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Biomedical subjects

Y Wu

Publications and source records attributed to Y Wu.

At least 631 records · Page 35Linked to original sources

Evaluation of bone mineral density using three-dimensional solid state phosphorus-31 NMR projection imaging.

A solid state magnetic resonance imaging technique is used to measure true three-dimensional mineral density of synthetic hydroxyapatite phantoms and specimens of bone ex vivo. The phosphorus-31 free induction decay at 2.0 T magnetic field strength is sampled following application of a short, hard radiofrequency excitation pulse in the presence of a fixed amplitude magnetic field gradient. Multiple gradient directions covering the unit sphere are used in an efficient spherical polar to Cartesian interpolation and Fourier transform projection reconstruction scheme to image the three-dimensional distribution of phosphorus within the specimen. Using 3-6 Gauss/cm magnetic field gradients, a spatial resolution of 0.2 cm over a field of view of 10 cm is achieved in an imaging time of 20-35 minutes. Comparison of solid state magnetic resonance imaging with dual energy X-ray absorptiometry (DXA), gravimetric analysis, and chemical analysis of calcium and phosphorus demonstrates good quantitative accuracy. Direct measurement of bone mineral by solid state magnetic resonance opens up the possibility of imaging variations in mineral composition as well as density. Advantages of the solid state magnetic resonance technique include avoidance of ionizing radiation; direct measurement of a constituent of the mineral without reliance on assumptions about, or models of, tissue composition; the absence of shielding, beam hardening, or multiple scattering artifacts; and its three-dimensional character. Disadvantages include longer measurement times and lower spatial resolution than DXA and computed tomography, and the inability to scan large areas of the body in a single measurement, although spatial resolution is sufficient to resolve cortical from trabecular bone for the purpose of measuring bone mineral density.

Animals↗

Sturge-Weber syndrome with no leptomeningeal enhancement on MRI.

Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome characterized by a facial nevus flammeus associated with seizures, developmental delay, and, often, with hemiparesis and hemianopia. On MRI, the most characteristic finding has been reported to be leptomeningeal enhancement, believed to represent leakage of contrast medium through the anomalous pial vessels that characterize the disease. We present a case of SWS with no evidence of leptomeningeal enhancement. This case illustrates that leptomeningeal enhancement need not be present in SWS, and the absence of this characteristic finding does not preclude the diagnosis.

Adolescent↗

A high proportion of mutations in the BRCA1 gene in German breast/ovarian cancer families with clustering of mutations in the 3' third of the gene.

We have analyzed 61 German breast and breast/ovarian cancer families for BRCA1 mutations using single-strand conformation polymorphism analysis (SSCP) followed by sequencing. Forty-seven of the families had at least three cases (at least two under 60 years) and 14 families had only two cases of breast/ovarian cancer (at least one under 50 years). Twenty-eight families were breast/ovarian and 33 were breast cancer-only families. Eighteen mutations in BRCA1 were detected in 11/28 breast/ovarian cancer families and 7/33 breast cancer families and none in the families with only two cases. We identified 17 truncation mutations (8 frameshift, 7 nonsense and 2 splice variants) and one missense mutation. Seven of these are novel and two, the 5382insC and 5622C-->T mutations, occurred in two apparently unrelated families. The genotype of the two families with the 5382insC mutation is compatible with the rare haplotype segregating with the 5382insC mutation in different populations, further supporting its European origin. One unclassified missense alteration, R841W, was found in one family but did not segregate with the disease, suggesting that it is more likely a polymorphism. We also report and discuss the sequence of several new unclassified single-nucleotide changes first identified by SSCP. Of the 18 mutations, 13 occurred in the 3' third of the gene (end of exon 11-24) and ovarian cancers were found in eight of these families.

BRCA1 Protein↗

[Cancer of the thyroid gland with mediastinal extension].

AIM OF THE STUDY: Thyroid carcinomas with upper mediastinal invasion are rare: 24 out of 1,204 thyroid carcinomas operated in the Cancer Center Hospital of Shanghai (2%). For this reason, the report of our experience seems useful. MATERIAL AND METHODS: The 24 patients (13 male and 11 female) had a mean age of 45 years. Ten patients presented symtoms, nine had a palpable cervical mass and in five, the lesion was discovered by an upper mediastinal scan. The operation was performed through an upper partiel sternotomy (n = 12) associated with resection of the internal part of the clavicle (n = 8) and of the first two costal cartilages (n = 4). Tumoral removal was complete in 15 patients and incomplete in nine. RESULTS: There were no peroperative and postoperative deaths. During the procedure, the "brachio-cephalique" vein was injured and sutured in three patients. During the postoperative period, a pneumothorax was observed in three patients and a mediastinal infection in two. When the tumor removal was incomplete (n = 9), postoperative radiotherapy was performed. The only patients with papillary thyroid carcinoma (n = 16) have survived more than 5 years. For the entire group of patients, the 5-year and 10-year survival rate was respectively 65% and 47%. After incomplete tumoral resection followed by radiotherapy, two patients survived with a 28-year follow-up. CONCLUSION: This experience demonstrates that patients may survive beyond 10 years, even after incomplete resection of thyroid carcinoma with upper mediastinal invasion, if the carcinoma is differentiated.

Adult↗

Topical capsaicin as an adjuvant analgesic for the treatment of traumatic amputee neurogenic residual limb pain.

The treatment of amputee residual limb pain can at times be a challenge for the physician. Occasionally, traditional analgesic medication regimens cannot be used or are ineffective in relieving the pain. Topical capsaicin cream has been a beneficial adjuvant medication in the treatment of some painful conditions. The authors present three patients with traumatic upper limb amputations where topical capsaicin cream was of benefit in the treatment of neurogenic residual limb pain. The hope is that these cases will increase awareness of the potential use of capsaicin cream as an adjuvant analgesic in patients with residual limb pain. Common causes of residual limb pain and the pharmacology of capsaicin cream are discussed.

Adult↗

Identification of conserved amino acids in murine B7-1IgV domain critical for CTLA4/CD28:B7 interaction by site-directed mutagenesis: a novel structural model of the binding site.

The B7: CD28/CTLA4 interaction plays a major role in T cell responses. Immune intervention targeted at this interaction has demonstrated a vast potential in enhancing tumor immunity and blocking autoimmunity and transplant rejection. However, the structural basis for this interaction is unclear. While we and others have performed site-directed mutagenesis to define amino acids involved in binding CD28 and CTLA4, these residues are localized in different regions, and it is unlikely for all of them to be directly involved. In addition, the effect of the mutations on the overall conformation of B7 has not been systematically evaluated. In this study, we have carried out site-directed mutagenesis to define the amino acids within B7-1 IgV-like domain which participate B7:CD28/CTLA4 interaction. Four anti-B7-1 mAbs that recognize three independent antigenic epitopes on B7-1 were used to monitor the effect of mutations on the overall conformation of B7-1. Of the five mutations in the IgV domain that we have produced, D113 > A appears to interfere with cell surface expression and/or overall conformation of B7-1. while four others do not significantly affect the overall conformation and cell surface expression of B7-1. Among them, G115 > A and Y91 > A eliminated B7-1 binding to both CD28Ig and CTLA4Ig; our previously reported mutants L109 > A and W88 > A selectively affect the B7-1 binding to either CD28Ig or CTLA4Ig. Structural modeling of B7-1 based on the structure of immunoglobulin revealed that these four and other previously identified critical amino acids in both IgV- and IgC-like domains can form a localized structure.

Abatacept↗

Effects of Erkang, a modified formulation of Chinese folk medicine Shi-Quan-Da-Bu-Tang, on mice.

Shi-Quan-Da-Bu-Tang is a traditional Chinese herbal medicine formula used to increase vital energy, and strengthen health and immunity. Data from previous studies demonstrated that this formula also has the ability to attack tumor tissue. The Erkang capsule is a modified formula of Shi-Quan-Da-Bu-Tang, with the addition of four other herbs to increase the adaptogen effects and ergogenic properties. Results from this study in mice indicated that the Erkang treated group had significant differences in mortality, body weight change, fatigue, cold temperature endurance, and immune function related organ weight change, compared to the control animals.

Animals↗

Functional interactions of cytoplasmic domains of the skeletal muscle Ca2+ release channel.

The skeletal muscle Ca(2+) release channel (RYR1) is a homotetramer with subunits of 565 kD. Although the channel part of this protein is probably formed by the C-terminal one fifth of the protein, most of the regulation of channel activity is likely to arise from intermolecular and intramolecular interactions of its large cytoplasmic domain. This cytoplasmic region of the protein is thought to contain binding sites for a variety of modulators, including the t-tubule voltage sensor, and mutations in some cases of malignant hyperthermia and central core disease. Regulation of channel activity must, therefore, involve long-distance allosteric modulation arising from changes in both intersubunit and intrasubunit interactions within the cytoplasmic domain of the RYR1 tetramer. Biochemical studies are beginning to elucidate some of the sites within the cytoplasmic domains important for modulting channel activity in the membrane-spanning domain. This review summarizes these findings and presents a working model for the regulation of the channel by the interactions of its cytoplasmic domains.

Journal Article↗

Meropenem exists in equilibrium with a carbon dioxide adduct in bicarbonate solution.

Evidence is provided for the existence of a second discrete chemical form of meropenem at clinically relevant concentrations prepared from the marketed formulation of the drug. Proton and carbon-13 NMR spectra in D2O, coupled with tandem mass spectroscopy (MS/MS) and cross polarization/magic angle spinning (CP-MAS) NMR experiments, allow structural assignment of the compound as a covalent carbon dioxide adduct of meropenem. This carbon dioxide adduct exists in equilibrium with the free drug in solution and can be observed in the solid state following lyophilization. The equilibrium constant of formation of the adduct (Keq = 20 +/- 8 M-1) was estimated in D2O at 25 degreesC.

Bicarbonates↗

User acceptability of a female condom (Reality) in Shanghai.

Thirty married couples evaluated the Reality female condom on questionnaires about its acceptability for 300 acts of coitus (10 per couple). An analysis of the summary questionnaires showed: 90% of couples considered the female condom an acceptable method and 87% felt it was a good contraceptive device; the majority of couples (87%) found it easy to use; and 80% of females and 73% of males reported that, in comparison with the male condom, the effect on sexual pleasure was either improved or no different. A little more than half of the couples (55%) preferred it to male condoms. To look at the learning curve effect, an additional analysis was completed by pooling the first 5 applications of each user and comparing the results with the pooled results of the second 5 uses. All the findings suggest that a certain proportion of couples of childbearing age will choose the Reality female condom for contraception if it enters into the Chinese market. As a new contraceptive barrier device, the female condom may require a certain amount of education and awareness before it will be fully recognized as an important option to help prevent pregnancy as well as sexually transmitted infections.

Adult↗

Genomic DNA transfer with a high-capacity adenovirus vector results in improved in vivo gene expression and decreased toxicity.

Many applications for human gene therapy would be facilitated by high levels and long duration of physiologic gene expression. Adenoviral vectors are frequently used for gene transfer because of their high cellular transduction efficiency in vitro and in vivo. Expression of viral proteins and the low capacity for foreign DNA limits the clinical application of first- and second-generation adenoviral vectors. Adenoviral vectors with all viral coding sequences deleted offer the prospect of decreased host immune responses to viral proteins, decreased cellular toxicity of viral proteins and increased capacity to accommodate large regulatory DNA regions. Currently most vectors used in vivo for preclinical and clinical studies express cDNAs under the control of heterologous eukaryotic or viral promoters. Using an adenoviral vector with all viral coding sequences deleted and containing the complete human alpha1-antitrypsin (PI) locus, we observed tissue-specific transcriptional regulation in cell culture and in vivo; intravenous injection in mice resulted in high levels of very stable expression for more than ten months and decreased acute and chronic toxicity. These results indicate significant advantages of regulated gene expression using genomic DNA for gene transfer and of adenoviral gene transfer vectors devoid of all viral coding sequences.

Adenoviridae↗

Evidence for a role for AtMYB2 in the induction of the Arabidopsis alcohol dehydrogenase gene (ADH1) by low oxygen.

The transcription factor AtMYB2 binds to two sequence motifs in the promoter of the Arabidopsis ADH1 gene. The binding to the GT-motif (5'-TGGTTT-3') is essential for induction of ADH1 by low oxygen, while binding to the second motif, MBS-2, is not essential for induction. We show that AtMYB2 is induced by hypoxia with kinetics compatible with a role in the regulation of ADH1. Like ADH1, AtMYB2 has root-limited expression. When driven by a constitutive promoter, AtMYB2 is able to transactivate ADH1 expression in transient assays in both Arabidopsis and Nicotiana plumbaginifolia protoplasts, and in particle bombardment of Pisum sativum leaves. Mutation of the GT-motif abolished binding of AtMYB2 and caused loss of activity of the ADH1 promoter in both transient assays and transgenic Arabidopsis plants. These results are consistent with AtMYB2 being a key regulatory factor in the induction of the ADH1 promoter by low oxygen.

Alcohol Dehydrogenase↗

Relationship between lung function and blood pressure in Chinese men and women of Beijing and Guangzhou. PRC-USA Cardiovascular and Cardiopulmonary Epidemiology Research Group.

BACKGROUND: Previous studies of western populations have shown an inverse association between lung function and blood pressure. METHODS: As part of a People's Republic of China-United States cardiopulmonary epidemiology study, we investigated the cross-sectional relationship between lung function and blood pressure in 6757 Chinese men and women, aged 35-54, from Beijing and Guangzhou, China. We also evaluated the longitudinal association between lung function and incident hypertension among 4818 initially normotensive subjects followed up between 2 and 4 years later. RESULTS: In our cross-sectional analyses of baseline data, lung function varied inversely with baseline systolic (SBP) and diastolic blood pressure (DBP) in all women and in Beijing men. This association held for absolute and height-standardized forced vital capacity (FVC) and one-second forced expiratory volume (FEV1) (correlations: 0.10, -0.18, P < 0.0001), but was weaker after adjustment for age (correlations: -0.02, -0.11). The longitudinal follow-up showed that lower initial lung function levels were associated with a higher incidence of hypertension (SBP > or = 140 mmHg or DBP > or = 90 mmHg or currently using antihypertensive medications), but only among women in Guangzhou. Relative risks for hypertension incidence for those in the two lowest quintiles for FEV1 and FVC, compared to those in the two highest quintiles, ranged from 1.9 to 2.3 for Guangzhou women and from 0.9 to 1.4 for all other gender-city subgroups. Logistic regression analyses adjusting for age, baseline SBP, body mass index, smoking, education, and urban versus rural setting generally confirmed these patterns. CONCLUSIONS: These results suggest a statistically significant, though weak, inverse relationship between lung function and blood pressure in Chinese men and women. This association is largely attributable to age and is present prospectively only in women.

Adult↗

Identification of polypeptides associated with an enriched cytoskeleton-protein body fraction from developing rice endosperm.

Recent evidence has shown that the prolamine polysomes are attached not only to the endoplasmic reticulum membranes that bound the prolamine protein bodies (PBs) but also to cytoskeleton elements associated with this subcellular fraction. To learn more about the nature of the proteins that are associated with this supra-macromolecular complex, proteins extracted from an enriched cytoskeleton-PB fraction were resolved by two-dimensional polyacrylamide gel electrophoresis under non-equilibrium conditions and analyzed for their composition by immunological and biochemical methods. Immunoblot analysis indicated the presence of the cytoskeletal proteins, actin and tubulin, and the cytoskeletal-associated protein EF1 alpha in this fraction. Microsequencing of selected polypeptides revealed a diversity of protein sequences. In addition to contaminating storage proteins which are selectively solubilized by the isolation procedure, several ribosomal proteins and histone H3 were also identified. Some of the remaining polypeptides showed partial homology to protein sequences deposited in the database, several of which are cytoskeleton-associated proteins.

Amino Acid Sequence↗

Binding and lysing of blood clots using MRX-408.

RATIONALE AND OBJECTIVES: A thrombus-specific ultrasound contrast agent, MRX-408, has been developed recently. This agent consists of phospholipid-coated microbubbles with a ligand capable of targeting the GPIIb/IIIa receptor, thereby allowing the microbubbles to bind with thrombi rich in activated platelets. In vitro and in vivo animal experiments have been conducted to examine imaging enhancement and sonothrombolysis using this agent compared with a nontargeted agent. METHODS: For clot binding, blood-smeared slides were incubated with microbubbles and examined under a light microscope. Change in backscatter signals from the blood clots after binding was examined by both an ultrasound scanner and two single-element transducers arranged in a transmitter-receiver pair. For clot lysis, either 1-MHz or 20-KHz ultrasound was used to enhance the lysing effects of MRX-408 with or without urokinase. RESULTS: Evidence of binding was demonstrated under a microscope. In vitro experiments showed that the "acoustic signature", or properties, of blood clots changed after binding. Clots became more echogenic and nonlinear. In vivo fundamental ultrasound imaging confirmed that as a result of binding, blood clots were more visible, the area of detection was improved, and shadowing behind clots was more noticeable. Under 1-MHz ultrasound and 30 minutes of treatment, lysis efficiency reached 34% with MRX-408, whereas there was no visible clot lysis with saline. CONCLUSION: The results of these preliminary studies show that as a contrast agent, MRX-408 enhanced clots under ultrasound imaging and facilitated sonothrombolysis with or without thrombolytic drugs.

Animals↗

Acoustically active lipospheres containing paclitaxel: a new therapeutic ultrasound contrast agent.

RATIONALE AND OBJECTIVES: Paclitaxel-carrying lipospheres (MRX-552) were developed and evaluated as a new ultrasound contrast agent for chemotherapeutic drug delivery. METHODS: Paclitaxel was suspended in soybean oil and added to an aqueous suspension of phospholipids in vials. The headspace of the vials was replaced with perfluorobutane gas; the vials were sealed, and they were agitated at 4200 rpm on a shaking device. The resulting lipospheres containing paclitaxel were studied for concentration, size, acute toxicity in mice, and acoustic activity and drug release with ultrasound. Lipospheres containing sudan black dye were produced to demonstrate the acoustically active liposphere (AAL)-ultrasound release concept. RESULTS: Acoustically active lipospheres containing paclitaxel had a mean particle count of approximately 1 x 10(9) particles per mL and a mean size of 2.9 microns. Acute toxicity studies in mice showed a 10-fold reduction in toxicity for paclitaxel in AALs compared with free paclitaxel. The AALs reflected ultrasound as a contrast agent. Increasing amounts of ultrasound energy selectively ruptured the AALs and released the paclitaxel. CONCLUSIONS: Acoustically active lipospheres represent a new class of acoustically active drug delivery vehicles. Future studies will assess efficacy of AALs for ultrasound-mediated drug delivery.

Animals↗

Diminished angiotensin-II and intact vasopressin response to hemorrhage in portal hypertension.

Portal hypertension is characterized by splanchnic vasodilation and diminished arterial vasoconstrictor response to hemorrhage. Angiotensin-II and arginine vasopressin are critical modulators of the splanchnic response to hemorrhage in normal animals. We hypothesized that alterations in endogenous renin, angiotensin-II, or arginine vasopressin production or release could contribute to the abnormal response to hemorrhage in portal hypertension. Hemodynamics were studied in normal and portal hypertensive rabbits following either graded isovolumetric or single large volume hemorrhage, followed by reinfusion of blood. Hemodynamic and renin-angiotensin-II, and arginine vasopressin activities were determined. The experiments demonstrated a significantly diminished appearance in angiotensin-II (110.87+/-30 vs. 245+/-51.0 pg/mL) and aldosterone (54.2+/-9.5 vs. 119.4+/-13.5 ng/dL), and plasma renin activity (19.4+/-4.2 vs. 29.1+/-2.8 ng/mL/h) in portal hypertension compared with normal, but an appropriate rise in arginine vasopressin levels following hemorrhage in portal hypertension. These findings suggest a diminished angiotensin-II production or release in portal hypertension, which may mediate the failure of the appropriate splanchnic vasoconstrictive response to hemorrhage.

Angiotensin II↗