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Biomedical subjects

C Zhu

Publications and source records attributed to C Zhu.

At least 145 records · Page 8Linked to original sources

A targeted DNA-PKcs-null mutation reveals DNA-PK-independent functions for KU in V(D)J recombination.

The DNA-dependent protein kinase (DNA-PK) consists of Ku70, Ku80, and a large catalytic subunit, DNA-PKcs. Targeted inactivation of the Ku70 or Ku80 genes results in elevated ionizing radiation (IR) sensitivity and inability to perform both V(D)J coding-end and signal (RS)-end joining in cells, with severe growth retardation plus immunodeficiency in mice. In contrast, we now demonstrate that DNA-PKcs-null mice generated by gene-targeted mutation, while also severely immunodeficient, exhibit no growth retardation. Furthermore, DNA-PKcs-null cells are blocked for V(D)J coding-end joining, but retain normal RS-end joining. Finally, while DNA-PK-null fibroblasts exhibited increased IR sensitivity, DNA-PKcs-deficient ES cells did not. We conclude that Ku70 and Ku80 may have functions in V(D)J recombination and DNA repair that are independent of DNA-PKcs.

Animals↗

Matrilysin activity in the rat uterus during the oestrous cycle and implantation.

The objective of this study was to follow changes in the activity of the small matrix metalloproteinase matrilysin (MMP-7) in the rat uterus during the oestrous cycle and embryo implantation. Matrilysin was extracted from rat uteri, partially purified and separated into active and latent forms. The two forms of the enzyme were quantified at all stages of the oestrous cycle and after oestradiol and progesterone treatment. The activity was also measured during the first 7 days of pregnancy. Both latent and active forms of MMP-7 reached a peak during the pro-oestrous stage of the cycle; the concentrations were three times higher than at dioestrus and metoestrus. In rats treated with 0.1 mg oestradiol at metoestrus, both latent and active forms of the enzyme increased by more than two-fold after 24 h. In rats treated at pro-oestrus with 0.4 mg progesterone, there was a 70% increase in latent MMP-7, but no change in the active form. The highest concentrations of MMP-7 were observed on the first day of pregnancy. Between days 3 and 7 of pregnancy, the concentrations were relatively constant and comparable to the low concentrations at dioestrus. Enzyme activities were not different at implantation sites compared with remote sites.

Analysis of Variance↗

[The protective effects of baicalin on pertussis bacilli-induced brain edema in rats].

OBJECTIVE: To evaluate the inhibitory effect of baicalin on iron-dependent lipid peroxidation (IDLPO) and the protective effect on pertussis bacilli-induced brain edema in rats. METHODS: In vitro, the inhibitory effect of baicalin and deferoxamine (DFX) was studied at different concentrations on IDLPO in brain homogenates of Sprague-Dawley rats. In vivo, the protective effect was studied of baicalin and DFX on brain edema induced by injecting purtussis bacilli into the left internal carotid artery in rats. Forty Sprague-Dawley rats were randomly divided into four groups. Group 1 (NS, n = 10), as control; Group 2 (PB, n = 10), pertussis bacilli control; Group 3 (DFX, n = 10), PB + deferoxamine; and Group 4 (BAI, n = 10), PB + baicalin. RESULTS: The baicalin was possessed of an inhibitory effect on IDLPO in rat brain homogenate, moreover, the inhibitory potency of baicalin was approximately 20 times higher than DFX treated alone. In vivo, the increase in the content of water(CW) and Evans blue (EB) was attenuated in groups DFX and BAI (CW: 79.8 +/- 0.7)% and (79.5 +/- 0.6)%; (EB: 11 +/- 7 micrograms/g and 12 +/- 5 micrograms/g) as compared with the group PB (CW: 80.4 +/- 0.9%, EB: 24 +/- 10 micrograms/g). The content of iron was significantly lower than in the left hemispheres (injected side) in the group DFX and the group BAI (79 +/- 9 micrograms/g and 77 +/- 10 micrograms/g) than in the left hemispheres in the group PB(132 +/- 28 micrograms.d-1.g), P < 0.05. The activation of CuZn-SOD (L155 +/- 36 U/mg pr, R177 +/- 75 U/mg pr) was decreased in the group BP compared with the group NS(L 201 +/- 49 U/mg pr, R 249 +/- 49 U/mg pr), P < 0.05. The activation of CuZn-SOD was significantly higher in the left brain tissues in the groups DFX and BAI (222 +/- 49 U/mg pr and 230 +/- 45 U/mg pr, respectively) than in the left brain tissues of the group of PB (P < 0.05). CONCLUSION: The baicalin and DFX have a protective effects on the pertussis bacilli-induced brain edema in rats, and the protective effects are related to the inhibitory effect on IDLPO, chelating Fe2+, and activated CuZn-SOD.

Animals↗

[Resources investigation of Actinidia in Hunan Province].

Based on the resources investigation and taxonomic research on the plants of Actinidia in Hunan Province, 15 species and 5 varieties together with their distribution and utilization are reported. A key is set forth according to the differences among the above species and varieties.

China↗

[Polymorphism analysis of D6S366 STR locus].

The polymorphic STR locus D6S366 was analyzed using PCR and PAG electrophoresis and 7 alleles were detected from 200 unrelated individuals in Wuhan. The allete distribution of the locus was in accordance with Hardy-Weinberg equilibrium. The H, Dp, P, E, and PIC of the D6S366 were calculated in this paper.

Alleles↗

[Radioimmunological image in tumor bearing nude mice with monoclonal antibody against human laryngeal carcinoma].

OBJECTIVE: To investigate the specific autoradiographic diagnosis of laryngeal carcinoma and its metastasis. METHODS: Three strains of the mixed monoclonal antibodies against human laryngeal carcinoma (McAbLC9, 11, 12) labelled with 131I were injected(intraperitoneally) into the nude mice bearing squamous cell carcinoma. The tumor autoradiography was done by single photo-emission computed tomography (ECT). The percent injected dose/g of tumor were measured, and the radioactivity ratio of tumor to non-tumor tissues(T/NT) were calculated. RESULTS: The 131I-McAbLC 9, 11, 12 can accumulate in the area of the laryngeal carcinoma within limited time, and demonstrate a satisfactory tumor imaging at 96 h. In experimental groups: The %ID/g of tumor tissues (mean +/- s, n = 6) was 18.8 +/- 0.61; The %ID/g of tumor tissues in the control group was 4.46 +/- 0.82 (mean +/- s, n = 6) at 96 h. The difference was statistically significant (P < 0.01, t = 34.97). CONCLUSION: The results suggest that 131I McAbLC9, 11, 12 is specific and sensitive in recognising human laryngeal carcinoma cell, and the area and size of tumor can be easily detected by ECT. It is feasible for localization of tumor and its metastasis.

Animals↗

[Study on the rifampicin polylactic acid microspheres for lung targeting].

In this paper, the effects of different variables on the preparation of polylactic acid microspheres (PLA-MS) were studied. The optimized preparation conditions of rifampicin polylactic acid microspheres (RFP-PLA-MS) were aquired through orthogonal test. The paddle method was used to study the drug release properties of RFP-PLA-MS. Stability of RFP-PLA-MS at different temperatures was also studied. Pharmacokinetic and tissue distribution of RFP-PLA-MS after intravenous administration were carried out in rabbits. The experiments revealed that the RFP-PLA-MS was regular in its morphology with a mean diameter of 9.00 +/- 4.08 microns. The drug loading was 16.0% and encapsulation efficiency was 31.9%. The release properties could be expressed by the following equation: Q = 20.77 + 10.12 T 1/2 (gamma = 0.9892). The RFP-PLA-MS was stable after stored at 4 degrees C and room temperature under desiccated condition for three months. RFP-PLA-MS showed a combination of lung targeting and sustained drug release in experiments on rabbits.

Animals↗

[Genetic analysis of deltamethrin resistance in Culex pipiens pallens].

AIM: To analyse the genetic character of deltamethrin resistant laboratory strain (resistant factor being 518) of Cx. pipiens pallens. METHODS: Genetic studies were made of deltamethrin-susceptible and-resistant strains of Cx. pipiens pallens with LC-P curve constructed from the response of fourth instar larvae to deltamethrin treatment, and the resistance mechanisms were analysed with synergetic tests in PB, DEF and TPP. RESULTS: The resistant factors of F1 generation from cross and reciprocal cross are respectively 154.8 and 159.2; the LC-P curve of F1 generation gets near to that of resistant parents, D = 0.625; there exist no obvious platform in 50% mortality of BC generation and 25% and 75% mortality of F2 generation, and there are larger differences between the determining curve and theoretical curve in both BC and F2 generations, P < 0.01; the synergetic ratios of PB, DEF and TPP are 27.13, 1.22 and 1.05. CONCLUSION: Deltamethrin resistance of Cx. pipiens pallens is controlled by two or more autosomal genes, and the main gene involved is incompletely dominant; multi-functional oxidase is mainly responsible for the resistance.

Animals↗

A critical period of ear development controlled by distinct populations of ciliated cells in the zebrafish.

The zebrafish (Danio rerio) is a useful model system for analyzing development of the inner ear. A number of mutations affecting the inner ear have been identified. Here we investigate the initial stages of otolith morphogenesis in wild-type embryos as well as in monolith (mnl) mutant embryos, which fail to form anterior otoliths but otherwise appear normal. Otolith growth is initiated at 18-18.5 h by localized accretion of free-moving precursor particles. This process, referred to as otolith seeding, is regulated by two classes of cilia: First, kinocilia of precociously forming hair cells (tether cells) bind seeding particles, thereby localizing otolith formation. Tether cells usually occur in pairs at the anterior and posterior ends of the ear. Despite the presence of functional kinocilia, tether cells initially appear immature and do not acquire the characteristics of mature hair cells until approximately 21.5 h. Second, beating cilia distributed throughout the ear agitate seeding particles, thereby inhibiting premature agglutination. Constraining particles with laser tweezers caused them to fuse into large untethered masses. Bringing such masses into contact with tethered otoliths caused them to fuse, greatly enhancing otolith growth. Selectively enhancing one otolith greatly inhibited growth of the second, creating an imbalance that persisted for many days. Seeding particles and beating cilia disappear soon after 24 h, and the rate of otolith growth decreases by nearly 90%. In mnl mutant embryos, tethers and beating cilia are distributed normally, but anterior otoliths fail to form in 80-85% of mutant ears. The binding properties of seeding particles appear normal, as shown by their ability to fuse when entrapped by laser tweezers and their binding to posterior tethers. We infer that anterior tethers have a weakened ability to bind seeding particles in mnl embryos. Immobilizing mnl embryos with the anterior end of the ear oriented downward effectively concentrated the dense seeding particles near the anterior tethers and permitted all to form anterior otoliths. However, immobilizing mnl embryos after 24 h when seeding particles were depleted did not facilitate anterior otolith formation. Together, these data demonstrate that the ability to initiate otolith formation is limited to a critical period, from 18.5 to 24 h, and that interfering with the functions of tether cell kinocilia or beating cilia impairs otolith seeding and subsequent otolith morphogenesis.

Animals↗

Identification of redox/repair protein Ref-1 as a potent activator of p53.

p53 can be isolated from cells in a form that is inert for binding to DNA but that can be stimulated dramatically by phosphorylation, antibody binding, or short single strands of DNA. This suggests that upon genotoxic stress, cells can convert latent p53 to one that is active for DNA binding. Surprisingly, we observed that latent p53 is as effective in activating transcription in vitro as is active p53. We found that HeLa nuclear extracts can stimulate DNA binding by latent p53 and have purified from them a p53-stimulating protein that we have determined to be the product of the Ref-1 gene. Interestingly, Ref-1 is a dual function protein that can both regulate the redox state of a number of proteins and function as a DNA repair (A/P) endonuclease. We observed that oxidized forms of full-length and carboxy-terminally truncated p53 (p53 delta30), which are inactive for DNA binding, are both stimulated by the Ref-1 protein. However, in the presence of reducing agent, Ref-1 is an extremely potent stimulator of full-length p53 but not p53 delta30. These and additional data indicate that Ref-1 protein stimulates p53 by both redox-dependent and -independent means and imply a key role for it in p53 regulation. Importantly, we have also determined that Ref-1 can stimulate p53 transactivation in vivo. This is the first example of a noncovalent protein modifier of p53 function identified in cells.

Carbon-Oxygen Lyases↗

Effect of dexamethasone on Glu-IR and GABA-IR neurons of hippocampus in rats.

Dexamethasone (Dex) was injected into the rat lateral ventricle and the changes of glutamate-immunoreactivity (Glu-IR) and gamma-aminobulyric acid immunoreactivity (GABA-IR) neurons in the hippocampus were immunocytochemically examined 2 h after injection. The results showed that Glu-IR neurons increased and GABA-IR neurons did not show marked change. The mechanism remains to be further studied.

Animals↗

A longitudinal study of tooth wear in orthodontically treated patients.

The primary objective of this study was to determine whether there is a relationship between incisal/occlusal tooth wear during the mixed dentition and subsequent wear of the adult dentition. Pretreatment orthodontic records taken during the mixed dentition (T1), as well as follow-up records taken an average of 20 years later (T2), were available for 223 orthodontically treated patients. Incisal/occlusal tooth wear was measured on a tooth-by-tooth basis from T1 and T2 stone casts with a four-category scoring system. Multiple regression analysis (R2 = 0.33) indicated that wear could be predicted at a given age during adulthood from wear observed on the deciduous mandibular canines and molars at T1 (p < 0.0001). This predictive relationship was modified by the age at which the T1 wear was observed (p = 0.029) and possibly by the sex of the patient (p = 0.10). These results indicate that adult tooth wear is not independent of the tooth wear that occurred as a child. Bruxism is suggested as a possible common etiologic mechanism that may account for the relationship between childhood and adult tooth wear.

Adolescent↗

Growth retardation and leaky SCID phenotype of Ku70-deficient mice.

Ku70, Ku80, and DNA-PKcs are subunits of the DNA-dependent protein kinase (DNA-PK), an enzyme implicated in DNA double-stranded break repair and V(D)J recombination. Our Ku70-deficient mice were about 50% the size of control littermates, and their fibroblasts were ionizing radiation sensitive and displayed premature senescence associated with the accumulation of nondividing cells. Ku70-deficient mice lacked mature B cells or serum immunoglobulin but, unexpectedly, reproducibly developed small populations of thymic and peripheral alpha/beta T lineage cells and had a significant incidence of thymic lymphomas. In association with B and T cell developmental defects, Ku70-deficient cells were severely impaired for joining of V(D)J coding and recombination signal sequences. These unanticipated features of the Ku70-deficient phenotype with respect to lymphocyte development and V(D)J recombination may reflect differential functions of the three DNA-PK components.

Animals↗

V(D)J recombination in Ku86-deficient mice: distinct effects on coding, signal, and hybrid joint formation.

Ku, a heterodimer of 70 and 86 kDa subunits, plays a critical but poorly understood role in V(D)J recombination. Although Ku86-deficient mice are defective in coding and signal joint formation, rare recombination products have been detected by PCR. Here, we report nucleotide sequences of 99 junctions from Ku86-deficient mice. Over 90% of the coding joints, but not signal or hybrid joints, exhibit short sequence homologies, indicating that homology is required to join coding ends in the absence of Ku86. Our results suggest that Ku86 may normally have distinct functions in the formation of these different types of junctions. Furthermore, Ku86(-/-) joints are unexpectedly devoid of N-region diversity, suggesting a novel role for Ku in the addition of N nucleotides by terminal deoxynucleotidyl transferase.

Animals↗

The Sex-lethal early splicing pattern uses a default mechanism dependent on the alternative 5' splice sites.

The Sex-lethal (Sxl) early transcripts have a unique 5' exon and a splicing pattern that differs from that of the late transcripts. While the late transcripts are regulated sex specifically by control of exon 3 inclusion, the early transcripts are not. While the late transcripts include exon 3 by default, the early transcripts skip exon 3. Splicing patterns of a reporter gene that mimics the early transcript, and its variants, were analyzed in Drosophila transformants and tissue culture cells. The results demonstrate that the early, in contrast to the late, splicing pattern is not regulated by stage-specific or sex-specific trans-acting factors, and so the pattern appears to arise from some type of intrinsic splice site preference or compatibility. Inclusion or exclusion of exon 3 is determined by the identity of the upstream 5' splice site region as late or early. The important region of the early exon lies within 233 nucleotides of the immediately adjacent intron.

Alternative Splicing↗