Organic pollution of street dust in the Handan City, China.
Explore the source record for details and available documents.
Air Pollutants↗
Biomedical subjects
H J Zhang
Publications and source records attributed to H J Zhang.
Distributions of allelic frequencies and haplotypes of three new Y-STR loci in a Chinese Han population.
Explore the source record for details and available documents.
China↗
H(2)O(2)-induced O(2) production by a non-phagocytic NAD(P)H oxidase causes oxidant injury.
Non-phagocytic NAD(P)H oxidases have been implicated as major sources of reactive oxygen species in blood vessels. These oxidases can be activated by cytokines, thereby generating O(2), which is subsequently converted to H(2)O(2) and other oxidant species. The oxidants, in turn, act as important second messengers in cell signaling cascades. We hypothesized that reactive oxygen species, themselves, can activate the non-phagocytic NAD(P)H oxidases in vascular cells to induce oxidant production and, consequently, cellular injury. The current report demonstrates that exogenous exposure of non-phagocytic cell types of vascular origin (smooth muscle cells and fibroblasts) to H(2)O(2) activates these cell types to produce O(2) via an NAD(P)H oxidase. The ensuing endogenous production of O(2) contributes significantly to vascular cell injury following exposure to H(2)O(2). These results suggest the existence of a feed-forward mechanism, whereby reactive oxygen species such as H(2)O(2) can activate NAD(P)H oxidases in non-phagocytic cells to produce additional oxidant species, thereby amplifying the vascular injury process. Moreover, these findings implicate the non-phagocytic NAD(P)H oxidase as a novel therapeutic target for the amelioration of the biological effects of chronic oxidant stress.
Animals↗
Antimalarial compounds from Rhaphidophora decursiva.
Bioassay-directed fractionation led to the isolation of 14 compounds, six of which possess antimalarial activity, from the dried leaves and stems of Rhaphidophora decursiva. Polysyphorin (1) and rhaphidecurperoxin (6) showed strong activities against Plasmodium falciparum. Rhaphidecursinol A (2), rhaphidecursinol B (3), grandisin (4), and epigrandisin (5) were less active against the same organism. Among the isolates, rhaphidecursinol A (2) and rhaphidecursinol B (3) were determined to be new neolignans, and rhaphidecurperoxin (6) is a new benzoperoxide. Known compounds isolated include polysyphorin (1), grandisin (4), epigrandisin (5), (+)-medioresinol, (-)-pinoresinol, (-)-syringaresinol, (+)-glaberide I, (+)-dehydrovomifoliol, (-)-liliolide, (-)-hydroxydihydrobovolide, and N-butylbenzamide, of which compound 1 appears worthy of further evaluation as an antimalarial agent. Structure elucidation and identification were accomplished by spectroscopic means including 1D and 2D NMR analyses.
Animals↗
V-Ha-Ras overexpression induces superoxide production and alters levels of primary antioxidant enzymes.
Reactive oxygen species have been shown to play important roles in v-Ha-Ras mitogenic signaling. We hypothesized that v-Ha-Ras overexpression would induce superoxide production, and therefore modify expression of the primary antioxidant enzyme system. We have demonstrated that immortal rat kidney epithelial cells stably transduced with constitutively active v-Ha-ras produced significantly larger amounts of superoxide radical than wild-type or vector-transfected control cells. The levels of the primary antioxidant enzymes copper- and zinc-containing superoxide dismutase, manganese-containing superoxide dismutase, catalase, and glutathione peroxidase were increased in the superoxide-overproducing cells. DNA-binding activities of the transcription factors activator protein-1, activator protein-2, and nuclear factor-kappaB were all enhanced in the superoxide-overproducing cells. These v-Ha-ras transduced cells also had a shortened cell doubling time and higher plating efficiency, and displayed greater constitutive levels of phosphorylated mitogen-activated protein kinases. These data demonstrate that v-Ha-Ras overexpression increases superoxide production and this apparently affects a wide variety of cell signaling and redox systems.
Animals↗
Aging lowers steady-state antioxidant enzyme and stress protein expression in primary hepatocytes.
It has been reported that the isolation and culture of primary hepatocytes can compromise cellular ability to constituitively express antioxidant enzyme (AE) genes, making it difficult to study their regulation ex vivo. In the present study, the steady-state expression of manganese-containing superoxide dismutase, copper- and zinc-containing superoxide dismutase, catalase, and glutathione peroxidase was assessed in primary hepatocytes isolated from young and senescent rats and cultured in MATRIGEL: There was no change in steady-state superoxide dismutase protein or activity levels in cells collected from young animals and cultured for 7 days. Catalase expression was initially increased, and then it declined 30%. In contrast, superoxide dismutase expression declined 60% and catalase expression declined 50% in cells from senescent animals. Constitutive and inducible 70-kDa heat shock protein expression increased coincident with declining AE levels in the young cells but not senescent cells. For both age groups, electron micrographs showed rounded hepatocytes with abundant rough endoplasmic reticulum, mitochondria, and peroxisomes. Hepatocytes were organized into clusters of 6-12 cells surrounding a large central lumen devoid of microvilli. Each cluster also contained smaller microvilli-lined lumens between adjacent hepatocytes that resembled canniculi. The plasma membranes of these lumens were sealed from the extracellular space by junctional complexes. Gap junctions in the plasma membrane suggest that hepatocytes were capable of intercellular communication. We conclude that the Matrigel system can be used to study AE regulation in primary hepatocytes from young and senescent animals, provided that experiments can be conducted within a time frame of 5-7 days in culture. These data also support the hypothesis that aging compromises hepatocellular ability to maintain AE status and upregulate stress protein expression.
Aging↗
Repair of cardiac defects through a shorter right lateral thoracotomy in children.
BACKGROUND: Median sternotomy is a conventional approach for correction of cardiac defects for many years; however, the cosmetic result is poor. Therefore, right lateral thoracotomy was tested as an alternative procedure with a better cosmetic outcome. METHODS: Between October 1994 and February 1999, 683 patients underwent correction of congenital cardiac malformations during a cardiopulmonary bypass through right lateral thoracotomy involving a shorter incision through the third or the fourth intercostal space. All of the patients were children. The average age was 3.26+/-1.67 years (range, 4 months to 7 years). The average weight was 13.59+/-4.37 kg (5 to 40). The patients had various cardiac defects and associated anomalies. RESULTS: Only 2 patients died after operation, 1 from low cardiac output and the other from severe pulmonary infection. The hospital morbidity was lower. The mean cardiopulmonary bypass time was 58.67+/-35.11 minutes (range, 16 to 430 minutes), the mean aortic cross-clamping time was 35.03+/-24.84 minutes (range, 3 to 205 minutes). The postoperative average mechanical ventilation time was 19.23+/-39.11 hours (range, 2 to 391 hours), and the mean postoperative stay was 8.55+/-12.54 days (range, 5 to 293 days). CONCLUSIONS: The right lateral thoracotomy incision is a safe and effective alternative to a median sternotomy for correction of cardiac defects. Advantages of this approach compared with median sternotomy are less injury, maintenance of the continuity and the integrity of the bony thorax, and prevention of the development of "pigeon-chesting." The scar is less visible, hence, the cosmetic result can meet patient expectations. This procedure is consistent with the idea of minimal invasive surgery.
Cardiopulmonary Bypass↗
Design and development of selective muscarinic agonists for the treatment of Alzheimer's disease: characterization of tetrahydropyrimidine derivatives and development of new approaches for improved affinity and selectivity for M1 receptors.
Cholinergic neurons degenerate in Alzheimer's disease, resulting in cognitive impairments and memory deficits, and drug development efforts have focused on selective M1 muscarinic agonists. 5-(3-Ethyl-1,2,4- oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidine trifluoroacetic acid (CDD-0102) stimulates M1 muscarinic receptors in rat brain [Messer, W.S., Jr., Abuh, Y.F., Liu, Y., Periyasamy, S., Ngur, D.O., Edgar, M.A., El-Assadi, A.A., Sbeih, S., Dunbar, P.G., Roknich, S., Rho, T., Fang, Z., Ojo, B., Zhang, H., Huzl, J.J., III, Nagy, P.I., 1997a. J. Med. Chem. 40, 1230-1246.] and improves memory function in rats with lesions of the basal forebrain cholinergic system. Moreover, CDD-0102 exhibits oral bioavailability, few side effects and low toxicity, and thus represents a viable candidate for clinical studies. Despite the development of functionally selective agonists such as xanomeline and CDD-0102, there is room for improvements in ligand affinity and selectivity. The high degree of amino acid homology within transmembrane domains has hindered the development of truly selective agonists. Site-directed mutagenesis, biochemical and molecular modeling studies have identified key amino acid residues such as Thr192 and Asn382 in the binding of agonist to M1 receptors [Huang, X.P., Nagy, P.I., Williams, F.E., Peseckis, S.M., Messer, W.S., Jr., 1999. Br. J. Pharmacol. 126, 735-745.]. Recent work has implicated residues at the top of transmembrane domain VI in the binding of muscarinic agonists and activation of M1 receptors [Huang, X.P., Williams, F.E., Peseckis, S.M., Messer, W.S., Jr., 1998. J. Pharmacol. Exp. Ther. 286, 1129-1139.]. Thus, residues such as Ser388 represent molecular targets for the further development of agonists with improved M1 receptor affinity, selectivity and activity.
Alzheimer Disease↗
Diterpenoids from Isodon lophanthoides.
A new diterpenoid was isolated from the leaves of Isodon lophanthoides, together with two known diterpenoids, lophanic acid and 8(17),12,14-labdatriene-19-oic acid. The structure of the new compound was determined to be 11 beta-hydroxyisopimara-8,15-diene-3-one (1) on the basis of spectroscopic evidence.
Diterpenes↗
Rearranged taxanes from the bark of Taxus yunnanensis.
Five new 11(15-->1)-abeo-taxane diterpenoids, taxuyunnanines K-O (1-5), were isolated from an ethanol extract of the bark of Taxus yunnanensis, and their structures were determined using MS and NMR techniques. Compounds 1/2 and 4/5 are rearranged taxane diterpenoids possessing an opened oxetane ring moiety at C4(20). Compounds 4/5 are rearranged taxoids lacking an oxygenated functionality at C-4.
Bridged-Ring Compounds↗
Comparison of effects of two polymorphic variants of manganese superoxide dismutase on human breast MCF-7 cancer cell phenotype.
Two polymorphic variants of manganese superoxide dismutase (MnSOD), with either Ile or Thr at amino acid 58, (Ile58MnSOD or Thr58MnSOD), have been found in the human population. The MnSOD activity of these two variants and their effects on the malignant phenotype of human breast cancer MCF-7 cells were compared. It was demonstrated that MnSOD-overexpressing clones obtained from transfection of the two MnSOD cDNAs into MCF-7 cells had increased MnSOD immunoreactive protein and increased MnSOD activity. Cells overexpressing Ile58MnSOD had 3-fold higher MnSOD activity than cells overexpressing Thr58MnSOD in vivo at an equal MnSOD protein level. Tumor-suppressive effects of MnSOD-overexpressing cells were indicated by: (a) decreased plating efficiency; (b) elongated cell population doubling time; (c) lower clonogenic fraction in soft agar; and (d) complete inhibition or delayed onset of tumor formation in nude mice. When compared on the same activity basis, the suppressive effects of Ile58MnSOD were similar to those of Thr58MnSOD. However, far more Thrs58MnSOD protein was required to obtain the same amount of MnSOD activity, making the Thr58MnSOD far less effective. A dose-response suppressive effect was observed when the increase of MnSOD activity was moderate. We conclude that MnSOD is a tumor suppressor in human breast cancer, but the Thr58 form of the protein is a much less effective tumor suppressor than the Ile58 form of the protein.
Alleles↗
[Cardiovascular response to high sustained +Gz stress in dogs].
Objective. To investigate features of electrocardiography (ECG) and arterial pressure in dog during and after +Gz stress. Method. Six anesthetized dogs were catheterized for the measurement of ascending aortic pressure (AP) and common iliac arterial pressure (CIAP). A lead of ECG was monitored continuously. Then, dogs were placed supine in rotatable platform on one arm of an 1.7 m radius centrifuge. The animals were exposed serially to acceleration profiles of up to +7 Gz, consisting of a slow onset to peak acceleration, 90 s peak G, and a rapid decline back to control. A recovery time of at least 20 min was allowed after each acceleration profile. Result. (1) The amplitude of P-wave was influenced by the magnitude of the acceleration (2.3 +/- 0.2 mV at rest vs. 4.5 +/- 0.5 mV at +3 Gz, 4.8 +/- 0.3 mV at +5 Gz and 5.3 +/- 0.7 mV at +7 Gz, respectively P<0.05). (2) It appeared that arterial mean pressure increased and pulse pressure decreased in CIAP during high +Gz stress. (3) AP increased greatly after +Gz stress (17.29 +/- 5.59/11.31 +/- 3.86 kPa at rest vs. 27.53 +/- 6.12/20.62 +/- 1.86 kPa 30s after +7 Gz P<0.01). Conclusion. (1) The change of the amplitude of P-wave reflected the atrial displacement which may be the reason of arrhythmia. (2) The perfusion pressure is an important physiological parameter to the cardiovascular dysfunction during high +Gz stress. (3) Greatly higher AP after +Gz stress could be a feature of vascular exhaustion.
Acceleration↗
Overexpression of manganese superoxide dismutase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappaB and activated protein-1.
Several recently identified intracellular proteins associate with the tumor necrosis factor (TNF) receptor and activate nuclear transcription factor (NF)-kappaB, c-Jun kinase, and apoptosis. However, the mechanism is not understood. In the present report, we investigated the role of reactive oxygen intermediates in TNF-induced signaling. Overexpression of manganese superoxide dismutase (Mn-SOD) in human breast cancer MCF-7 cells completely abolished TNF-mediated NF-kappaB activation, IkappaB alpha degradation, p65 nuclear translocation, and NF-kappaB-dependent reporter gene expression. Besides TNF, phorbol ester-, okadaic acid-, ceramide-, and lipopolysaccharide-induced activation of NF-kappaB was blocked by Mn-SOD, indicating a common pathway of activation. H2O2-induced NF-kappaB activation, however, was potentiated. In addition, Mn-SOD blocked the TNF-mediated activation of activated protein-1, stress-activated c-Jun protein kinase, and mitogen-activated protein kinase kinase. TNF-induced antiproliferative effects and caspase-3 activation, indicators of apoptosis, were also completely suppressed by transfection of cells with Mn-SOD. Suppression of apoptosis induced by okadaic acid, H2O2, and taxol was also inhibited by Mn-SOD but not that induced by vincristine, vinblastine, or daunomycin. Overall, these results demonstrate that, in addition to several recently identified signaling molecules, reactive oxygen intermediates play a critical role in activation of NF-kappaB, activated protein-1, c-Jun kinase, and apoptosis induced by TNF and other agents.
Apoptosis↗
Evidence for at least two native forms of rabbit muscle adenylate kinase in equilibrium in aqueous solution.
The time course of 8-anilino-1-naphthalenesulfonic acid (ANS) binding to adenylate kinase (AK) is a biphasic process. The burst phase ends in the dead-time of the stopped-flow apparatus (about 15 ms), whereas the slow phase completes in about 10 min. A Job's plot tests of the binding stoichiometry demonstrates that there is one ANS binding site on AK, but only about 70% of the enzyme can rapidly bind with ANS, indicating that the conformation of native AK molecules is not homogeneous. Further kinetic analysis shows that the effects of ANS and substrates concentration on the burst and slow phase fluorescence building agree well with the multiple native forms mechanism. One form (denoted N1) binds with ANS, whereas the other (denoted N2) does not. ANS binding to N1 results in a burst phase fluorescence increase, followed by the interconversion of N2 to N1, to give the slow phase ANS binding. Under urea denaturation conditions, N2 is easily perturbed by urea and unfolds completely at low denaturant concentrations, whereas N1 is relatively resistant to denaturation and unfolds at higher denaturant concentrations. The existence of multiple native forms in solution may shed some light on the interpretation of the enzyme catalytic mechanism.
Adenylate Kinase↗
Basal expression of cyclooxygenase-2 and nuclear factor-interleukin 6 are dominant and coordinately regulated by interleukin 1 in the pancreatic islet.
The enzyme cyclooxygenase (COX)-1 is constitutive whereas COX-2 is regulated in virtually all tissues. To assess whether this dogma holds true in the pancreatic islet, we examined basal and interleukin (IL)-1-regulated expression of COX-2 in HIT-T15 cells, Syrian hamster and human islets, and other Syrian hamster tissues. We found that COX-2, and not COX-1, gene expression is dominant in pancreatic islet tissue under both basal and IL-1-stimulated conditions. Control tissues (liver, spleen, and kidney) showed the expected predominance of COX-1 gene expression. Basal and IL-1-stimulated prostaglandin E2 synthesis were blocked by a specific COX-2 inhibitor. IL-1 stimulation had a biphasic effect on COX-2 mRNA levels with an initial mild increase at 2-4 hr followed by a more dramatic decrease below basal level by 24 hr. The IL-1-induced increase in COX-2 mRNA levels was accompanied by a parallel increase in NF-kappaB binding to COX-2 promoter elements. The subsequent decrease in COX-2 mRNA levels was accompanied by a parallel decrease in NF-IL-6 binding activity and COX-2 promoter activity. Specific mutation of the NF-IL-6 binding motif within the COX-2 promoter reduced basal promoter activity by 50% whereas mutation of the NF-kappaB motif had no effect. These studies provide documentation of NF-IL-6 in the pancreatic islet and that COX-2, rather than COX-1, is dominantly expressed. They suggest coordinate regulation by IL-1 of COX-2 mRNA, NF-kappaB, and NF-IL-6 and raise the issue of whether intrinsically high levels of COX-2 gene expression predisposes the normal islet for microenvironmentally induced overproduction of islet prostaglandin E2.
Animals↗
Correction of cardiac defects through a right thoracotomy in children.
Explore the source record for details and available documents.
Cardiac Surgical Procedures↗
Use of commercial antibodies for detection of the primary antioxidant enzymes.
Fourteen commercial antibodies against human antioxidant enzymes were tested on whole cell lysates by Western analysis for specificity and species crossreactivity. All antibodies, except one, recognized pure protein antigen. All four catalase antibodies were of high quality, and they could also recognize the catalases from rat, mouse, dog, and hamster cells. Two CuZnSOD antibodies were very specific for CuZnSOD protein. They could also crossreact with CuZnSOD from rat, mouse, and hamster cells, but not from dog cells. All five MnSOD antibodies detected only very high levels of MnSOD. We believe that they could not properly be used in immunohistochemistry. Three GPX antibodies could not detect the specific GPX band from cell lysates. We believe that it is difficult to use these GPX antibodies in both Western blotting and immunohistochemistry.
Antibodies↗
Activation of adenylate kinase by denaturants is due to the increasing conformational flexibility at its active sites.
The unfolding of adenylate kinase in urea or guanidine hydrochloride solutions was measured by UV absorbance at 287 nm, circular dichroism at 222 nm and 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence. At concentrations less than 1.8 M of urea, the secondary and tertiary structures of AK were not noticeably perturbed. In contrast, the activity of the enzyme underwent significant changes, increasing about 1.6-fold when the urea concentration was increased to 1 M. The enzyme activity then decreased with further increases of the urea concentration. We also observed that the kinetics of ANS binding to AK by fluorescence was biphasic. The fast phase completed within the dead-time of the stopped-flow apparatus used, while the slow phase ended in about 10 minutes. The slow phase fluorescence rate constants increased from 0.0073 s-1 in the absence of denaturants to 0.0100 s-1 (about 1.4-fold) at 1 M urea and then decreased at higher urea concentrations. Similar results were obtained when guanidine hydrochloride was used as a denaturant. The change of the enzyme activity coincided with that of the rate of ANS binding during denaturation by low concentration of denaturants, suggesting that the activation of AK by denaturants may be due to the increasing conformational flexibility at its active site.
Adenylate Kinase↗