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Biomedical subjects

H Zhao

Publications and source records attributed to H Zhao.

At least 271 records · Page 15Linked to original sources

Phosphorylation of c-Jun and its localization with heme oxygenase-1 and cyclooxygenase-2 in CA1 pyramidal neurons after transient forebrain ischemia.

Accumulating evidence on the molecular and cellular basis of ischemia/reperfusion-induced neurodegeneration suggests that oxidative stress is involved. Heme oxygenase (HO) and cyclooxygenase (COX) play physiologically important roles in the CNS. Conversely, HO and COX also can increase oxidative stress. Recent studies suggest that c-Jun phosphorylation is an important step in some forms of stress-induced neuronal apoptosis. In this study, the authors tried to clarify the association of HO and COX with c-Jun phosphorylation. Inducible forms of HO and COX (HO-1 and COX-2, respectively) were transiently induced in CA1 pyramidal neurons after ischemia. c-Jun also was induced in pyramidal neurons throughout the hippocampal formation, but its phosphorylation was limited to CA1. In contrast, these molecules were constitutively expressed at low levels. Most (84%) of the CA1 pyramidal neurons examined expressed HO-1, COX-2, or both, and such expression showed good co-localization with c-Jun phosphorylation. These results suggest the following: (1) c-Jun phosphorylation was associated with ischemia/reperfusion-induced neuronal apoptosis; (2) HO-1 and COX-2 were induced in CA1 pyramidal neurons, which undergo cell death; and (3) most CA1 pyramidal neurons expressed HO-1, COX-2, or both, which strongly suggests that these are candidates for neuron killers.

Animals↗

Long-term vascular effects of Nomega-nitro-L-arginine methyl ester are not soley mediated by inhibition of endothelial nitric oxide synthesis in the rat mesenteric artery.

Nomega-nitro-L-arginine methyl ester (L-NAME), one of the synthetic L-arginine analogues with inhibitory effects of nitric oxide (NO) synthesis, is now widely used to examine the role of NO in various organs. We and others demonstrated that long-term treatment with L-NAME causes hypertension and cardiovascular lesions (perivascular fibrosis and medial thickening), especially at microvascular levels. However, convincing evidence is still lacking that these long-term cardiovascular effects of L-NAME are solely mediated by the inhibition of the synthesis of endothelium-derived NO (EDNO). This study was thus designed to better understand the effects of long-term treatment with L-NAME with special reference to EDNO synthesis. Male Wister-Kyoto rats were orally administered L-NAME for 8 weeks. Blood pressure significantly increased at 3 days and 1 and 8 weeks of the treatment. Endothelium-dependent relaxations to acetylcholine (ACh) of the aorta were reduced 3 days after the treatment, recovered at 1 week, and again reduced at 8 weeks, whereas the relaxations of the small mesenteric artery were unaltered throughout the experimental periods. At 8 weeks, indomethacin-sensitive, endothelium-dependent contractions to ACh were noted. The relative contributions of NO and endothelium-derived hyperpolarizing factor also were unchanged. Citrulline assay demonstrated that substantial levels of constitutive NO synthase activity remained in the aorta during the experiments. The long-term treatment with L-NAME caused perivascular fibrosis and medial thickening, not only in the aorta but also in the mesenteric artery. These results suggest that mechanism(s) other than simple inhibition of EDNO synthesis is involved in the long-term cardiovascular effects of L-NAME in the rat mesenteric artery.

Animals↗

Important role of endothelium-derived hyperpolarizing factor in shear stress--induced endothelium-dependent relaxations in the rat mesenteric artery.

Shear stress is one of the most important stimulators for the release of endothelium-derived relaxing factors. Although shear stress-induced release of nitric oxide (NO) has been extensively investigated, it remains to be elucidated whether endothelium-derived hyperpolarizing factor (EDHF) contributes to the endothelium-dependent relaxations to shear stress. This study was designed to address this point in the isolated rat mesenteric artery. Large mesenteric arteries (400-500 microm) and resistance mesenteric arteries (150-250 microm) of the rat were precontracted with phenylephrine (at 80 mm Hg of perfusion pressure), and the changes in vessel diameter in response to variable flow (0-300 microl/min) were continuously examined. The relative contributions of vasodilator prostaglandins, NO, and EDHF were analyzed by the inhibitory effects of indomethacin (10(-5) M), N(G)-nitro-L-arginine (L-NNA, 10(-4) M), and KCl (40 mM), respectively. The shear stress-induced relaxations were totally endothelium dependent in both-sized blood vessels, and the contribution of NO was more prominent in large arteries than in resistance arteries, whereas that of EDHF was noted in both-sized blood vessels. Tetrabutylammonium (a nonselective inhibitor of K channels) almost abolished, whereas the combination of charybdotoxin (an inhibitor of both large- and intermediate-conductance Ca2+ -activated K channels) and apamin (an inhibitor of small-conductance Ca2+ -activated K channels) significantly inhibited the EDHF-mediated component of the shear stress-induced relaxations. These results indicate that EDHF plays an important role in shear stress-induced endothelium-dependent relaxations, where K channels, especially calcium-activated K channels, appear to be involved.

Animals↗

Quality of life of adult survivors of germinomas treated with craniospinal irradiation.

OBJECTIVE: To assess the quality of life (QOL) of a group of patients treated for intracranial germinoma with biopsy followed by prophylactic whole-neuraxis radiation therapy. METHODS: The Short-form-36 and Functional Assessment of Cancer Therapy QOL questionnaires were completed by 22 of 27 eligible adults treated with whole-neuraxis irradiation for biopsy-proven, marker-negative intracranial germinomas between 1976 and 1996. In addition, data were obtained regarding height and weight, medications, ability to work, and educational achievement. RESULTS: The patients' QOL was generally good. All of the patients are in or have completed high school; nine are in or have completed college, and five have advanced degrees. Patients rated themselves lower on the physical composite scale of the Short-form-36 (average, 46 versus 54 in a normal population). On the mental composite scale, patients rated themselves more favorably than the normal population (average, 54 versus 49 in a normal population). Patients were normally proportioned for height and weight, but female patients tended to be short. Age at radiation did not correlate with QOL. CONCLUSION: The QOL of adults treated for marker-negative germinoma with prophylactic whole-neuraxis irradiation is generally good. These data should serve as a benchmark for newer treatment protocols eliminating or reducing radiation.

Achievement↗

Efficient estimation of the distribution of quality-adjusted survival time.

Quality of life is an important aspect in evaluation of clinical trials of chronic diseases, such as cancer and AIDS. Quality-adjusted survival analysis is a method that combines both the quantity and quality of a patient's life into one single measure. In this paper, we discuss the efficiency of weighted estimators for the distribution of quality-adjusted survival time. Using the general representation theorem for missing data processes, we are able to derive an estimator that is more efficient than the one proposed in Zhao and Tsiatis (1997, Biometrika 84, 339-348). Simulation experiments are conducted to assess the small sample properties of this estimator and to compare it with the semiparametric efficiency bound. The value of this estimator is demonstrated from an application of the method to a data set obtained from a breast cancer clinical trial.

Biometry↗

Internal circulation in a drop in an acoustic field.

An investigation of the internal flow field for a drop at the antinode of a standing wave has been carried out. The main difference from the solid sphere case is the inclusion of the shear stress and velocity continuity conditions at the liquid-gas interface. To the leading order of calculation, the internal flow field was found to be quite weak. Also, this order being fully time dependent has a zero mean flow. At the next higher order, steady internal flows are predicted and, as in the case of a solid sphere, there is a recirculating layer consisting of closed streamlines near the surface. In the case of a liquid drop, however, the behavior of this recirculating Stokes layer is quite interesting. It is predicted that the layer ceases to have recirculation when [formula: see text], where [symbol: see text] is the liquid viscosity, mu is the exterior gas-phase viscosity, and M is the dimensionless frequency parameter for the gas phase, defined by M = i omega a2 rho/mu, with a being the drop radius. Thorough experimental confirmation of this interesting new development needs to be conducted. Although it seems to agree with many experiments with levitated drops where no recirculating layer has been clearly observed, a new set of experiments for specifically testing this interesting development need to be carried out.

Acoustics↗

Acute regulation of Na/H exchanger NHE3 activity by protein kinase C: role of NHE3 phosphorylation.

Acute hormonal modulation of NHE3 activity is partly mediated by kinases, including protein kinase C (PKC). We examined the role of NHE3 phosphorylation in regulating its activity in response to PKC activation by phorbol 12-myristate 13-acetate (PMA). In pooled NHE-deficient fibroblasts transfected with NHE3, PMA increased NHE3 activity and phosphorylation. When six potential PKC target serines were mutated, NHE3 phosphorylation was drastically reduced and PMA failed to regulate NHE3 phosphorylation or function. To examine whether NHE3 phosphorylation is sufficient for functional regulation by PKC, we exploited the heterogeneous response of NHE3 activity to PMA in individual clones of transfectants. Clones with stimulatory, inhibitory, or null responses to PMA were observed. Despite the diverse functional response, changes in NHE3 phosphorylation as revealed by tryptic phosphopeptide maps were similar in all clones. We conclude that although phosphorylation appears to be necessary, it is insufficient to mediate PKC regulation of NHE3 function and factors extrinsic to the NHE3 protein must be involved.

Animals↗

Pregnancy and steroid hormones enhance the vasodilation responses to CGRP in rats.

We recently reported that calcitonin gene-related peptide (CGRP) reversed the hypertension induced by nitric oxide inhibition in pregnant rats and that this effect appeared to be progesterone dependent. In the present study, we examined whether the vasodilator responses to CGRP are increased during pregnancy and whether these responses are steroid hormone dependent. Three groups of ovariectomized (Ovx) rats (n = 4-8 rats/group) were studied 3 days after daily treatment (subcutaneous injection) with progesterone (P; 2 mg/injection, twice daily for 3 days, in 0.2 ml of sesame oil), 17beta-estradiol (E; 2.5 microgram/injection, twice daily for 3 days, in 0.2 ml of sesame oil), or vehicle (sesame oil). A fourth group (n = 6 rats) of pregnant rats was studied on day 19 of gestation. A fifth group of adult, nonpregnant rats (n = 6 rats), regardless of stage of estrous cycle, was also used in this study. Mean arterial blood pressure (MAP) was continuously monitored in fully awake and free-moving instrumented rats. MAP was measured before and after administration of either saline or varying bolus doses of CGRP (9-360 pmol/kg body wt). CGRP produced a dose-dependent decrease in MAP in all rats with a significant (P < 0.05) reduction in MAP beginning with a CGRP dose of 90 pmol/kg and with maximal effects observed at 360 pmol/kg. Decreases in MAP in response to CGRP were significantly (P < 0.05) greater in pregnant compared with nonpregnant rats. Similarly to pregnant rats, Ovx rats given both E and P treatments produced greater decreases in MAP in response to CGRP at 90, 180, and 360 pmol/kg doses compared with both ovary-intact and Ovx nonpregnant rats, which were not different from each other. In summary, these data show that 1) the hypotensive effects of CGRP are dose dependent and 2) the hypotensive effects of CGRP are enhanced during pregnancy and in Ovx rats treated with either E or P. Therefore, we suggest that the decrease in vascular tone that is seen during pregnancy may be mediated, at least in part, by a sex steroid hormone-induced increase in the vascular sensitivity to the vasodilator effects of CGRP.

Animals↗

alpha-MSH and its receptors in regulation of tumor necrosis factor-alpha production by human monocyte/macrophages.

The hypothesis that macrophages contain an autocrine circuit based on melanocortin [ACTH and alpha-melanocyte-stimulating hormone (alpha-MSH)] peptides has major implications for neuroimmunomodulation research and inflammation therapy. To test this hypothesis, cells of the THP-1 human monocyte/macrophage line were stimulated with lipopolysaccharide (LPS) in the presence and absence of alpha-MSH. The inflammatory cytokine tumor necrosis factor (TNF)-alpha was inhibited in relation to alpha-MSH concentration. Similar inhibitory effects on TNF-alpha were observed with ACTH peptides that contain the alpha-MSH amino acid sequence and act on melanocortin receptors. Nuclease protection assays indicated that expression of the human melanocortin-1 receptor subtype (hMC-1R) occurs in THP-1 cells; Southern blots of RT-PCR product revealed that additional subtypes, hMC-3R and hMC-5R, also occur. Incubation of resting macrophages with antibody to hMC-1R increased TNF-alpha concentration; the antibody also markedly reduced the inhibitory influence of alpha-MSH on TNF-alpha in macrophages treated with LPS. These results in cells known to produce alpha-MSH at rest and to increase secretion of the peptide when challenged are consistent with an endogenous regulatory circuit based on melanocortin peptides and their receptors. Targeting of this neuroimmunomodulatory circuit in inflammatory diseases in which myelomonocytic cells are prominent should be beneficial.

Adrenocorticotropic Hormone↗

High-level expression of EPHB6, EFNB2, and EFNB3 is associated with low tumor stage and high TrkA expression in human neuroblastomas.

Neuroblastoma (NB) is a common pediatric tumor of neural crest origin that is biologically and clinically heterogeneous. EPH family receptor tyrosine kinases and ephrin ligands play fundamental roles in neurodevelopmental processes. Recently, we found that NB cell lines expressed several EPHB and EFNB transcripts, which encode EPHB subgroup receptors and ephrin-B subgroup ligands, respectively. To explore the role of EPHB receptors and ephrin-B ligands in the biology of NB, we examined the expression of EPHB and EFNB transcripts in 47 primary NB specimens. Multiple EPHB and EFNB transcripts were expressed in all of the NB tumors examined, suggesting the involvement of these transcripts in modulating the biological behavior of NB. Higher levels of EPHB6, EFNB2, and EFNB3 expression were found in low-stage tumors (stage 1, 2, and 4S) than in advanced-stage tumors (stage 3 and 4; P = 0.0013, P = 0.0048, and P = 0.027, respectively). Expression of TrkA, a well-established prognostic marker of favorable NB, was positively correlated with EPHB6, EFNB2, and EFNB3 expression (P < 0.0001, P = 0.0019, and P = 0.0001, respectively). MYCN-amplified tumors expressed lower levels of EPHB6, EFNB2, EFNB3, and TrkA transcripts compared to nonamplified tumors (P = 0.0006, P = 0.0023, P = 0.0048, and P = 0.0001, respectively). These data suggest that high-level expression of EPHB6, EFNB2, and EFNB3 is associated with favorable NB and that low-level expression of EPHB6, EFNB2, and EFNB3 correlates with aggressive MYCN-amplified NB. Thus, EPHB6, EFNB2, and EFNB3 may have biological relevance in NB. Further investigation on the biology of these genes may help provide insight into the treatment of NB.

Ephrin-B2↗

[A new explanation for shadow bands on denaturing PAGE for products of STRS--the difference between sense and antisense strands in electrophoresis].

OBJECTIVE: To explore the mechanism of shadow bands on denaturing PAGE for PCR products of STR sequences and try to eliminate them. METHODS: PCR and asymmetric PCR were employed. The amplified fragments were separated on denaturing PAGE and visualized by silver stain. RESULTS: By asymmetric PCR, half of shadow bands of dinucleotide repeats were eliminated and there was only one band for each allele for tetranucleotide sequence. A different migration between the sense strand and antisense strand was identified. CONCLUSION: The difference between sense and antisense strands in electrophoresis is one of the causes in shadow bands, and these shadow bands can be eliminated by asymmetric PCR partly or totally.

Electrophoresis, Polyacrylamide Gel↗

Studies on the callus cultures of Ginkgo biloba and its metabolites-ginkgolides.

The production of ginkgolides in callus culture of Ginkgo biloba was reported. The affection of some physical factors and chemical substances on the induction and growth of calli was also investigated. A biologically quantitative method (platelet aggregation induced by PAF) and HPLC were successfully used for the determination of Ginkgolides A and B in all kinds of callus cultures. The result showed that the content of Ginkgolides B in the callus cultures varies from 0.005% to 0.01%, which is one of the best results for the callus culture of G.biloba in the world.

2,4-Dichlorophenoxyacetic Acid↗

[Prevalence of HCV and HBV infection in patients with primary hepatocellular carcinoma in Shanxi Province].

OBJECTIVE: To study the prevalence of hepatitis C and B viruses (HCV and HBV) infection in the patients with primary hepatocellular carcinoma (PHC) in Shanxi Province and evaluate their etiologic roles in the pathogenecity of PHC to lay a foundation for the prevention and control of it. METHODS: Ninety-eight patients with PHC and 196 non-PHC controls matched in age and sex were selected from the four hospitals at provincial level in Shanxi Province. Serum antibodies against HCV (anti-HCV), HBs (anti-HBs), HBe (anti-HBe) and HBc (anti-HBc), IgM-antibody against HBc (anti-HBc-IgM), HBsAg and HBeAg were determined for all of them with enzyme-linked immunosorbent assay (ELISA). RESULTS: Positivity for anti-HCV and rate of HBV infection were 8.16% and 63.37%, respectively, in the PHC patients, both significantly higher than those in the controls (P < 0.05), with attributable risk proportions of (ARP) 94%, and 91%, respectively. Multiple conditional logistic regression analysis showed that positive serum anti-HCV, HBsAg and anti-HBc a risk factors for PHC, all entered the regression model, with odds ratios (ORs) of 55.06, 10.18 and 9.85, respectively. Dichotomized contingency table analysis showed that OR for those positive both for anti-HCV and HBsAg was 61.37, significantly higher than that for single positive of either one, with an additive effect. CONCLUSION: It suggested that both HCV and HBV infection were main etiologic factors for PHC in local. HBV also was an important factor in the pathogenecity of PHC, especially in those with both positive for HBsAg and anti-HBc. Coinfection with HBV and HCV had an additive effect on PHC pathogenecity.

Carcinoma, Hepatocellular↗

[Cellular immunity and epidemiologic analysis of pediatric patients with Mycoplasma pneumonia].

OBJECTIVE: To understand the of immuno-reactions of pediatrics patients with Mycoplasma pneumonia. METHODS: 90 patients suffered from M. pneumonia were administered and divided into three groups: mild group, severe group, and normal control group. T cell subset parameters, natural killer cell and the serumsoluble interleukin-2 recepter of all of above were determined. RESULTS: Data showed:CD4 decreased at both acute and recovery stage of M. pneumonia, while CD8 remarkably increased (t = 2.63, 66, 2.77, 3.36, P < 0.05). SIL-2R level of all patients also greatly increased (t = 5.26, 3.19, P < 0.01), especially in the serious group. CONCLUSION: There are disturbances of cell-immune in M. pneumonia. The level of SIL-2R can serve as monitor on the degree of severeness of M. pneumonia. The incidence M. pneumonia appeared highest in the 10-14 year-old group.

Adolescent↗

Measurement of erythrocyte deformability by two laser diffraction methods.

The aim of this work is to study the deformability of red blood cells (RBC) by two laser diffraction methods: the Laser-assisted Optical Rotational Cell Analyser (LORCA, Mechatronics, Amsterdam, Netherlands) and a Shear Stress Diffractometer (RHEODYN SSD, Myrenne, Roetgen, Germany). Experiments were carried out on 46 healthy human subjects. The elongation index EI of normal and hardened RBCs (obtained by heating blood at 49 degrees C or by incubating RBCs in solutions of diamide) was measured. The results showed that the standard deviations of the experimental data for normal RBCs were relatively small, especially at high shear stresses (more than 3.0 Pa), but higher than those reported before. Some correlations between the results given by the two instruments were also found. It should be noted that for hardened RBCs, the standard deviations of the measurements were important compared with the mean values in the two instruments.

Adult↗

Comparison of three optical methods to study erythrocyte aggregation.

The aim of this work was to evaluate three optical methods designed to determine erythrocyte aggregation: Erythroaggregometer (EA; Regulest, France), Laser-assisted Optical Rotational Cell Analyzer (LORCA; Mechatronics, Netherlands) and Fully Automatic Erythrocyte Aggregometer (FAEA; Myrenne, GmbH, Germany). Blood samples were taken from fifty donors (26 males and 24 females). The aggregation of normal red blood cell (RBC) and RBCs suspended in three normo- and hyperaggregating suspending media was studied. The results revealed some significant correlations between parameters measured by these instruments, in particular, between the indexes of aggregation of EA and LORCA. Further, RBC aggregation of multiple myeloma patients was also studied and a hyper erythrocyte aggregation state was found by EA and LORCA.

Adult↗

Circumferential resection and "Z"-shape plastic end-to-end anastomosis of canine trachea.

OBJECTIVE: To prevent anastomotic stricture of the trachea. METHODS: Forty young mongrel dogs, weighing 5-7 kg, were randomly divided into two groups: experimental group and control group, with 20 dogs in each group. Four tracheal rings were removed from each dog. In the experimental group, two "Z"-shape tracheoplastic anastomoses were performed on each dog, one on the anterior wall and the other on the membranous part of the trachea. In the control group, each dog received only simple end-to-end anastomosis. Vicryl 3-0 absorbable suture and OB fibrin glue were used for both groups. All dogs were killed when their body weight doubled. RESULTS: The average sagittal stenotic ratio were 1.20 +/- 0.12 for the experimental group and 0.83 +/- 0.05 for the control group. The average cross-sectional area stenotic ratio were 0.90 +/- 0.12 and 0.69 +/- 0.09 and T values were 8.71 and 4.57 for the two groups (P < 0.01). CONCLUSION: "Z"-shape tracheoplasty is superior to simple end-to-end anastomosis in preventing anastomotic stricture of canine trachea.

Anastomosis, Surgical↗

[Effects of homocysteine on human vascular endothelial cells, platelet aggregation and heparin cofactor activity].

OBJECTIVES: To elucidate partly the mechanism of homocysteine-associated thrombosis. METHODS: 1. Thrombomodulin (TM) antigen distribution on human vascular endothelial cell (EC) membrane was assayed by immune-fluorescence histochemistry stain and flow cytometry; 2. Plasma heparin cofactor activity was measured by chromogenic method. RESULTS: Homocysteine (Hcy) significantly down-regulated the expression of TM on EC, with a concentration-dependent manner; 2. Hcy did not influence platelet aggregation induced by ADP and thrombin; 3. Hcy exerted no effects on the activities of antithrombin III or heparin cofactor. CONCLUSION: The effect of Hcy in developing thrombosis may be associated with an inhibitory action on EC TM expression; which was independent of platelet aggregation or heparin cofactor activity.

Adult↗