L-NAME in the lingual artery and tongue, but not in the gingival circulation. The neuronally selective NOS inhibitor, 7-nitroindazole (7-NI, 30 mg/kg i.p.), was devoid of effect on any of the measured parameters. These results suggest that endothelial (but not neuronally derived) NO plays an important role in control of basal blood flow in oral tissues of the cat.

Adjuvants, Anesthesia↗

Computational analysis of the high pass birdcage resonator: finite difference time domain simulations for high-field MRI.

In this work, a finite difference time domain (FDTD) algorithm is validated at 1.5 tesla using the standard GE Signa quadrature head coil and a muscle phantom. The electrical characteristics of the birdcage head coil are then calculated for the linear and quadrature cases. Unlike previous computational analysis which assume idealized currents on the end rings and the struts of the resonator, a complete computational analysis is provided. This treatment considers the coupling between the resonator and the sample and includes a real coil excitation, a complete current derivation, and a thorough description of both B(1) fields and RF radiation. With this improvement, electromagnetic phenomena such as radiation, standing wave currents on the wires, and field inhomogeneities due to interactions between the coil and the load inside the coil are observed. At 200 MHz, it is demonstrated that this particular coil does not work well due to radiation and non-uniformities on the struts of the device. Also, at this frequency magnetic field inhomogeneities become large when the coil is loaded with a phantom.

Computer Simulation↗

Multi-objective optimization in radiotherapy: applications to stereotactic radiosurgery and prostate brachytherapy.

Treatment planning for radiation therapy is a multi-objective optimization process. Here we present a machine intelligent scheme for treatment planning based on multi-objective decision analysis (MODA) and genetic algorithm (GA) optimization. Multi-objective ranking strategies are represented in the L(p) metric under the displaced ideal model. Goal setting, protocol satisficing and fuzzy ranking of objective importance can be incorporated into the decision scheme to assimilate clinical decision making. For distance measures in the L(p) metric, a dynamic gauge function is defined based on the state energy of the decision system, which is assumed to undergo thermodynamic cooling with iteration time. The MODA scheme interacts with a robust GA engine, which adaptively evolves in the multi-modal landscape that defines the treatment plan quality. A conventionally challenging case of stereotactic radiosurgery of a brain lesion was selected for GA optimization. The resulting dose distributions are compared to human-developed plans, which are commonly regarded as clinically relevant and empirically optimal. The GA-optimized plans achieve substantially better sparing of critical normal neuroanatomy surrounding the brain lesion while respecting the preset constraints on tumor dose uniformity. In addition, machine optimization tends to produce novel treatment strategies which complements expert knowledge. The run time for producing an optimal plan is considerably shorter than the typical planning time for human experts, thus GA can also be used to aid the human treatment planning process. In prostate brachytherapy, MODA-GA was specifically applied to non-ideal conditions in which typical surgical uncertainties in seed implant positioning occur, where noisy objectives were introduced into the optimization scheme. The noisy system is found to be manageable by MODA-GA at uncertainty levels corresponding to reasonably proficient surgery teams. In contrast, noisy objectives would be very difficult to explore by human expert planners. Potential use of noisy optimization with time series analysis is being explored for error-corrective computer guidance in the operating room for prostate seed implantation. In conclusion, the combination of MODA and GA optimization offers both a solution to practical treatment planning tasks and the potential for real time applications in radiotherapy.

Algorithms↗

Dominant negative mutants of the yeast splicing factor Prp2 map to a putative cleft region in the helicase domain of DExD/H-box proteins.

The Prp2 protein of Saccharomyces cerevisiae is an RNA-dependent ATPase required before the first transesterification reaction in pre-mRNA splicing. Prp2 binds to the spliceosome in the absence of ATP and is released following ATP hydrolysis. We determined what regions in Prp2 are essential for release from the spliceosome by analyzing dominant negative mutants in vivo and in vitro. We made mutations in conserved motif II (DExH) and motif VI (QRxGR) of the helicase (H) domain. Mutations that inactivated PRP2 had a dominant negative phenotype when overexpressed in vivo. To test whether mutations outside of the H domain could confer a dominant negative phenotype, we mutagenized a GAL1-PRP2 construct and screened for mutants unable to grow on galactose-containing media. Five dominant negative mutants were characterized; three mapped within the H domain and two mapped downstream of motif VI, indicating that an extended helicase domain is required for release of Prp2 from the spliceosome. Most mutants stalled in the spliceosome in vitro. However, not all mutants that were dominant negative in vivo were dominant negative in vitro, indicating that multiple mechanisms may cause a dominant negative phenotype. Structural modeling of the H domain of Prp2 suggests that mutants map to a cleft region found in helicases of known structure.

Adenosine Triphosphatases↗

Identification of oxidation products of (-)-epigallocatechin gallate and (-)-epigallocatechin with H(2)O(2).

(-)-Epigallocatechin gallate (EGCG) and (-)-epigallocatechin (EGC) are two important antioxidants in tea. They also display some antitumor activities, and these activities are believed to be mainly due to their antioxidative effects. However, the specific mechanisms of antioxidant action of tea catechins remain unclear. In this study are isolated and identified two novel reaction products of EGCG and one product of EGC when they were reacted separately with H(2)O(2). These products are formed by the oxidation and decarboxylation of the A ring in the catechin molecule. This study provides unequivocal proof that the A ring of EGCG and EGC may also be an antioxidant site. This study also indicates an additional reaction pathway for the oxidation chemistry of tea catechins.

Antioxidants↗

B-lymphocytes in CLL and NHL differ in the mRNA splicing pattern of the CD45 molecule.

In the present study the cell surface expression of CD45 isoforms on normal and neoplastic human B cells was correlated with splice products of the CD45 mRNA, using RT-PCR technology. In non-Hodgkin's lymphoma cells in the leukemic phase (NHL) the majority of the cells expressed a high level of CD45RA, while in CLL most of the cells expressed a low level. In the Raji and Daudi Burkitt B-cell lymphoma lines the main CD45 mRNA product was the largest, unspliced, full-length isoform (456) and the 56 splice product. Similar results were obtained with B-cell lymphoma cells isolated from the peripheral blood of patients with NHL in the leukemic phase. In EBV-transformed B-cell lines, the 456 and the 56 isoform of CD45 mRNA were predominant, but in addition a low level of the 5- and 0-exon splice products was detected. A strikingly different pattern was obtained with B-CLL cells. In CLL the level of the 456 and the 56 isoforms was low, while that of the 5- and 0-exon splice products was increased. Thus, in contrast to the heterogeneity in the expression of CD45RO in B-CLL, the majority of the cells contained the CD45 mRNA splice product coding for CD45RO. Analysis of splice products of the CD45 mRNA may serve as an additional tool to differentiate CLL from the leukemic phase of NHL.

B-Lymphocytes↗

Induction of potent antitumor response by vaccination with tumor lysate-pulsed macrophages engineered to secrete macrophage colony-stimulating factor and interferon-gamma.

Adoptive transfer of activated macrophages, being both effector cells and antigen-presenting cells, represents a promising approach to immunotherapy of cancer. In order to get activated macrophages with increased antitumor potential, in the present study, murine peritoneal macrophages were transduced with human macrophage colony-stimulating factor (M-CSF) and murine interferon-gamma (IFNgamma) by recombinant adenovirus infection. The results demonstrate that M-CSF and IFNgamma gene-modified macrophages exhibited higher expression of MHC-II, B7.1 and ICAM-1, increased antigen-presenting activity and cytotoxicity. It was also shown that they secreted more tumor necrosis factor, interleukin-1 and nitric oxide. In vivo experiments showed that in previously initiated murine pulmonary metastatic melanoma, tumor lysate-pulsed, M-CSF and IFNgamma gene-modified macrophages elicited more potent antitumor effects than tumor lysate pulsed M-CSF or IFNgamma gene-modified macrophages. Cytotoxic T lymphocyte (CTL) activity, IFNgamma and tumor-necrosis factor production of the splenocytes increased significantly in mice after intravenous injection of the gene-modified macrophages. M-CSF and IFNgamma gene-modified macrophages may act as activated effector and antigen-presenting cells, thus eliciting a more potent antitumor response.

Animals↗

Arsenic trioxide-induced apoptosis and differentiation are associated respectively with mitochondrial transmembrane potential collapse and retinoic acid signaling pathways in acute promyelocytic leukemia.

Recent studies showed that arsenic trioxide (As2O3) could induce apoptosis and partial differentiation of leukemic promyelocytes. Here, we addressed the possible mechanisms underlying these two different effects. 1.0 microM As2O3-induced apoptosis was associated with condensation of the mitochondrial matrix, disruption of mitochondrial transmembrane potentials (DeltaPsim) and activation of caspase-3 in acute promyelocytic leukemia (APL) cells regardless of their sensitivity to all-trans retinoic acid (ATRA). All these effects were inhibited by dithiothreitol (DTT) and enhanced by buthionine sulfoximine (BSO). Furthermore, BSO could also render HL60 and U937 cells, which had the higher cellular catalase activity, sensitive to As2O3-induced apoptosis. Surprisingly, 1.0 microM As2O3 did not induce the DeltaPsim collapse and apoptosis, while 0.1 microM As2O3 induced partial differentiation of fresh BM cells from a de novo APL patient. In this study, we also showed that 0.2 mM DTT did not block low-dose As2O3-induced NB4 cell differentiation, and 0. 10.5 microM As2O3 did not induce differentiation of ATRA-resistant NB4-derived sublines, which were confirmed by cytomorphology, expression of CD11b, CD33 and CD14 as well as NBT reduction. Another interesting finding was that 0.10.5 microM As2O3 could also induce differentiation-related changes in ATRA-sensitive HL60 cells. However, the differentiation-inducing effect could not be seen in ATRA-resistant HL60 sublines with RARalpha mutation. Moreover, low-dose As2O3 and ATRA yielded similar gene expression profiles in APL cells. These results encouraged us to hypothesize that As2O3 induces APL cell differentiation through direct or indirect activation of retinoic acid receptor-related signaling pathway(s), while DeltaPsim collapse is the common mechanism of As2O3-induced apoptosis.

Antineoplastic Agents↗

Delayed wound healing in CXCR2 knockout mice.

Previous studies demonstrated that the CXC chemokine, MGSA/GRO-alpha and its receptor, CXCR2, are expressed during wound healing by keratinocytes and endothelial cells at areas where epithelialization and neovascularization occur. The process of wound healing is dependent on leukocyte recruitment, keratinocyte proliferation and migration, and angiogenesis. These processes may be mediated in part by CXC chemokines, such as interleukin-8 and MGSA/GRO-alpha. To examine further the significance of CXC chemokines in wound healing, full excisional wounds were created on CXCR2 wild-type (+/+), heterozygous (+/-), or knockout (-/-) mice. Wounds were histologically analyzed for neutrophil and monocyte infiltration, neovascularization and epithelialization at days 3, 5, 7, and 10 postwounding. The CXCR2 -/- mice exhibited defective neutrophil recruitment, an altered temporal pattern of monocyte recruitment, and altered secretion of interleukin-1beta. Significant delays in wound healing parameters, including epithelialization and decreased neovascularization, were also observed in CXCR2 -/- mice. In vitro wounding experiments with cultures of keratinocytes established from -/- and +/+ mice revealed a retardation in wound closure in CXCR2 -/- keratinocytes, suggesting a role for this receptor on keratinocytes in epithelial resurfacing that is independent of neutrophil recruitment. These in vitro and in vivo studies further establish a pathophysiologic role for CXCR2 during cutaneous wound repair.

Animals↗

Tyrosine phosphorylation of a 34-kDa protein induced by cross-linking a novel glycosylphosphatidylinositol-anchored glycoprotein (GPI-80) on human neutrophils that may regulate their adherence and migration.

We previously found a novel glycosylphosphatidylinositol (GPI)-anchored glycoprotein designated GPI-80 that modulates complement receptor 3 integrin-dependent adhesion and in vitro transendothelial migration of neutrophils. In this study, we show that antibody-mediated cross-linking of GPI-80 led to rapid tyrosine phosphorylation mainly of a 34-kDa protein (pp34). Chemical inhibitors, such as genistein, sodium orthovanadate, wortmannin, cytochalasin B, Ro 31-8220, and 1,2-bis(2-aminophenoxy)ethane-N,N,N',N',-tetraacetic acid inhibited this response, whereas pertussis toxin had no effect. These findings demonstrate that the tyrosine phosphorylation of pp34 by cross-linking GPI-80 in human neutrophils involves tyrosine kinases, tyrosine phosphatases, phosphatidylinositol 3-kinase, cytoskeleton reorganization, protein kinase C, and cytoplasmic calcium, but not heterotrimeric G proteins.

Amidohydrolases↗

Effects of troglitazone on collagen accumulation and distensibility of aortic wall in prestage of non-insulin-dependent diabetes mellitus of Otsuka Long-Evans Tokushima Fatty rats.

We investigated the effect of troglitazone (TG) on aortic distensibility and histopathology at the preclinical stage in the non-insulin-dependent diabetes mellitus (NIDDM) model. Twenty male diabetic and 20 male nondiabetic rats were each divided into two groups: treated-DM, untreated-DM, treated-nonDM, and untreated-nonDM. TG (0.2%) was mixed in chow in the treated groups. From age 5 to 15 weeks, fast blood glucose and insulin were monitored. At 15 weeks, oral glucose tolerance test results, aortic wall histopathology, and collagen content were studied, and intravascular ultrasound images and aortic pressure were recorded. Aortic diameter was measured during the cardiac cycle, and the stiffness parameter beta was calculated. Blood glucose (mg/dl) 2 h after loading in treated-DM (139+/-20) was normalized (untreated-DM, 188+/-27; p<0.05). Insulin concentration (ng/ml) in treated-DM (3.2+/-0.4) was lower than that in untreated-DM (8.1+/-1.5; p<0.01). At 15 weeks, beta in untreated-DM (2.4+/-0.8) was larger than those in untreated-nonDM (1.5+/-0.4; p<0.0001) and in treated-DM (1.9+/-0.4, p = 0.0081). Aortic wall collagen (mg/g dry weight) increased in untreated-DM (32.8+/-3.3) as compared with treated-DM (28.1+/-3.8; p = 0.048). Histomorphometry showed decreased medial area (mm2) in treated-DM (0.55+/-0.05) compared with untreated-DM (0.78+/-0.12; p<0.0001). This study suggests that TG may prevent metabolic abnormalities and the deterioration of aortic distensibility at an early prediabetic stage.

Animals↗

Effect of olprinone, phosphodiesterase III inhibitor, on cerebral blood flow assessed with technetium-99m-ECD SPECT.

Few clinical reports exist regarding the effects of phosphodiesterase III inhibitors on cerebral arteries. Therefore we used a [99mTc]-ECD brain SPECT and an ultrasound method to quantitatively evaluate cerebral and systemic flow dynamics after the administration of olprinone, a phosphodiesterase III inhibitor. In 15 patients (65 +/- 8 years, M/F = 13/2) with no abnormalities on a brain computed tomography (CT), cerebral blood flow and cardiac output were measured using [99mTc]-ECD brain SPECT and Doppler echocardiography, respectively. Measurements were repeated at baseline and after the administration of olprinone. Significant increases in cerebral blood flow (p = 0.0007) and cardiac output (p = 0.001) were observed, and systolic blood pressure (p = 0.02) and systemic vascular resistance (p = 0.002) significantly decreased. No significant correlation between the increase in cerebral blood flow and the increase in cardiac output was observed. The data indicate that olprinone has a direct vasodilator effect on the cerebral artery, which was little related to the increase in cardiac output in patients who had not experienced stroke.

Aged↗