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Biomedical subjects

X Yu

Publications and source records attributed to X Yu.

At least 37 records · Page 2Linked to original sources
PubMed2001

Study on the degeneracy of antisense peptides using affinity chromatography.

The degeneracy of antisense peptides was studied by high-performance affinity chromatography. A model sense peptide (AAAA) and its antisense peptides (CGGG, GGGG, RGGG, SGGG) were designed and synthesized according to the degeneracy of genetic codes. An affinity column with AAAA as the ligand was prepared. The affinity chromatographic behaviors of antisense peptides on the column were evaluated. The results indicated that model antisense peptides have clear retention on the immobilized AAAA affinity column. RGGG showed the strongest affinity interaction. Similar result was obtained from another experiment that Arg-substituted antisense peptide of fusion peptide (1-11) of influenza virus A was also shown the highest affinity binding to immobilized fusion peptide.

Amino Acid Sequence↗
PubMed2001

Human ornithine transcarbamylase: crystallographic insights into substrate recognition and conformational changes.

Two crystal structures of human ornithine transcarbamylase (OTCase) complexed with the substrate carbamoyl phosphate (CP) have been solved. One structure, whose crystals were prepared by substituting N-phosphonacetyl-L-ornithine (PALO) liganded crystals with CP, has been refined at 2.4 A (1 A=0.1 nm) resolution to a crystallographic R factor of 18.4%. The second structure, whose crystals were prepared by co-crystallization with CP, has been refined at 2.6 A resolution to a crystallographic R factor of 20.2%. These structures provide important new insights into substrate recognition and ligand-induced conformational changes. Comparison of these structures with the structures of OTCase complexed with the bisubstrate analogue PALO or CP and L-norvaline reveals that binding of the first substrate, CP, induces a global conformational change involving relative domain movement, whereas the binding of the second substrate brings the flexible SMG loop, which is equivalent to the 240s loop in aspartate transcarbamylase, into the active site. The model reveals structural features that define the substrate specificity of the enzyme and that regulate the order of binding and release of products.

Amino Acid Sequence↗
PubMed2001

Lipid-based microtubular drug delivery vehicles.

Lipid microtubules that self-assemble from a diacetylenic lipid are suitable structures for the sustained release of bioactive agents. Microtubules were loaded with agents under aqueous conditions and embedded in an agarose hydrogel for localization at areas of interest. Protein release from our microtubule-hydrogel delivery system was characterized in vitro, and in vivo biocompatibility was examined. The influences of protein molecular weight and initial loading concentration on release profile were evaluated by releasing test proteins myoglobin, albumin, and thyroglobulin. Protein molecular weight inversely affected the release rate, and loading with a higher protein concentration increased the mass but not the percent of initially loaded protein released daily. Preservation of protein activity was demonstrated by the ability of a neurotrophic factor released from the delivery system to induce neurite extension in PC12 cells. Bovine aortic smooth muscle cells co-cultured with the microtubule-hydrogel system showed no evidence of cytotoxicity and proliferated in the presence of the microtubules. Subcutaneous implantation of microtubules in rodents revealed no significant inflammatory response after 10 days. Our microtubule-hydrogel system is useful for applications where sustained release without contact between agent and organic solvents is desired.

Animals↗
PubMed2001

A primitive sarcopterygian fish with an eyestalk.

The discovery of two Early Devonian osteichthyan (bony fish) fossils has challenged established ideas about the origin of osteichthyans and their divergence into actinopterygians (teleosts and their relatives) and sarcopterygians (tetrapods, coelacanths, lungfishes and related groups). Psarolepis from China and an unnamed braincase from Australia combine derived sarcopterygian and actinopterygian characters with primitive features previously restricted to non-osteichthyans, suggesting that early osteichthyan evolution may have involved substantial parallellism between sarcopterygians and actinopterygians. But interpretation of these fossils has been hampered by poor phylogenetic resolution. Here we describe a basal sarcopterygian fish, Achoania gen, et sp. nov., that fills the morphological gap between Psarolepis and higher sarcoptergyians. We also report the presence of eyestalk attachments in both Achoania and Psarolepis, showing that this supposedly non-osteichthyan feature occurs in basal sarcopterygians as well as the actinoptergyian-like Australian braincase.

Animals↗
PubMed2001

[Urodynamic characteristics of patients with tethered cord syndrome and its clinical significance].

OBJECTIVE: To evaluate the urodynamic characteristics of children with tethered cord syndrome (TCS) and its clinical significance. METHODS: We conducted urodynamic studies in 94 cases of TCS who underwent microsurgical release within one week preoperatively and 3 to 6 months postoperatively. RESULTS: 80 out of 94 (85.1%) children with TCS presented with lower urinary tract symptoms. Neuropathic injuries were found both in patients in group A (with lower urinary tract symptoms) and in 11 out of 14 patient in group B (without lower urinary tract symptoms). The maximum urethral closing pressure (MUCP) and maximum detrusor pressure (MDP) were significantly lower in group alpha (without upper urinary tract injury), which were 45 cm H(2)O +/- 18 cm H(2)O and 27 cm H(2)O +/- 15 cm H(2)O respectively, than in group beta (with upper urinary tract injury), which were 69 cm H(2)O +/- 24 cm H(2)O and 44 cm H(2)O +/- 17 cm H(2)O respectively, while bladder compliance (BC) in group alpha (5.6 cm H(2)O +/- 0.9 ml/cm H(2)O) was significantly higher than in group beta (2.5 ml/cm H(2)O +/- 1.2 ml/cm H(2)O). MUCP, MDP and BC were improved in group I (primary TCS) after cord untethering, 32 cm H(2)O +/- 14 cm H(2)O, 21 cm H(2)O +/- 12 cm H(2)O, 9.5 ml/cm H(2)O +/- 1.3 ml/cm H(2)O postoperatively and 63 cm H(2)O +/- 245 cm H(2)O, 37 cm H(2)O +/- 156 cm H(2)O, 5.1 ml/cm H(2)O +/- 0.8 ml/cm H(2)O preoperatively respectively, while in group II remained unchangeable. CONCLUSION: Urodynamic studies are effective methods to identify neuropathic characteristics of lower urinary tract symptom in children with TCS and to find neuropathic injury during subclinical period. According to urodynamic studies, increase of MUCP and DP and decrease of BC are high risk factors of vesicoureteral reflux and upper urinary tract injury. Microsurgical release can improve bladder function in primary TCS, while do no good to bladder function in secondary TCS.

Adolescent↗
PubMed2001

p53-dependent radiation-induced crypt intestinal epithelial cells apoptosis is mediated in part through TNF-TNFR1 system.

Radiation induces apoptosis of crypt intestinal epithelial cells (IEC) through a pathway that is largely dependent on p53. However, exactly how p53 mediates IEC apoptosis is unclear. Studies in vitro suggest that one mechanism by which p53 mediates apoptosis is through its ability to transactivate members of the TNF receptor family of 'Death Receptors'. Here, we examined the role of one of its member, TNF receptor type 1 (TNFR1), in an in vivo model of p53-dependent radiation-induced IEC apoptosis. We demonstrate that mice genetically engineered to be deficient in TNF receptor type 1 (TNFR1(-/-)) and mice injected with TNFR1-fusion chimeric protein (TNFR1-Fc; a competitive inhibitor of TNFR1) were partially protected (30-40%) from p53-dependent radiation-induced IEC apoptosis. However, we found no evidence to support the possibility p53 transcriptionally regulates the expression of TNFR1 nor increases the susceptibility of IEC to TNF-mediated apoptosis. Interestingly, we found that injection of TNF readily induced IEC apoptosis and that radiation induced a p53-dependent increase in the intestinal level of TNF. Furthermore, injection of a neutralizing anti-TNF mAb reduced p53-dependent radiation-induced IEC apoptosis by approximately 60%. Overall, these results suggest that p53-dependent radiation-induced IEC apoptosis is mediated in part through ability of p53 to regulate TNF, which subsequently induces IEC apoptosis through TNFR1.

Animals↗
PubMed2001

[Combination treatment for craniopharyngiomas with stereotactic intracavitary irradiation and gamma knife surgery].

OBJECTIVE: To evaluate the effectiveness of the combination treatment for craniopharygiomas with stereotactic intracavitary irradiation and gamma knife surgery. METHODS: Combination treatment of stereotactic instillation of radioisotopes and gamma knife surgery was performed in 46 patients with craniopharyngioma between October 1996 and June 1999. There were 24 men and 22 women, with age ranging from 3 to 60 years (average 38.6 years). There were 13 solid tumors and 33 mixed solid and cystic tumors. Twenty-eight patients had undergone prior caraniotomies with total or partial resection of tumors, with or without followed external beam radiation therapy. Gamma knife surgery was done in solid tumors and the combination treatment was done in mixed tumors: the cyst being treated with stereotactic intracavitary radiation and the solid part with Gamma knife. RESULTS: Thirty-eight patients (10 solid and 28 mixed) were followed up from 6 months to two years (averaged 16 months). The tumor control rate (disappeared, decreased and unchanged) was 90% in solid tumor, 85.7% in mixed tumors, and 92.1% in solid segment and the total control rate was 89.5%. CONCLUSION: The combination treatment is a simple, safe and effective method for craniopharyngiomas, especially for the recurrent mixed solid and cystic tumors. Gamma knife surgery plays an important role in the treatment of solid component of the craniopharyngiomas.

Adolescent↗
PubMed2001

Anti-CD69 autoantibodies cross-react with low density lipoprotein receptor-related protein 2 in systemic autoimmune diseases.

We investigated whether autoantibodies to CD69, one of the earliest markers of lymphocyte activation, exist in the sera of patients with systemic autoimmune disease. Serum samples were obtained from patients with rheumatoid arthritis (RA), systemic lupus erythematosus, and Behcet's disease, and were tested for the presence of anti-CD69 autoantibodies by ELISA and Western blotting using rCD69 fusion proteins. IgG-type autoantibodies to CD69 were detected in the sera of 38.3% of the RA patients, 14.5% of the systemic lupus erythematosus patients, and 4.0% of the patients with Behcet's disease. Among those with RA, the anti-CD69 autoantibody-positive patients had a higher serum level of rheumatoid factors and a more accelerated erythrocyte sedimentation rate than the anti-CD69 autoantibody-negative patients. Further, the predominant epitope on the CD69 molecule to which most of the anti-CD69 autoantibody-positive serum samples exclusively reacted, was mapped at the C terminus of CD69. Of interest, this epitope is homologous to a stretch of amino acids in the protein sequence of low-density lipoprotein receptor-related protein 2 (LRP2), which is a receptor for multiple ligands including beta-very low density lipoprotein and is also an autoantigen responsible for Heymann nephritis in rats. The anti-CD69 autoantibody cross-reacted to LRP2 through the homologous amino acid sequence. To our knowledge, this is the first evidence of the existence of anti-CD69 autoantibodies. This autoantibody may modulate the function of CD69- and LRP2-expressing cells.

Adult↗
PubMed2001

DNA-mediated protection against classical swine fever virus.

Four eukaryotic expression plasmids containing the entire E2 gene sequence of classical swine fever virus (CSFV) were constructed: (a) pcDST, with 5' signal and 3' transmembrane sequences; (b) pcDSW, with 5' signal sequence only; (c) pcDWT, with transmembrane sequences only; and (d) pcDWW, containing the E2 gene alone. All four plasmids were readily transfected into BHK-21 cells, with pcDST and pcDSW resulting in secretion of E2 antigen. The latter two plasmids were also shown to induce a humoral immune response against CSFV in mice when administered intramuscularly, but no immune responses were detected with either pcDWT or pcDWW. The antibody level elicited by pcDSW was higher than that induced by pcDST. When pcDSW was used to immunize rabbits and pigs, both species were shown to be protected from challenge with virulent CSFV (hog cholera lapinized virus for rabbits and Shimen strain for pigs).

Animals↗
PubMed2001

Neurotoxicity of 2-bromopropane and 1-bromopropane, alternative solvents for chlorofluorocarbons.

To clarify the neurotoxicity of 2-bromopropane (2-BP) in comparison with 1-bromopropane (1-BP), 36 Wistar strain male rats were divided into 4 groups of 9 and exposed daily to 100-ppm 2-BP, 1000-ppm 2-BP, 1000-ppm 1-BP, or fresh air for 8 h a day. Exposure to 1000 ppm of 1-BP was discontinued after 5 or 7 weeks' exposure because of the unexpected appearance of incomplete hindlimb paralysis followed by serious emaciation. The other groups were sacrificed at the end of 12 weeks' exposure. Exposure to 1000 ppm of 2-BP resulted in significant decreases in body weight and motor nerve conduction velocity (MCV) and elongation in distal latency (DL). A ball-like enlargement of myelin sheaths was observed. Significant reductions in the number of erythrocytes, platelets, and leukocytes, testicular germ cell loss, and seminiferous atrophy were also observed in this group, but not in 100-ppm 2-BP group. Exposure to 1000 ppm of 1-BP for 5 or 7 weeks caused a significant decrease in body weight and MCV and elongation in DL. Linearly arranged ovoid- or bubble-like debris of the axons and myelin sheaths in the teased tibial nerves and axonal swelling in gracilis nucleus were found in this group. No significant changes in hematological indices or histopathological findings of the testis were found in this group. In conclusion, 2-BP is neurotoxic to the peripheral nerves in addition to its toxic effects on the reproductive and hematopoietic systems at 1000 ppm. No noticeable changes were found in the rats exposed to 100 ppm of 2-BP. 1-BP is a potent neurotoxicant at 1000 ppm for 5 or 7 weeks, while testicular and hematopoietic toxicity was not found.

Animals↗
PubMed2001

Electron microscopic studies of the translin octameric ring.

Translin is thought to participate in a variety of cellular activities including chromosomal translocations, translational regulation of mRNA expression, and mRNA transport. It forms an octameric ring structure capable of sequence-specific binding of both DNA and RNA substrates. We have used electron microscopy and single-particle image analysis to generate a three-dimensional reconstruction of the Translin ring. The subunits appear to have two distinct domains that assemble to form an open channel with diameter of approximately 30 A at one end and approximately 50 A at the opposite end. In the presence of either DNA or RNA containing consensus binding sequences, the largest opening into the central cavity is filled with density. Strikingly, although Translin shows significant sequence homology to only one other protein, Translin-associated factor X, the quaternary organization and the dimerization of subunits in the ring are very similar to those observed for hexameric ring helicases. This suggests that many of the structures in DNA and RNA metabolism may have similar quaternary organization.

Algorithms↗
PubMed2001

Lack of nigral pathology in transgenic mice expressing human alpha-synuclein driven by the tyrosine hydroxylase promoter.

alpha-Synuclein has been identified as a major component of Lewy body inclusions, which are one of the pathologic hallmarks of idiopathic Parkinson's disease. Mutations in alpha-synuclein have been found to be responsible for rare familial cases of Parkinsonism. To test whether overexpression of human alpha-synuclein leads to inclusion formation and neuronal loss of dopaminergic cells in the substantia nigra, we made transgenic mice in which the expression of wild-type or mutant (A30P and A53T) human alpha-synuclein protein was driven by the promoter from the tyrosine hydroxylase gene. Even though high levels of human alpha-synuclein accumulated in dopaminergic cell bodies, Lewy-type-positive inclusions did not develop in the nigrostriatal system. In addition, the number of nigral neurons and the levels of striatal dopamine were unchanged relative to non-transgenic littermates, in mice up to one year of age. These findings suggest that overexpression of alpha-synuclein within nigrostriatal dopaminergic neurons is not in itself sufficient to cause aggregation into Lewy body-like inclusions, nor does it trigger overt neurodegenerative changes.

Animals↗
PubMed2001

Sensory modification of leech swimming: interactions between ventral stretch receptors and swim-related neurons.

The neuronal circuits that generate the leech swimming rhythm comprise oscillatory interneurons that provide appropriately phased output to drive swim-related motoneurons. Within ganglia, these interneurons express three phases; between ganglia there exists a phase delay between homologs. Our earlier experiments revealed that stretch receptors embedded in the body wall participate in intersegmental coordination and setting intersegmental phases. To identify the basis for these sensory effects, we mapped interactions between a ventral stretch receptor and swim-related neurons. Connections between this receptor and motoneurons are weak and variable in quiescent preparations, but during fictive swimming stretch receptor activation modulates motoneuron oscillations, hence, these effects are polysynaptic, mediated by interneurons. We identified a strong, nonrectifying, and apparently direct electrical connection between the stretch receptor and oscillator neuron 33. The ventral stretch receptor also interacts with most of the other oscillatory interneurons, including inhibitory inputs to cells 28 and 208, excitatory input to the contralateral cell 115, and mixed input to the ipsilateral cell 115. These direct and indirect interactions can account for previously described effects of body-wall stretch on motoneuron activity. They also could mediate the previously described modification of intersegmental phase relationships by appropriately phased stretch receptor activation.

Animals↗
PubMed2001

Agarose gel stiffness determines rate of DRG neurite extension in 3D cultures.

The optimization of scaffold mechanical properties for neurite extension is critical for neural tissue engineering. Agarose hydrogels can be used to stimulate and maintain three-dimensional neurite extension from primary sensory ganglia in vitro. The present study explores the structure-function relationship between dorsal root ganglion (DRG) neurite extension and agarose gel mechanical properties. A range of agarose gels of differing concentrations were generated and the corresponding rate of E9 DRG neurite extension was measured. Rate of neurite extension was inversely correlated to the mechanical stiffness of agarose gels in the range of 0.75-2.00% (wt/vol) gel concentrations. In addition, we postulate a physical model that predicts the rate of neurite extension in agarose gels, if gel stiffness is a known parameter. This model is based on Heidemann and Buxbaum's model of neurite extension. These results, if extended to scaffolds of other morphological and chemical features, would contribute significantly to the design criteria of three-dimensional scaffolds for neural tissue engineering.

Animals↗
PubMed2001

Mutations of ATP2C1 in Japanese patients with Hailey-Hailey disease: intrafamilial and interfamilial phenotype variations and lack of correlation with mutation patterns.

We report herein mutations of ATP2C1 in 11 Japanese patients with Hailey-Hailey disease gene (including five previously reported) and compare the mutation pattern with clinical phenotypes. Patients with missense mutations and some of those with mutations causing premature termination showed erythema and erosions primarily at intertriginous areas. In two families with unique mutations, one with an in-frame three amino acid deletion plus an eight amino acid insertion and one with a two base pair deletion predicted to cause premature truncation, some affected individuals had unique clinical features -- generalization of Hailey-Hailey disease and generalized skin eruption resembling keratotic papules in Darier's disease -- but other affected individuals did not, suggesting the presence of severe intrafamilial phenotype variations. Our findings suggest that differences in clinical phenotypes are probably related to factors other than the type of causative mutation.

Adolescent↗
PubMed2001

Dipyridamole stress ultrasonic myocardial tissue characterization in patients with Kawasaki disease.

Dipyridamole stress integrated backscatter (IBS) was used for evaluation of myocardial ischemia or damage in 31 children with coronary artery lesions caused by Kawasaki disease, in comparison with thallium-201 myocardial imaging. All patients underwent echocardiography at rest and after dipyridamole stress at the anterior interventricular septum, posterior wall (PW), and inferior wall (INF). At rest, no significant difference was seen in cyclic variation (CV) of IBS in the regions with normal or abnormal distribution on Tl-201 imaging. But in the regions showing abnormal distribution after stress, CV decreased significantly. A delayed study after stress showed the recovery of CV to the level at rest in all patients. Sensitivity of abnormal cyclic variation integrated backscatter was 75% in the PW and 91% in the INF, and specificity was 91% in the PW and 90% in the INF, compared with the results of thallium-201 imaging. Dipyridamole stress IBS can provide sensitive detection of myocardial ischemia or damage in Kawasaki disease.

Adolescent↗
PubMed2001

Detection of bacterial DNA by PCR and reverse hybridization in the 16S rRNA gene with particular reference to neonatal septicemia.

AIM: The clinical diagnosis of sepsis is difficult, particularly in neonates. It is necessary to develop a rapid and reliable method for detecting bacteria in blood and cerebrospinal fluid (CSF). Polymerase chain reaction (PCR) and reverse hybridization of the 16S rRNA gene would permit fast and sensitive determination of the presence of bacteria and differentiate gram-positive bacteria from gram-negative ones in clinical specimens. METHODS: We developed a pair of primers according to the gene encoding 16SrRNA found in all bacteria. DNA fragments from different bacterial species and from clinical samples were detected with PCR, and with reverse hybridization using a universal bacterial probe, a gram-positive probe and a gram-negative probe. RESULTS: A 371 bp DNA fragment was amplified from 20 different bacterial species. No signal was observed when human DNA and viruses were used as templates. The sensitivity could be improved to 10(-12) g. All 26 culture-positive clinical samples (22 blood samples and 4 CSF samples) were positive with PCR. The gram-negative and gram-positive probes hybridized to clinical samples and to known bacterial controls, as predicted by Gram's stain characteristics. CONCLUSIONS: Our results suggest that the method of PCR and reverse hybridization is rapid, sensitive and specific in detecting bacterial infections. This finding may be significant in the clinical diagnosis of sepsis in neonates.

Bacteremia↗