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Biomedical subjects

J Zhu

Publications and source records attributed to J Zhu.

At least 289 records · Page 16Linked to original sources

[Expression of recombinant human stem cell factor in insect cells].

The cDNA of human stem cell factor(hSCF) containing signal sequence was cloned into the transfer vector pVL941 of AcNPV to construct a recombinant transfer vector pVL941-SCF. Sf9 cells were cotransfected with wild type viral DNA and pVL914-SCF to produce the recombinant virus AcNPV-SCF by homologous recombination in cell. Southern-hybridization analysis suggested that the recombinant viral DNA contained hSCF cDNA fragment. The Sf9 cells infected with the recombinant baculovirus AcNPV-SCF expressed biologically active rhSCF which was secreted into the cell culture. The synergistic activities of SCF in conjunction with human interleukin-3(hIL-3) was measured by MTT colorimetric method and TF-1 cell line. The expression level of Sf9 cells reached its highest at about 1970 units/ml in the 3rd day after the infection with AcNPV-SCF. Three SCF bands with molecular masses of 18 x 10(3), 20 x 10(3) and 22 x 10(3) were detected by immunoblotting.

Animals↗

[Studies on the toxicity of polymer of glycolide and lactide(PLGA) and the anti-fertility effect of levonorgestrel(LNG)].

PLGA(9:1), a chemical degraded from biomaterials, has been subjected to the tests of acute toxicity, irritations on conjunctiva and muscle, haemolysis in vitro and allergic reaction of mice and rats. The anti-fertility effect of PLGA-LNG microphere composite on the same animals also has been tested. The studies demonstrated that PLGA had fine biological compatibility without side effects such as toxicity, irritations on conjunctiva and muscle, pyrogenicity, haemolysis in vitro and allergic reaction. The contraception period of mice lasted 11.5, 34.6 and 81.2 days respectively after the subcutaneous (s.c.) injection of PLGA-LNG microphere which contains LNG 5, 10 and 20 mg/kg separately. The intramuscular(i.m.) injection of PLGA-LNG microphere containing LNG 13.6, 19.8 and 30 mg/kg respectively could keep the estrus of rats supressed for 76.3, 104.1 and 131.8 days. The injections of PLGA-LNG microphere through s.c. or i.m. showed more significant effects than the same dosages of PLGA-LNG micro-crystal. These results suggest that PLGA-LNG microphere injection has long-term anti-fertility effect.

Animals↗

[An epidemiological investigation of anotia and microtia in China during 1988-1992].

OBJECTIVE: To investigate the epidemiological characteristics of cases with anotia and microtia in China. METHOD: The birth defect monitoring program was undertaken by a hospital-based monitoring method in 443-588 hospitals from 30 provinces, cities and autonomous regions across China. Data including intrauterine death and stillbirth from 28 weeks of gestation to a period of 7 days postpartum were collected between 1988 and 1992. RESULTS: A total of 3,246,408 births was monitored from 1988 to 1992, in which 453 cases had anotia and microtia. The average incidence was 1.40 per 10,000 during the five-year period. The decreased tendency of incidence was noted during the period (chi 2 = 5.5588, P < 0.05). The incidence in the urban area was significantly higher than that in the rural area. There was no sex difference in the incidence of anotia and microtia. The incidence varied among 30 provinces with highest incidence in Xinjiang province (2.08 per 10,000 births) and lowest in the Inner Mongolia Autonomous Region (0.33 per 10,000 births). In cases with the defects of anotia and microtia, 60.4% were accompanied with other congenital malformations. The proportion of multiple malformations with microtia and anotia was significantly higher than that of isolated case (chi 2 = 36.9277, P < 0.01). The highest incidence of concurrent malformations was anophthalmia or microphthalmia (13.1%), followed by facial cleft (12.6%), neural tube defects (10.0%), limb reduction defects (9.6%) and polydactyly (5.4%). There were also 3.5% cardiac defects. CONCLUSIONS: The prevalence of anotia and microtia varied among provinces across China. The high proportions of cases with anotia and microtia had multiple malformations. Therefore, careful examination of other malformations in patients with anotia and microtia is necessary.

Abnormalities, Multiple↗

[Effects of urapidil and cimetidine on wedged hepatic venous pressure and systemic hemodynamics in cirrhotic patients with portal hypertension].

OBJECTIVE: To compare the effects of urapidil and cimetidine on portal pressure and systemic hemodynamics. METHODS: We observed the effects of urapidil (urapidil HCl, n = 15), cimetidine (n = 20) and placebo (0.9% sodium chloride, n = 10) on wedged hepatic venous pressure (WHVP), hepatic venous pressure gradient (HVPG), and systemic hemodynamics. RESULTS: Urapidil at a dosage of 25 mg intravenously reduced WHVP from 33.33 +/- 7.85 cm H2O to 23.75 +/- 6.83 cm H2O, the average value was 28.75% +/- 9.81% (P > 0.01); and HVPG from 21.92 +/- 2.34 cm H2O to 14.07 +/- 3.57 cm H2O, the average value was 35.81% +/- 8.71% (P < 0.01). The free hepatic venous pressure (FHVP) however was not changed significantly (P > 0.05). The heart rate was increased from 70 +/- 13 BPM to 79 +/- 21 BPM (P < 0.05), and the systolic blood pressure and the diastolic blood pressure were reduced from 122 +/- 40 mm Hg to 95 +/- 32 mm Hg and 75 +/- 17 mm Hg to 55 +/- 15 mm Hg respectively (P < 0.01). After cimetidine administered at a dosage of 400 mg intravenously, WHVP and HVPG were reduced from 34.25 +/- 7.34 cm H2O to 29.05 +/- 7.03 cm H2O and 23.14 +- 8.15 cm H2O to 17.13 +/- 4.28 cm H2O; and the average value was 15.18% +/- 8.64% and 26.00% +/- 12.19% respectively (P < 0.01). But heart rate, blood pressure and FHVP were not altered after use of cimetidine ( P > 0.05). In the control group (n = 10), WHVP, HVPG, FHVP, heart rate, as well as blood pressure were not changed after placebo treatment. CONCLUSIONS: Both urapidil and cimetidine could reduce WHVP and HVPG significantly in cirrhotic patients with portal hypertension, and the effect of the two agents on WHVP and HVPG was not obviously different (P > 0.05). However, the systemic hemodynamic effects induced by urapidil were more significant compared with cimetidine.

Adult↗

Retinoic acid induces proteasome-dependent degradation of retinoic acid receptor alpha (RARalpha) and oncogenic RARalpha fusion proteins.

Analyzing the pathways by which retinoic acid (RA) induces promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha) catabolism in acute promyelocytic leukemia (APL), we found that, in addition to caspase-mediated PML/RARalpha cleavage, RA triggers degradation of both PML/RARalpha and RARalpha. Similarly, in non-APL cells, RA directly targeted RARalpha and RARalpha fusions to the proteasome degradation pathway. Activation of either RARalpha or RXRalpha by specific agonists induced degradation of both proteins. Conversely, a mutation in RARalpha that abolishes heterodimer formation and DNA binding, blocked both RARalpha and RXRalpha degradation. Mutations in the RARalpha DNA-binding domain or AF-2 transcriptional activation region also impaired RARalpha catabolism. Hence, our results link transcriptional activation to receptor catabolism and suggest that transcriptional up-regulation of nuclear receptors by their ligands may be a feedback mechanism allowing sustained target-gene activation.

Caspases↗

Interaction of the Ras-related protein associated with diabetes rad and the putative tumor metastasis suppressor NM23 provides a novel mechanism of GTPase regulation.

Rad is the prototypic member of a new class of Ras-related GTPases. Purification of the GTPase-activating protein (GAP) for Rad revealed nm23, a putative tumor metastasis suppressor and a development gene in Drosophila. Antibodies against nm23 depleted Rad-GAP activity from human skeletal muscle cytosol, and bacterially expressed nm23 reconstituted the activity. The GAP activity of nm23 was specific for Rad, was absent with the S105N putative dominant negative mutant of Rad, and was reduced with mutations of nm23. In the presence of ATP, GDP.Rad was also reconverted to GTP.Rad by the nucleoside diphosphate (NDP) kinase activity of nm23. Simultaneously, Rad regulated nm23 by enhancing its NDP kinase activity and decreasing its autophosphorylation. Melanoma cells transfected with wild-type Rad, but not the S105N-Rad, showed enhanced DNA synthesis in response to serum; this effect was lost with coexpression of nm23. Thus, the interaction of nm23 and Rad provides a potential novel mechanism for bidirectional, bimolecular regulation in which nm23 stimulates both GTP hydrolysis and GTP loading of Rad whereas Rad regulates activity of nm23. This interaction may play important roles in the effects of Rad on glucose metabolism and the effects of nm23 on tumor metastasis and developmental regulation.

Animals↗

Identification of a novel 0.7-kb polyadenylated transcript in the LAT promoter region of HSV-1 that is strain specific and may contribute to virulence.

Herpes Simplex virus expresses latency-associated transcripts (LATs) the function of which remains obscure despite increasing knowledge of their structure and expression. Upstream of the LAT coding region is a region of the genome that is poorly characterized although it lies in an area that is responsible for modulation of reactivation efficiency in two different animal models. Transcript mapping with strains 17, McKrae, KOS, and F has revealed strain differences in this region of the viral genome. Strain 17 and McKrae expressed a novel polyadenylated 0.7-kb transcript that is absent from KOS and F. This transcript is expressed in the LAT direction and has the kinetics of a true late gene during the lytic cycle of infection. A deletion mutant, 17DeltaBsa, which does not express the 0.7-kb RNA, is less virulent than the parental strain 17. A rescuant with F sequence (17DeltaBsa/RF) shows virulence similar to F, whereas a rescuant with strain 17 sequence (17DeltaBsa/R17) is similar to strain 17. Virulence is altered by deletion or substitution in the region encoding the 0.7-kb transcript (BsaI-BsaI); however, reactivation in the mouse explant cocultivation assay or the adrenergically induced rabbit reactivation model remained unchanged. The importance of this region for virulence is discussed.

Animals↗

p53 induces TAP1 and enhances the transport of MHC class I peptides.

The transporter associated with antigen processing (TAP) 1 is required for the major histocompatibility complex (MHC) class I antigen presentation pathway, which plays a key role in host tumor surveillance. Since more than 50% of tumors have a dysfunctional p53, evasion of tumor surveillance by tumor cells may be linked to loss of p53 function. Here we found that TAP1 is strongly induced by p53 and DNA-damaging agents through a p53-responsive element. We also found that p73, which is homologous to p53, is capable of inducing TAP1 and cooperates with p53 to activate TAP1. Furthermore, we found that by inducing TAP1, p53 enhances the transport of MHC class I peptides and expression of surface MHC-peptide complexes, and cooperates with interferon gamma to activate the MHC class I pathway. These results suggest that tumor surveillance may be a mechanism by which p53 and/or p73 function as tumor suppressors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The effect of base sequence on the stability of RNA and DNA single base bulges.

Forty-eight RNA duplexes were constructed that contained all common single base bulges at six different locations. The stabilities of the RNAs were determined by temperature gradient gel electrophoresis (TGGE). The relative stability of a single base bulge was dependent on both base identity and the nearest neighbor context. The single base bulges were placed into two categories. A bulged base with no identical neighboring base was defined as a Group I base bulge. Group II-bulged bases had at least one neighboring base identical to it. Group II bulges were generally more stable than Group I bulges in the same nearest neighbor environments. This indicates that position degeneracy of an unpaired base enhances stability. Differences in the mobility transition temperatures between the RNA fragments with bulges and the completely base-paired reference RNAs were related to free energy differences. Simple models for estimating the free energy contribution of single base bulges were evaluated from the free energy difference data. The contribution of a Group I bulge 5'-(XNZ)-3'.5'-(Z'-X')-3' where N is the unpaired base and X.X' and Z.Z' the neighboring base pairs, could be well-represented (+/-0.34 kcal/mol) by the equation, DeltaG((X)(N)()(Z))(.)((Z)(')(-)(X)(')()) = 3.11 + 0. 40DeltaG(s)()((XZ))(.)((Z)(')(X)(')()). DeltaG(s)()((XZ))(. )((Z)(')(X)(')()) is the stacking energy of the closing base pair doublet. By adding a constant term, delta = -0.3 kcal/mol, to the right side of the above equation, free energies of Group II bulges could also be predicted with the same accuracy. The term delta represents the stabilizing effect due to position degeneracy. A similar equation/model was applied to previous data from 32 DNA fragments with single base bulges. It predicted the free energy differences with a similar standard deviation.

Base Sequence↗

Cytomegalovirus in the pathogenesis of atherosclerosis: the role of inflammation as reflected by elevated C-reactive protein levels.

OBJECTIVES: We hypothesized that cytomegalovirus (CMV) infection: 1) stimulates an inflammatory response, reflected by elevated C-reactive protein (CRP) levels, and 2) predisposes to coronary artery disease (CAD), in part, through CMV-induced inflammation. BACKGROUND: Although some studies show an association between CMV and atherosclerosis, others do not. We believed that CMV exerted an atherogenic effect by inducing inflammation, and the disparate results may derive partly from individual variability in the capacity to control CMV inflammatory activity. METHODS: Blood samples were tested for CMV seropositivity and CRP levels from 238 individuals being evaluated for CAD by coronary angiography. RESULTS: An elevated CRP level (>0.5 mg/dl) was a significant CAD determinant even after adjustment for traditional CAD risk factors (odds ratio [OR] = 2.4; p = 0.02). Moreover, CMV seropositivity was significantly associated with increased CRP levels (p = 0.04 after adjustment for CAD risk factors), suggesting that CMV could evoke a subclinical inflammatory response. However, considerable host variation existed in this response to CMV. When adjusted for CAD risk factors, the OR for CAD were 1.3 in the subgroup with CMV seropositivity alone (p = 0.7), 2.3 in the subgroup with elevated CRP levels alone (p = 0.2), and 4.3 in the subgroup with combined CMV seropositivity and elevated CRP levels (p = 0.01). CONCLUSIONS: Our results suggest that 1) CMV elicits a subclinical inflammatory response, but only in certain individuals, and 2) individuals with an inflammatory response appear susceptible to the atherogenic effects of CMV, whereas those without appear resistant. These results may partly explain the disparate results of studies attempting to relate CMV to atherogenesis.

Adult↗

A(2A) adenosine receptor deficiency attenuates brain injury induced by transient focal ischemia in mice.

Extracellular adenosine critically modulates ischemic brain injury, at least in part through activation of the A(1) adenosine receptor. However, the role played by the A(2A) receptor has been obscured by intrinsic limitations of A(2A) adenosinergic agents. To overcome these pharmacological limitations, we explored the consequences of deleting the A(2A) adenosine receptor on brain damage after transient focal ischemia. Cerebral morphology, as well as vascular and physiological measures (before, during, and after ischemia) did not differ between A(2A) receptor knock-out and wild-type littermates. The volume of cerebral infarction, as well as the associated neurological deficit induced by transient filament occlusion of the middle cerebral artery, were significantly attenuated in A(2A) receptor knock-out mice. This neuroprotective phenotype of A(2A) receptor-deficient mice was observed in different genetic backgrounds, confirming A(2A) receptor disruption as its cause. Together with complimentary pharmacological studies, these data suggest that A(2A) receptors play a prominent role in the development of ischemic injury within brain and demonstrate the potential for anatomical and functional neuroprotection against stroke by A(2A) receptor antagonists.

Aging↗

Reconstituted HDL containing human apolipoprotein A-1 reduces VCAM-1 expression and neointima formation following periadventitial cuff-induced carotid injury in apoE null mice.

Arterial injury triggers an inflammatory response in part mediated by induction of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and is implicated in neointimal thickening. Since HDL is known to reduce cytokine-activated VCAM-1 expression, we tested the hypothesis that VCAM-1 expression and neontimal thickening following arterial injury are inhibited by reconstituted human HDL containing plasma-derived apoA-1 (rHDL). We used the carotid cuff injury in apoE (-/-) mice fed high cholesterol. Mice received rHDL (40 mg/kg) intravenously every other day for 3 weeks. Compared to control, rHDL treatment inhibited neointima formation (0. 008 +/- 0.004 mm(2) vs. 0.037 +/- 0.019 mm(2); P < 0.01) 21 days after injury, reduced VCAM-1 expression, and decreased monocyte/macrophage infiltration as assessed by histomorphometric analysis within the first week after injury. These changes occurred without any effect on plasma total and HDL cholesterol levels as well as the arterial tissue cholesterol levels. rHDL treatment also reduced the formation of modified lipoprotein in the arterial wall compared to control within the first week after injury. This finding suggests an antioxidant effect of rHDL associated with reduced VCAM-1 expression and neointimal formation after arterial injury.

Animals↗

Multiple ink nanolithography: toward a multiple-Pen nano-plotter

The formation of intricate nanostructures will require the ability to maintain surface registry during several patterning steps. A scanning probe method, dip-pen nanolithography (DPN), can be used to pattern monolayers of different organic molecules down to a 5-nanometer separation. An "overwriting" capability of DPN allows one nanostructure to be generated and the areas surrounding that nanostructure to be filled in with a second type of "ink."

Journal Article↗

Age-related variation in the interstitial tissues of the cardiac conduction system; and autopsy study of 230 Han Chinese.

The amount of fatty and fibrous tissues in 230 Han Chinese who died of noncardio-vascular diseases has been studied by a semi-quantitative method and analysed by chi-square test. The results have shown some consistency. Generally, in the sino-atrial node (SAN), fibrosis and fatty influtratin appear only after 40 years of age and increase one grade with every 20 years. The atrio-ventricular node (AVN) showed fatty change after 30 years of age and fibrosis appeared after 60. In the His bundle (HB), fatty infiltration and fibrosis appear after 40 years. The left bundle branch (LBB) showed similar changes. The appearance of fibrosis in the AVN seems to be later than that reported by Lev.

Adolescent↗

Identification of seven serotypes of bluetongue virus from the People's Republic of China.

Seven serotypes (1, 2, 3, 4, 12, 15 and 16) of bluetongue virus were isolated from the blood of sheep and cattle in the People's Republic of China between 1986 and 1996. Six of these viruses were isolated in Yunnan province. The sheep from which serotypes 1 and 16 were isolated showed obvious signs of bluetongue disease, whereas the cattle from which serotypes 2, 3, 4, 12 and 15 were isolated were clinically normal. Phylogenetic analyses of these viruses indicate that they are more closely related to one another, and to an Australian strain of serotype 1, than they are to prototype strains of bluetongue virus serotypes 2, 10, 11, 13 and 17 from the USA.

Animals↗

Suppression of macrophage responses to bacterial lipopolysaccharide by a non-secretory form of secretory leukocyte protease inhibitor.

Expression of secretory leukocyte protease inhibitor (SLPI) suppresses the ability of macrophages to respond to bacterial lipopolysaccharide (LPS). Here, addition of recombinant or native SLPI to the extracellular medium was non-suppressive, while transfection with a non-secretory form of SLPI was fully suppressive, an effect overcome by treatment with interferon-gamma. A portion of the SLPI produced by untransfected macrophages was localized in the cytosol. Thus, SLPI can act intracellularly to block macrophage activation by LPS.

Animals↗