Biomedical subjects
Publications and source records attributed to Z Yao.
It has been proved that Rhodiola Capsules can obviously decrease the oxygen consumption of myocardium and oxygen consumption index in anesthetic dogs, decrease the coronary artery resistance, but have no marked effect on the coronary artery blood flow. The Capsules also have the function of decreasing blood presure and slowing heart rate.
OBJECTIVE: To study the accuracy and predictability of photorefractive keratectomy (PKR) for astigmatism correction. METHODS: 53 eyes of 30 cases with compound myopia astigmatism and 33 eyes of 23 cases with simple myopia were treated with PRK and followed up for 6 months. The differences of corneal refractive power provided by corneal topography between the values at postoperative 6 months and that of the preoperative one were calculated with Holladay Ways to get real corrective degree and axis of astigmatism. The results were analyzed and compared with the preoperative predicted values. RESULTS: Six months after PRK, among the compound myopia astigmatism group, the ratio of over correction or under correction of real corrected astigmatic power within +/- 0.50D was 60.4%, the ratio of axis deviation between real and predicted correction within +/- 15 degrees was 58.5%. Among simple myopia group, 48.5% appeared more than -0.50 D myopia astigmatism in real correction, and the cylinder axis position was within 180 degrees +/- 44 degrees. The ratios of uncorrected visual acuity after PRK in the two groups equal to or better than 1.0 were 77.4% and 78.8%, respectively. There was no difference between these two groups (chi(2) = 0.024, P > 0.75). CONCLUSIONS: The method of myopia astigmatism correction using this PRK machine needs to be improved. After PRK treatment, the visual acuity of myopia astigmatism is similar to that of simple myopia group. It shows good efficacy. It is indicated that for myopia astigmatism lower than -2.00D, especially for the astigmatism with the rule, PRK could be performed according to equivalent spherical value.
We have constructed pSG5-RAR gamma-neo plasmid containing mouse retinoic acid receptor gamma (RAR gamma) gene and neo gene, and introduced it into embryonic stem ES-5 cells, by calcium phosphate mediated transfection. Some G418-resistant clones were isolated and from RNA dot blot analysis of these clones, a clone overexpressing RAR gamma gene was established, designated as ES-gamma cell line. Northern blot hydridization and Southern blot hydridization analysis of ES-gamma cells (Fig 3, 4) demonstrated that ES-gamma cells overexpressed exogenous RAR gamma mRNA and the exogenous RAR gamma cDNA integrated into the genome of ES cells. ES-gamma cells retained undifferentiated morphology and positive alkaline phosphatase activity (Plate I, Fig. 1, 2), so it resembled ES-5 cells in terms of stem cell characteristics. When ES-gamma cells were subcutaneously inoculated into nude mouse and differentiated in vivo, tumorous nodules containing various tissue structures were obtained, demonstrating their pluripotent properties just like parent ES-5 cells. Contrasting with ES-5 cells, the histological features of tumors showed no cartilage tissues, but abundant muscle tissues and keratinized cyst like structures constituted by stratified squamous epithelia (Plate I, Fig. 3). Differentiating in vitro by hanging drop culture methods, ES-gamma cells differentiated mostly into fibroblast-like cells, (Plate II, Fig. 1-5). The above results indicated that overexpression of RAR gamma gene changed the cell type of ES cells differentiating in vivo and in vitro. During the differentiation of ES-5 cells induced by RA, a large number of cells rounded up, detached from the dish and tended to die. We suspected that this phenomenon may be apoptosis. The ultrastructure appearance of the dying cells displayed typical apoptotic changes including chromatin condensation and nuclear fragmentation (Plate I, Fig. 4, 5). Detection of DNA fragments using agarose gel electrophoresis showed characteristic laddered patterns of apoptotic DNA fragments (Fig. 5). The above results indicated that RA induced apoptosis of ES-5 cells in the course of differentiation. The percentage of apoptosis of ES-5 cells increased accordingly, with the increase of RA concentration (Fig. 6). With the same concentration of RA 10(-7) mol/L, the percentage of apoptotic of ES-gamma death was roughly one times more than that of ES-5 cells (Fig. 7), a fact indicating that RAR gamma may mediate the apoptotic signal transduction of ES cells by RA.
Blood vessel tissue mechanical performance and cerebral aneurysm clip mechanical property are investigated. Results show that physical character of cerebral aneurysm clip, such as pressure value, maximum opening width of the blade tip, width, thickness and material is very important for its medical purpose. Surveying instrument is devised successfully.
In order to investigate inhibition of HLA-I expression by antisense oligonucleotides in vitro, three pieces of antisense phosphorothioate oligonucleotides (ASODN) complementary to hepatitis B virus (HBV) x gene key regions namely, 1510-1530, 1555-1581, 1768-1791 were synthesized. We also synthesized a SOND (sense strand) with same sequence of 1510-1530 as control. The specificity of inhibitory effect of the ASOND was determined using 2215 cell line by detection of HBxAg. In addition, we observed the inhibitory effect of ASODN on human HLA-I utilizing 2215 cells, the cells were stained with monoclonal antibody against human HLA-I heavy chain molecules, with fluorescenated sheep antimouse antibody as the second antibody and then analyzed on a EPICS profile II flow cytometer. HLA-I mRNA were assayed by in situ hybridization with a HLA-I heavy chain cDNA probe. The results indicated these ASODN could inhibit the expression of HBxAg, as well as HLA-I in cell surface. The result of 1 in situ hybridization showed that the decreased cell surface expression was correlated with steadily decreasing state of mRNA levels. The mechanism of action may be due to the inhibition of HBxAg by sequence specific ASODN, then resulting in decreasing of its transactivating effect on the HLA-I promoter.
Adiminstration of extracts from flesh of Cridtaria plecata Lea and Hyriopsis cumingii Lea (EFCH), in 3.6 g/kg and 1.8 g/kg i.g for 7 days, can stimulate macrophage phagcytoic function and humoral immunolgical response to cook's RBC in mice. EFCH 3.6 g/kg i.g for 7 days, inhibite allergic reaction IV induced by 2,4-Dinitroclorobenzne. Swimming time of mice can be prolonged by EFCH 3.6 g/kg, 1.8 g/kg, 0.9 g/kg i.g and EFCH 3.6 g/kg enhence mice's toleranetowards hypoxia. Analgesic tests showed that EFCH 3.6 g/kg, 1.8 g/kg, 0.9 g/kg i.g have significent analgesic activities on mice.
UNLABELLED: Inefficient intratumoral penetration of pharmaceuticals is one of the major limiting factors against effective tumor-targeting therapy. This study investigated the effect of the distribution pattern of the binding site in tumors on the penetration of target material. METHODS: In the first experiment, radiolabeled biotinylated monoclonal antibody, MLS128, was injected intraperitoneally or intravenously into nude mice bearing intraperitoneal human colon cancer xenografts. In the second experiment, radiolabeled streptavidin was injected intraperitoneally in the tumor-bearing mice after the pretargeting with the unlabeled biotinylated antibody. Intratumoral distribution of radioactivity was examined with quantitative autoradiography. RESULTS: There was no difference in the biodistribution of biotinylated antibody between intraperitoneal and intravenous administrations, but autoradiography showed a higher uptake in the margin and a lower uptake in the center of radioactivity in tumor nodules with intraperitoneal injection and a more uniform intratumoral radioactivity distribution with intravenous injection. In the two-step method, radioactivity in a low dose of streptavidin with intraperitoneal pretargeting primarily localized at the tumor margin. By increasing the dose, streptavidin penetrated more deeply. In tumors with intravenous pretargeting, a more uniform intratumoral distribution of streptavidin was obtained. The biodistribution of radiolabeled streptavidin was the same between different pretargeting routes. CONCLUSION: The better intratumoral penetration of radiolabeled streptavidin after intravenous pretargeting than intraperitoneal pretargeting with biotinylated antibody may be the result of different intratumoral distribution of the binding site for the radiolabel.
Mitogen-activated protein kinase (MAPK) kinases (MKKs) are dual-specificity protein kinases that phosphorylate and activate MAPK. We have isolated a cDNA encoding a novel protein kinase that has significant homology to MKKs. The novel kinase MKK7 has a nucleotide sequence that encodes an open reading frame of 347 amino acids with 11 kinase subdomains. MKK7 is ubiquitously expressed in all adult and embryonic organs but displays high expression in epithelial tissues at later stages of fetal development. When transiently expressed in 293 cells, MKK7 specifically activated stress-activated protein kinases (SAPKs)/c-Jun N-terminal protein kinases (JNKs) but not extracellular-regulated kinase or p38 kinase. A kinase-negative mutant of MKK7 inhibits interleukin-1beta, lipopolysaccharide, and MEKK1-induced SAPK/JNK activation. Thus, MKK7 is a new member of the MAPK kinase family that functions upstream of SAPK/JNK in the SAPK/JNK signaling pathway.
The p38 mitogen-activated protein kinases (MAPK) are activated by cellular stresses and play an important role in regulating gene expression. We have isolated a cDNA encoding a novel protein kinase that has significant homology (57% amino acid identity) to human p38alpha/CSBP. The novel kinase, p38delta, has a nucleotide sequence encoding a protein of 365 amino acids with a putative TGY dual phosphorylation motif. Dot-blot analysis of p38delta mRNA in 50 human tissues revealed a distribution profile of p38delta that differs from p38alpha. p38delta is highly expressed in salivary gland, pituitary gland, and adrenal gland, whereas p38alpha is highly expressed in placenta, cerebellum, bone marrow, thyroid gland, peripheral leukocytes, liver, and spleen. Like p38alpha, p38delta is activated by cellular stress and proinflammatory cytokines. p38delta phosphorylates ATF-2 and PHAS-I, but not MAPK-activated protein kinase-2 and -3, known in vivo and in vitro substrates of p38alpha. We also observed that p38delta was strongly activated by MKK3 and MKK6, while p38alpha was preferentially activated by MKK6. Other experiments showed that a potent p38alpha kinase inhibitor AMG 2372 minimally inhibited the kinase activity of p38delta. Taken together, these data indicate that p38delta is a new member of the p38 MAPK family and that p38delta likely has functions distinct from that of p38alpha.
Transforming growth factor beta (TGF-beta)-activated kinase (TAK1) is known for its involvement in TGF-beta signaling and its ability to activate the p38-mitogen-activated protein kinase (MAPK) pathway. This report shows that TAK1 is also a strong activator of c-Jun N-terminal kinase (JNK). Both the wild-type and a constitutively active mutant of TAK1 stimulated JNK in transient transfection assays. Mitogen-activated protein kinase kinase 4 (MKK4)/stress-activated protein kinase/extracellular signal-regulated kinase (SEK1), a dual-specificity kinase that phosphorylates and activates JNK, synergized with TAK1 in activating JNK. Conversely, a dominant-negative (MKK4/SEK1 mutant inhibited TAK1-induced JNK activation. A kinasedefective mutant of TAK1 effectively suppressed hematopoietic progenitor kinase-1 (HPK1)-induced JNK activity but had little effect on germinal center kinase activation of JNK. There are two additional MAPK kinase kinases, MEKK1 and mixed lineage kinase 3 (MLK3), that are also downstream of HPK1 and upstream of MKK4/SEK mutant. However, because the dominant-negative mutants of MEKK1 and MLK3 did not inhibit TAK1-induced JNK activity, we conclude that activation of JNK1 by TAK1 is independent of MEKK1 and MLK3. In addition to TAK1, TGF-beta also stimulated JNK activity. Taken together, these results identify TAK1 as a regulator in the HPK1 --> TAK1 --> MKK4/SEK1 --> JNK kinase cascade and indicate the involvement of JNK in the TGF-beta signaling pathway. Our results also suggest the potential roles of TAK1 not only in the TGF-beta pathway but also in the other HPK1/JNK1-mediated pathways.
The c-Jun N-terminal kinase (JNK), or stress-activated protein kinase plays a crucial role in cellular responses stimulated by environmental stress and proinflammatory cytokines. However, the mechanisms that lead to the activation of the JNK pathway have not been elucidated. We have isolated a cDNA encoding a novel protein kinase that has significant sequence similarities to human germinal center kinase (GCK) and human hematopoietic progenitor kinase 1. The novel GCK-like kinase (GLK) has a nucleotide sequence that encodes an ORF of 885 amino acids with 11 kinase subdomains. Endogenous GLK could be activated by UV radiation and proinflammatory cytokine tumor necrosis factor alpha. When transiently expressed in 293 cells, GLK specifically activated the JNK, but not the p42/44(MAPK)/extracellular signal-regulated kinase or p38 kinase signaling pathways. Interestingly, deletion of amino acids 353-835 in the putative C-terminal regulatory region, or mutation of Lys-35 in the putative ATP-binding domain, markedly reduced the ability of GLK to activate JNK. This result indicates that both kinase activity and the C-terminal region of GLK are required for maximal activation of JNK. Furthermore, GLK-induced JNK activation could be inhibited by a dominant-negative mutant of mitogen-activated protein kinase kinase kinase 1 (MEKK1) or mitogen-activated protein kinase kinase 4/SAPK/ERK kinase 1 (SEK1), suggesting that GLK may function upstream of MEKK1 in the JNK signaling pathway.
The mitogen-activated protein kinase, ERK is activated by a dual phosphorylation on threonine and tyrosine residues. Using a synthetic diphospho peptide, we have generated a monoclonal antibody directed to the active ERK. The antibody specifically identified the active doubly phosphorylated, but not the inactive mono- or non- phosphorylated forms of ERKs. A direct correlation was observed between ERK activity and the intensity in Western blot of mitogen-activated protein kinases from several species. The antibody was proven suitable for immunofluorescence staining, revealing a transient reactivity with ERKs that were translocated to the nucleus upon stimulation. In conclusion, the antibody can serve as a useful tool in the study of ERK signaling in a wide variety of organisms.
The requirement of the activity of microsomal triglyceride transfer protein (MTP) for very low density lipoprotein (VLDL) secretion was determined using McA-RH7777 cells stably transfected with human apoB48 (hB48). Secretion of VLDL containing hB48 (hB48-VLDL) by the transfected cells was induced by exogenous oleate (0.4 mM), and oleate-dependent VLDL secretion was selectively inhibited by brefeldin A (0.2 microg/ml). Two protocols were used to determine the effect of MTP inhibition on VLDL secretion. In the first protocol, cell protein and lipid were labeled with radioactive amino acids and oleate prior to MTP inhibition (using 5 microM of the photoaffinity inhibitor BMS-192951 to reduce MTP activity by 65-70%), and secretion of prelabeled apoB and triacylglycerol (TG) associated with lipoproteins was monitored during oleate-supplemented chase. In control cells, a 6-fold increase in incorporation of prelabeled TG into hB48-VLDL was observed after oleate supplement, while incorporation of prelabeled TG into VLDL containing endogenous rat apoB100 (rB100-VLDL) was unaffected. Inhibition of MTP activity abolished the oleate-induced utilization of prelabeled TG (by 80%) and hB48 (by 70%) for hB48-VLDL secretion but decreased utilization of pre-existing TG (by <25%) and B100 (by 45%) for rB100-VLDL secretion to a lesser extent. Inhibition of MTP did not affect incorporation of prelabeled TG or hB48 into high density lipoproteins containing hB48 (hB48-HDL). In the second protocol, MTP was inactivated prior to metabolic labeling of protein and lipid, and secretion of newly labeled apoB and TG as lipoproteins was monitored after oleate supplement. Under this condition, MTP inhibition decreased incorporation of newly labeled TG (by 80%) and hB48 (80%) into hB48-VLDL but did not affect their incorporation into hB48-HDL. Additionally, MTP inhibition decreased incorporation of newly labeled TG (by 50%) and rB100 (by 90%) into rB100-VLDL. Thus, normal activity of MTP is required for the oleate-induced secretion of hB48-VLDL from McA-RH7777 cells.
Human interleukin 17 (hIL-17) is a T-cell derived cytokine that exhibits 63% amino acid sequence identity to mouse IL-17 (mIL-17) and 57% identity to a viral protein encoded by the herpesvirus saimiri (HSV) gene 13 (HVS13). The IL-17 family of proteins binds to a unique mouse receptor (mIL-17R). Using nucleic acid hybridization techniques, a cDNA encoding a human homologue of the mIL-17R (hIL-17R) was isolated from a human T cell library. The predicted amino acid sequence of the hIL-17R is 69% identical to the mIL-17R, shares no homology with previously identified cytokine receptor families, and exhibits a broad tissue distribution. The hIL-17R gene was localized to chromosome 22. Monoclonal antibodies (mAbs) generated against the hIL-17R were able to block the IL-17-induced production of cytokine from human foreskin fibroblast (HFF) cells. Binding studies suggest that recombinant hIL-17 binds to the hIL-17R with low affinity.
UNLABELLED: We compared technetium-99m methoxyisobutylisonitrile (MIBI) myocardial perfusion single-photon emission tomography (SPET) (MPS) and electron beam computed tomography (EBCT) in order to assess their respective value in the detection of coronary artery disease (CAD). 99mTc-MIBI SPET (stress-resting) and EBCT studies were performed in 51 patients with suspected CAD who underwent coronary angiography (CAG). CAG showed that of the 51 patients, 36 had coronary stenosis >/=50% while 15 had normal results. A moderate positive rank correlation was found between coronary calcification detected by EBCT and MPS score (rs=0.5283, P<0.01). The concordance between EBCT and MPS for the evaluation of CAD was 72.5% (37/51). The sensitivity of EBCT in detecting CAD in 51 patients was comparable to that of MPS (81% vs 94%, NS). However, the accuracy of EBCT was lower than that of MPS (78% vs 94%, P<0.025). As regards the detection of individual coronary artery disease, there was no significant difference in sensitivity between EBCT and MPS (65% vs 75%, NS); however, the specificity and accuracy of EBCT were lower than those of MPS (specificity: 77% vs 95%, P<0.005; accuracy 71% vs 85%, P<0.005). The sensitivity, specificity and accuracy of MPS in detecting single-vessel disease were higher than those of EBCT (sensitivity: 86% vs 42%, P<0.025; specificity: 96% vs 70%, P<0.025; accuracy: 93% vs 61%, P<0.005). However, no significant differences in the sensitivity, specificity and accuracy of MPS and EBCT were found in respect of multivessel disease. IN CONCLUSION: 99mTc-MIBI myocardial perfusion SPET and EBCT provide different information in the assessment of CAD. The sensitivity of EBCT for the detection of CAD is comparable with that of MPS; however, the specificity and accuracy of EBCT are lower than those of MPS. More reliable results will be obtained if both myocardial perfusion SPET and EBCT are performed.
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In the present study, we examined the effect of avidin administered intravenously (i.v.) on the biodistribution of radiolabeled streptavidin in mice bearing intraperitoneal (IP) xenografts pretargeted with biotinylated antibody. Tumors were established in nude mice by IP inoculation of LS180 human colon cancer cells. Monoclonal antibody MLS128, which recognizes Tn antigen on mucin, was biotinylated and injected IP into the IP tumor-bearing mice. Radioiodinated streptavidin was administered IP or i.v. 48 h after pretargeting of biotinylated antibody. Avidin was administered i.v. 30 min prior to streptavidin injection. The localization of radioiodinated streptavidin in the tumor pretargeted with biotinylated antibody was significantly higher than that without pretargeting and that of radioiodinated MLS128 by the one-step method. Avidin administration significantly accelerated the clearance of radioiodinated streptavidin in blood and other normal tissues and increased the tumor-to-blood radioactivity ratio regardless of administration route of streptavidin. The i.v. avidin chase improved tumor localization of radiolabeled streptavidin in the IP xenografts pretargeted with biotinylated antibody.
DRB1*08 haplotypes have not been known to carry a DRB3 gene. We have found a patient suffering from liver disease who has a novel HLA haplotype of DRB1*0801 with DRB3*0202 as established by family segregation. These two genes were confirmed by sequencing. DR8 and DR52 antigen specificities were serologically detected, indicating expression of these genes.