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Biomedical subjects

Z Han

Publications and source records attributed to Z Han.

At least 37 records · Page 2Linked to original sources
PubMed2001

Extracellular matrix protein 1 (ECM1) has angiogenic properties and is expressed by breast tumor cells.

Tumor growth and metastasis are critically dependent on the formation of new blood vessels. The present study found that extracellular matrix protein 1 (ECM1), a newly described secretory glycoprotein, promotes angiogenesis. This was initially suggested by in situ hybridization studies of mouse embryos indicating that the ECM1 message was associated with blood vessels and its expression pattern was similar to that of flk-1, a recognized marker for endothelium. More direct evidence for the role of ECM1 in angiogenesis was provided by the fact that highly purified recombinant ECM1 stimulated the proliferation of cultured endothelial cells and promoted blood vessel formation in the chorioallantoic membrane of chicken embryos. Immunohistochemical staining with specific antibodies indicated that ECM1 was expressed by the human breast cancer cell lines MDA-435 and LCC15, both of which are highly tumorigenic. In addition, staining of tissue sections from patients with breast cancer revealed that ECM1 was present in a significant proportion of primary and secondary tumors. Collectively, the results of this study suggest that ECM1 possesses angiogenic properties that may promote tumor progression.

Angiogenesis Inducing Agents↗
PubMed2001

Multiple immediate-early gene-deficient herpes simplex virus vectors allowing efficient gene delivery to neurons in culture and widespread gene delivery to the central nervous system in vivo.

Herpes simplex virus (HSV) has several potential advantages as a vector for delivering genes to the nervous system. The virus naturally infects and remains latent in neurons and has evolved the ability of highly efficient retrograde transport from the site of infection at the periphery to the site of latency in the spinal ganglia. HSV is a large virus, potentially allowing the insertion of multiple or very large transgenes. Furthermore, HSV does not integrate into the host chromosome, removing any potential for insertional activation or inactivation of cellular genes. However, the development of HSV vectors for the central nervous system that exploit these properties has been problematical. This has mainly been due to either vector toxicity or an inability to maintain transgene expression. Here we report the development of highly disabled versions of HSV-1 deleted for ICP27, ICP4, and ICP34.5/open reading frame P and with an inactivating mutation in VP16. These viruses express only minimal levels of any of the immediate-early genes in noncomplementing cells. Transgene expression is maintained for extended periods with promoter systems containing elements from the HSV latency-associated transcript promoter (J. A. Palmer et al., J. Virol. 74:5604-5618, 2000). Unlike less-disabled viruses, these vectors allow highly effective gene delivery both to neurons in culture and to the central nervous system in vivo. Gene delivery in vivo is further enhanced by the retrograde transport capabilities of HSV. Here the vector is efficiently transported from the site of inoculation to connected sites within the nervous system. This is demonstrated by gene delivery to both the striatum and substantia nigra following striatal inoculation; to the spinal cord, spinal ganglia, and brainstem following injection into the spinal cord; and to retinal ganglion neurons following injection into the superior colliculus and thalamus.

Animals↗
PubMed2001

c-Myc is necessary for DNA damage-induced apoptosis in the G(2) phase of the cell cycle.

The c-myc proto-oncogene encodes a transcription factor that participates in the regulation of cellular proliferation, differentiation, and apoptosis. Ectopic overexpression of c-Myc has been shown to sensitize cells to apoptosis. We report here that cells lacking c-Myc activity due to disruption of the c-myc gene by targeted homologous recombination are defective in DNA damage-initiated apoptosis in the G(2) phase of the cell cycle. The downstream effector of c-Myc is cyclin A, whose ectopic expression in c-myc(-/-) cells rescues the apoptosis defect. The kinetics of the G(2) response indicate that the induction of cyclin A and the concomitant activation of Cdk2 represent an early step during commitment to apoptosis. In contrast, expression of cyclins E and D1 does not rescue the apoptosis defect, and apoptotic processes in G(1) phase are not affected in c-myc(-/-) cells. These observations link DNA damage-induced apoptosis with cell cycle progression and implicate c-Myc in the functioning of a subset of these pathways.

Adenine↗
PubMed2001

Fluid transport by human nonpigmented ciliary epithelial layers in culture: a homeostatic role for aquaporin-1.

We report for the first time that cultured nonpigmented human ciliary epithelial (NPE) cell layers transport fluid. Cells were grown to confluence on permeable membrane inserts, and fluid transport across the resulting cell layers was determined by volume clamp at 37 degrees C. These cell layers translocated fluid from the apical to the basal side at a steady rate of 3.6 microl x h(-1) x cm(-2) (n = 4) for 8 h. This fluid movement was independent of hydrostatic pressure and was completely inhibited by 1 mM ouabain, suggesting it arose from fluid transport. Mercuric chloride, a nonspecific but potent blocker of Hg(2+)-sensitive aquaporins, and aquaporin-1 antisense oligonucleotides both partially inhibited fluid transport across the cell layers, which suggests that water channels have a role in NPE cell homeostasis. In addition, these results suggest that of the two ciliary epithelial layers in tandem, the NPE layer by itself can transport fluid. This cultured layer, therefore, constitutes an interesting model that may be useful for physiological and pharmacological characterization of ciliary epithelial fluid secretion.

Anti-Infective Agents, Local↗
PubMed2001

c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis.

Mitogen-activated protein kinase (MAPK) cascades are involved in inflammation and tissue destruction in rheumatoid arthritis (RA). In particular, c-Jun N-terminal kinase (JNK) is highly activated in RA fibroblast-like synoviocytes and synovium. However, defining the precise function of this kinase has been difficult because a selective JNK inhibitor has not been available. We now report the use of a novel selective JNK inhibitor and JNK knockout mice to determine the function of JNK in synoviocyte biology and inflammatory arthritis. The novel JNK inhibitor SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) completely blocked IL-1--induced accumulation of phospho-Jun and induction of c-Jun transcription in synoviocytes. Furthermore, AP-1 binding and collagenase mRNA accumulation were completely suppressed by SP600125. In contrast, complete inhibition of p38 had no effect, and ERK inhibition had only a modest effect. The essential role of JNK was confirmed in cultured synoviocytes from JNK1 knockout mice and JNK2 knockout mice, each of which had a partial defect in IL-1--induced AP-1 activation and collagenase-3 expression. Administration of SP600125 modestly decreased the rat paw swelling in rat adjuvant-induced arthritis. More striking was the near-complete inhibition of radiographic damage that was associated with decreased AP-1 activity and collagenase-3 gene expression. Therefore, JNK is a critical MAPK pathway for IL-1--induced collagenase gene expression in synoviocytes and in joint arthritis, indicating that JNK is an important therapeutic target for RA.

Activating Transcription Factor 2↗
PubMed2001

Promoter polymorphisms of hepatic lipase gene influence HDL(2) but not HDL(3) in African American men: CARDIA study.

Hepatic lipase encoded by the hepatic lipase gene (LIPC) is involved in the metabolism of several lipoproteins. Four promoter polymorphisms in LIPC have been found to be in complete disequilibrium and associated with high density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo)A-I levels in both white and black populations. We investigated the association between the promoter polymorphism and lipid profiles as well as anthropometric phenotypes in African American men in the Coronary Artery Risk Development in Young Adults study. We performed serial cross-sectional analyses and longitudinal analyses of lipids from 578 subjects in five examinations over 10 years of follow-up. Results showed that the allele frequency (0.52) in our black population was consistent with that reported in black subjects but much higher than that reported (approximately 0.2) in white populations. Analysis of covariance tests of the three genotypic means in each examination showed that the P values ranged from 0.01 to 0.08 for HDL-C (except P = 0.54 in the fourth examination), from 0.006 to 0.01 for HDL(2)-C, and from 0.06 to 0.07 for apoA-I. Mean HDL(3)-C levels were essentially identical among the three genotypes. Total cholesterol, low density lipoprotein cholesterol (LDL-C), triglycerides, and apoB, which are mainly involved in the very low density lipoprotein-LDL pathway, were not significantly different according to the promoter polymorphism, except for triglycerides in the third examination (P = 0.01). No significant association was found between anthropometric phenotypes and the LIPC polymorphism in any of five examinations. The change of the anthropometric variables was not significantly associated with genotypes. In conclusion, our results indicated that the LIPC promoter polymorphism has exclusive effects on HDL(2)-C but not HDL(3)-C levels.

Adolescent↗
PubMed2001

[A retrospective analysis of therapeutic outcome of various types of severe virus hepatitis].

OBJECTIVE: To explore combined therapeutic schemes for severe virus hepatitis and to raise survival rate. METHODS: The therapeutic outcomes of different schemes were analyzed in 1020 cases of severe viral hepatitis treated in our hospital in recent twenty years. The treatments were classified as basic and combination of Chinese traditional and Western medicine therapies in which embryonic liver cell suspend liquid or hepatic growth factor, or/and artificial liver as blood cleaner were also used for the latter. RESULTS: The survival rate was 30.28% (33/109) treated by basic procedures and 60.15% (548/911) by combined procedures. There was obvious statistical difference in survival rate between the two groups (P<0.001). Among all the patients, 219 (21.47%) suffered from acute or sub-acute severe hepatitis, 801 (78.53%) chronic severe hepatitis; 446 started their treatment at the early stage of the disease and the survival rate was 77.13% (344/446); 404 at the mid stage and 170 at the late stage and the survival rates were 52.72% (213/404) and 14.12% (24/170), respectively. The survival rate for the patients treated at the early or the mid stage was much higher than that at the late stage (P<0.001), and had a positive correlation with the activity of prothrombin. CONCLUSION: The combined therapies used in present study are effective to raise the survival rate of the patients with severe virus hepatitis. Early treatment is extremely important for the patients' prognosis.

Adolescent↗
PubMed2001

[Use of microsatellites in zygosity diagnosis of twins].

OBJECTIVE: To diagnose zygosity of twins by microsatellite polymorphism. METHODS: One hundred and eighty-four samples, including 69 pairs of twins with the same gender and 6 pairs of twins with different gender were recruited. Seventeen sib pairs were also collected for controls. Nine highly polymorphic microsatellite loci were amplified by polymerase chain reaction (PCR) using fluorescence-labeled primers and the products were sized by automated fragment analysis after electrophoresis and laser detection. Zygosity was diagnosed by comparing the concordance of the genotype of the 9 markers. RESULTS: Sixty-three pairs of monozygotic (MZ) and 12 pairs of dizygotic (DZ) twins were assigned their zygosity by comparison of polymorphism of 9 microsatellite loci. Within each of the 63 monozygotic (MZ) pairs there was complete concordance. However, within each of the 12 dizygotic pairs and other 17 sib pairs, discordant loci were found. With five or six markers, the probability that any twin pair was MZ if all markers were concordant was 99% or 99.6%, respectively. With all the nine markers, the probability that any twin pair was MZ if all markers were concordant was 99.95%. CONCLUSION: The technology of gene scan and genotyping provides a rapid and reliable approach to zygosity detection.

DNA↗
PubMed2001

[The change in the plasma contents of adrenomedullin and endothelin in burn patients during early postburn stage].

OBJECTIVE: To observe the change in the plasma contents of adrenomedullin (ADM) and endothelin (ET) in burn patients, so as for us to explore their roles in the pathogenesis in the physiological disturbance in burn patients. METHODS: The plasma concentrations of ADM and ET were determined at 6, 12, 24 and 48 postburn hours (PBHs) in 40 burn patients with radioimmunoassay (RIA) and compared with those of 25 healthy people. RESULTS: The postburn plasma levels of ADM and ET in burn patients increased immediately after injury, and they were positively correlated to burn area. The plasma ADM reached peak level at 12 PBHs and decreased thereafter, but remained at higher level than that in healthy people at 48 PBHs (P < 0.01). Plasma ET increased to top level at 6 PBH and decreased thereafter. But it remained at high level at 48 PBHs in severe burn patients (burned area larger than 45% TBSA) (P < 0.05 approximately 0.01). The plasma levels of ET and ADM increased proportionally and their ratio was close to that in normal control, but it decreased obviously after 6 PBH in all groups (P < 0.01). CONCLUSION: There were evident postburn changes in plasma ADM and ET contents, and the results implied that ADM and ET played some roles in the development of postburn physiological disturbance.

Adolescent↗
PubMed2001

Effects of free radicals and amyloid beta protein on the currents of expressed rat receptors in Xenopus oocytes.

OBJECTIVE: To investigate the effects of free radicals (FRs) and amyloid beta protein 1-40 (A beta 1-40) on the functions of expressed neurotransmitter receptors (NRs) in Xenopus oocytes. METHODS: Total RNA and messenger RNA (mRNA) was prepared from 3-month-old Wistar rat brain tissues with Promega kits and microinjected into maturated Xenopus oocytes (stages V-VI) with 50 nl (50 ng) for each oocyte. The microinjected oocytes were incubated with modified Bath's solution at 19.0 degrees C +/- 1.0 degree C for receptor expression and their currents were recorded with double electrode voltage clamp technique. Superoxide anion free radicals (SAFRs) were produced via a reaction system (HPX/XO) with hypoxanthine (HPX, 0.05 mol/L) and xanthine oxidase (XO, 0.1 U/L). In order to observe the effects of A beta and SAFRs on the expressed glutamate receptor, HPX/XO and A beta 1-40 were added to incubation solution at 12 h, 24 h and 96 h before recording. RESULTS: The results showed that the oocytes expressed functional NRs originating from rat brain tissues. These NRs included muscarinic acetylcholine (mACh), glutamate (Glu), dopamine (DA), serotonin (5-HT) and gamma-aminobutyric acid (GABA). The current characteristics of expressed receptors were inward currents carried by chloride ion with their equibrilium potentials close to -22 mV. The extent of effect on the current of expressed glutamate receptor from rat brain was different among different A beta concentrations and incubation times. A beta 1-40 at a concentration of 20 nmol/L had little effect on the currents of expressed rat brain glutamate receptors up to 24 h of incubation period; but the currents of glutamate receptor were significantly decreased (25% off, P < 0.01) in the treatment of 60 nmol/L A beta 1-40 over 24 h. Moreover, when 20 nmol/L A beta 1-40 was co-incubated over 12 h with SAFRs produced by the reaction system of HPX/XO, it was found that the currents of expressed rat brain glutamate receptors had been changed markedly. When the oocytes were co-treated with 60 nmol/L A beta 1-40 and SAFRs over a period of 12 h, the currents of glutamate receptor significantly decreased (21% off, P < 0.05), and the decreased percentage reached 52% over 24 h co-treatment with 60 nmol/L A beta 1-40 and SAFRs. In addition, vitamin E had a partial effect against this inhibitory effect. CONCLUSION: The results suggest that A beta has a kind of inhibitory effect upon the current of the glutamate receptor, similar to the effects of free radicals. The effects can be antagonized by vitamin E. These imply that A beta may play a role via inhibiting receptor function in the pathophysiology of Alzheimer's disease.

Amyloid beta-Peptides↗
PubMed2001

[Clindamycin soluble suppository-production and its efficacy in treating bacterial vaginosis].

OBJECTIVE: To make the soluble suppository of clindamycin which is an effective drug for treatment of Bacterial vaginosis and to treat patients in clinical trials. METHODS: Outpatients who had vaginal infections from Sept. 1998 to Jan. 1999 were investigated. The diagnoses of bacterial vaginosis were made according to Amsel's criteria and 80 patients were included in this study. They were divided into two groups to be treated respectively by metronidanole suppository and clindamycin suppository which were made by our hospital pharmacy. RESULTS: The cure rate of metronidanole was 87.5% and that of clindamycin 90.3%; No significant difference was noted between the two groups(P > 0.05). The new clindamycin suppository was not irritant and it was easy to dissolve in vagina. There was no discontinued treatment because of side-effect. CONCLUSION: The clindamycin suppository does not irritate the mucosa of vagina, it is an efficacious remedy for bacterial vaginosis.

Administration, Intravaginal↗
PubMed2001

[The study on the occult metastases to cervical lymph node in squamous cell carcinoma of the larynx and hypopharynx].

OBJECTIVE: To study the metastastic regularity of cervical lymph node in squamous cell carcinoma of the larynx and hypopharynx, which will provide some theoretical basis for surgeon to use selective neck dissection (SND) in some patients with carcinoma above. METHOD: Sixty-nine originally cN0 staged neck dissection specimens from 40 patients were evaluated using mutipl-level sectioning in 4 microns intervals, which were respectively processed by H&E-staining and immunostaining with an antibody to cytokeratin (CK AE3). These patients weren't given any treatment (radiotherapy or chemotherapy or surgery in neck) before surgery. All cases had been followed up 1 year or more. RESULT: The examination of lymph nodes from 40 patients revealed 31 (0.59% 31/2219) occult metastases in 14 (35% 14/40) patients. Among them, six patients with supraglottic cancer, 1 patient with transglottic cancer and 7 patients with hypopharyngeal cancer. There were no occult metastases to cervical lymph node among 9 patients with glottic cancer. All occult metastases mainly located in ipsilateral level II and/or level III. Occult metastases weren't found in nodes from level I, level IV and level V. CONCLUSION: The study further prove that metastases to cervical lymph node mainly occur in the ipsilateral level II and level III among patients with carcinoma of the larynx and hypopharynx. According to the risks of occurring occult metastases to cervical lymph node, we suggest applying to ipsilateral or bilateral SND (level II and level III be dissected) among patients with carcinoma of the larynx and hypopharynx which staged T2-T4 N0M0 clinically.

Adult↗
PubMed2001

[Influence of clinical staging of type III sinusitis on the operative effectiveness].

OBJECTIVE: To explore the influences of different degree of pathological changes in chronic polypous sinusitis patients on the effectiveness of endoscopic sinus surgery. METHOD: According to history, anatomic structures and severity of lesions, 104 cases (208 sides) of Type III sinusitis were divided into 3 stages. Rates of clinical effectiveness and complications were compared and analyzed. RESULTS: The total effective rates were 93.06%, 82.89% and 70.00% and the rates of complications were 5.56%, 14.47% and 25.00% in stages 1, 2, 3 respectively. CONCLUSION: The effective rates, difficulties and risks of operation depend upon the anatomic variations (integration of ostiomeatal complex) and the degree of lesions (augmentation of granulation and osseous hypertrophy of ethmoid bone). All these should be listed as objective bases in classifying stages of patients which will play a directional role in clinical work.

Adolescent↗
PubMed2000

Pathways of dehydroepiandrosterone formation in rat brain glia.

In peripheral steroidogenic tissues, dehydroepiandrosterone (D) is formed from pregnenolone (P) by the microsomal cytochrome P450c17 enzyme. Although some steroidogenic P450s have been found in brain tissue, no enzyme has been shown to possess P450c17 activity. We recently demonstrated the presence of an alternative, Fe(2+)-dependent pathway responsible for D formation from alternative precursors in rat glioma cells. We and others could not find P450c17 mRNA and protein in rat brain, but demonstrate herein the presence of Fe(2+)-dependent alternative pathway for D formation in rat brain cortex microsomes. Using primary cultures of differentiating rat glial cells, we observed that P450c17 mRNA and protein were present in O-2A oligodendrocyte precursors and mature oligodendrocytes. In the presence of P, O-2A and mature oligodendrocytes formed D. Addition of Fe(2+) together with submaximal concentrations of P increased D formation by these cells. Treatment of oligodendrocytes with the P450c17 inhibitor SU 10603 in the presence or absence of P failed to inhibit D production. These data suggest that D formation in oligodendrocytes occurs independently of the P450c17 protein present in the cells. In isolated type I astrocytes we did not find neither P450c17 mRNA nor protein. These cells responded to Fe(2+) by producing D and addition of P together with Fe(2+) further increased D synthesis. SU 10603 failed to inhibit D formation by astrocytes. Taken together these results suggest that in differentiating rat brain oligodendrocytes and astrocytes D is formed via a P450c17-independent and oxidative stress-dependent alternative pathway.

Animals↗
PubMed2000

The effect of a T cell-specific NF-kappa B inhibitor on in vitro cytokine production and collagen-induced arthritis.

NF-kappa B plays a key role in the production of cytokines in inflammatory diseases. The effects of a novel T cell-specific NF-kappa B inhibitor, SP100030, were evaluated in cultured Jurkat cells and in murine collagen-induced arthritis (CIA). Chemical libraries were screened for NF-kappa B-inhibitory activity. SP100030, a compound identified in this process, inhibited NF-kappa B activation in PMA/PHA-activated Jurkat cells by EMSA at a concentration of 1 microM. Jurkat cells and the monocytic cell line THP-1 were transfected with an NF-kappa B promotor/luciferase construct and activated. SP100030 inhibited luciferase production in the Jurkat cells (IC50 = 30 nM). ELISA and RT-PCR confirmed that IL-2, IL-8, and TNF-alpha production by activated Jurkat and other T cell lines were inhibited by SP100030. However, cytokine expression was not blocked by the compound in THP-1 cells, fibroblasts, endothelial cells, or epithelial cells. Subsequently, DBA/1J mice were immunized with type II collagen. Treatment with SP100030 (10 mg/kg/day i.p. beginning on day 21) significantly decreased arthritis severity from onset of clinical signs to the end of the study on day 34 (arthritis score, 5.6 +/- 1.7 for SP100030 and 9.8 +/- 1.5 for control; p < 0.001). Histologic evaluation demonstrated a trend toward improvement in SP100030-treated animals. EMSA of arthritic mouse ankles in CIA showed that synovial NF-kappa B binding was suppressed in the SP100030-treated mice. SP100030 inhibits NF-kappa B activation in T cells, resulting in reduced NF-kappa B-regulated gene expression and decreased CIA. Its selectivity for T cells could provide potent immunosuppression with less toxicity than other NF-kappa B inhibitors.

Animals↗
PubMed2000

Protein kinase A-dependent phosphorylation of aquaporin-1.

The molecular mechanisms for regulating water balance in many tissues are unknown. Like the kidney, the eye contains multiple water channel proteins (aquaporins) that transport water through membranes, including two (AQP1 and AQP4) in the ciliary body, the site of aqueous humor production. Previous results from our laboratory demonstrated that water channel activity of AQP1 was significantly increased by protein kinase A (PKA) activators such as cyclic-AMP (cAMP) and forskolin. The purpose of this study is to determine whether PKA-dependent protein phosphorylation is involved in the regulation of water channel activity of AQP1. Results presented here suggest that catalytic subunit of protein kinase A significantly increased the amount of phosphorylated AQP1 protein. In addition, these results indicated that cAMP-responsive redistribution of AQP1 may be regulated by phosphorylation of AQP1. Moreover, they provide new insights on the molecular mechanisms for regulating water balance in several tissues involving rapid water transport such as ciliary epithelium. In addition, they suggest important potential roles for AQP1 in several clinical disorders involving rapid water transport such as glaucoma.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

Reaction of reducing hydroxyl radical adducts of pyrimidine nucleotides with riboflavin and flavin adenine dinucleotide (FAD) via electron transfer: a pulse radiolysis study.

Using the techniques of pulse radiolysis with time-resolved spectrophotometric detection, it has been demonstrated that the interaction of reducing OH radical adducts of dCMP, TMP and UMP with riboflavin (RF) and flavin adenine dinucleotide (FAD) does proceed via an electron transfer reaction. From buildup kinetics of radical species, the rate constants of electron transfer from reducing OH adducts of pyrimidines to RF and FAD have been determined, respectively. It could be deduced that RF and FAD would reduce the probability of repair of the damaged DNA in the presence of enzymes and antioxidants, accordingly RF and FAD might have a radiosensitization effect on DNA damage.

DNA↗