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Biomedical subjects

C L Zhang

Publications and source records attributed to C L Zhang.

At least 37 records · Page 2Linked to original sources

Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases.

Skeletal muscle differentiation is controlled by associations between myogenic basic-helix-loop-helix and MEF2 transcription factors. We show that chromatin associated with muscle genes regulated by these transcription factors becomes acetylated during myogenesis and that class II histone deacetylases (HDACs), which interact with MEF2, specifically suppress myoblast differentiation. These HDACs do not interact directly with MyoD, yet they suppress its myogenic activity through association with MEF2. Elevating the level of MyoD can override the repression imposed by HDACs on muscle genes. HDAC-mediated repression of myogenesis also can be overcome by CaM kinase and insulin-like growth factor (IGF) signaling. These findings reveal central roles for HDACs in chromatin remodeling during myogenesis and as intranuclear targets for signaling pathways controlled by IGF and CaM kinase.

Amino Acid Sequence↗

[Studies of salt tolerance of alloplasmic wheat].

Using Aegilops crassa cytoplasm wheat as test material, salt tolerance of alloplasmic wheat was identified by tissue culture, nutrient solution culture and artificial saline pond, from calli, seeding stage, recovering stage and mature period. The results showed Ae. crassa cytoplasm lines indicated the difference of salt tolerance in varying degree; the difference of cytoplasm effect among different nucleoplasm combinations showed certain nucleoplasm interaction relation. The salt tolerance of (Ae. crassa)-jian 26 was stronger than that other tested alloplasmic lines. The result demonstrated that at recovering date and at mature period indicated salt tolerance of alloplasmic lines was not only stronger than its nuclear parent but also over control variety. As compared with common wheat, lines having strong salt tolerance were more proportions in tested alloplasmic lines. The study of alloplasmic wheat should be significant for breeding salt tolerance wheat.

Cytoplasm↗

[Effects of qufengshi prescription on release of hydrogen peroxide and interleukin-1 from peritoneal macrophage in adjuvant arthritis rat].

OBJECTIVE: To study the mechanism of antiarthritis effects of Qufengshi Prescription. METHODS: Adjuvant arthritis (AA) was applied as pathological model of rheumatoid arthritis and prednisone was used as positive control. RESULTS: The Prescription at high and medium dosages significantly decreased the rising level of hydrogen peroxide and interleukin-1 in AA rats (P < 0.05), the potency being similar to prednisone. CONCLUSION: Qufengshi Prescription Could reduce the rising level of interleukin-1 and hydrogen peroxide in AA rats, which may be part of mechanism of the antiarthritis effect.

Animals↗

Specific alteration of spontaneous GABAergic inhibition in cerebellar purkinje cells in mice lacking the potassium channel Kv1. 1.

In the cerebellum, the basket cell innervation on Purkinje cells provides a major GABAergic inhibitory control of the single efferent output from the cerebellum. The Shaker-type K channel Kv1.1 is localized at the axon arborization preceding the terminal of the basket cells and is therefore a potential candidate for regulating the GABAergic inhibition. In this study, we directly assess this role of Kv1.1 by electrophysiological analysis of Kv1.1 null mutant mice. Whole-cell patch-clamp recordings of spontaneous IPSCs (sIPSCs) were made from Purkinje cells in thin cerebellar slices from postnatal day (P)10-15 Kv1.1-null mutants using wild-type littermates as controls. The null mutation confers a very specific change in the sIPSC: the frequency increases about twofold, without accompanying changes in the mean and variance of its amplitude distribution. The frequency and amplitude of the miniature IPSCs (mIPSCs) are unaffected. Spontaneous firing rate of the basket cells is unaltered. Evoked IPSC does not show multiple activity in the mutants. Motor skills tests show that Kv1.1 null mice display a compromised ability to maintain balance on a thin stationary rod. We conclude that the Kv1.1 null mutation results in a persistent elevation of the tonic inhibitory tone on the cerebellum Purkinje cell efferent and that this is not fully compensated for by residual Shaker-type channels. We further suggest that the increase in inhibitory tone in the mutants might underlie the behavioral deficits. At the cellular level, we propose that Kv1.1 deletion enhances excitability of the basket cells by selectively enhancing the likelihood of action potential propagation past axonal branch points.

Action Potentials↗

Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression.

Loss of function of the p53 tumor suppressor gene due to mutation occurs early in astrocytoma tumorigenesis in about 30-40% of cases. This is believed to confer a growth advantage to the cells, allowing them to clonally expand due to loss of the p53-controlled G1 checkpoint and apoptosis. Genetic instability due to the impaired ability of p53 to mediate DNA damage repair further facilitates the acquisition of new genetic abnormalities, leading to malignant progression of an astrocytoma into anaplastic astrocytoma. This is reflected by a high rate of p53 mutation (60-70%) in anaplastic astrocytomas. The cell cycle control gets further compromised in astrocytoma by alterations in one of the G1/S transition control genes, either loss of the p16/CDKN2 or RB genes or amplification of the cyclin D gene. The final progression process leading to glioblastoma multiforme seems to need additional genetic abnormalities in the long arm of chromosome 10; one of which is deletion and/or functional loss of the PTEN/MMAC1 gene. Glioblastomas also occur as primary (de novo) lesions in patients of older age, without p53 gene loss but with amplification of the epidermal growth factor receptor (EGFR) genes. In contrast to the secondary glioblastomas that evolve from astrocytoma cells with p53 mutations in younger patients, primary glioblastomas seem to be resistant to radiation therapy and thus show a poorer prognosis. The evaluation and design of therapeutic modalities aimed at preventing malignant progression of astrocytomas and glioblastomas should now be based on stratifying patients with astrocytic tumors according to their genetic diagnosis.

Alleles↗

Miscarriage prevention tea affects plasma beta-endorphin concentrations in women with early threatened abortions.

Twenty threatened abortive patients in the 7-8th week of gestation were treated with a classical miscarriage prevention tea (Shou-Tai-Tang) combined with psychological consultation. All of the patients had a history of unexplained recurrent abortions. This treatment succeeded in sixteen out of 20 patients. The plasma concentrations of beta-endorphin (beta-EP), gonadotrophin releasing hormone (GnRH), human chorionic gonadotrophin (hCG), and progesterone (P4) were measured by radioimmunoassay before and after treatment. Compared to control subjects, beta-EP levels were significantly higher, while GnRH, hCG, and P4 were lower than before treatment. Concentrations of these peptides/hormones returned to normal ranges after successful treatment.

Abortion, Spontaneous↗

[Technical consideration of setting up a specification for human centrifuge evaluation of anti-G equipment].

Anti-G equipment needs to be evaluated using human centrifuge before further developed. However, there isn't a general specification for human centrifuge evaluation of anti-G equipment. From related literature and from our over thirty years experience in this area, we sum up to five aspect technical consideration below: human centrifuge, medical specification for using human in +Gz stress experiment, anti-G equipment experimental assembly, principle should be abided by during human centrifuge evaluation of anti-G equipment. We hope that the technical considerations mentioned in the paper should be helpful to the work of setting up a specification for human centrifuge evaluation anti-G equipment. After we have a specification, the research will be conducted orderly and the anti-G [correction of an-G] equipment will be developed sequentially.

Acceleration↗

Temperature-sensitive neuromuscular transmission in Kv1.1 null mice: role of potassium channels under the myelin sheath in young nerves.

In mammalian myelinated nerves, the internodal axon that is normally concealed by the myelin sheath expresses a rich repertoire of K channel subtypes thought to be important in modulating action potential propagation. The function of myelin-covered K channels at transition zones, however, has remained unexplored. Here we show that deleting the voltage-sensitive potassium channel Kv1.1 from mice confers a marked temperature-sensitivity to neuromuscular transmission in postnatal day 14 (P14)-P21 mice. Using immunofluorescence and electrophysiology, we examined contributions of four regions of the peripheral nervous system to the mutant phenotype: the nerve trunk, the myelinated segment preceding the terminal, the presynaptic terminal membrane itself, and the muscle. We conclude that the temperature-sensitive neuromuscular transmission is accounted for solely by a deficiency in Kv1.1 normally concealed in the myelinated segments just preceding the terminal. This paper demonstrates that under certain situations of physiological stress, the functional role of myelin-covered K channels is dramatically enhanced as the transition zone at the neuromuscular junction is approached.

Age Factors↗

Short alternative splice transcripts of the mdm2 oncogene correlate to malignancy in human astrocytic neoplasms.

The mdm2 oncogene encodes a 90-kDa nuclear phosphoprotein that binds and inhibits the function of the p53 tumor suppressor protein. It was recently reported that the expression of alternatively spliced variants of mdm2 correlated with malignancy in ovarian tumors and bladder carcinomas. We analyzed the presence of alternatively spliced mdm2 variants and studied their correlation to p53 status in a total of 66 human astrocytic tumors, including 32 glioblastomas multiforme, 17 anaplastic astrocytomas, 12 astrocytomas, and 5 pilocytic astrocytomas, using a specific nested reverse transcription-PCR technique. The full-length mdm2 transcript was demonstrated in all of the cases. Multiple-sized PCR products were found in 29 cases. Two of 5 pilocytic astrocytomas (40%), none of 12 astrocytomas, and 5 of 17 anaplastic astrocytomas (29%) showed alternative splice variants. In contrast, 22 of 32 glioblastomas (69%) showed the presence of splice variants, demonstrating a significantly higher frequency than in lower-grade astrocytomas (P < 0.0003). A majority of the splice variants were 707 base-type (mdm2-b), which was confirmed by sequence analysis. There was no apparent correlation of the presence of mdm2 splice variants with p53 gene status. These results suggest a new role for mdm2, independent of p53 gene status, as an oncogene in the development of malignant astrocytic tumors.

Alternative Splicing↗

Targeted diagnosis of bladder and ureteral carcinoma using radiolabelled BDI-1.

The aim of this study is to investigate the possibility of radioimmunoimaging (RII) by radiolabelled anti-bladder carcinoma monoclonal antibody BDI-1 applied to diagnosis of bladder cancer and ureteral cancer. BDI-1 was labelled with 131I and 99mTc. The immunoreactivity, pharmacokinetics and biodistribution in mice were studied. RII was performed in 46 patients. The results showed that 131I, 99mTc-BDI-1 have satisfactory immunoreactivity and excellent tumor-locating properties. The blood clearance half-life T1/2alpha and T1/2beta were 35 h in the first phase and 151 h in the second phase, respectively. Thirty-nine patients were studied by an intravesical administration method; the sensitivity was 90.5%. Seven patients were studied by an intravenous administration method. The RII results of three cases with primary or recurrent bladder cancer and three cases with ureteral cancer were confirmed histologically. RII was negative in one patient with suspected lung metastasis that was shown on radiography. The investigation revealed that RII can be used as an auxiliary method for the detection of bladder cancer and may be valuable for the diagnosis of ureteral cancer.

Aged↗

Altered balance between matrix metalloproteinases and their inhibitors in experimental biliary fibrosis.

A rat model of common bile duct ligation (BDL)-induced hepatic fibrosis was used to assess the expression and activities of collagen-degrading proteinases and their inhibitors during the progression of fibrosis. Expression of four members of the matrix metalloproteinase (MMP) family (MMP-2/gelatinase A, MMP-3, MMP-9/gelatinase B, and MMP-13) and three tissue inhibitors of metalloproteinases-1, -2, and -3 (TIMP-1, TIMP-2, and TIMP-3) were evaluated by Northern blot analysis of RNA from liver tissue isolated at 0, 2, 5, 10, 20, and 30 days after either a BDL or sham operation. In addition, we analyzed free gelatinase and TIMP activities by zymography and reverse zymography, respectively. We found that the proteolytic activities of MMP-2 and MMP-9 increased by 2 days after ligation, reached maximal levels at day 10, and remained high through the study period, whereas the gelatinolytic activities in plasma were unchanged. The increase in gelatinase activities was accompanied by an increase in the TIMP mRNA transcripts. TIMP-1 transcripts appeared at day 2, increased until day 10, and remained elevated throughout the study period. TIMP-2 and TIMP-3 transcripts become detectable on day 10 and remained stable afterwards. No corresponding increase in TIMP protein activity was detected by reverse zymography. This appears to result from the formation of TIMP/MMP complexes. These findings indicate a likely surplus in the BDL model of fibrosis of free gelatinases as compared with the TIMPs. Thus, excessive TIMP production is not a sufficient explanation for the observed extracellular matrix accumulation, but complex changes in the local MMP/TIMP balance may underlie the pathomechanisms of fibrosis.

Animals↗

Studies on the localization of 5-hydroxytryptamine and its receptors in human placenta.

The localization of 5-hydroxytryptamine (5-HT) and its receptors in human placenta was studied under light and electron microscopy using immunohistochemistry and in situ hybridization. The syncytiotrophoblast, cytotrophoblast, stromal cells and decidual cells in human placentae all appeared to be 5-HT immunoreactive. The 5-HT immunoreactive material was distributed in cytoplasm with negative nuclei. The 5-HT immunoreactive material was also found in capillary endothelium. Trophoblast cells cultured in serum-free medium also showed 5-HT immunoreactivity in the cytoplasm. Fetal white blood cells and both syncytiotrophoblast and cytotrophoblast in human placenta showed 5-HT receptor immunoreactivity and 5-HT1A receptor mRNA hybridized signal was also detected in cytoplasm. The stromal cells and capillary endothelium in placental villi and maternal decidual cells all showed 5-HT receptor immunoreactivity in cytoplasm. The small flattened vesicles and large dense cored vesicles within trophoblast cells showed electron-dense 5-HT receptor immunoreactivity using immunoelectron microscopy. These results suggest that human placenta may not only produce 5-HT but also be a 5-HT target organ, and that 5-HT may not only play roles in placental development and pregnancy maintenance by paracrine and autocrine interactions but may also take part in regulating fetal development.

Adult↗

Deletion of the K(V)1.1 potassium channel causes epilepsy in mice.

Mice lacking the voltage-gated potassium channel alpha subunit, K(V)1.1, display frequent spontaneous seizures throughout adult life. In hippocampal slices from homozygous K(V)1.1 null animals, intrinsic passive properties of CA3 pyramidal cells are normal. However, antidromic action potentials are recruited at lower thresholds in K(V)1.1 null slices. Furthermore, in a subset of slices, mossy fiber stimulation triggers synaptically mediated long-latency epileptiform burst discharges. These data indicate that loss of K(V)1.1 from its normal localization in axons and terminals of the CA3 region results in increased excitability in the CA3 recurrent axon collateral system, perhaps contributing to the limbic and tonic-clonic components of the observed epileptic phenotype. Axonal action potential conduction was altered as well in the sciatic nerve--a deficit potentially related to the pathophysiology of episodic ataxia/myokymia, a disease associated with missense mutations of the human K(V)1.1 gene.

Action Potentials↗

Comparison of effects of valproate and trans-2-en-valproate on different forms of epileptiform activity in rat hippocampal and temporal cortex slices.

PURPOSE: Reducing the extracellular magnesium or calcium or increasing the extracellular potassium induces different patterns of epileptiform activity in the hippocampus and the entorhinal cortex. Although in the low Ca2+ and K+ models, seizure-like events (SLEs) develop in area CA1 of the hippocampus, only short recurrent discharges develop in the low Mg2+ model. In contrast, in low Mg2+, SLEs and late recurrent discharges (LRDs) are observed in the entorhinal cortex. METHODS: We compared the effects of valproate (VPA) and its major metabolite, trans-2-en-VPA (TVPA), on all these different model activities using extracellular field potential measurements. We also investigated the equilibration time course of VPA in the slice by using VPA-sensitive microelectrodes. RESULTS: Both drugs reversibly blocked most forms of epileptiform activity. The only exception was the LRDs in the entorhinal cortex. In paired experiments, TVPA appeared to be more effective than VPA bath applied with the same concentration to the same slice. With our measurements of the VPA concentrations in slices, we showed that the concentrations used were close to therapeutic drug levels. CONCLUSIONS: If TVPA stands the toxicological tests, it might be a useful alternative in the treatment of seizures.

Action Potentials↗

Phenytoin, phenobarbital, and midazolam fail to stop status epilepticus-like activity induced by low magnesium in rat entorhinal slices, but can prevent its development.

OBJECTIVES: It was shown previously that low-Mg2+-induced epileptiform activity in rat entorhinal cortex slices changes with time from a pattern of serial seizure-like events (SLEs) to a state of continuously recurring epileptiform activity. Valproic acid blocked the early SLEs but not the late activity. It was proposed that the late activity is a model for pharmacoresistant status epilepticus since it was also refractory to phenytoin, carbamazepine, phenobarbital, and midazolam. In the present study, it is demonstrated that phenytoin (50 microM, n=6), phenobarbital (150 microM, n=7), and midazolam (50 microM, n=5) were able to block the early SLEs but not the late activity at the same concentrations. Carbamazepine (50 microM) reduced the duration of the SLEs from 21 +/-5 s to 4+/-3 s (P<0.01), the interictal interval from 123+/-27 s to 27+/-19 s (P<0.01), the SLE-associated rise of [K+]o from 7.7+/-0.5 mM to 5.7+/-0.8 mM (n=4, P<0.05), and the spread of the SLE between entorhinal cortex and neocortex from 4.0+/-0.6 s to 0.8+/-0.1 s (n=4, P<0.05). Lower concentrations of phenytoin (5 and 10 microM, n=5), carbamazepine (10 microM, n =6), and phenobarbital (50 microM, n = 4) had no effect. In conclusion, the hypothesis is supported that low-Mg2+-induced epileptiform activity in rat entorhinal cortex is an in vitro model for the transition from pharmacosensitive to pharmacoresistant status epilepticus.

Animals↗

Proteolytic activity of human non-Hodgkin's lymphomas.

This study was conducted to assess the net proteolytic activity of human non-Hodgkin's lymphomas (NHLs). We have compared the extracellular matrix (ECM)-degradative abilities of human NHLs, reactive lymphoid hyperplasias, and established lymphoid cell lines using Matrigel invasion and elastin degradation assays. The inhibition studies allowed identification of the classes of proteinases involved in ECM degradation. Our results indicate that lymphocytes and other leukocytes derived from both human NHLs and reactive lymphoid hyperplasias are capable of Matrigel penetration, but only cells derived from the high-grade human NHLs degrade elastin in vitro. Established lymphoid cell lines (both malignant and Epstein-Barr virus immortalized) do not produce MMP-9, do not penetrate the Matrigel, and do not degrade elastin. Moreover, in human NHLs, elastolytic activity is blocked by metalloproteinase inhibitors, while inhibitors of the other classes of proteolytic enzymes have only minor effects. This study identifies metalloproteinases as the most important class of proteinases involved in ECM degradation by NHLs. The previous studies suggest that, within this class, MMP-9 represents the key enzyme that plays a role in the biological aggressiveness of human NHLs.

Cell Line↗

Live astrocytes visualized by green fluorescent protein in transgenic mice.

Green fluorescent protein (hGFP-S65T) was expressed in transgenic mice under the control of the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter. Tissues from two independent transgenic lines were characterized by Northern blot analysis and by confocal microscopy. The expression pattern in these two lines was identical in all tissues examined, and similar to that found previously with a lacZ transgene driven by the same promoter. Bright fluorescence was observed in the cell bodies and processes of unfixed or fixed astrocytes, using both whole mount and brain slice preparations, from multiple areas of the central nervous system. However, in contrast to GFAP-lacZ transgenics, retinal Müller cells expressed the GFP transgene in response to degeneration of neighboring photoreceptors. These data indicate that the 2.2-kb hGFAP promoter contains sufficient regulatory elements to direct expression in Müller cells, and that GFP is a suitable reporter gene for use in living preparations of the mammalian nervous system. Such mice should prove useful for studies of dynamic changes in astrocyte morphology during development, and in response to physiological and pathological conditions.

Animals↗

Urban-rural comparison of HBV and HCV infection prevalence among adult women in Shandong Province, China.

In order to make urban-rural comparison of the prevalence of hepatitis B and C virus (HBV and HCV, respectively) infection in China, a twin survey was conducted in 1996 on two groups (50 subjects each) of 21-55 year-old, apparently healthy women for infection markers and serum enzyme levels; one group (the urban group) was in Jinan, the provincial capital of Shandong Province, and the other (the rural group) was in a farming village in Zhangqiu area some 30 km away from Jinan City. Comparison between the two groups showed that there was no significant (p > 0.10) difference in the prevalence of HBsAg+, anti-HBs+, anti-HBc+ and the cases positive to any of three HBV infection markers (i.e. HBV+). No age-dependent difference was detected within or between the groups. Thus the overall positivity rate was 8% for HBsAg+, 47% for anti-HBs+, 48% for anti-HBc+, and 64% for HBV+. No anti-HCV+ case was found either in the urban group or in the rural group. Liver function remained normal in all cases studied. The results together with perusal of published data suggest the urban-rural difference will not be remarkable, if present, in HBV and HCV infection in the regions studied, and possibly in China as a whole.

Adult↗