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Biomedical subjects

P Zhu

Publications and source records attributed to P Zhu.

At least 37 records · Page 2Linked to original sources

Intra-hepatic expression of scavenger receptor and CD14 and their relationship with local inflammatory responses in endotoxemia in mice.

Our objective was to investigate the expression of scavenger receptor (SR) and CD14 in the liver and their relationship with local anti-inflammatory and proinflammatory responses in endotoxemia in order to uncover the mechanism for the liver to turn into effector organ from defense one at the level of cell receptors in sepsis. Mouse models of endotoxemia of different severity were reproduced by injection of different doses of lipopolysaccharide (LPS) via tail vein. Expression of SR and CD14 in the liver was assayed by immunohistochemistry and was then analyzed with an image analysis system. The levels of TNFalpha, IL-6, IL-4, and IL-10 in liver tissue were determined with ELISA. Expression of SR in the liver in the high-dose group was markedly decreased 1 h after injection of LPS, and also in low- and medium-dose groups at 3 h. The expression of SR in the liver in the three groups was shown to be progressively decreased with the time prolonged. There was significant difference in average optical density (OD) values of SR among the three groups. The expression of CD14 in the liver in the three groups was shown to be significantly increased 1 h after injection of LPS, and much more with the time prolonged. But there was no significant difference in OD values of CD14 among the three groups. The contents of intrahepatic proinflammatory mediators TNFalpha and IL-6 and anti-inflammatory mediators IL-4 and IL-10 were successively significantly increased after injection of LPS. The release of anti-inflammatory mediators was shown to be later than that of proinflammatory mediators. Correlation analysis indicated that there was negative correlation between expression of SR and CD14, and that changes of TNFalpha, IL-6, IL-4, and IL-10 levels in liver tissues were correlated significantly positively with OD values of CD14 and negatively with OD values of SR. Expression of SR in the liver was shown to be progressively decreased, and that of CD14 increased in endotoxemia, which was closely related to the uncontrolled inflammatory response in liver. This might be an important mechanism for the liver to turn into effector organ from defense one in sepsis.

Animals↗

Molecular characterization of a new abortive infection system (AbiU) from Lactococcus lactis LL51-1.

This study reports on the identification and characterization of a novel abortive infection system, AbiU, from Lactococcus lactis. AbiU confers resistance to phages from the three main industrially relevant lactococcal phage species: c2, 936, and P335. The presence of AbiU reduced the efficiency of plaquing against specific phage from each species as follows: 3.7 x 10(-1), 1.0 x 10(-2), and 1.0 x 10(-1), respectively. abiU involves two open reading frames, abiU1 (1,772 bp) and abiU2 (1,019 bp). Evidence indicates that AbiU1 is responsible for phage resistance and that AbiU2 may downregulate phage resistance against 936 and P335 type phages but not c2 type phage. AbiU appeared to delay transcription of both phage 712 and c2, with the effect being more marked on phage c2.

Amino Acid Sequence↗

Structural flexibility and functional valence of CD4-IgG2 (PRO 542): potential for cross-linking human immunodeficiency virus type 1 envelope spikes.

CD4-immunoglobulin G2 (CD4-IgG2) incorporates four copies of the D1D2 domains of CD4 into an antibody-like molecule that potently neutralizes primary human immunodeficiency virus type 1. Here electron microscopy was used to explore the structure and functional valence of CD4-IgG2 in complex with gp120. CD4-gamma2, a divalent CD4-immunoglobulin fusion protein, was evaluated in parallel. Whereas CD4-gamma2-gp120 complexes adopted a simple Y-shaped structure, CD4-IgG2-gp120 complexes consisted of four gp120s arrayed about a central CD4-IgG2 molecule, a structure more reminiscent of complement C1q. Molecular modeling corroborated the electron microscopy data and further indicated that CD4-IgG2 but not CD4-gamma2 has significant potential to cross-link gp120-gp41 trimers on the virion surface, suggesting a mechanism for the heightened antiviral activity of CD4-IgG2.

CD4 Immunoadhesins↗

A common mechanism for concurrent changes of diastolic muscle length and systolic function in intact hearts.

Mechanical properties of the myocardium at end diastole have been thought to be dominated by passive material properties rather than by active sarcomere cross-bridge interactions. This study tested the hypothesis that residual cross-bridges significantly contribute to end-diastolic mechanics in vivo and that changes in end-diastolic cross-bridge interaction parallel concurrent changes in systolic cross-bridge interaction. Open-chest anesthetized pigs were treated with intracoronary verapamil (n = 7) or 2,3-butanedione monoxime (BDM; n = 8). Regional left ventricular external work and end-diastolic pressure (EDP) versus end-diastolic segment length (EDL) relations were determined in the treated and untreated regions of each heart. Both agents reduced external work of treated regions to 31-38% of baseline and concurrently shifted EDP versus EDL relations to the right (i.e., greater EDL at a given EDP) by an average of 5% (P < 0.05). During washout of the drugs, EDP versus EDL returned to baseline in parallel with recovery of external work. Sarcomere length, measured by transmission electron microscopy in BDM-treated and untreated regions of the same hearts after diastolic arrest and perfusion fixation, was 8% greater in BDM-treated regions (P < 0.01). We concluded that residual diastolic cross-bridges significantly and reversibly influence end-diastolic mechanics in vivo. Alterations of end-diastolic and systolic cross-bridge interactions occur in parallel.

Animals↗

[Large-capacity expanded cytoline-induced killer cells and its cytotoxic activity].

This study was conducted to establish the large-capacity culture methd of cytokine-induced killer (CIK) cells for clinical therapy and assess its effect on the fuction of cell-mediated immunity following autologous CIK cells reinfusion. Autologus CIK cells were expanded in 1000 ml culture-bag and reinfused back. The MTT method was used to test the cytotoxic activity of CIK cells before and after reinfusion. The results showed that the total amount of autologous CIK cells reinfusion exceeded 1.6 x 10(10) with the use of the culture method of large-capacity. The PBMNC from patients treated by CIK cells showed significant increase in cytotoxic activity, no side effects were observed, and therefore the large-capacity culture method of CIK cells is a simle and safe therapy for treating the minimum residue of diseases.

Adult↗

[Relationship between the dynamic expression of scavenger receptor on Kupffer cells and endotoxin-induced hepatic injury].

OBJECTIVE: To observe the change of scavenger receptor (SR) expression on Kupffer cells and study its role in pathogenesis of liver injury in mice. METHODS: 1mg/kg or 10 mg/kg of E.Coli 026: B6 LPS was bolus injected via i.a.to reproduce an animal model for this experiment. The change of SR on Kupffer cells was determined with immunohistochemistry. TNF-alpha and IL-6 level in hepatic tissue were assayed using ELISA. RESULTS: The expression of SR on Kupffer cells was aggressively downregulated in a LPS does dependent fashion. TNF-alpha, IL-6 level in hepatic tissue and ALT, TBIL in plasma were significantly negatively correlated with the expression of SR. CONCLUSIONS: With the down-regulation of SR expression on Kupffer cells, the clearance of endotoxin by Kupffer cells is decreased and the activation of Kupffer cells by endotoxin is accordingly enhanced. SR expression is closely related to hepatic injury.

Animals↗

5-hydroxytryptamine3 (5-HT3) receptors mediate spinal 5-HT antinociception: an antisense approach.

To examine the role of the 5-hydroxytryptamine(1B) (5-HT1B) and 5-HT3 receptor subtypes in the analgesia produced by 5-HT (serotonin) agonists, we assessed the effect of antisense oligodeoxynucleotides (AODNs) designed to "knock down" the number of these receptor subtypes on analgesia produced by intrathecal (i.t.) 5-HT, the 5-HT1B receptor agonist, 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline maleate (CGS-12066A), and the 5-HT3 receptor agonist, 2-methyl-5-HT. Groups of mice (n = 17-20) were injected i.t. on days 1, 3, and 5 with one of the AODNs, a mismatch oligo, or saline. On day 6, all mice were injected i.t. with 70.5 nmol of 5-HT, 44.4 nmol of CGS-12066A, or 49 nmol of 2-methyl-5-HT by lumbar puncture. Following testing, spinal cords were rapidly removed and prepared for receptor binding assays. Treatment with AODN for 5-HT1B receptors produced a 70% reduction in ligand binding to this receptor subtype. After treatment with AODN for 5-HT3 receptors, ligand binding to this receptor subtype was undetectable. In mice tested with i.t. 5-HT, tail-flick analgesia was attenuated only in mice treated with the 5-HT3 receptor AODN. Mice treated with the AODN designed to knock down 5-HT(1B) receptors or with its mismatch oligo were not significantly different from controls. In mice tested with i.t. administration of CGS-12066A, none of the oligo treatments produced a significant attenuation of analgesia. In mice tested with i.t. administration of 2-methyl-5-HT, only 5-HT3 receptor AODN attenuated analgesia. Thus, 5-HT and 2-methyl-5-HT analgesia are mediated by the 5-HT3 receptor subtype. However, spinal CGS-12066A analgesia appears not to be mediated by either the 5-HT1B or the 5-HT3 receptor subtypes.

Animals↗

How to use progestin in hormone replacement therapy: an animal experiment.

OBJECTIVE: To determine whether continuous or cyclic hormone replacement therapy (estrogen and progestogen) is better. METHODS: One hundred and forty Sprague-Dawley rats were randomly divided into seven groups. The 1st and 2nd groups were normal estrous and ovariectomy (OVX) controls. Treatment of the other groups imitated the clinical regimen (continuous and cyclic) with estradiol valerate (E2V) and medroxy progesterone (MPA) in different ratios of combination. The rats were sacrificed and sections of uterus were stained with HE and histochemical methods to detect mitosis and proliferating cell nuclear antigen (PCNA), respectively. The mitotic index (MI) and PCNA index were calculated. RESULTS: The MI and PCNA index were similar in luminal and glandular cells. Both markers were low in the two control groups. When E2V was given for 1 to 6 days, both the MI and PCNA index increased with duration of treatment. When MPA was added, both markers were reduced to a very low level. In the continuous regimen, both markers decreased as the MPA dosage increased. The ratio of E2V: MPA = 1:0.5 was enough to suppress markers to a low level similar to that of normal estrous rats. A further increase in the ratio to 1:1.0 showed no further decrease in PCNA index. In the cyclic regimen, MPA was added for the last 5 days. The mitotic index reached a significantly low level near 0 in all ratios, but the PCNA index in each subgroup was still as high as the positive control, even though the dosage of MPA was increased several times to 1:8.0. When MPA was added for the last 10 days, the PCNA index at a ratio of 1:4.0 could be reduced to a low level. CONCLUSION: The results of this study suggest that the continuous regimen was better than the cyclic regimen in postmenopausal hormone replacement therapy (HRT). Progestin should be given for at least 10 days in the cyclic regimen.

Animals↗

Regulative effect of P38MAPK on release of TNFalpha and NO from alveolar macrophages under endotoxin stimulation.

OBJECTIVE: To evaluate activation of P38 mitogen-activated protein kinase (P38MAPK) in alveolar macrophage (AM), release of TNFalpha and NO from cells, and their relationship following lipopolysaccharide (LPS) stimulation. METHODS: AM was isolated from branch alveolar lavage fluid (BALF). The activation of P38MAPK was assayed by Western blot. SB203580, a specific inhibitor of P38MAPK, was used with gradient concentration to evaluate the regulative effect of P38MAPK on the release of TNFalpha and NO from AM. RESULTS: P38MAPK was activated by LPS (100 ng/ml) with peak activation at 30 minutes. The activation of P38MAPK was inhibited by SB203580. The secretion of TNFalpha and NO stimulated with LPS increased (P<0.01) and was inhibited by SB203580 significantly. CONCLUSIONS: The results indicate that P38MAPK is involved in the secreting process of TNFalpha and NO following LPS stimulation. P38MAPK may be an important site for controlling the secretion of both inflammatory mediators during lung inflammatory disorders.

Animals↗

Retinochoroidal changes after severe brain impact injury in rabbits.

OBJECTIVE: To investigate retinochoroidal changes and establish eye damage model after brain impact injury. METHODS: An eye damage model after brain impact injury was established by striking the frontoparietal zone in rabbits with BIM-II bioimpact machine. Seventeen rabbits were killed at 4 different intervals after injury. The pathological characteristics of the retinal and choroid damages were observed. RESULTS: All the rabbits had severe brain injury with subarachnoid hemorrhage and brain contusion. The eye damage occurred in all of the 17 rabbits. Hemorrhage in optic nerve sheaths was observed and retinal edema and bleeding was discovered with ophthalmoscope. Histopathologic study displayed subarachnoid hemorrhage in the retrobulbar portion of the retinal nerve, general choroid blood vessel dilatation, retinal nerve fibre swelling within 6 hours after injury, and flat retinal detachment with subretinal proteinoid exudation, and degeneration and disappearance of the outer segment of the optic cell over 6 hours after injury. CONCLUSIONS: The pathological characteristic of the eye damage at early stage following brain impact injury is local circulation disturbance. At late stage, it features in retinal detachment, and optic cellular degeneration and necrosis.

Animals↗

The regulatory effect of ERK1/2 signal pathway on production of TNFalpha induced by LPS in mice Kupffer cells.

OBJECTIVE: To study the rule of ERK1/2 activity and regulative effect of ERK1/2 pathway on the production of pro-inflammatory cytokine TNFalpha in mice Kupffer cells (mKC) induced by LPS, and to exploring novel methods to prevent and treat clinical patients of endotoxemia. METHODS: Immunoprecipitate kinase assay and Western blotting analysis were used to detect the phosphorylated ERK1/2 kinase activity in mKC stimulated by LPS, and ELISA was used to study the effect of ERK1/2 signaling cascade on LPS-induced TNFalpha production in mKC. RESULTS: In mKC, LPS treatment resulted in transient and rapid increase of kinase activity of ERK1/2 that phosphorylated their specific substrate ELK-1, with maximal value at 30 minutes and a return near to baseline within 2 hours, and LPS-induced ERK1/2 activity from LPS concentration of 10 pg/ml to the top activity at 100 ng/ml. No activity was observed in unstimulated mKC. Inhibition of the ERK1/2 pathway using the specific ERK1/2 signal pathway inhibitor PD98059 caused a marked and concentration-dependent reduction of TNFalpha production. CONCLUSIONS: The results show that LPS can markedly activate ERK1/2 pathway in mKC. PD98059 causes a significant and concentration-dependent reduction of TNFalpha production. ERK1/2 may be a novel target to treat clinical patient of endotoxemia.

Animals↗

[The clonal origin of the myeloma cells secreting three kinds of immunoglobulin from a multiple myeloma patient].

OBJECTIVE: To explore the clonal origin of myeloma cells from a multiple myeloma (MM) patient with 3 kinds of immunoglobulin (Ig). METHODS: Six primers for IgH variable region gene families VH1-VH6 and one primer of common join region (J) were used to perform reverse transcriptase polymerase chain reaction(RT-PCR). Five oligonucleotides of constant region gene (C mu, C delta, C gamma, C alpha and C epsilon) were also used as reverse primers. Different combination of primers were used to perform PCR. PCR products of IgH gene rearrangement were cloned and sequenced. RESULTS: A sharp and dense gene band appeared by using Ig VH3 gene family primer and J primer. The specific IgH gene bands also appeared by using primers of VH3 with C mu and C gamma and C alpha but not by primers of VH1, VH2, VH4, VH5 with J as well as VH3 with C delta and C epsilon. It indicated that there were IgM, IgG and IgA gene rearrangement. These gene products were cloned and sequenced. All 3 IgM, IgG and IgA gene sequences are identical. CONCLUSION: Despite the oligoclonality of MM cell, the sequencing results of 3 IgH genes showed that all the malignant cells were monoclonal origin.

Base Sequence↗

[The MRI diagnosis of aortic dissection].

OBJECTIVE: To analyze and address the MRI manifestations and diagnostic importance of aortic dissection. METHODS: The MRI manifestations in 31 cases of aortic dissection were analyzed retrospectively. Sixteen cases were proved by operation and pathology. RESULTS: MRI depicted an intimal flap and a double lumen in all 31 patients. The site of intimal tear was located in 7 cases. Also demonstrated were the complications: aortic dilation in 15 cases, aortic branches involvement in 5, thrombus formation in the false lumen in 5, aortic regurgitation in 10, left ventricle hypertrophy in 10, and leak into thorax in 2. CONCLUSION: As a non-invading imaging method, MRI can demonstrate the site, range and complications of aortic dissection; it is very valuable in the diagnosis of aortic dissection.

Adult↗

[Study on mutations in the connexin 26 gene among Chinese with nonsyndromic hearing loss].

OBJECTIVE: To study the relation between nonsyndromic hearing loss in Chinese and mutations in connexin 26 (Cx 26) gene and to explore the pathogenic mechanism. METHODS: One hundred and thirty-eight individuals from thirty-five pedigrees with nonsyndromic hearing loss, 99 children with sporadic nonsyndromic hearing loss and 100 normal adults as control were collected in present studies. The Cx 26 coding sequence was screened by single strand conformational polymorphism (SSCP) and analyzed by direct sequencing when SSCP shifts were observed. RESULTS: Five SSCP shifts in 2 pedigrees were observed. Homozygous deletion C at position 233-235 of Cx 26 cDNA, which resulted in frameshift mutation, was found in 2 pedigrees with nonsyndromic hearing loss. CONCLUSION: The hot-spot mutations of Cx 26 gene in Chinese with nonsyndromic hearing loss may be different from other ethnic groups. The 233-235 delC homozygous mutation of Cx 26 cDNA can result in autosomal recessive nonsyndromic hearing loss in Chinese population.

Adult↗

Carotid intima-media thickness and the association with cardiovascular risk factors in the elderly.

OBJECTIVE: To investigate the association of carotid arterial intima-media thickness (IMT) with principal cardiovascular risk factors in the elderly. METHODS: Carotid arterial IMT was measured by high resolution B mode ultrasound in 94 elderly subjects (old-aged group), and compared with subjects aged < 60 (middle-aged group). RESULTS: In comparison with the middle-aged group, the prevalence of coronary heart disease, cerebral vascular disease, hypertension and diabetes mellitus was significantly higher, and serum cholesterol and systolic blood pressure were also significantly higher in old-aged group. Although there was no obvious difference in IMT between the two groups, carotid plaque and carotid wall thickening were more frequently found in old-aged group. Age, systolic blood pressure and serum cholesterol were shown as the independent determinants for carotid IMT in the total participants, whereas no such independent relation was found in old-aged group. CONCLUSION: Age is the major risk factor for carotid atherosclerosis in the elderly. In other words, the occurrence of carotid atherosclerosis is the result of advancing age combined with the effect of multiple cardiovascular risk factors.

Aged↗

[Effect of recombinant epidermal growth factor on corneal epithelial cells after excision of pterygium].

OBJECTIVE: To investigate the effects of recombinant epidermal growth factor on the wounded corneal healing after excision of pterygium. METHODS: Simple and unrecurrent pterygium was selected, excised and sewed up conjunctival flap under local anaesthesia and microscope. After operation two drops of EGF eyedrop were used, and five minutes later 0.3% Tarivid Eye Oint was used again, and then the operated eye was enswathed. Everyday the wound cornea was observed and the EGF eyedrop was used. RESULTS: The wound cornea healing time of control group was seven days and that of the EGF group was five days and gave a remarkable difference (P < 0.05). The same results were obtained after comparing the effective group and ineffective group, P < 0.05. CONCLUSIONS: EGF eyedrop can accelerate proliferation and recovery of wound corneal epithelial cells. In the clinical trial, every body felt well and no side-effect was observed.

Adolescent↗

[Raman analysis of SiGe films grown by UHV/CVD].

This paper presents a Raman method, which is no deconstructed, to measure Ge content and strain in SiGe alloy films and some samples, which is grown by UHV/CVD with different Ge content and thickness, have been tested by above method. Two samples among them were measured by DCXRD, the results tested by DCXRD are consistent with Raman results that proves that the method in this paper is reliable and accurate. The SiGe PHMOSFET has been fabricated by the samples, the transconductance reaches 112 ms.mm-1 for the device with 0.5 micron channel.

Alloys↗

Troglitazone improves recovery of left ventricular function after regional ischemia in pigs.

BACKGROUND: This study determined whether treatment of normal (nondiabetic) pigs with the insulin-sensitizing agent troglitazone improves recovery of left ventricular (LV) function after acute ischemia and whether such effects are associated with altered myocardial substrate metabolism. METHODS AND RESULTS: Juvenile pigs (n=6) were treated with troglitazone (75 mg. kg(-1). d(-1) PO) for 8 weeks. Untreated pigs (n=8) served as controls. Under anesthetized, open-chest conditions, pigs underwent 90 minutes of moderate regional LV ischemia and 90 minutes of reperfusion. Regional LV function was assessed with subendocardial sonomicrometry crystals. Fasting plasma insulin and free fatty acid levels were lower in troglitazone-treated pigs than in untreated pigs, whereas blood glucose did not differ between groups. These findings suggest that treatment enhanced systemic insulin sensitivity. Baseline hemodynamics and regional LV function did not differ between groups. After ischemia and reperfusion, systolic function (external work) of the ischemic region recovered to 44+/-6% of baseline in troglitazone-treated pigs versus 18+/-6% of baseline in untreated pigs (P<0.05). Regional diastolic function (maximum rate of wall expansion) recovered to 78+/-7% of baseline in treated pigs versus 52+/-7% of baseline in untreated pigs (P<0.05). Recovery of global LV systolic and diastolic function was also significantly greater in treated pigs. Myocardial glucose uptake did not differ between groups under any condition; however, net myocardial lactate uptake after reperfusion was 7 times greater in troglitazone-treated pigs than in untreated pigs, suggesting that treatment enhanced myocardial carbohydrate oxidation after reperfusion. CONCLUSIONS: In nondiabetic pigs, chronic troglitazone treatment improves recovery of LV systolic and diastolic function after acute ischemia.

Animals↗