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Biomedical subjects

W Yu

Publications and source records attributed to W Yu.

At least 37 records · Page 2Linked to original sources

Comparative genomic hybridisation using a proximal 17p BAC/PAC array detects rearrangements responsible for four genomic disorders.

BACKGROUND: Proximal chromosome 17p is a region rich in low copy repeats (LCRs) and prone to chromosomal rearrangements. Four genomic disorders map within the interval 17p11-p12: Charcot-Marie-Tooth disease type 1A, hereditary neuropathy with liability to pressure palsies, Smith-Magenis syndrome, and dup(17)(p11.2p11.2) syndrome. While 80-90% or more of the rearrangements resulting in each disorder are recurrent, several non-recurrent deletions or duplications of varying sizes within proximal 17p also have been characterised using fluorescence in situ hybridisation (FISH). METHODS: A BAC/PAC array based comparative genomic hybridisation (array-CGH) method was tested for its ability to detect these genomic dosage differences and map breakpoints in 25 patients with recurrent and non-recurrent rearrangements. RESULTS: Array-CGH detected the dosage imbalances resulting from either deletion or duplication in all the samples examined. The array-CGH approach, in combination with a dependent statistical inference method, mapped 45/46 (97.8%) of the analysed breakpoints to within one overlapping BAC/PAC clone, compared with determinations done independently by FISH. Several clones within the array that contained large LCRs did not have an adverse effect on the interpretation of the array-CGH data. CONCLUSIONS: Array-CGH is an accurate and sensitive method for detecting genomic dosage differences and identifying rearrangement breakpoints, even in LCR-rich regions of the genome.

Centromere↗

Hereditary neuropathy with liability to pressure palsy: fulminant development with axonal loss during military training.

Hereditary neuropathy with liability to pressure palsy (HNPP) is characterised by recurrent mononeuropathies following minor trauma. We describe a case of fulminant HNPP beginning on the first day of military physical training. Protracted weakness, muscle atrophy, hand contractures, and multifocal sensory loss developed during a further three weeks of basic training. Nerve conduction changes were typical of HNPP, but without segmental slowing. Electromyographically, there was prominent acute denervation in muscles of the hands and right shoulder. Sural nerve biopsy demonstrated tomaculae and remyelination. Genetic testing revealed PMP-22 gene deletion. This case report demonstrates that HNPP can present with rapidly progressive peripheral nerve dysfunction and electrophysiological evidence of focal axonal loss.

Adult↗

Endovascular embolectomy of acute basilar artery occlusion.

Acute basilar artery occlusion has a mortality rate approaching 90%. The authors describe a case of acute basilar artery occlusion managed successfully with endovascular embolectomy. A 31-year-old man sought treatment for confusion, dysarthria, and right-sided weakness. He soon became unresponsive and was found to have a vertebral artery dissection and an associated basilar artery embolism. The dissection was managed with endovascular stenting, and the basilar artery embolus was removed with a clot retriever at 7 hours. The patient recovered without neurologic deficit.

Acute Disease↗

Comparison of fixed-flexion positioning with fluoroscopic semi-flexed positioning for quantifying radiographic joint-space width in the knee: test-retest reproducibility.

OBJECTIVE: To compare fixed-flexion radiography of the knee with fluoroscopic semi-flexed radiography in terms of the reproducibility of measurements of minimum joint-space width (JSW) in the medial femorotibial joint. METHODS: Posteroanterior radiographs of the right knees of 18 normal volunteers were acquired with the patients standing on an upright fluoroscopy table, the feet externally rotated 10 degrees and the toes touching the vertical table. Knees were positioned and radiographed with two different techniques: (1) semi-flexed positioning under fluoroscopic guidance using a horizontal X-ray beam; and (2) fixed-flexion positioning, with the knees and thighs touching the vertical table, using 10 degrees caudal beam angulation without fluoroscopy. Foot maps were drawn in each case. Subjects were repositioned and radiographed twice using each technique. The posteroanterior beam angle that optimally projected the medial tibia plateau with the patient in the fixed-flexion position was also determined for each subject in a separate examination using fluoroscopy. Ten patients with osteoarthritis were also examined with the fixed-flexion technique using a conventional radiographic unit. Minimum medial joint-space width (JSW) in the medial femorotibial joint was measured manually with a graduated lens and also with a semi-automated computer algorithm. RESULTS: Reproducibility errors (root-mean-square SD) for manual and automated JSW measurement were 0.2 mm and 0.1 mm, respectively, for fluoroscopic semi-flexed positioning in volunteers; 0.3 mm and 0.1 mm, respectively, for fixed-flexion positioning in volunteers; and 0.2 mm and 0.1 mm, respectively, for fixed-flexion positioning in osteoarthritic patients. The optimal beam angle for visualizing the joint space was 9.0 degrees +/-3.6 degrees. CONCLUSION: Fixed-flexion, non-fluoroscopic radiography of the knee can provide reproducible JSW measurement using widely available X-ray equipment. This technique is more feasible for multicenter clinical studies and routine clinical use than are methods that rely on fluoroscopic alignment of the tibial plateau.

Adult↗

Third-order harmonic generation by self-guided femtosecond pulses in air.

Strong third-order harmonic (TH) emission is observed with a conversion efficiency higher than 10(-3) from a plasma channel formed by self-guided femtosecond laser pulses propagating in air. The main characteristics of TH emission in various conditions and the phase-matching condition between the fundamental and the TH wave are investigated. An optimized condition is found, under which the TH conversion efficiency is maximized. Our experimental results show that radiation of the emission in ultraviolet wavelength range makes a major attribution to TH emission, whereas the effects of self-phase modulation are not important when intense laser pulses interact with gaseous media.

Journal Article↗

Construction of a pepO gene-deficient mutant of Porphyromonas gingivalis: potential role of endopeptidase O in the invasion of host cells.

Porphyromonas gingivalis has been isolated from lesions of advanced adult periodontitis, and implicated as a periodontal pathogen. We have previously cloned a novel endopeptidase, designated PepO, from P. gingivalis 381, which exhibited significant homology to human endothelin-converting enzyme (ECE)-1. In order to determine the nature and function of the PepO in the host, a pepO gene-deficient mutant strain was constructed by allelic exchange mutagenesis using the ermF-ermAM cassette. No endopeptidase activity was detected in the pepO-deficient mutant. In addition, adherent HeLa (HEp-2) cells were infected with the mutant and the two wild-type strains for assessment of bacterial invasion by an antibiotic protection assay. The invasion efficiency of the mutant strain was about a quarter of the wild type strains. These results suggest that PepO is involved in the first step, i.e. invasion/lysis of mammalian cell membrane, which affects the kinetics of rate of invasion.

Adult↗

A novel light source for SICM-SNOM of living cells.

We have developed a novel light source for use in a scanning near-field optical microscope (SNOM or NSOM) based on a nanopipette whose distance from the sample surface is controlled using scanning ion conductance microscopy. The light source is based on the general principle of the chemical reaction between a fluorophore in the pipette and ligand in the bath, to produce a highly fluorescent complex that is continually renewed at the pipette tip. In these experiments we used fluo-3 and calcium, respectively. This complex is then excited with an Ar+ laser, focused on the pipette tip, to produce the light source. This method overcomes the transmission problem of more traditional SNOM probes and has been used to acquire simultaneous high-resolution topographic and optical images of biological samples in physiological buffer. A resolution of approximately 220 nm topographic and approximately 190 nm optical was determined through imaging fixed sea-urchin sperm flagella. Live A6 cells were also imaged, demonstrating the potential of this system for SNOM imaging of living cells.

Aniline Compounds↗

Kashin-Beck disease in children: radiographic findings in the wrist.

OBJECTIVE: To characterize the features and prevalence of radiographic abnormalities of the wrist in children with Kashin-Beck disease (KBD) and to determine whether the presence of radiographic abnormalities in the wrist correlates with the severity of KBD. DESIGN AND PATIENTS: Two hundred and eight posteroanterior radiographs of the right hand (including wrist) in children with KBD, ranging in age from 4 to 11 years (mean age 7.7 years), from endemic areas of China were reviewed. Carpal bony margins were evaluated for blurring, thinning, irregularity with and without sclerosis, interruption, depression or destruction. The radiocarpal, intercarpal and carpometacarpal joints were assessed for widening or narrowing. The severity of the disease was graded using the hand criteria from the Chinese Radiographic Criteria of KBD Diagnosis, which classifies the following five types according to the location of the hand involved: I, metaphysis; II, diaphysis; III, I+II; IV, metaphysis and epiphysis; V, II+IV. RESULTS: Of the 208 children, 95 had abnormalities in the hand but not in the wrist; 108 had both hand and wrist abnormalities; only five had abnormal wrist findings without any hand abnormalities. Of the 108 cases with wrist abnormalities, all the carpal bones were involved in 33 cases, of which the hand types were either IV or V. However, any individual carpal bone, or combination of bones, may become involved. The carpal bones most likely to show abnormalities were the capitate and the hamate (93%), followed by the triquetrum (31%), the lunate (9%), the scaphoid (6%), and the trapezoid and the trapezium (5%). The pisiform bones were not evaluated because they cannot be seen on the overlapping posteroanterior radiographs. The most commonly involved carpal joint was the midcarpal joint (42%). CONCLUSIONS: Recognizing carpal abnormalities on radiographs is helpful for the diagnosis of KBD and the evaluation of the severity of the disease. The more severe the KBD, the more likely that the carpal bones will be involved. The capitate and hamate are frequently affected if the disease involves the carpal bones.

Bone Diseases, Developmental↗

The chemical syntheses and bioactivities of novel peptide-based endothelin antagonists.

Endothelin antagonists, novel tripeptides containing a series of unnatural amino acids, were synthesized and characterized. A linear peptide BQ-485, perhydroazepin-1-yl-L-leucyl (1)-D-tryptophanyl (2)-D-tryptophan (3), was selected as the parent compound. The introduction of D-Phe derivatives into these peptidic ET antagonists resulted in potent activity against the contraction of rat aortic smooth muscles induced by ET-1 (10 nM) which activated the ET receptors. Among these compounds, 15 tripeptides had high enough antagonistic activity at the level of 10(-7) mol/L (IC50). The activity of three compounds was 10(-6) mol/L (IC50). These HIM-CO-Leu-D-Trp-D-Phe(-R)-OH compounds as ETA antagonists may provide a tool for the development of therapeutic agents in the treatment of putative ET-1-related disorders.

Animals↗

Postoperative body-weight loss and survival after curative resection for gastric cancer.

BACKGROUND: Body-weight loss has been reported as a poor prognostic factor for some malignancies. The purpose of this study was to evaluate the prognostic value of postoperative body-weight loss in patients with gastric cancer. METHODS: In 564 patients who underwent curative resection for gastric cancer, usual body-weight, body-weight at the time of resection and that 6 and 12 months after resection were recorded prospectively. RESULTS: The 5-year survival rate of patients who lost more than 5 per cent of their 6-month postoperative weight by 12 months after resection was 63 per cent while that of patients who maintained 95 per cent or more of their 6-month postoperative weight was 84 per cent (P < 0.001). Multivariate analysis revealed that serosal invasion, nodal metastasis, body-weight loss during the second 6-month interval after resection and extent of gastric resection were independent prognostic indicators. CONCLUSION: When a patient loses body-weight during the second 6-month interval after curative resection for gastric cancer, recurrent disease should be suspected.

Chemotherapy, Adjuvant↗

NS-398: cyclooxygenase-2 independent inhibition of leukocyte priming for lipid body formation and enhanced leukotriene generation.

Because the induction of new lipid body formation in leukocytes correlates with and likely contributes to their enhanced 'primed' prostaglandin and leukotriene formation, we evaluated two selective cyclooxygenase (COX)-2 inhibitors. Three types of stimuli, cis -unsaturated fatty acids, platelet activating factor and protein kinase C activators, stimulate lipid body formation. NS-398 (0.1-10 microM), but not another COX-2 inhibitor, SC58125 (0.1- 10 microM), blocked leukocyte lipid body formation elicited by all three types of stimuli and also blocked priming for enhanced LTB(4) production and PGE(2) production. The effect of NS-398 on lipid body formation was independent of its inhibitory effects on COX-2 since arachidonate-induced lipid body formation in COX-2-deficient mouse leukocytes was also inhibited by NS-398. By means of its ability to inhibit leukocyte lipid body formation, NS-398 may exert actions independent of its COX-2 inhibition and more broadly contribute to the suppression of formation of COX-1 and lipoxygenase-derived eicosanoids.

Animals↗

Long plasma channels generated by femtosecond laser pulses.

Generation of a long plasma channel by femtosecond laser pulses is investigated. The results show that the balance between the nonlinear self-focusing of the laser beam and plasma defocusing forms a long plasma channel, which guides the laser beam to propagate a long distance in air. This phenomenon can be used to trigger lightning.

Journal Article↗

A rapid method for targeted modification and screening of recombinant bacterial artificial chromosome.

Modification of bacterial artificial chromosomes (BACs) has been a useful method to produce genomic DNA fragments for studying gene expression and function in vitro and in vivo. The original technique involved restrictions for BAC modification and required multiple cloning steps to target sequences into the shuttle vector. Selection and screening of BAC recombinants was accomplished by drug resistance and Southern blotting. We have developed a PCR-based method for producing the modified shuttle vectors and for screening for BACs carrying homologous integrants. The combination of these techniques allows for rapid and easy targeted BAC sequence deletion or insertion.

Base Sequence↗

Influence of age on Medicare expenditures and medical care in the last year of life.

CONTEXT: Expenditures for Medicare beneficiaries in the last year of life decrease with increasing age. The cause of this phenomenon is uncertain. OBJECTIVES: To examine this pattern in detail and evaluate whether decreases in aggressiveness of medical care explain the phenomenon. DESIGN, SETTING, AND PATIENTS: Analysis of sample Medicare data for beneficiaries aged 65 years or older from Massachusetts (n = 34 131) and California (n = 19 064) who died in 1996. MAIN OUTCOME MEASURE: Medical expenditures during the last year of life, analyzed by age group, sex, race, place and cause of death, comorbidity, and use of hospital services. RESULTS: For Massachusetts and California, respectively, Medicare expenditures per beneficiary were $35 300 and $27 800 among those aged 65 through 74 years vs $22 000 and $21 600 for those aged 85 years or older. The pattern of decreasing Medicare expenditures with age is pervasive, persisting throughout the last year of life in both states for both sexes, for black and white beneficiaries, for persons with varying levels of comorbidity, and for those receiving hospice vs conventional care, regardless of cause and site of death. The aggressiveness of medical care in both Massachusetts and California also decreased with age, as judged by less frequent hospital and intensive care unit admissions and by markedly decreasing use of cardiac catheterization, dialysis, ventilators, and pulmonary artery monitors, regardless of cause of death. Decrease in the cost of hospital services accounts for approximately 80% of the decrease in Medicare expenditures with age in both states. CONCLUSIONS: Medicare expenditures in the last year of life decrease with age, especially for those aged 85 years or older. This is in large part because the aggressiveness of medical care in the last year of life decreases with increasing age.

Age Factors↗

Activation of extracellular signal-regulated kinase and c-Jun-NH(2)-terminal kinase but not p38 mitogen-activated protein kinases is required for RRR-alpha-tocopheryl succinate-induced apoptosis of human breast cancer cells.

RRR-alpha-tocopherol succinate (vitamin E succinate, VES) is a potent, selective apoptotic agent for cancer cells but not normal cells. VES has been shown to inhibit the growth of a wide variety of tumor cells in cell culture and animal models. Studies addressing mechanisms of action of VES-induced apoptosis have identified transforming growth factor-beta, Fas/CD95-APO-1, and mitogen-activated protein kinase (MAPK) signaling pathway involvement. Here we show that MAPKs, the extracellular signal-regulated kinases (ERK), and the stress-activated protein kinases, c-Jun NH2-terminal kinases (JNK), but not p38, are critical mediators in VES-induced apoptosis of human breast cancer MDA-MB-435 cells. VES activates ERK1/2 and JNK both in level and duration of kinase activity. Expression of dominant negative mutants of ERK1, MAPK/ERK activator-1, or JNK1 but not p38 blocked phosphorylation of the substrate glutathione S-transferase-c-Jun and inhibited VES-induced apoptosis. Increased phosphorylation and transactivation activity of nuclear transcription factors c-Jun, ATF-2, and Elk-1 are observed after VES treatments; however, only c-Jun and ATF-2 appear to be involved in VES-induced apoptosis based on antisense blockage experiments. Collectively, these results imply a critical role for ERK1 and JNK1 but not p38 in VES-induced apoptosis of human MDA-MB-435 breast cancer cells.

Activating Transcription Factor 2↗

The role of recombination activating gene (RAG) reinduction in thymocyte development in vivo.

Assembly of T cell receptor (TCR)alpha/beta genes by variable/diversity/joining (V[D]J) rearrangement is an ordered process beginning with recombination activating gene (RAG) expression and TCRbeta recombination in CD4(-)CD8(-)CD25(+) thymocytes. In these cells, TCRbeta expression leads to clonal expansion, RAG downregulation, and TCRbeta allelic exclusion. At the subsequent CD4(+)CD8(+) stage, RAG expression is reinduced and V(D)J recombination is initiated at the TCRalpha locus. This second wave of RAG expression is terminated upon expression of a positively selected alpha/beta TCR. To examine the physiologic role of the second wave of RAG expression, we analyzed mice that cannot reinduce RAG expression in CD4(+)CD8(+) T cells because the transgenic locus that directs RAG1 and RAG2 expression in these mice is missing a distal regulatory element essential for reinduction. In the absence of RAG reinduction we find normal numbers of CD4(+)CD8(+) cells but a 50-70% reduction in the number of mature CD4(+)CD8(-) and CD4(-)CD8(+) thymocytes. TCRalpha rearrangement is restricted to the 5' end of the Jalpha cluster and there is little apparent secondary TCRalpha recombination. Comparison of the TCRalpha genes expressed in wild-type or mutant mice shows that 65% of all alpha/beta T cells carry receptors that are normally assembled by secondary TCRalpha rearrangement. We conclude that RAG reinduction in CD4(+)CD8(+) thymocytes is not required for initial TCRalpha recombination but is essential for secondary TCRalpha recombination and that the majority of TCRalpha chains expressed in mature T cells are products of secondary recombination.

Animals↗