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Hong Zhang

Publications and source records attributed to Hong Zhang.

At least 451 records · Page 25Linked to original sources
PubMed2003

[Yixintong tablet's protection against experimental myocardial ischemia].

OBJECTIVE: Various models of experimental myocardial ischemia were set up to ovbserve the Yixinton's protection against ischemia. METHOD: Models of experimentally acute myocardial ischemia were made by ligature or medication (pituitrin or isoprenaline) to check the indices of ECG, hemodynamics, and morphology. RESULT: A dosage of Yixintong tablets 100 mg/kg, 200 mg/kg was given to rats by gavage; the rats had undergone a thirty-minute ligatute of coronary lef anterior descending branch, and used as a model of ischemic reperfusion. The observations showed that Yixintong tablets exerted a recovery effect on heart rate, blood pressure, internal pressure of left ventricule and its peak/trough rate (+/- dp/dtmax), and ST segment (electrocardiogram). The tablet markedly reduced the myocardial infarct size of the coronary-ligatured rats. The tablet benefited the rats with pituitrin(iv)- or isoprenaline(ip)-induced acute myocardial ischemia to reverse any ST deviation and T-wave fall. CONCLUSION: Yixintong has a protective and therapeutic action to the experimental myocardial ischemia.

Animals↗
PubMed2002

hREV3 is essential for error-prone translesion synthesis past UV or benzo[a]pyrene diol epoxide-induced DNA lesions in human fibroblasts.

In S. cerevisiae, the REV3 gene, encoding the catalytic subunit of polymerase zeta, is involved in translesion synthesis and required for the production of mutations induced by ultraviolet radiation (UV) photoproducts and other DNA fork-blocking lesions, and for the majority of spontaneous mutations. To determine whether hREV3, the human homolog of yeast REV3, is similarly involved in error-prone translesion synthesis past UV photoproducts and other lesions that block DNA replication, an hREV3 antisense construct under the control of the TetP promoter was transfected into an infinite life span human fibroblast cell strain that expresses a high level of tTAk, the activator of that promoter. Three transfectant strains expressing high levels of hREV3 antisense RNA were identified and compared with their parental cell strain for sensitivity to the cytotoxic and mutagenic effects of UV. The three hREV3 antisense-expressing cell strains were not more sensitive than the parental strain to the cytotoxic effect of UV, but the frequency of mutants induced by UV in their HPRT gene was significantly reduced, i.e. to 14% that of the parent. Two of these hREV3 antisense-expressing cell strains were compared with the parental strain for sensitivity to (+/-)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE). They were not more sensitive than the parent strain to the cytotoxic effect of BPDE, but the frequency of mutants induced was significantly reduced, i.e. in one strain, to 17% that of the parent, and in the other, to 24%. DNA sequencing showed that the kinds of mutations induced by BPDE in the parental and the derivative strains did not differ and were similar to those found previously with finite life span human fibroblasts. The data strongly support the hypothesis that hRev3 plays a critical role in the induction of mutations by UV or BPDE. Because the level of hRev3 protein in human fibroblasts is below the level of antibody detection, it was not possible to demonstrate that the decrease in mutagenesis reflected decreased hRev3 protein. However, the conclusion is supported by the fact that in a similar study with a strain expressing a high level of antisense hREV1, a very similar result was obtained, i.e. UV or BPDE mutagenesis was virtually eliminated.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2002

Oxidation-triggered c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways for apoptosis in human leukaemic cells stimulated by epigallocatechin-3-gallate (EGCG): a distinct pathway from those of chemically induced and receptor-mediated apoptosis.

We investigated intracellular signalling pathways for apoptosis induced by epigallocatechin-3-gallate (EGCG) as compared with those induced by a toxic chemical substance (etoposide, VP16) or the death receptor ligand [tumour necrosis factor (TNF)]. EGCG as well as VP16 and TNF induced activation of two apoptosis-regulating mitogen-activated protein (MAP) kinases, namely c-Jun N-terminal kinase (JNK) and p38 MAP kinase, in both human leukaemic U937 and OCI-AML1a cells. In U937 cells, the apoptosis and activation of caspases-3 and -9 induced by EGCG but not VP16 and TNF were inhibited with SB203580, a specific inhibitor of p38, while those induced by EGCG and VP16 but not TNF were inhibited with SB202190, a rather broad inhibitor of JNK and p38. In contrast, the EGCG-induced apoptosis in OCI-AML1a cells was resistant to SB203580 but not to SB202190. Unlike TNF, EGCG did not induce the activation of nuclear factor-kappaB but rather induced the primary activation of caspase-9. N -Acetyl-L-cysteine (NAC) almost completely abolished apoptosis induced by EGCG under conditions in which the apoptosis induced by VP16 or TNF was not affected. The JNK/p38 activation by EGCG was also potently inhibited by NAC, whereas those by VP16 and TNF were either not or only minimally affected by NAC. In addition, dithiothreitol also suppressed both apoptosis and JNK/p38 activation by EGCG, and EGCG-induced activation of MAP kinase kinase (MKK) 3/6, MKK4 and apoptosis-regulating kinase 1 (ASK1) was suppressed by NAC. Dominant negative ASK1, MKK6, MKK4 and JNK1 potently inhibited EGCG-induced cell death. EGCG induced an intracellular increase in reactive oxygen species and GSSG, both of which were also inhibited by NAC, and the decreased synthesis of glutathione rendered the cell susceptible to EGCG-induced apoptosis. Taken together these results strongly suggest that EGCG executed apoptotic cell death via an ASK1, MKK and JNK/p38 cascade which is triggered by NAC-sensitive intracellular oxidative events in a manner distinct from chemically induced or receptor-mediated apoptosis.

Antioxidants↗
PubMed2002

Phylogenetic and phenotypic analysis of HIV type 1 env gp120 in cases of subtype C mother-to-child transmission.

Human immunodeficiency virus type 1 (HIV-1) subtype C constitutes a majority of the newly transmitted cases of HIV-1 in many developing countries. There is growing evidence suggesting that subtype C viruses may display characteristics that make them distinct from subtype B and other subtypes, and such differences may affect its transmission and pathogenesis in infected individuals. In this study, HIV-1 sequences from the C2-V4 region of the envelope gene were analyzed from four infected mother-infant pairs (MIPs) after perinatal transmission in Zambia. We found that all viral isolates from four Zambian MIPs were of the subtype C HIV-1 subgroup. All tested isolates were macrophage tropic and did not infect any tested T cell lines or form syncytia in vitro. In addition, the isolates appear to use exclusively the CCR5 coreceptor. Phylogenetic analyses clearly indicated two contrasting phylogenetic transmission patterns for the four MIPs analyzed in the present study. Three cases displayed a pattern of selective transmission of a single or a few variants, and one case was found to transmit multiple maternal HIV-1 variants to her infant. The differences in the mode and timing of transmission may account for the observed transmission pattern among four MIPs.

Adolescent↗
PubMed2002

Plasticity of the kinomes in monkey and rat tissues.

The Kinetworks KPKS 1.0 immunoblotting screen was used to investigate the differential expression of 58 protein serine-threonine kinases, five protein threonine-tyrosine kinases, and 15 other nonreceptor protein tyrosine kinases in three types of human blood cells, 14 monkey organs, and six rat organs. The results demonstrate striking differences in the kineome profiles of diverse organs and even between the same organs in different species.

Animals↗
PubMed2002

Cost-effectiveness implications of the timing of antiretroviral therapy in HIV-infected adults.

BACKGROUND: The appropriate time to initiate antiretroviral therapy is controversial for human immunodeficiency virus (HIV)-infected patients with CD4 cell counts between 200/microL and 350/microL and low levels of HIV RNA, potentially leading to barriers to treatment access. OBJECTIVE: To examine the effect of cholesterol changes and fat redistribution symptoms on the clinical benefits and cost-effectiveness of early antiretroviral therapy in these patients. METHODS: We used a state-transition model to compare initiating antiretroviral therapy at CD4 cell counts of 350/microL (early therapy) with initiating therapy at CD4 cell counts of 200/microL (deferred therapy) in patients with HIV RNA levels of 10,000 to 30,000 copies/mL. Data were from randomized clinical trials, cohort studies, and other published literature. RESULTS: If cholesterol changes associated with antiretroviral therapy resulted in a permanent increase in coronary heart disease risk, life expectancy with early therapy was 16.54 years (vs 16.66 years without this risk) and with deferred therapy was 13.73 years (vs 13.80 years without this risk). Early therapy was a more efficient use of resources (ie, dominated) compared with deferred therapy. Early therapy cost $13,000 per quality-adjusted life-year compared with no therapy with or without increased coronary heart disease risk, and $17,000 to $24,000 per quality-adjusted life-year taking into account the quality-of-life reduction in patients with fat distribution symptoms. Early therapy had a higher quality-adjusted life expectancy than deferred therapy as long as this quality-of-life reduction was 70% or less. CONCLUSIONS: Changes in cholesterol or quality of life associated with antiretroviral therapy do not justify limiting access to early HIV treatment. The effect of fat redistribution symptoms on quality of life will determine the optimal choice of early vs deferred therapy for an individual patient.

AIDS-Related Opportunistic Infections↗
PubMed2002

Cellular response to hypoxia involves signaling via Smad proteins.

The transforming growth factor-beta (TGF-beta) family of cytokines regulates vascular development and inflammatory responses. We have recently shown that exposure of human umbilical vein endothelial cells (HUVECs) to hypoxia (1% O(2)) increases gene expression and bioactivation of TGF-beta2 and induces its downstream effectors, Smad proteins (Smads), to associate with DNA. In the present study, we show that hypoxia-induced TGF-beta2 gene expression is dependent on thrombospondin-1-mediated bioactivation of latent TGF-beta. Blocking TGF-beta2 but not TGF-beta1 in hypoxic endothelial cell cultures inhibited induction of the TGF-beta2 gene, indicating that an autocrine mechanism driven by bioactivation of TGF-beta2 leads to its gene expression in hypoxic HUVECs. Exposure of HUVECs to hypoxia resulted in phosphorylation and nuclear transportation of Smad2 and Smad3 proteins as well as stimulation of transcriptional activities of Smad3 and the transcription factor hypoxia-inducible factor-1alpha and culminated in up-regulation of TGF-beta2 gene expression. Autocrine regulation of TGF-beta2 production in hypoxia may involve cross-talk between Smad3 and HIF-1alpha signaling pathways, and could be an important mechanism by which endothelial cells respond to hypoxic stress.

Biological Transport↗
PubMed2002

Turbulence control by developing a spiral wave with a periodic signal injection in the complex Ginzburg-Landau equation.

Turbulence control in the two-dimensional complex Ginzburg-Landau equation is investigated. An approach is proposed for the purpose of control. In the presence of a small spiral wave seed initiation, a fully developed turbulence can be completely annihilated by injecting a single periodic signal into a small fixed space area around the spiral wave tip. The control is achieved in a parameter region where the spiral wave of the uncontrolled system is absolutely unstable. The robustness, convenience, and high control efficiency of this method are emphasized, and the mechanism underlying these practical advantages is intuitively understood.

Journal Article↗
PubMed2002

[Perioperative lung injury in ventricular septal defect with severe pulmonary hypertension, a clinical study of 31 cases].

OBJECTIVE: To investigate the mechanism of perioperative lung injury in patients of ventricular septal defect (VSD) with severe pulmonary hypertension. METHOD: The thromboxane B(2) (TXB(2)), 6-keto-prostagladin F(1 alpha) (6-keto-PGF(1 alpha)), malonyldiadehyde (MDA), interleukin-6 (IL-6), and IL-8, and blood pressure, pulmonary arterial pressure (PAP) and total pulmonary pressure (TPR) in thirty-one patients of VSD, 16 cases without pulmonary hypertension and 15 cases with severe pulmonary hypertension, were examined after anesthesia (AA), over extracorporeal circulation (OEC), and 1 hour (PEC1), 6 hours (PEC6), 24 hours (PEC24), 48 hours (PEC48), and 72 hours (PEC72) post extracorporeal circulation. The respiratory index (RI) and ratio of 6-keto-PGF(1alpha) and TXB(2) (P/T) were calculated. Before and after extracorporeal circulation, pulmonary tissues were taken to be examined by light microscopy and electron microscopy. RESULT: In the cases with severe pulmonary hypertension the P/T was 0.81 +/- 0.26 after anesthesia, then decreased 0.65 +/- 0.28 over extracorporeal circulation, and reached its lowest value (0.51 +/- 0.32) 1 hour post extracorporeal circulation. MDA was 2.4 micromol/L +/- 0.6 micromol/L after anesthesia, then increased, was 7.0 micromol/L +/- 1.7 micromol/L OEC, and reached its peak value (7.3 micromol/L +/- 0.9 micromol/L) PEC1. IL-6 was 0.27 ng/L +/- 0.12 ng/L after anesthesia, then increased, and reached its peak value (0.50 ng/L +/- 0.19 ng/L) PEC1. IL-8 was 7.5 ng/L +/- 1.5 ng/L after anesthesia, then increased, was 152 ng/L +/- 50 ng/L PEC1, and reached its peak (183 ng/L +/- 63 ng/L) PEC6. TXB(2) was 251 ng/L +/- 44 ng/L after anesthesia, then increased, and reached its peak (967 ng/L +/- 145 ng/L) at PEC1. The PAP was 72.1 +/- 18.8 mm Hg after anesthesia, 55 mm Hg +/- 15.3 mm Hg OPC, and 7.4 +/- 2.1 at PEC1, then decreased, and was 53 mm Hg +/- 15 mm Hg at PEC72. The total pulmonary resistance (TPR) was 10.6 +/- 2.9 mm Hg x min(-1) x L(-1) after anesthesia, then increased, and reached its peak (15.0 +/- 3.9 mm Hg x min(-1) x L(-1) at PEC6. Respiratory index (RI) was 0.88 +/- 0.23, then increased, and reached its peak (2.35 +/- 0.72) at PEC6. TXB(2) and RI were positively correlated with pulmonary vascular resistance (gamma = 0.283, P < 0.05; gamma = 0.403, P < 0.05). RI was positively correlated with MDA (gamma = 0.403, P < 0.05). Morphologic studies revealed discontinuities in the endothelial cell lining of pulmonary capillaries, infiltration of inflammatory cells, plugging of pulmonary capillaries with neutrophils, and intraalveolar hemorrhage. CONCLUSION: During the perioperative period, the pulmonary damage, which leads to pulmonary hypertensive crisis, is more severe among the cases of VSD with severe pulmonary hypertension than among the case without pulmonary hypertension.

Adolescent↗
PubMed2002

Biochemical evidence for multiple dimeric states of the Sinorhizobium meliloti DctD receiver domain.

X-ray crystal structures suggest very different dimeric states for the inactive and active forms of the two-component receiver domain of Sinorhizobium meliloti DctD, a sigma(54)-dependent AAA+ ATPase. Moreover, the receiver domain in crystals grown from unphosphorylated protein is refractory to phosphorylation whereas solution protein is fully phosphorylatable, and equilibrium analytical ultracentrifugation data are consistent with solution dimers for both phosphorylated and unphosphorylated forms of the protein. Here we report biochemical data consistent with the presence of multiple dimeric conformations in the inactive and active states, and evidence for significant change in the dimeric state upon activation by phosphorylation or binding of Mg(2+) and BeF(3)(-).

Bacterial Proteins↗
PubMed2002

[Effect of propofol on protecting Rhesus macaques from reperfusion lung injury during hemorrhagic shock and resuscitation].

OBJECTIVE: To investigate the protective efficacy of propofol against lung injury during hemorrhagic shock and resuscitation among Rhesus macaques. METHODS: Two healthy rhesus monkeys (Rhesus macaques) were killed and their lungs were taken out as samples of normal lung. Two healthy rhesus monkeys were made animal models of hemorrhagic shock and then were killed with their lungs taken out as samples of hemorrhagic shock lung. Another 12 healthy rhesus monkeys were randomly divided into two groups of six animals: propofol group (administered with propofol to a plasma concentration of 8 mg/L by target control infusion with computer before hemorrhagic shock) and control group. The monkeys were bled through the right femoral vein till the mean arterial pressure remained at the shock level of 40 mm Hg +/- 5 mm Hg. Two hours later, the total amount of bled blood and normal saline of the volume 2 times the volume of blood loss were reinfused into the animals quickly. Another 2 hours later hemodynamic parameters were measured, and blood samples were taken for measurement of malondialdehyde (MDA), superoxidedismutase (SOD) and lactate before bleeding, two hours after shock appeared, and 2 hours after resuscitation. The monkeys were killed 2 hours after resuscitation; their lungs were taken for pathologic examination and determination of water-to-dry weight ratio. RESULTS: The lungs of the 2 normal rhesus monkeys were normal with the W/D of 5.545 +/- 0.191. There is not remarkable change in the lung constitution of the 2 shock rhesus monkeys with a W/D ratio of 5.655 +/- 0.474. The mean pulmonary arterial pressure (MPA) and pulmonary vascular resistance index (PVRI) of the control group 2 hours after hemorrhagic shock and 2 hours after resuscitation were 17.00 +/- 4.42 and 22.83 +/- 5.11 respectively, both significantly higher than those of the propofol group (10.83 +/- 2.71 and 18.66 +/- 3.38, both P < 0.05). The pulmonary vascular resistance index (PVRI) of the control group 2 hours after hemorrhagic shock and 2 hours after resuscitation were 458.67 +/- 91.92 and 260.17 +/- 57.85 respectively, both significantly higher than those of the propofol group (258.67 +/- 63.02 and 159.17 +/- 47.98 respectively, both P < 0.05). The W/D ratio of the control group 2 hours after resuscitation was significantly higher than that of the propofol group (P < 0.05). The pulmonary edema of the control group was more serious than that of the propofol group by light microscopy and electron microscopy. CONCLUSION: Propofol remarkably relieves the lung injury occurring during hemorrhagic shock and resuscitation stage by ameliorating pulmonary circulation.

Animals↗
PubMed2002

Nocodazole-induced p53-dependent c-Jun N-terminal kinase activation reduces apoptosis in human colon carcinoma HCT116 cells.

Microtubule-interfering agents are widely used in cancer chemotherapy, and prognostic results vary significantly from tumor to tumor, depending on the p53 status. In preliminary experiments, we compared the expression and phosphorylation profiles of more than 100 protein kinases and protein phosphatases in human colorectal carcinoma cell line HCT116 between p53+/+ and p53-/- cells in response to short term nocodazole treatment through application of Kinetworks immunoblotting screens. Among the proteins tracked, the regulation of the phosphorylation of c-Jun N-terminal kinase (JNK)1/2 at Thr-183/Tyr-185 was the major difference between p53+/+ and p53-/- cells. With the loss of the p53 gene, the levels of phosphorylation of Ser-63 of c-Jun and Thr-183/Tyr-185 of JNK1/2 in p53-/- cells did not increase as markedly as in p53+/+ cells in response to a 1-h treatment with nocodazole or other microtubule-disrupting drugs such as vinblastine and colchicine. Similar observations were also made in MCF-7 and A549 tumor cells, which were rendered p53-deficient by E6 oncoprotein expression. However, arsenate-induced JNK activation in p53-/- cells was preserved. Inhibition of p53 expression by its antisense oligonucleotide also attenuated nocodazole-induced JNK activation in p53+/+ cells. Surprisingly, cotransfection of p53+/+ cells with dominant negative mutants of JNK isoforms and treatment of p53+/+ cells with the JNK inhibitor SP600125 actually further enhanced apoptosis in p53+/+ cells by up to 2-fold in response to nocodazole. These findings indicate that inhibition of p53-mediated JNK1/2 activity in certain tumor cells could serve to enhance the apoptosis-inducing actions of cancer chemotherapeutic agents that disrupt mitotic spindle function.

Antineoplastic Agents↗
PubMed2002

Treatment for primary HIV infection: projecting outcomes of immediate, interrupted, or delayed therapy.

With limited data available on the optimal treatment of primary HIV infection, disease modeling can be used to project clinical outcomes and inform decision makers. The authors developed a simulation model to evaluate the clinical outcomes and life expectancy projections for three primary HIV infection treatment strategies: 1) continuous antiretroviral therapy (ART) initiated at CD4 count <350 cells/mm(3); 2) continuous ART initiated immediately on diagnosis of primary HIV infection; and 3) ART initiated on diagnosis followed by structured treatment interruption. Projected life expectancies for the three strategies were 23.92, 24.46, and 26.07 years, respectively. The impact of key variables was assessed in sensitivity analysis, with the structured treatment interruption strategy remaining the most effective over a broad range of inputs. The immunologic benefit associated with immediate therapy and the potential for antiretroviral resistance due to structured treatment interruption have the most important impact on the optimal strategy. Based on current data, immediate treatment on diagnosis of primary HIV infection followed by structured treatment interruption will likely yield the best outcome. These results can assist decision makers and those planning clinical trials in defining evidence-based performance measures for primary HIV infection treatment and future trials.

Anti-HIV Agents↗
PubMed2002

A cyclin-dependent protein kinase homologue associated with the basal body domains in the ciliate Tetrahymena thermophila.

The tight coupling between cell cycle progression and morphogenetic development in the unicellular ciliates presents a unique model system for examination of the roles of Cdks in developmental processes. We here describe the isolation and characterization of the first cyclin-dependent kinase (Cdk) homologue, TtCdk1, from Tetrahymena thermophila. TtCdk1 corresponds to the larger of the two polypeptides recognized by anti-PSTAIRE antibody in a whole cell lysate, which differ from each other in their affinity for yeast p13(suc1) protein. In contrast to the constant protein expression levels of typical eukaryotic Cdks, the TtCdk1 protein level fluctuates periodically over the vegetative cell cycle, reaching a maximum at the end of the cell cycle, correlating with its histone H1 kinase activity. Its association with the membrane-skeletal domains that surround mature, but not nascent, basal bodies in the cell cortex suggests that TtCdk1 plays a role in the regulation of cortical morphogenesis in T. thermophila. A partial TtCDK1 knockout cell line constructed through somatic biolistic transformation resulted in a reduction of the regularity of the rows of basal bodies plus an additional effect on chromatin condensation in both macro- and micronuclei. Unlike the situations in higher eukaryotic cells, no apparent effect on basal body duplication was found upon disruption of the TtCDK1 gene.

Amino Acid Sequence↗
PubMed2002

[Therapeutic effects of pulmonary surfactant on smoking-induced lung injury in rats, an experimental study].

OBJECTIVE: To investigate the therapeutic effects of pulmonary surfactant (PS) on smoking-induced lung injury in rats. METHODS: Thirty male Wistar rats were randomly divided into four groups: normal control group (n = 8, killed by the end of the 7th week), 3-week smoking group (n = 8, in haling mainstream smoke of cigarette for 3 weeks and killed by the end of the 3rd week), 7-week smoking group (n = 8, in haling mainstream smoke of cigarette for 7 weeks and killed by the end of the 7th week), and PS treatment group (n = 6, inhaling mainstream smoke of cigarette for 7 weeks and given PS 25 mg/kg via trachea per week for 4 weeks since the end of the 3rd week of smoking, totally 5 times, and then killed by the end of the 7th week). The histological changes of respiratory bronchioles were observed by light microscopy and transmission electron microscopy. The airway resistance in expiratory phase was tested by pulmonary function test apparatus. The expression of Clara cell 16KD protein (CC16) mRNA and SP-C mRNA in lung tissue was determined by RT-PCR and the expression of CC16 protein in bronchiole epithelial cells was determined by immunohistochemistry. RESULTS: The proportion of Clara cell to the respiratory bronchiole epithelial cells was 62% in the normal controls, 40% in the 3-week smoking group, 33% in the 7-week smoking group, and 56% in the PS treatment group (significantly lower in comparison with that in the 7-week group, P < 0.05). Degeneration of Clara cells, hyperplasis of type II pneumocytes and increase of area of smooth muscle in bronchioles were observed in the three smoking groups, however, such changes were the most distinct in the 7-week smoking group and the less distinct in the PS treatment group (P < 0.05). In comparison with those in the normal control group, the expression of CC16 mRNA, SP-C mRNA and CC16 protein were lower in the three smoking groups. However, the expressions of CC16 mRNA and the expression of SP-C mRNA in the PS treatment group were significantly higher than those in the 7-week smoking group (11.8 +/- 5.1 vs 3.0 +/- 0.9, and 8.5 +/- 3.4 vs 2.5 +/- 0.9, both P < 0.05). The mean area of smooth muscle in bronchioles with the diameter less than 200 micro m was significantly larger than that in the control group, however, the mean area in the PS treatment group was significantly less than that in the 7-week smoking group (P < 0.05). The airway resistance in the control group (1.62 +/- 0.08 cmH(2)O. L(-1). s(-1)) was lower than those in the 3 smoking groups, however, the airway resistance in the PS treatment group was significantly lower than that in the 7-week group (1.70 +/- 0.07 cmH(2)O. L(-1). s(-1) vs 2.98 +/- 0.65 cmH(2)O. L(-1). s(-1), P < 0.05). CONCLUSION: PS is effective in alleviating smoking-induced lung injury in rats. One of the mechanisms might be attenuation of the damage in Clara cells and type II pneumocytes due to cigarette smoking.

Animals↗
PubMed2002

Tumor necrosis factor-alpha-induced leukocyte adhesion and microvessel permeability.

The objective of this study was to investigate whether leukocyte adhesion and/or emigration are critical steps in increased microvessel permeability during acute inflammation. To conduct this study, we combined autologous blood perfusion with a single microvessel perfusion technique, which allows microvessel permeability to be measured precisely after the endothelium has interacted with blood-borne stimuli. Experiments were carried out in intact venular microvessels in rat mesenteries. Firm attachment of leukocytes to endothelial cells was induced by intravenous injection of TNF-alpha (3.5 microg/kg) and resuming autoperfusion in a precannulated microvessel. Leukocyte emigration was facilitated by superfusion of formyl-Met-Leu-Phe-OH. Microvessel permeability was measured as hydraulic conductivity (L(p)) or the solute permeability coefficient to tetramethylrhodamine isothiocyanate-labeled alpha-lactalbumin before and after leukocyte adhesion and emigration in individually perfused microvessels. We found that perfusion of a microvessel with TNF-alpha did not affect basal microvessel permeability, but intravenous injection of TNF-alpha caused significant leukocyte adhesion. However, the significant leukocyte adhesion and emigration did not cause corresponding increases in either L(p) or solute permeability. Thus our results suggest that leukocyte adhesion and emigration do not necessarily increase microvessel permeability and the mechanisms that regulate the adhesion process act independently from mechanisms that regulate permeability. In addition, silver staining of endothelial boundaries demonstrated that leukocytes preferentially adhere at the junctions of endothelial cells. The appearance of the silver lines indicates that the TNF-alpha-induced firm adhesion of leukocyte to microvessel walls did not involve apparent changes in the junctional structure of endothelial cells, which is consistent with the results of permeability measurements.

Animals↗
PubMed2002

Sequence and structure classification of kinases.

Kinases are a ubiquitous group of enzymes that catalyze the phosphoryl transfer reaction from a phosphate donor (usually ATP) to a receptor substrate. Although all kinases catalyze essentially the same phosphoryl transfer reaction, they display remarkable diversity in their substrate specificity, structure, and the pathways in which they participate. In order to learn the relationship between structural fold and functional specificities in kinases, we have done a comprehensive survey of all available kinase sequences (>17,000) and classified them into 30 distinct families based on sequence similarities. Of these families, 19, covering nearly 98% of all sequences, fall into seven general structural folds for which three-dimensional structures are known. These fold groups include some of the most widespread protein folds, such as Rossmann fold, ferredoxin fold, ribonuclease H fold, and TIM beta/alpha-barrel. On the basis of this classification system, we examined the shared substrate binding and catalytic mechanisms as well as variations of these mechanisms in the same fold groups. Cases of convergent evolution of identical kinase activities occurring in different folds are discussed.

Amino Acid Sequence↗