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Biomedical subjects

Z Ye

Publications and source records attributed to Z Ye.

At least 55 records · Page 3Linked to original sources
PubMed2000

Neurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulin-degrading enzyme.

Progressive cerebral accumulation of amyloid beta-protein (Abeta) is an early and invariant feature of Alzheimer's disease. Little is known about how Abeta, after being secreted, is degraded and cleared from the extracellular space of the brain. Defective Abeta degradation could be a risk factor for the development of Alzheimer's disease in some subjects. We reported previously that microglial cells release substantial amounts of an Abeta-degrading protease that, after purification, is indistinguishable from insulin-degrading enzyme (IDE). Here we searched for and characterized a role for IDE in Abeta degradation by neurons, the principal cell type that produces Abeta. Whole cultures of differentiated pheochromocytoma (PC12) cells and primary rat cortical neurons actively degraded endogenously secreted Abeta via IDE. However, unlike that in microglia, IDE in differentiated neurons was not released but localized to the cell surface, as demonstrated by biotinylation. Undifferentiated PC12 cells released IDE into their medium, whereas after differentiation, IDE was cell associated but still degraded Abeta in the medium. Overexpression of IDE in mammalian cells markedly reduced the steady-state levels of extracellular Abeta(40) and Abeta(42), and the catalytic site mutation (E111Q) abolished this effect. We observed a novel membrane-associated form of IDE that is approximately 5 kDa larger than the known cytosolic form in a variety of cells, including differentiated PC12 cells. Our results support a principal role for membrane-associated and secreted IDE isoforms in the degradation and clearance of naturally secreted Abeta by neurons and microglia.

Alzheimer Disease↗
PubMed2000

Estimation of HIV infection and incubation via state space models.

By using the state space model (Kalman filter model) of the HIV epidemic, in this paper we have developed a general Bayesian procedure to estimate simultaneously the HIV infection distribution, the HIV incubation distribution, the numbers of susceptible people, infective people and AIDS cases. The basic approach is to use the Gibbs sampling method combined with the weighted bootstrap method. We have applied this method to the San Francisco AIDS incidence data from January 1981 to December 1992. The results show clearly that both the probability density function of the HIV infection and the probability density function of the HIV incubation are curves with two peaks. The results of the HIV infection distribution are clearly consistent with the finding by Tan et al. [W.Y. Tan, S.C. Tang, S.R. Lee, Estimation of HIV seroconversion and effects of age in San Francisco homosexual populations, J. Appl. Stat. 25 (1998) 85]. The results of HIV incubation distribution seem to confirm the staged model used by Satten and Longini [G. Satten, I. Longini, Markov chain with measurement error: estimating the 'true' course of marker of the progression of human immunodeficiency virus disease, Appl. Stat. 45 (1996) 275].

Acquired Immunodeficiency Syndrome↗
PubMed2000

A comprehensive systematic approach to identification of influenza A virus genotype using RT-PCR and RFLP.

Amplification of influenza A virus gene segments by reverse transcription-polymerase chain reaction (RT-PCR) can be combined with enzymatic digestion to reveal unique restriction fragment length polymorphisms specific for H1N1 and H3N2 subtype viruses. We have used the method to provide a rapid, specific and reproducible identification of the genotype of high-growth influenza reassortants derived from A/Puerto Rico/8/34 (PR8). Digestion of the gene segments amplified from wild-type viruses, PR8 and reassortants at sites unique to either the wild-type strain or to PR8 provided positive, unambiguous identification of the origin of each of the internal genes, and distinguished the internal genes of both H1N1 and H3N2 strains from those of PR8. This method has also permitted us to quickly confirm that reassorting has occurred and to optimize the selection of reassortant clones with maximum number of PR8 internal genes. Since the method can detect 1-10% of a second strain in a mixed population, the method can also be used to detect samples containing more than one viral subtype and to assess the purity of influenza viruses used for manufacturing vaccines.

DNA, Complementary↗
PubMed2000

Tongue reconstruction with a combined brachioradialis-radial forearm flap.

Total glossectomy adversely affects speech and swallowing, and subsequent reconstruction results in limited functional return. The radial forearm flap has been reliably used to resurface glossectomy defects, but has limited bulk with which to aid in palatoglossal contact for speech. The authors have modified the forearm flap by incorporating a segment of brachioradialis muscle, to increase bulk posteriorly and to aid in speech. Sufficient muscle perforators arise from the proximal brachial artery and enter the brachioradialis to permit transfer of the muscle with the fasciocutaneous forearm flap as a single free-flap unit. The muscle is folded onto itself and enclosed within the forearm flap skin to create a neotongue. Coaptation of the antebrachial cutaneous nerves can provide a senate flap. Successful transfer of the combined brachioradialis/forearm flap in a patient who had undergone total glossectomy resulted in a neotongue good shape. Speech was rated good by a speech pathologist, and palatoglossal contact was observed on cineoradiograph. No functional loss at the donor site occurred. Inclusion of the brachioradialis muscle with the radial forearm flap as a combined unit results in a neotongue with good form and increased bulk posteriorly at the base, compared to a standard fasciocutaneous flap alone. This is a useful variation of the forearm flap. Sensory return is possible if the medial and/or lateral antebrachial cutaneous nerves of the flap are coapted to the lingual nerve.

Carcinoma, Squamous Cell↗
PubMed2000

Target strength of an oily deep-water fish, orange roughy (Hoplostethus atlanticus). II. Modeling.

Orange roughy consist of approximately 18% lipids by weight, mostly as wax esters, and the lipids must be taken into account when modeling target strength. A deformed cylinder model incorporating the effect of temperature and pressure on sound speed through wax ester was used to scale experimental measurements of target strength to the temperatures and pressures where orange roughy live (approximately 6 degrees C, depths approximately 800-1300 m). The effect of decreasing temperature and increasing pressure is to increase the sound speed in orange roughy lipids. Modeling shows that the net effect of this is to reduce tilt-averaged target strength, 'TS', by approximately 2 dB. Adjusting experimental results to compensate for temperature and pressure effects gives a predicted 'TS' for a 35-cm orange roughy of -48.3 dB. Adjusting in situ estimates of orange roughy 'TS' for avoidance behavior [McClatchie et al., J. Acoust. Soc. Am. 106, 131-142 (1999)] suggests the correct 'TS' is approximately -47.5 dB, rather than -50 dB as previously reported [Kloser et al., ICES J. Mar. Sci. 54, 60-71 (1997)]. We conclude that experimental and in situ estimates now converge at a 'TS' of approximately -48 dB for a 35-cm fish.

Animals↗
PubMed2000

Enhancement and inhibition of acoustic radiation in spherical cavities

Acoustic radiation from a source located inside layered cavities is studied using the transfer matrix method. It is shown that the radiation can be either enhanced or inhibited, depending on the characteristics and the material composition of the cavities. The analysis predicts well-defined spectral peaks and nodes in some cavities. It is found that significant enhancement and inhibition are possible by varying acoustic parameters. The results also show that the strength of the radiating source can be significantly modified due to the presence of layered structures. The link to the similar phenomena in the optical cavities is discussed.

Journal Article↗
PubMed2000

[Relations of chemotherapy-induced tumor necrosis to plasma platin concentration and primary tumor temperature in patients with osteosarcoma in the lower extremities treated by hyperthermic isolation limb perfusion with cisplatin].

OBJECTIVES: To study the relations of chemotherapy-induced tumor necrosis to plasma concentration of platin and primary tumor temperature in hyperthermic isolation limb perfusion (HILP) with cisplatin, and to investigate the correlation between the tumor necrosis rate and the relapse-free survival (RFS). METHODS: Fifteen patients with II B osteosarcoma in the lower extremities were treated with neoadjuvant chemotherapy. Among them, 10 were male and 5 female. The average age was 18 years (ranging from 13 to 29). Chemotherapy included a single bonus dose of HILP with cisplatin (CDDP, 15 mg/m(2)). The plasma concentration of platin and the tumor temperature in the affected limb were measured during the course of the HILP with CDDP. Limb salvage surgery was performed in 9 patients and amputation in 6. After surgery, serial sections of the excised tumor specimens were made to determine the tumor necrosis rate. All of the patients were followed up for more than 5 years. RESULTS: The highest attained tumor temperature was between 41.4 degrees C - 43.0 degrees C (mean 42.3 degrees C +/- 0.46 degrees C), and the platin concentration ranged from 4.56 microg/mL to 14.66 microg/mL (mean 8.93 microg/mL +/- 3.16 microg/mL) during the course of HILP with CDDP. Thirteen patients with a necrosis rate of over 90% were well responded, and the remaining two with a necrosis rate 87.2% and 86.3% were poor responded. Eight patients remained tumor-free for 5 years. Primary tumor temperature and platin concentration were significantly related to the tumor necrosis rate (P = 0.001 and P < 0.001, respectively). No significant correlation was noted between the long-term survival rate and the three parameters in the regression analysis. CONCLUSIONS: HILP with CDDP is useful in the treatment of primary osteosarcoma. Increased tumor necrosis ensure a successful surgical excision of tumor. HILP however is still limited to the patients who are not candidates for lime salvage surgery, because the same condition of high temperature and high concentration of platin are not applicable to distant metastasis.

Adolescent↗
PubMed2000

[Cultivation of Lactobacillus in microcapsule].

The NaCS-PDMDAAC capsules were used to immobilize the two kinds of lactobacillus. The experiment results showed that two kinds of lactobacillus could grow well, and the densities of cells were 1.8 x 10(11)/mL capsule and 2.79 x 10(11)/mL capsule, respectively which was much higher than that in free cell culture. The conversion rate of lactic acid could be 2-5 folds higher than that in free cell culture.

Capsules↗
PubMed1999

Screening of transcriptionally regulated genes following iron chelation in human astrocytoma cells.

Deferoxamine is an effective iron chelator and a potential therapeutic agent for use in minimizing free radical-mediated injury following trauma. Iron chelation may also be an effective means of limiting tumor growth by decreasing bioavailable iron. Deferoxamine can modulate gene expression through manipulation of intracellular iron levels; specifically at the posttranscription level by changing the activity of iron regulatory proteins (IRPs). The effect of iron chelation on the transcription of genes is still unclear, but iron-binding sites on DNA have been reported. Here we investigate the influence of deferoxamine on gene transcription. Two-directional (forward and backward) suppression subtraction hybridization (SSH) was performed on human astrocytoma cells (SW1088) cultured in either standard media or treated for 48 hours with deferoxamine. To restrict the number of false-positive clones, reverse Northern blotting was used to further verify the differentially expressed cDNA clones. Positive clones were sequenced and the mRNAs were re-examined on Northern blots for changes in expression over time of deferoxamine exposure. The results of these analyses have identified both novel and known genes whose expression is influenced by iron chelation. The known genes include a group related to energy production and a group related to protease function. These results provide examples of genes not previously known to be directly influenced by iron availability, and as such may be potential targets for iron chelation therapy.

Astrocytoma↗
PubMed1999

Isolation of a zeta class wheat glutathione S-transferase gene.

A new Zeta class glutathione S-transferases (GST) gene, pGST, has been cloned from wheat for the first time by the differential display PCR (DD-PCR) method. The genomic sequence of pGST, TA-GSTZ1, contains nine exons that encode a polypeptide of 213 amino acids and eight introns. The deduced amino acid sequence of TA-GSTZ1 as well as the exon:intron placement are more similar to the GSTs of the Zeta class than to the two wheat GSTs reported earlier. The pGST cDNA gene product expressed in Escherichia coli and purified by affinity chromatography showed typical Zeta class GST and glutathione peroxidase activities. Sequence polymorphism in the 3' untranslated region (UTR) of TA-GSTZ1 gene in wheat has been discovered. In this study, an 89 bp sequence is present in the 3' UTR of TA-GSTZ1gene in 16 wheat cultivars but absent in the other five. Although the biological importance of this polymorphism is unknown, it can be useful as a genetic marker in wheat breeding.

Amino Acid Sequence↗
PubMed1999

Soluble member(s) of the mesothelin/megakaryocyte potentiating factor family are detectable in sera from patients with ovarian carcinoma.

mAb OV569 was made by immunizing mice with ovarian carcinoma cells. It binds to cells from ovarian carcinomas and, to a lesser extent, to cells from certain other carcinomas whereas the binding to normal tissues is low to nondetectable. It also binds to soluble molecule(s) in culture supernatants from antigen-positive carcinomas. OV569 recognizes a protein(s) of 42-45 kDa with the same N-terminal amino acid sequence as the membrane-bound portion of mesothelin and megakaryocyte potentiating factor (MPF). Binding assays with fusion proteins comprising either the N-terminal part of mesothelin/MPF (D1Ig), reported to be easily cleaved off, or a noncleavable, membrane-associated part (D2Ig) showed that OV569 only binds to D2hIg. A new member of the mesothelin/MPF family was discovered, which has an 82-bp insert in the membrane-associated part, leading to a frameshift of 212 bp, and whose predicted molecular structure indicates that it is soluble. To test patient sera for soluble tumor antigen, antigen was isolated from cell-free tumor culture supernatants via immunoadsorption with OV569 and used to generate murine mAbs to an epitope different from the one to which OV569 binds, after which mAbs to two different epitopes were used to develop a "sandwich ELISA." Using this assay, the level of circulating antigen was elevated significantly in 23 of 30 sera from patients with ovarian carcinoma, as compared with 0 of 68 sera from healthy controls, 0 of 3 sera from patients with nonneoplastic diseases, and 25 of 75 sera from patients with other tumors. Soluble molecules of the mesothelin/MPF family may provide useful new marker(s) for diagnosis of ovarian carcinoma and/or monitoring its response to therapy.

Amino Acid Sequence↗
PubMed1999

[Study on the risk factors influencing the epidemicity of epidemic cerebrospinal meningitis].

Based on a 8-year surveillance data, a factor analysis theory was used to analyze the 12 risk factors influencing the epidemicity of epidemic cerebrospinal meningitis. The results showed that the first sixth risk factors were the rate of carrying meningococci A and B in the population, relative air humidity in January, morbidity rate in January, vaccination rate before epidemic, and the titre of antibody. Although the incidences of epidemic cerebrospinal meningitis are scattered, the risk factors influencing the epidemicity did not disappear. It is important to use meningococci A vaccine continuously and widely to strengthen the surveillance among migrated population and population at high risk.

Carrier State↗
PubMed1999

Receptor for calcitonin gene-related peptide: localization in the dorsal and ventral spinal cord.

Although the distribution of calcitonin gene-related peptide has been extensively studied in the spinal cord, little is known about the precise subcellular localization of receptors for calcitonin gene-related peptide. The present study was undertaken to localize calcitonin gene-related peptide receptors in both the dorsal and ventral horns of the rat spinal cord. Immunocytochemical localization with specific monoclonal antibodies was performed at the light and electron microscopic levels. Calcitonin gene-related peptide receptor was expressed in neuronal but not glial elements. Discrete postsynaptic localization of receptor for the calcitonin gene-related peptide was evident in the cells and dendrites of the superficial dorsal horn. Some of the terminal endings apposing the stained synapses formed the central terminals of glomerular complexes. The endings were scallop shaped (Type I), typical of primary afferent terminations. Other dorsal horn structures with postsynaptic labeling were contacted by dome-shaped or elongated axonal endings. Presynaptic localization on some dorsal horn terminations may serve an autoreceptor function. Motoneurons, on the other hand, were contacted by axonal terminals with presynaptic calcitonin gene-related peptide receptors. These data suggest that (i) dorsal horn neurons are capable of direct primary afferent, calcitonin gene-related peptide receptor-mediated interactions and (ii) neuronal terminals contacting motor horn cells can be influenced through presynaptic paracrine-like calcitonin gene-related peptide receptor-mediated interactions. Thus, calcitonin gene-related peptide can have multiple modulatory effects on spinal cord neurons through site-specific receptors.

Animals↗
PubMed1999

Diffuse T1 reduction in gray matter of sickle cell disease patients: evidence of selective vulnerability to damage?

The objective of our study was to test the hypothesis that subtle brain abnormality can be present in pediatric sickle cell disease (SCD) patients normal by conventional MR imaging (cMRI). We examined 50 SCD patients to identify those patients who were normal by cMRI. Quantitative MR imaging (qMRI) was then used to map spin-lattice relaxation time (T1) in a single slice in brain tissue of all 50 patients and in 52 healthy age-similar controls. We also used a radiofrequency (RF) pulse to saturate blood spins flowing into the T1 map slice, to characterize the effect of blood flow on brain T1. Abnormalities were noted by cMRI in 42% (21/50) of patients, with lacunae in 32%, and encephalo malacia in 20%. Brain T1 in patients normal by cMRI was significantly lower than controls, in caudate, thalamus, and cortex (p < or =0.007), and regression showed that gray matter T1 abnormality was present in caudate and cortex by age 4 (p < or =0.002). In patients abnormal by cMRI, T1 reductions in gray matter were larger and more significant. White matter T1 was not significantly increased except in patients abnormal by cMRI. RF saturation in a slab below the T1 map produced no significant change in T1, compared to RF saturation in a slab above the T1 map, suggesting that inflow of untipped spins in blood does not cause an artifactual shortening of T1. Gray matter T1 abnormality was present in patients normal by cMRI, while white matter T1 abnormality was present only in patients also abnormal by cMRI. These findings suggest that gray matter is selectively vulnerable to damage in pediatric SCD patients and that white matter damage occurs later in the disease process. Our inability to find an effect from saturation of inflowing blood implies that rapid perfusion cannot account for T1 reduction in gray matter.

Anemia, Sickle Cell↗
PubMed1999

Association of influenza virus matrix protein with ribonucleoproteins.

To characterize the sites and nature of binding of influenza A virus matrix protein (M1) to ribonucleoprotein (RNP), M1 of A/WSN/33 was altered by deletion or site-directed mutagenesis, expressed in vitro, and allowed to attach to RNP under a variety of conditions. Approximately 70% of the wild-type (Wt) M1 bound to RNP at pH 7.0, but less than 5% of M1 associated with RNP at pH 5.0. Increasing the concentration of NaCl reduced M1 binding, but even at a high salt concentration (0.6 M NaCl), approximately 20% of the input M1 was capable of binding to RNP. Mutations altering potential M1 RNA-binding regions (basic amino acids 101RKLKR105 and the zinc finger motif at amino acids 148 to 162) had varied effect: mutations of amino acids 101 to 105 reduced RNP binding compared to the Wt M1, but mutations of zinc finger motif did not. Treatment of RNP with RNase reduced M1 binding by approximately half, but even M1 mutants lacking RNA-binding regions had residual binding to RNase-treated RNP provided that the N-terminal 76 amino acids of M1 (containing two hydrophobic domains) were intact. Addition of detergent to the reaction mixture further reduced binding related to the N-terminal 76 amino acids and showed the greatest effect for mutations affecting the RNA-binding regions of basic amino acids. The data suggest that M1 interacts with both the RNA and protein components of RNP in assembly and disassembly of influenza A viruses.

Animals↗