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Biomedical subjects

J Miao

Publications and source records attributed to J Miao.

At least 19 recordsLinked to original sources

Evaluation of polyaluminium ferric chloride (PAFC) as a composite coagulant for water and wastewater treatment.

Coal gangue is a kind of waste from coal mine processing. Polyaluminium ferric chloride (PAFC), a new type of inorganic composite coagulant, was prepared by using the waste from the Mineral Bureau of Yanzhou, China, hydrochloric acid and calcium carbonate as raw materials. The relationship between the stability of ferric ion and the ionic strength of solution was investigated. The zeta potential of PAFC hydrolysis products of PAFC and the coagulation performances under different pH value were discussed. The turbidity removal properties of PAFC, polyaluminium (PAC) and polyferric sulfate (PFS) were compared, and the color removal effect of PAFC for the wastewater containing suspended dyes was also tested. In addition, the coagulation performance of PAFC for actual wastewaters from petrochemical plant, iron and steel plant, and coal mining processing was evaluated. The experimental results suggest that PAFC took a maximum value of zeta potential at about pH 5.8 on the positive side. Compared with PAC, PAFC gives better turbidity removal performance in the range of pH from 7.0 to 8.4. PAFC gives good color removal performance on suspension dyes. PAFC also gives good wastewater purifying results for the actual wastewater. Therefore, PAFC is a high-effect and stable water treatment agent.

Aluminum Hydroxide↗

An approach to three-dimensional structures of biomolecules by using single-molecule diffraction images.

We describe an approach to the high-resolution three-dimensional structural determination of macromolecules that utilizes ultrashort, intense x-ray pulses to record diffraction data in combination with direct phase retrieval by the oversampling technique. It is shown that a simulated molecular diffraction pattern at 2.5-A resolution accumulated from multiple copies of single rubisco biomolecules, each generated by a femtosecond-level x-ray free electron laser pulse, can be successfully phased and transformed into an accurate electron density map comparable to that obtained by more conventional methods. The phase problem is solved by using an iterative algorithm with a random phase set as an initial input. The convergence speed of the algorithm is reasonably fast, typically around a few hundred iterations. This approach and phasing method do not require any ab initio information about the molecule, do not require an extended ordered lattice array, and can tolerate high noise and some missing intensity data at the center of the diffraction pattern. With the prospects of the x-ray free electron lasers, this approach could provide a major new opportunity for the high-resolution three-dimensional structure determination of single biomolecules.

Computer Simulation↗

High frequency of beta-catenin mutations in hepatoblastoma.

Hepatoblastoma (HB) is an embryonic neoplasm representing the most frequent malignant liver tumour in childhood. Its tumourigenesis at the molecular level is still poorly understood, and candidate genes are yet to be identified. According to recent reports describing beta-catenin mutations (BCM) at hot-spot regions involving exon 3 in several types of malignancies including HB, we investigated BCM in 16 HBs classified into different histological types. One tumour had been previously confirmed to harbour adenomatous polyposis coli (APC) mutations that exhibit a similar oncogenic effect to that of BCM. Mutations in both exon 3 and its flanking region of the beta-catenin gene were investigated and determined. Twelve tumours (75%) revealed pathogenic BCM, including 5 with missense mutations at codons 32, 34, or 37 and 7 with interstitial deletions that partially or totally affected exon 3. All 7 deletions were in-frame deletions without frameshift. A single nucleotide change at codon 31 regarded as non-pathogenic polymorphism was detected in the tumour possessing APC mutations. Therefore, a total of 13 tumours (81%) were compromised by an enhanced beta-catenin-mediated transcription pathway. Mutations were observed in every histological type of HB. The very high frequency without correlation to histological type indicates that BCM are crucial events in the tumourigenesis of HB.

Child↗

Lensless imaging: a workshop on "new approaches to the phase problem for non-periodic objects.".

Over the past two decades, theoretical tools and algorithms have been developed which, under not very restrictive conditions, allow the reconstruction of images from diffraction patterns of non-periodic objects. These methods promise lensless imaging for any radiation, free of aberrations, with wavelength-limited resolution. Recent experimental successes prompted an interdisciplinary international workshop on this topic at the Lawrence Berkeley National Laboratory, Berkeley, CA, USA, on May 17-19 2001, supported by the DOE, LBL and the Advanced Light Source. Our aim was to review the field, and to stimulate communication between the Signal Recovery, Coherent Optics, X-ray, Electron Microscopy and Applied Mathematics communities. The results are summarized in this paper and on the web. A second workshop is planned for 2003.

Journal Article↗

Differential expression of a stress-modulating gene, BRE, in the adrenal gland, in adrenal neoplasia, and in abnormal adrenal tissues.

Genes that modulate the action of hormones and cytokines play a critical role in stress response, survival, and in growth and differentiation of cells. Many of these biological response modifiers are responsible for various pathological conditions, including inflammation, infection, cachexia, aging, genetic disorders, and cancer. We have previously identified a new gene, BRE, that is responsive to DNA damage and retinoic acid. Using multiple-tissue dot-blotting and Northern blotting, BRE was recently found to be strongly expressed in adrenal cortex and medulla, in testis, and in pancreas, whereas low expression was found in the thyroid, thymus, small intestine and stomach. In situ hybridization and immunohistochemical staining indicated that BRE was strongly expressed in the zona glomerulosa of the adrenal cortex, which synthesizes and secretes the mineralocorticoid hormones. It is also highly expressed in the glial and neuronal cells of the brain and in the round spermatids, Sertoli cells, and Leydig cells of the testis, all of which are associated with steroid hormones and/or TNF synthesis. However, BRE expression was downregulated in human adrenal adenoma and pheochromocytoma, whereas its expression was enhanced in abnormal adrenal tissues of rats chronically treated with nitrate or nitrite. These data, taken together, indicate that the expression of BRE is apparently associated with steroids and/or TNF production and the regulation of endocrine functions. BRE may play an important role in the endocrine and immune system, such as the cytokine-endocrine interaction of the adrenal gland.

Adrenal Gland Neoplasms↗

[Analysis of causes of death and YPLL on residents in the industrial pollution area in Chongqing from 1991 to 1998].

OBJECTIVE: To investigate the causes of death in residents living in the area of industrial pollution in Chongqing. METHODS: Mortality rate, sequence of causes of death, years of potential life lost (YPLL) and the valued years of potential life lost (VYPLL) were used to analyze causes of death in 1991 - 1998. Community not polluted by industry was chosen to serve as control. RESULTS: The annual average mortality rate of the residents was 7.34 per thousand (standard mortality rate 4.61 per thousand). The sequence of major causes of death was shown as below: malignant tumors (mortality rate 198.07/10(5), standard mortality rate 126.35/10(5)), cerebrovascular diseases (mortality rate 159.13/10(5), standard mortality rate 92.66/10(5)), respiratory system diseases (mortality rate 107.33/10(5), standard mortality rate 84.85/10(5)), cardiac diseases (mortality rate 95.36/10(5), standard mortality rate 59.37/10(5)) and accidental deaths (mortality rate 47.08/10(5), standard mortality rate 43.28/10(5)). Among malignant tumors, lung cancer took the lead with a mortality rate of 65.49/10(5) (standard mortality rate 45.27/10(5)). In both sequences of standard rates of YPLL and VYPLL for major causes of deaths, accidental death was always took the first place. CONCLUSION: In order to reduce mortality rate of the residents in the area, it is necessary to strengthen the administration of natural and social environment of the area.

Accidents↗

[Comparison of immune responses elicited by recombinant protein and eukaryotic expression plasmid based on histidine rich protein 2 of Plasmodium falciparum].

OBJECTIVE: To identify the immune characteristics of different vaccine prototypes based on HRP2 and to provide experimental evidence for developing P. f. blood stage vaccines. METHODS: BALB/c mice were immunized with recombinant protein TP-HRP2 or eukaryotic expression plasmid pcDNA3.1(-)/HRP2. The kinetics and specificities of antibody responses were analyzed. The proliferation tests of spleen cells were done, and P. f. growth inhibition assays were done with immune sera. RESULTS: The mice immunized with TP-HRP2 in Freund's adjuvant produced high-level and high-specificity antibody response. The antibodies appeared rapidly and lasted for a longer time. Cellular responses were induced simultaneously, and the immune sera could inhibit the development of parasite in IRBCs. The mice immunized with pcDNA3.1(-)/HRP2 produced middle-level antibody response which had some specificity, however, the induction of antibodies required repeated inoculation and a longer duration. Immune cells were well primed and the memorial immune response was obvious but the immune sera had no effect on the growth of P.f. in vitro. CONCLUSION: Both the recombinant protein and plasmid DNA based on HRP2 have different immune characteristics in mice. HRP2 recombinant protein has the potential in practical application.

Animals↗

[Three dimensional quantitative structure activity relationship of P450(17) alpha inhibitors of 17-substituted steroids].

AIM: To develop a three dimensional quantitative structure activity relationship (3D-QSAR) model and gain further insights into the requirements for potential P450(17) alpha inhibitors. METHODS AND RESULTS: A predictive 3D pharmacophore model was established based on comparative molecular field analysis (CoMFA). The correlation between the activities and structures was significant with cross-validated value (R2cv), non-cross-validated value (R2) and standard error of estimate (SEE) of 0.538, 0.799 and 0.257, respectively. According to this model, the predicted inhibition activities of three compounds synthesized in our laboratory were compatible to actual activities. CONCLUSION: This model would contribute to the understanding of the interaction between the inhibitors and P450(17) alpha and rational design of novel lead molecules.

Enzyme Inhibitors↗

Identification of the subcellular localization of daunorubicin in multidrug-resistant K562 cell line.

We examined the subcellular distribution of daunorubicin (DNR) in resistant K562 cell line which overexpress the P-glycoprotein by confocal laser scanning microscopy. Three fluorescent probes - Rhodamine123, neutral red, NBD-ceramide, which stain the mitochondria, lysosomes, Golgi apparatus respectively, were used to identify the nature of the subcellular compartment sequestering daunorubicin. In sensitive k562 cell line, nuclear and cytoplasmic DNR fluorescence was intense and diffuse. In contrast, resistant K562 cell line showed a different DNR distribution. A bright fluorescence signal was located in the perinuclear region and peripheral plasma, the nucleus and other cytoplasmic region appear as empty, as suggested by the distribution of fluorescent probe Rhodamine123 specifically for mitochondria. Verapamil, an effective resistance modulator in P-glycoprotein MDR cells, restored the DNR distribution closer to that in the parent cells. Golgic inhibitor brefeldin A and lysosomotropic agent chloroquine had little effect on drug sequestration. Our studies demonstrate that daunorubicin may be sequestered in mitochondrial compartment in the resistant cells and P-glycoprotein plays an important role on mediating DNR transport.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Bone-marrow microinvolvement in non-small cell lung cancer is not a reliable indicator of tumour recurrence and prognosis.

AIMS: This study aimed to examine the incidence of bone-marrow microinvolvement in non-small cell lung cancer (NSCLC) patients and its correlation with tumour recurrence and prognosis. METHODS: Between March 1997 and August 1998, we analysed 96 bone-marrow specimens (from the posterior iliac crest) of NSCLC patients before surgery. Tumour differentiation showed well differentiated carcinoma in six, moderately differentiated carcinoma in 69, and poorly differentiated carcinoma in 21. p-TNM staging showed stage Ia in five, stage Ib in 33, stage IIb in 19, stage IIIa in 26, stage IIIb in eight, and stage IV in five. The specimens were examined by immunohistochemical staining with anti-human cytokeratin AE1/AE3 and clone MNF116 mixed solution (Ab1, n=96) and/or Ber-EP4 (Ab2, n=80) to detect the presence of malignant epithelial cells in the bone marrow. RESULTS: Positive results were observed in 21 patients (21. 9%). The occurrence of bone-marrow microinvolvement was not related to patient age, sex, cell type, or TNM status. The 30-month disease-free survival rates were 50.2% and 53.9% in bone-marrow negative and bone-marrow positive patients, respectively (P=0.5670); the 30-month cumulative survival rates were 66.7% and 67.6% in bone-marrow negative and bone-marrow positive patients, respectively (P=0.9351). Multivariate analysis failed to demonstrate bone-marrow microinvolvement as an independent prognostic factor. CONCLUSIONS: Our results show that bone-marrow microinvolvement is not unusual, and its occurrence cannot be translated into early tumour recurrence or poor outcome during an intermediate-term follow-up, which means bone-marrow microinvolvement may be an epiphenomenon rather than true metastasis in NSCLC.

Adult↗

On possible extensions of X-ray crystallography through diffraction-pattern oversampling

It is known that sampling the diffraction pattern of a finite specimen, at a spacing somewhat finer than the Nyquist spacing (the inverse of the size of the diffracting specimen), corresponds to generating a no-density region surrounding the electron density of the specimen. This no-density region can then be used to retrieve the phase information. In earlier papers [Miao, Sayre & Chapman (1998). J. Opt. Soc. Am. A15, 1662-1669; Sayre, Chapman & Miao (1998). Acta Cryst. A54, 232-239], it was demonstrated, in the case of non-crystalline specimens, that this no-density region could be used to retrieve the phase information; here the same is performed for crystalline and near-crystalline specimens. By employment of an iterative algorithm, the phase information could be recovered from computer-generated oversampled diffraction patterns of small specimens that are (a) perfect or imperfect crystals, or (b) have a repeated motif without orientational regularity, or (c) are an unrepeated motif, such as an amorphous glass, a single molecule or a single biological cell. Cases (a) and (b) represent an extension over work recently published [Miao, Charalambous, Kirz & Sayre (1999). Nature (London), 400, 342-344]. Our algorithm requires an approximate envelope for the specimen. It does not require any structural knowledge concerning the specimen and does not require data to atomic resolution (although it can use such data if present). After a few hundred to a few thousand iterations, the correct phase set and image are recovered. The oversampling technique thus greatly extends the specimen range of X-ray crystallography but it imposes a high radiation dose on the specimens compared with the situation in crystallography, in which it is usual for the pattern to be sampled at the (much less fine) Bragg spacing (the inverse of the size of the unit cell). In cases where the specimen is a crystal, there are also possibilities for oversampling relative to Bragg (instead of Nyquist) sampling, thus providing a lesser degree of oversampling and the possibility of lower dosage. Damage of the specimen in consequence of the dose will in many cases seriously affect the quality and resolution of the imaging, but in at least one case [the biological cell in (c) above] the imaging obtainable with the aid of a cryogenic protective technique should surpass any other present method of whole-cell imaging. In addition, with the possible appearance in the future of free electron lasers (>10(12) photons and <200 fs per pulse), it is possible to circumvent the radiation-damage problem by recording diffraction patterns before damage manifests itself.

Journal Article↗

The oversampling phasing method.

Sampling the diffraction pattern of a finite specimen more finely than the Nyquist frequency (the inverse of the size of the diffracting specimen) corresponds to surrounding the electron density of the specimen with a no-density region. When the no-density region is bigger than the electron-density region, sufficient information is recorded so that the phase information can be retrieved from the oversampled diffraction pattern, at least in principle. By employing an iterative algorithm, the phase information from the oversampled diffraction pattern of a micrometre-sized test specimen has been successfully retrieved. This method is believed to be able to open a door for high-resolution three-dimensional structure determination of complex and non-crystalline biological specimens, i.e. whole cells and sub-micrometre molecular clusters and micrometre-sized protein crystals. With the possible appearance in the future of X-ray free-electron lasers, it may become possible to image single molecules by recording diffraction patterns before radiation damage manifests itself.

Image Processing, Computer-Assisted↗

[Molecular proof of wheat transformed by total DNA of Leymus racemosus].

Four repetitive DNA sequences (pHv7161, pHv7179, pHv7191 and pHv7293) cloned from barley (Hordeum vulgare) genome were used for a molecular hybridization in the genome of Leymus racemosus (donor), Spring wheat 761 (receptor) and the wheat transformed by total DNA of Leymus racemosus (donor) through pollen tube pathway. Our results indicate that some bands are common in Leymus racemosus and the transformed wheat but absent in Spring wheat 761. The HindIII fragments which are common in Leymus racemosus and the transformed wheat have been cloned. The clone of Leymus racemosus was nominated as pLR980. pLR980 contains the homologous sequences to the four repetitive sequences of barley. The pLR980 cloned from Leymus racemosus was used as probe to study Leymus racemosus, Spring wheat 761 and the transformed wheat. This study demonstrate that pLR980 is homologous in both genome of Leymus racemosus and wheat. Common bands absent in the Spring wheat 761 were also showed in Leymus racemosus and the transformed wheat. pLR980 was proved to be associated with the transform of wheat by total DNA of Leymus racemosus through pollen tube pathway. This provides a direct witness to the exogenous DNA introduction.

DNA, Plant↗

[Effects of PML and PML-RAR alpha antisense oligonucleotides on promyelocytic leukemia cell line NB4].

OBJECTIVE: To investigate the different effects of anti-PML (promyelocytic leukemia) and anti-PML/RAR alpha (promyelocytic leukemia/retionic acid receptor alpha) antisense oligonucleotides on cell growth, expression of PML-RAR alpha mRNA and PML-RAR alpha/PML protein location of NB4 cell line. METHODS: RT-PCR was used for PML-RAR alpha mRNA expression, trypan blue exclusion for cell count, methylcellulose assay for leukemic colony forming unit, immuno-fluorescence for PML-RAR alpha/PML protein localization. RESULTS: Both anti-PML start codon region antisense (STAS) and anti-PML-RAR alpha fusion region antisense (FUAS) could inhibit cell growth and formation AML-CFU. Cells became partially differentiated on day 5, being more marked in FUAS-treated cells than in STAS-treated ones. Down regulated PML-RAR alpha mRNA expression occurred at 24 h was in STAS and FUAS-treated cells and maintained for up to 72 h. Immuno-fluorescence analysis with anti-PML monoclonal antibody showed a remarkable decrease to almost complete disappearance of microgranules. The residual granules became enlarged to become discrete dots (< 10 per cell), similar to normal POD structure in some STAS-treated cells at 24 h. AT 72 h, nearly all the granules disappeared. Similar changes were observed in FUAS-treated cells. CONCLUSION: Both PML and PML-RAR alpha antisense oligonucleotides can specifically block the expression of PML-RAR alpha at mRNA and protein levels. PML protein is implicated in the regulation of cell differentiation.

Cell Division↗

[Immune response in mice induced by C terminal encoding gene of Plasmodium falciparum histidine rich protein. 2].

OBJECTIVE: To explore the humoral and cellular immune responses in mice to eukaryotic expression recombinant plasmid encoding histidine rich protein 2 (HRP-II) of Plasmodium falciparum. METHODS: The start and stop codes were introduced into HRP-II gene fragment, the reading frame and the position of start and stop codes in HRP-II were identified by sequencing. HRP-II fragment containing the start and stop codes was cloned into pcDNA3.1 (-) to form pcDNA3.1 (-)/HRP-II. The BALB/c mice were immunized i.m. with the plasmids for 3 times in 3 weeks intervals. Two weeks after the last immunization, the sera and splenocytes were collected to investigate anti-HRP-II antibodies by ELISA and the splenocytes proliferation response to HRP-II. RESULTS: Sequence data show that the reading frame and the position of start and stop codes are correct. Restriction enzyme digestion indicated that the HRP-II gene fragment containing start and stop codes was successfully cloned into pcDNA3.1 (-). Mice raised significant anti-HRP-II antibodies after pcDNA3.1 (-)/HRP-II immunization, and the splenocytes proliferated prominently when stimulated with HRP-II protein. CONCLUSION: Eukaryotic expression recombinant plasmid encoding HRP-II gene can induce significantly humoral and cellular immune response in mice. HRP-II gene may be a good candidate for P. falciparum blood-stage multiple DNA vaccine.

Animals↗