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Biomedical subjects

M Zhao

Publications and source records attributed to M Zhao.

At least 127 records · Page 7Linked to original sources

Establishment and pathological study of models of chronic obstructive pulmonary disease by SO2 inhalation method.

OBJECTIVE: To establish rat models of chronic obstructive pulmonary disease (COPD) and study the pathological characteristics of airflow obstruction. METHOD: SO2 inhalation method was used to establish rat models. After exposure to SO2 for 7 weeks, peak expiratory flow (PEF), peak inspiratory flow (PIF), intratracheal pressure (IP) and IP slope in rat were measured by Maclab data recording and analysis system. Experimental rats with PEF less than 80% of the mean of the normal rats were classified as airflow obstructed, while those with PEF greater than 80% of mean of normal rats were non-obstructed. Pathological changes in airway and lung tissue were compared between these two groups. RESULT: In experimental animals, PEF was significantly decreased (P < 0.005) and IP slope increased (P < 0.001) as compared with normal rats. Epithelial damage, goblet cell hyperplasia and inflammatory cell infiltration in cartilaginous bronchi were more remarkable in experimental rats with airflow obstruction than those without airflow obstruction (P < 0.001, < 0.01, < 0.001, respectively). Furthermore, pathological changes in airway lumen, epithelium and airway wall in membranous and respiratory bronchioles were more marked in experimental rats with airflow obstruction than those without airflow obstruction (P < 0.001 or P < 0.05). There was a negative correlation between PEF values and epithelial hyperplasia, goblet cell hyperplasia, inflammatory cell infiltration, smooth muscle hyperplasia and mucous plug in membranous and respiratory bronchioles (P < 0.001 or P < 0.05). CONCLUSION: SO2 inhalation may cause chronic bronchitis with airflow obstruction, i.e. COPD in rats. COPD was induced in 64% (16 of 25) of the experimental group rats.

Administration, Inhalation↗

[The effect of antisense hsp90 beta on the malignant phenotype and sensitivity of HeLa cells to chemotherapeutic drugs].

OBJECTIVE: To study the effects of hsp90 beta on tumorigenesis and sensitivity of HeLa cells to chemotherapeutic drugs. METHODS: A recombinant plasmid expressing either sense or antisense hsp90 beta RNA, and a vector pLXSN were transfected into HeLa cell line by lipofectin method. The transfected cells were screened by G418. The growth rates of the transfected HeLa cells and their sensitivity to adriamycin(ADM) and cisplatin (CDDP) were examined by cell count and MTT uptake. Colony formation in soft agar was used to embody the malignant phenotype in vitro. RESULTS: There was little difference between HeLa cells transfected with sense RNA plasmids and pLXSN vector. The growth rate of HeLa cells transfected with antisense RNA declined, and their ability to form colony in soft agar was decreased. The sensitity of the antisense hsp90 beta transfected HeLa cells to ADM and CDDP increased 2.1-5.8 fold; the LD50 decreased to 1/2-1/5 that of the wild-type HeLa cells. CONCLUSION: Hsp90 beta is involved in the maintenance of malignant phenotype and drug resistance in HeLa cells.

Antineoplastic Agents↗

[The changes of guanylin in plasma and lung tissue from asthmatic guinea pigs].

OBJECTIVE: To study the changes of guanylin in asthmatic guinea pig models. METHODS: Male guinea pigs were randomly divided into two groups: the control (n = 6) and the asthma group (n = 10). The levels of guanylin in plasma, BALF and lung tissue were measured by RIA kit. The mean thickness of airway wall and glands was determined by contour tracing, using a digitizing pad and microcomputer. RESULTS: The levels of guanylin in plasma and lung tissue from the asthma group were 56% and 183% higher than those of the control (P < 0.01). Concentrations of guanylin in BALF from the control were below the detection level in 4 guinea pigs, and 1.7 pg/ml and 1.6 pg/ml in two, respectively. The level of guanylin in BALF from asthma group was (3.1 +/- 1.2) pg/ml. The level of guanylin in the lung tissue correlated with that in plasma and BALF (r = 0.72, P < 0.01, r = 0.61, P < 0.05, respectively). The level of guanylin in plasma did not correlate with those of BALF (r = 0.32, P > 0.05). The mean thickness of airway wall and glands in asthma group were 86% and 87% greater than those of the control respectively (P < 0.01). The level of guanylin in lung tissue correlated with the thickness of glands (r = 0.95, P < 0.01). CONCLUSIONS: In the guinea pig model of asthma, guanylin in plasma, BALF and lung tissue were increased, indicating that it may play a role in the mechanism of airway hypersecretion in asthma.

Animals↗

[Immunologic experimental studies on the alkali burn of cornea in rats].

OBJECTIVE: To investigate the immune reaction of severe corneal alkali burns. METHODS: The models of severe corneal alkali burns were induced in rats. Immunohistochemistry was carried out on wholemounts of the cornea and iris at different time points after corneal burns to detect T-lymphocytes and their subpopulation, macrophages, dendritic cells and MHC class II -positive cells. RESULTS: In the early stage of the burns, there were small increasing number of T-lymphocytes and MHC class II-positive cells in the cornea and iris. At the period of corneal melting and perforation, a massive influx of lymphocytes (CD(+)(3), CD(+)(4), CD(+)(8)), macrophages and dendritic cells was seen in the cornea adjacent to the limbus and iris. CD(+)(4) lymphocytes were much more than CD(+)(8) in number. T-cells and MHC class II-positive cells were observed not only at the limbus but also in the melting area and corneal center. Morphological changes of these cells were also noted. In the restoration stage, a number of positive cells were still found in the iris. CONCLUSION: Immunological mechanism is involved in the pathological changes of the damage induced by corneal alkali burns, especially in the pathogenesis of the corneal melting and perforation.

Alkalies↗

[A study on apoptosis and activity of SAPK/JNK in adrenocortical cells induced by cadmium chloride].

OBJECTIVE: To study apoptosis induced by cadmium chloride and the alteration in activity of stress activated protein kinase (SAPK) in adrenocortical cells. METHODS: Fasciculata-glomerulosa (FG) cells of male guinea pigs were dispersed and primarily cultured in vitro. Features of apoptotic cells were observed using combined labeling with annexin-V and propidium iodide (PI) and flow cytometry, and activity of SAPK was determined with immunoprecipitation and chemiluminescence assay. RESULTS: Apoptosis rate of FG cells increased with dose of cadmium chloride (CdCl(2)) two hours after treatment with 6.25 - 200.00 micromol/L of it. The average percentages of apoptotic cells ranged from 9.90% to 82.35%, with significant difference in the groups treated with 25, 50, 100 and 200 micromol/L of CdCl(2), as compared with the control group (P < 0.01). Regression analysis showed that occurrence of apoptosis correlated with the dose of cadmium chloride in a dose-response pattern. In the meanwhile, there were obviously elevated percentages of apoptotic cells as the increase in duration of incubation, ranging from 5.58% to 73.08% for incubating cells with 50.00 micromol/L of CdCl(2), from 15 minutes to four hours. Duration of incubating cells with cadmium chloride correlated to occurrence of apoptosis in a time-effect manner. There were no remarkable changes in the activity of SAPK in adrenocortical cells two hours after incubation with 25.00 - 100.00 micromol/L of CdCl(2). CONCLUSIONS: Apoptosis can be induced by cadmium chloride in adrenocortical cells and its mechanism should be studied further.

Adrenal Cortex↗

[Establishment and identification of B cell lines with PNH phenotype].

OBJECTIVE: To establish B cell lines from patients with paroxysmal nocturnal haemoglobinuria (PNH) and normal controls. METHODS: B lymphoid cells prepared from PNH patients and normal controls were infected with EB virus. Phenotype of the immortal cells was analyzed by flow cytometry. The immunomagnetic beads were used to select CD(55)(-) and CD(59)(-) B lymphoid cells, which were cloned by limiting dilution. The clonality of the cloned cells was confirmed by testing the pattern of Ig rearrangements using polymerase chain reaction (PCR). RESULTS: From 2 PNH patients and 2 normal controls, CD(55)(-) and CD(59)(-) B lymphoblastoid cell lines were established which had PNH phenotype and normal phenotype, respectively. CONCLUSION: B lymphoid cell lines from PNH patients can be obtained by EB virus infection.

B-Lymphocytes↗

[Study on clinical and laboratory features of preleukemia patients].

OBJECTIVE: To explore prospective diagnostic criteria for preleukemia. METHODS: A case control study of the discrepancies of clinical and laboratory features between patients with preleukemia and those with chronic aplastic anemia (CAA) or atypical paroxysmal nocturnal hemoglubinuria (a-PNH). RESULTS: There were eight variables of significance: (1) lymphocytoid micromegakaryocytes in marrow; (2) immature granulocytes in peripheral blood; (3) >or= 2% myeloblasts in marrow; (4) positive periodic acid schiff (PAS) staining of nucleated erythrocytes; (5) myeloid differentiation index >or= 1.8; (6) clonal karyotypic abnormalities; (7) negative sister chromatid differentiation; (8) > 4.0 cluster/colony ratio of granulocyte-macrophage colony-forming units (CFU-GM). The following criteria was assigned: A: To meet (1) and at least two of the other seven variables; B: To meet at least four of the eight variables. All of the patients with preleukemia met A or B and none of the patients with CAA or a-PNH did. CONCLUSION: Preleukemia is different from CAA or a-PNH. It has its own clinical and laboratory features, which may be useful for prospective diagnosis.

Adolescent↗

[The preliminary analysis on the changes of the oral functional space in Class II division 1 malocclusion after triggered by functional appliance].

OBJECTIVE: The purpose of this paper is to study the area changes of the oral functional space in the patients with Angle's Class II division 1 malocclusion after triggered by FR-I functional appliances. METHODS: Twenty patients with Angle's Class II division 1 malocclusion were selected, and the patients were selected by the standards of an horizontal growth pattern with normal maxilla, retracted mandible and short lower facial height. All patients were triggered by FR-I functional appliances and achieved the Angle's Class I occlusion after treatments. The average periods of the treatments were about 9 months. The assessments were made from the lateral cephalograms taken in centric occlusion before and after treatments. The upper and behind borders of the oral functional space are hard palate and soft palate, the forward border is the lingual side of upper and lower incisors, the lower border is the line between apex of lower incisor and lower first molar. The graphics from the lateral cephalogram were painted and input into the computer by scaner, which were measured by special software. Self-controls of individuals before and after treatments were used in statistic analysis. RESULTS: The paired-samples t test confirmed the oral functional space was enlarged after triggered by FR-I functional appliance, which was induced by obviously increased mandibular body and ramus, anterior lower facial height and posterior facial height. At the same time, the angle of Y axis increased and the upper incisor inclined lingually, but the inclining angle of lower incisor was not obvious. CONCLUSION: Enlarged oral functional space facilitates the development of the maxilla, mandible and alveolar bones and consummates the functions of oral and jaw system. This study aids the design and application of FR-I functional appliance.

Adolescent↗

[The design, functions and clinic applications of lip bumper].

OBJECTIVE: This paper introduced the principle of design, methods of fabrication, indications and functions of lip bumper, and advocated the application of lip bumper in orthodontic clinic. METHODS: Two typical cases treated with lip bumper were introduced. Some notices and experiences of applying lip bumpers were summed up. RESULTS: There were following functions of lip bumper: as a space maintainer, Fränkel effect, headgear effect, post-maxillary expansion retention, derotation of molars, and combined using with headgear. CONCLUSION: The advantages of lip bumper are inclusions of a wide range of indication, wearing for 24 hours per day, easily fabricating and prefabricating, comfortable and hidden for patients.

Child↗

[Analysis of 19 cases adenoid cystic carcinoma of the nasal cavity].

OBJECTIVE: To study the biological features of adenoid cystic carcinoma of the nasal cavity in order to provide a basis for its clinical treatment. METHOD: A retrospective analysis was made to 19 cases which were treated with operation combined with preoperative chemotherapy and radiation. RESULT: 5, 8, and 10 years' follow-ups conducted post treatment showed the local recurrence rates were 5.3%, 21.1%, and 31.6% respectively. CONCLUSION: Adenoid cystic carcinoma of the nasal cavity is highlighted because of high-degree local infiltration, the specific anatomy of the cavity, and the difficulty of wide-ranging surgical resection. Preoperative chemotherapy combined with radiation has the advantages of extinguishing the recessive cancerous foci, inhibiting the primary foci and lowering local recurrences and cancerous metastases. Thus it constitutes an effective way to deal with this malignancy.

Adult↗

Identification of amino acids in the factor XI apple 3 domain required for activation of factor IX.

Activated coagulation factor XI (factor XIa) proteolytically cleaves its substrate, factor IX, in an interaction requiring the factor XI A3 domain (Sun, Y., and Gailani, D. (1996) J. Biol. Chem. 271, 29023-29028). To identify key amino acids involved in factor IX activation, recombinant factor XIa proteins containing alanine substitutions for wild-type sequence were expressed in 293 fibroblasts and tested in a plasma clotting assay. Substitutions for Ile(183)-Val(191) and Ser(195)-Ile(197) at the N terminus and for Ser(258)-Ser(264) at the C terminus of the A3 domain markedly decreased factor XI coagulant activity. The plasma protease prekallikrein is structurally homologous to factor XI, but activated factor IX poorly. A chimeric factor XIa molecule with the A3 domain replaced with A3 from prekallikrein (FXI/PKA3) activated factor IX with a K(m) 35-fold greater than that of wild-type factor XI. FXI/PKA3 was used as a template for a series of proteins in which prekallikrein A3 sequence was replaced with factor XI sequence to restore factor IX activation. Clotting and kinetics studies using these chimeras confirmed the results obtained with alanine mutants. Amino acids between Ile(183) and Val(191) are necessary for proper factor IX activation, but additional sequence between Ser(195) and Ile(197) or between Phe(260) and Ser(265) is required for complete restoration of activation.

Amino Acid Sequence↗

Stimulation of bone formation in vitro and in rodents by statins.

Osteoporosis and other diseases of bone loss are a major public health problem. Here it is shown that the statins, drugs widely used for lowering serum cholesterol, also enhance new bone formation in vitro and in rodents. This effect was associated with increased expression of the bone morphogenetic protein-2 (BMP-2) gene in bone cells. Lovastatin and simvastatin increased bone formation when injected subcutaneously over the calvaria of mice and increased cancellous bone volume when orally administered to rats. Thus, in appropriate doses, statins may have therapeutic applications for the treatment of osteoporosis.

Animals↗

Nitroxide scanning electron paramagnetic resonance of helices IV and V and the intervening loop in the lactose permease of Escherichia coli.

Glu126 and Arg144 in helices IV and V, respectively, in the lactose permease of Escherichia coli, which play an indispensable role in substrate binding, are charge-paired and in close proximity [Venkatesan, P., Kaback, H. R. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 9802-9807; Zhao, M., Zen, K.-C., et al. (1999) Biochemistry 38, 7407-7412]. Since hydropathy plots indicate that these residues are at the membrane-water interface at the cytoplasmic surface of the membrane, site-directed nitroxide scanning electron paramagnetic resonance (EPR) has been carried out on this region of the permease. Thirty-one single-Cys permease mutants were spin-labeled and examined by conventional and power saturation EPR. The motional freedom of the side chains, as well as accessibility to O(2) or potassium chromium oxalate (CrOx), indicates that the loop between helices IV and V (loop IV/V) is considerably smaller than predicted by hydropathy plots, extending only from about Val132 to Phe138 and that Glu126 and Arg144 are probably within the membrane. Although ligand binding has no effect on the mobility of the labeled side chains, a marked increase in CrOx and O(2) accessibility is observed at position 137, as well as significant changes in accessibility to CrOx on one face of helix V. It is concluded that ligand binding induces a conformational change in the vicinity of the binding site, resulting in increased accessibility of position 137 in loop IV/V to solvent.

Amino Acid Sequence↗

Quantification of substance P mRNA in human mononuclear phagocytes and lymphocytes using a mimic-based RT-PCR.

We have recently demonstrated that human monocytes and lymphocytes express the substance P (SP) gene at both the mRNA and protein level [Ho, W.Z., Lai, J.P., Zhu, X.H., Uvaydova, M., Douglas S.D., 1997. Human monocytes and macrophages express substance P and neurokinin-1 receptor. Journal of Immunology, 159, p. 5654; Lai, J.P., Douglas, S. D., Ho, W.Z., 1998. Human lymphocytes express substance P and its receptor. Journal of Neuroimmunology, 86, p. 80; Lai, J.-P., Douglas, S.D., Rappaport, E., Wu, J., Ho, W.-Z., 1998. Identification of a delta isoform of preprotachykinin mRNA in human mononuclear phagocytes and lymphocytes. Journal of Neuroimmunology, 91, p. 121]. Using RT-PCR assay with several specific human SP primer pairs, we were able to differentiate four isoforms of preprotachykinin (PPT-A, the SP precursor) mRNA transcripts on ethidium bromide-stained agarose gels and clone the PCR amplified cDNA of the four isoforms (alpha, beta, gamma, and delta) of the PPT-A gene. In an effort to quantitatively measure PPT-A mRNA levels, we have developed a mimic-based RT-PCR assay to analyze total PPT-A mRNA levels in human monocytes and lymphocytes. We designed a specific human SP primer pair (HSP4/HSP3) to amplify a single fragment of cDNA derived from all four isoforms of PPT-A mRNA transcripts, with a sensitivity of 120 molecules per reaction. Thus the PPT-A mRNA transcripts in an unknown sample can be quantitatively analyzed using the mimic-based RT-PCR. The accuracy and reproducibility of this assay were confirmed by the plasmids containing alpha, beta, gamma and delta cDNA inserts and by in vitro synthesized mRNA from a plasmid containing beta isoform cDNA insert. Our data indicate that the SP mimic-based RT-PCR assay has potential advantages in studies of SP levels in a variety of human cells as well as in clinical specimens.

Adult↗

Synthesis and antitumour activity of novel diterpenequinone salvicine and the analogs.

A novel diterpenequinone named salvicine (4), structurally modified derivative of a natural product, and a series of the novel analogs have been prepared. Most of the analogs were found to be potently active against tumor cell lines in vitro. Further study on 4 in vivo demonstrated that it possessed a significant antineoplastic activity against murine S-180 Sarcoma and Lewis lung cancer, and human lung adenocarcinoma xenografts A-549 and LAX-83. The preclinical studies of 4 are now under way.

Animals↗

Reduced expression of p27(Kip1) protein in relation to salivary adenoid cystic carcinoma metastasis.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a malignant tumor of salivary gland origin. It tends to grow slowly but shows frequent recurrence and metastasis, ultimately with a poor outcome. Reduced expression of a cyclin-dependent kinase inhibitor, p27(Kip1), has been reported to correlate with poor survival for patients with various types of carcinoma. However, there has been no previous study reported of p27(Kip1) expression in ACC, to the authors' knowledge. METHODS: To evaluate p27(Kip1) as a prognostic marker, the authors examined the immunohistochemical expression of p27(Kip1) protein in 29 ACCs and correlated its expression with clinicopathologic findings. Eleven pleomorphic adenomas (PAs) were also examined to compare the p27(Kip1) expression in benign and malignant salivary gland tumors. RESULTS: All PAs expressed p27(Kip1) at high levels, whereas 83% of ACCs (24 of 29) showed reduced expression of this protein. Furthermore, the expression levels were significantly lower in ACCs with metastasis than in those without metastasis. The authors also examined the expression of p27(Kip1) in 2 ACC cell lines (ACCh and ACC3) by Northern and Western blot analysis to elucidate the possible mechanism of p27(Kip1) reduction in ACC. Both ACCh and ACC3 expressed p27(Kip1) mRNA, but ACCh did not produce p27(Kip1) protein. In ACCh, the expression of p27(Kip1) protein was induced by treatment with a proteasome inhibitor. CONCLUSIONS: Overall, these findings suggest that reduced expression of p27(Kip1) may correlate with the development and progression of salivary ACC and can be an indicator of its malignant behavior. They also suggest that increased proteasome-mediated degradation may play an important role in this reduction of p27(Kip1) expression.

Adenoma, Pleomorphic↗

Molecular identification of the ryanodine receptor pore-forming segment.

A sequence motif, GXRXGGGXGD, located in the putative channel-forming domain, is conserved in all known ryanodine receptors and inositol 1,4,5-trisphosphate receptors. The functional significance of this conserved region was investigated by using site-directed mutagenesis together with functional assays consisting of Ca(2+) release measurements, [(3)H]ryanodine binding, and single channel recordings in planar lipid bilayers. We report here that single point mutations introduced into this region of the mouse cardiac ryanodine receptor reduce or abolish high affinity [(3)H]ryanodine binding. Single channel analysis revealed that a single substitution of alanine for glycine 4824 within this region reduced the single channel conductance by 97%, from 798 picosiemens (pS) for the wild type channel to 22 pS. The G4824A mutant channel was modulated by Ca(2+), Mg(2+), ATP, caffeine, ruthenium red, and ryanodine. Co-expression of the wild type and G4824A mutant proteins produced single channels that have intermediate unitary conductances of 516, 256, 176, and 60 pS. These data suggest that this conserved region constitutes an essential part of the ryanodine binding site and the channel conduction pathway of the ryanodine receptor.

Amino Acid Sequence↗

Inhibition of phosphatidylcholine biosynthesis following induction of apoptosis in HL-60 cells.

Induction of apoptosis in HL-60 cells, using a variety of cytotoxic drugs, resulted, in all cases, in inhibition of CDP-choline:1, 2-diacylglycerol choline phosphotransferase, leading to an accumulation of its substrate, CDP-choline, and inhibition of phosphatidylcholine biosynthesis. Incubation of the cells with phosphatidylcholine reduced the number displaying an apoptotic morphology following drug treatment, and this was inversely related to the degree to which the drugs inhibited phosphatidylcholine biosynthesis. Inhibition of choline phosphotransferase by two of the drugs, farnesol and chelerythrine, was shown to be due to direct inhibition of the enzyme, while inhibition by the other drugs, etoposide and camptothecin, could be explained by the intracellular acidification that followed induction of apoptosis.

Alkaloids↗