Biomedical subjects

S Zhong

Publications and source records attributed to S Zhong.

At least 37 records · Page 2Linked to original sources

PubMed2001

ASPP proteins specifically stimulate the apoptotic function of p53.

We identified a family of proteins termed ASPP. ASPP1 is a protein homologous to 53BP2, the C-terminal half of ASPP2. ASPP proteins interact with p53 and specifically enhance p53-induced apoptosis but not cell cycle arrest. Inhibition of endogenous ASPP function suppresses the apoptotic function of endogenous p53 in response to apoptotic stimuli. ASPP enhance the DNA binding and transactivation function of p53 on the promoters of proapoptotic genes in vivo. Two tumor-derived p53 mutants with reduced apoptotic function were defective in cooperating with ASPP in apoptosis induction. The expression of ASPP is frequently downregulated in human breast carcinomas expressing wild-type p53 but not mutant p53. Therefore, ASPP regulate the tumor suppression function of p53 in vivo.

Apoptosis↗

PubMed2001

Quantitative and genotypic analysis of TT virus infection in Chinese blood donors.

BACKGROUND: The TT virus (TTV) is a member of a newly described family of human viruses related to the C ircoviridae viruses. Its association with specific diseases has not been established, and screening of blood donors has not been implemented. To date, 16 genotypes have been identified. STUDY DESIGN AND METHODS: Sera from 471 healthy blood donors (aged 11-58 years) were randomly selected and tested for TTV by the use of two sets of primers: NG59d/NG61d/NG63d primers and T801/T935 primers. Quantitative competitive PCR (QC-PCR) was developed to measure the TTV DNA concentration among the blood donors. Sequencing of a part of the genome was performed to identify the various genotypes. Several samples showed a mixed genotype infection. RESULTS: TTV was detected in 251 (53.3%) of 471 healthy Hong Kong blood donors by the use of NG59d/NG61d/NG63d primers. The prevalence of the virus increased steadily with age (p = 0.03). TTV DNA was detected in 90 percent (90 of a randomly selected 100) of samples by the use of T801/T935 primers. TTV DNA concentration was also measured by QC-PCR in the blood donors who were positive for TTV DNA in the first round of the heminested PCR. TTV titers ranged from 4.8 x 10(2) copies per mL to 6 x 10(4) copies per mL, with a median value of 1.2 x 10(4) copies per mL. Sequencing and phylogenetic analysis of a 223-bp fragment from open reading frame 1 showed three main genotypes (G1 [60.7%], G2 [24.3%], and G3 [14%]) and a new genotype 17 (G17), with the latter bearing 60-percent nucleotide homology with other genotypes deposited at GenBank. In addition, a new TTV subtype, G2f, was found. CONCLUSION: The prevalence of TTV is high in healthy Chinese blood donors. Three main genotypes (G1, G2, and G3) were detected. In addition, a new TTV genotype, tentatively designated as G17, and a new subtype, G2f, were identified.

Adolescent↗

PubMed2001

Stem cell engraftment strategies.

The donor stem cell phenotype and host microenvironment determine the outcome of a stem cell transplant. In a series of transplant studies in syngeneic male to female or congenic Ly5.1/Ly5.2 models in which hosts have received no or minimal irradiation (100 cGy), evidence overwhelmingly supports the concept that syngeneic engraftment is determined by stem cell competition. These approaches can be extended to H-2 mismatched allogeneic mouse combination when antigen pre-exposure and CD40-CD40 ligand antibody blockage are employed. A human trial in patients with resistant neoplasia infusing pheresed blood with 10(8) CD3 cells/kg showed that tumor responses and complete chimerism occur with very low levels of CD34+ cells/kg and that the extent of previous treatment is a critical factor in determining chimerism. A major feature of transplants is the phenotype of the donor stem cell. This phenotype shows dramatic reversible plasticity involving differentiation, adhesion protein expression, and engraftment with cytokine-induced cell-cycle transit. Homing is probably also plastic. Marked fluctuations in engraftment capacity are also seen at different points in marrow circadian rhythm.

Adolescent↗

PubMed2001

Gross elevation of TT virus genome load in the peripheral blood mononuclear cells of cancer patients.

TT virus (TTV) is a recently described circular DNA virus of about 3.8 kb, which is related to the circoviridae viruses. It is commonly detected in healthy subjects and no association with any specific disease has been established. TTV was initially thought to be hepatotropic, but subsequent reports have shown that it is detectable in other tissues, including kidney, prostate, mammary gland, brain, bone marrow, and peripheral blood mononuclear cells. Plasma samples from cancer patients and healthy subjects were tested for the presence or absence of TTV by heminested polymerase chain reaction (PCR). We also developed a quantitative competitive PCR (QC-PCR) assay for TTV that permits accurate measurement of TTV DNA load. Using this assay, the TTV genome load in peripheral blood mononuclear cells (PBMCs) of healthy control subjects (n = 50) and patients with various types of cancer (n = 148), including breast cancer, non-Hodgkin's lymphoma, colon cancer, hepatocellular carcinoma, nasopharyngeal carcinoma, and other cancers, was measured. TTV DNA was detected in 69 of 100 plasma samples (69%) of cancer patients tested and in 39 of 100 plasma samples (39%) randomly selected from 1000 plasma samples of blood donors (p < 0.05). TTV DNA was detectable in the PBMCs of 99% of the cancer patients and 86% of the controls. However, the median virus load was more than 100-fold higher in the cancer patients (3599 copies/100,000 cells) than among the controls (30 copies/100,000 cells; p < 0.0001). There was no significant difference in TTV load among the different cancer types. Using a cutoff value of >250 copies per 100,000 PBMCs, 93.2% of cancer patients were "positive" compared to only 4% of healthy control subjects. Almost all the cancer patients have TTV infection and their TTV genome load in PBMCs is significantly higher than that in control subjects. It remains to be elucidated whether such findings are specific to cancer patients or occur in all seriously ill subjects.

Adult↗

PubMed2001

Sympathetic nerve and cardiovascular responses to chemical activation of the midbrain defense region.

The changes in mean arterial pressure (MAP), renal (RBF) and femoral (FBF) blood flows, and inferior cardiac (CN) and vertebral nerve (VN) sympathetic nerve discharges (SND) produced by chemical activation (D,L-homocysteic acid) of the midbrain periaqueductal gray (PAG) were compared in baroreceptor-denervated and -innervated cats anesthetized with urethan. Defenselike cardiovascular responses in both states were similar in magnitude and consisted of increased MAP and FBF and decreased RBF; however, the nerve responses differed. In baroreceptor-denervated cats, PAG activation increased CN 10-Hz activity, decreased VN 10-Hz activity, and lengthened the CN-VN phase angle. In baroreceptor-innervated cats in which the rhythm in SND was cardiac related, PAG activation increased CN activity, but VN activity and the CN-VN phase angle were unchanged. These results demonstrate that chemical activation of PAG neurons induces differential patterns of sympathetic outflow generally consistent with accompanying defenselike cardiovascular responses. However, the mechanisms responsible for the changes in 10-Hz and cardiac-related SND appear to be different.

Animals↗

PubMed2001

Effects of long-term enalapril and losartan therapy of hypertension on cardiovascular aldosterone.

BACKGROUND: Plasma aldosterone escape is found during long-term angiotensin-converting enzyme inhibitor therapy. Evidence for aldosterone production in cardiovascular tissues raised the question of whether or not aldosterone escape occurs in these tissues. METHOD: Spontaneously hypertensive rats were treated with enalapril (20 mg/kg/day) and losartan (50 mg/kg/day) for 20 weeks; untreated spontaneously hypertensive and Wistar rats were used as positive and normal controls, respectively. Ex vivo mesenteric artery and heart perfusion, high-performance liquid chromatography, and radioimmunoassay for aldosterone were performed. RESULTS: The results showed that enalapril failed to significantly inhibit aldosterone production in mesenteric artery, myocardium and plasma. Losartan significantly inhibited aldosterone production to that of Wistar rats in the mesenteric artery, myocardium and plasma. CONCLUSION: This study provides the first evidence that long-term angiotensin-converting enzyme inhibition therapy induces aldosterone escape in hypertensive cardiovascular tissues, and angiotensin II subtype 1 receptor antagonist does not induce aldosterone escape in mesenteric artery, myocardium and plasma of spontaneously hypertensive rats.

Aldosterone↗

PubMed2001

Histone deacetylase inhibitors induce remission in transgenic models of therapy-resistant acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is associated with chromosomal translocations, invariably involving the retinoic acid receptor alpha (RAR alpha) gene fused to one of several distinct loci, including the PML or PLZF genes, involved in t(15;17) or t(11;17), respectively. Patients with t(15;17) APL respond well to retinoic acid (RA) and other treatments, whereas those with t(11;17) APL do not. The PML-RAR alpha and PLZF-RAR alpha fusion oncoproteins function as aberrant transcriptional repressors, in part by recruiting nuclear receptor-transcriptional corepressors and histone deacetylases (HDACs). Transgenic mice harboring the RAR alpha fusion genes develop forms of leukemia that faithfully recapitulate both the clinical features and the response to RA observed in humans with the corresponding translocations. Here, we investigated the effects of HDAC inhibitors (HDACIs) in vitro and in these animal models. In cells from PLZF-RAR alpha/RAR alpha-PLZF transgenic mice and cells harboring t(15;17), HDACIs induced apoptosis and dramatic growth inhibition, effects that could be potentiated by RA. HDACIs also increased RA-induced differentiation. HDACIs, but not RA, induced accumulation of acetylated histones. Using microarray analysis, we identified genes induced by RA, HDACIs, or both together. In combination with RA, all HDACIs tested overcame the transcriptional repression exerted by the RAR alpha fusion oncoproteins. In vivo, HDACIs induced accumulation of acetylated histones in target organs. Strikingly, this combination of agents induced leukemia remission and prolonged survival, without apparent toxic side effects.

Animals↗

PubMed2001

Optical tomographic imaging of dynamic features of dense-scattering media.

Methods used in optical tomography have thus far proven to produce images of complex target media (e.g., tissue) having, at best, relatively modest spatial resolution. This presents a challenge in differentiating artifact from true features. Further complicating such efforts is the expectation that the optical properties of tissue for any individual are largely unknown and are likely to be quite variable due to the occurrence of natural vascular rhythms whose amplitudes are sensitive to a host of autonomic stimuli that are easily induced. We recognize, however, that rather than frustrating efforts to validate the accuracy of image features, the time-varying properties of the vasculature can be exploited to aid in such efforts, owing to the known structure-dependent frequency response of the vasculature and to the fact that hemoglobin is a principal contrast feature of the vasculature at near-infrared wavelengths. To accomplish this, it is necessary to generate a time series of image data. In this report we have tested the hypothesis that through analysis of time-series data, independent contrast features can be derived that serve to validate, at least qualitatively, the accuracy of imaging data, in effect establishing a self-referencing scheme. A significant finding is the observation that analysis of such data can produce high-contrast images that reveal features that are mainly obscured in individual image frames or in time-averaged image data. Given the central role of hemoglobin in tissue function, this finding suggests that a wealth of new features associated with vascular dynamics can be identified from the analysis of time-series image data.

Blood Vessels↗

PubMed2001

[The tissue engineering research on synovialization of non-synovial membrane tendon].

The synovial membrane tissue within the flexor digital tendon sheath of the rabbit's toes was cultured in vitro. The synovial cells suspension of the subculture was cultured with the segments of the non-synovial membrane tendon of the rabbit's toes. Under the light microscopy, scanning electronic microscopy and immunohistochemical examination, the result showed that the synovial cells crawled and covered the surface of the segments of the non-synovial membrane tendons. It is suggested that the non-synovial membrane tendon could transform into a synovial membrane tendon.

Animals↗

PubMed2001

[Inhibition of HBV gene expression by antisense oligonucleotides using galactosylated poly (L-lysine) as a hepatotropic carrier].

OBJECTIVE: To study the specific inhibition of HBV gene expression by antisense oligonucleotide (ASON) targeted by galactosylated poly (L-lysine) (Gal-PLL). METHODS: According to the results of direct sequencing of PCR amplified products, a 16 mer phosphorthioate analogue of the antisense oligonucleotide (PS-ASON) directed against the HBV U5-like region was synthesized and then linked with one liver-targeting ligand, the Gal-PLL. Using the 2.2.15 cells compared the effect of them on the expression of HBV gene. RESULTS: We identified that HBV DNA in the 2.2.15 cells was from HBV with surface antigen subtype ayw2 by sequencing. The fluorescent histochemistry test indicted that Gal-PLL had a selective affinity to the rat liver tissues. A 2:1 molar ratio of the Gal-PLL to DNA optimized the complex formation. In the same experimental conditions, the inhibitory effects of HBsAg and HBeAg by PS-ASON were 70% and 58%, respectively at a concentration of 10 mumol/L, while by ligand-PS-ASON were 96% and 82%, respectively, and the amount of HBV DNA in culture supernatant and cells was depressed significantly. An unrelated sequence oligonucleotide showed no effectiveness. All the oligonucleotide had no cytotoxicity. CONCLUSION: Antisense oligonucleotides complex with the liver-targeting ligand can be targeted to cells via asialoglycoprotein receptors resulting in specific inhibition of HBV gene expression and replication.

Animals↗

PubMed2001

[Significance of vascular endothelial growth factor expression in colorectal cancer].

OBJECTIVE: To investigate the expression of vascular endothelial growth factor (VEGF) mRNA in colorectal cancer (CRC) and its relation with the clinicopathologic features and explore new approaches to prevent and inhibit recurrence and metastasis of CRC. METHODS: Surgical samples of 68 patients with CRC were studied using reverse transcription-polymerase chain reaction (RT-PCR). The relative level of VEGF mRNA expression was measured by determining a ratio of PCR products of VEGF to that of beta-actin gene. RESULTS: (1) Expression of VEGF mRNA in tumor tissue was found in 67.6% (46/68) of the sample, whereas it was seen in 32.4% (22/68) of the surrounding nontumorous colorectal tissue. (2) The level of VEGF mRNA expression in tumors with serosal invasion, lymph node metastasis, distant metastasis or Dukes' D stage was higher than that without serosal invasion, lymph node metastasis, distant metastasis or Dukes' A and B and C stage (P < 0.01). (3) There was no significant difference in the expression of VEGF mRNA between large CRC (diameter > 5 cm) and small CRC (diameter < or = 5 cm) (P > 0.05) or histologic types (P > 0.05). CONCLUSION: VEGF may play an important role in the invasion and metastasis of CRC. It is thus show that angiogenesis in tumor correlates with the progression of CRC.

Adult↗

PubMed2001

[Study on antitumor effect and mechanism of aloe polysaccharides].

OBJECTIVE: To study the antitumor activity and mechanism of aloe polysaccharides (AP). METHODS: AP was administered i.p. or i.v. to Sarcoma 180(S180) bearing mice or Hepatoma22(H22) bearing mice solely or combining with CTX, FU and ADM respectively. 10 days later, for S180 mice, the blood was analyzed, the tumor was peeled off and weighed, and the spleen index, thymus index was calculated. For H22 bearing mice, the survival rate was observed or the IL-2, TNF content in serum was tested. RESULTS: 25 mg/kg.d or 50 mg/kg.d AP group could evidently reduce the tumor weight of S180 bearing mice and prolong the survival time of H22 bearing mice. AP also could improve the antitumor effects of CTX, ADM, FU, and lessen the chemotherapy side-effects. Furthermore, AP could improve the level of IL-2, TNF in the serum of mice bearing S180 or H22. CONCLUSION: AP has the effects of antitumor, enhancing the antitumor activity of chemotherapy drugs and lessening their side-effects. This effect was possibly derived from inducing IL-2 and TNF producing in body and improving the immunity activity.

Aloe↗

PubMed2001

[Expression of alpha and beta subunit isoforms of Na, K-ATPase in the guinea pig endolymphatic sac].

OBJECTIVE: To investigate the expression and significance of alpha and beta subunit isoforms of Na, K-ATPase in the guinea pig endolymphatic sac. METHODS: The distribution of alpha and beta subunit isoforms of Na, K-ATPase in endolymphatic sac of guinea pig was identified by immunocytochemistry and in situ hybridization. RESULTS: The expression of Na, K-ATPase alpha and beta subunit isoforms varied among different cell regions of the endolymphatic sac. Epithelial cells of the endolymphatic sac were observed to contain the alpha 1, beta 1 and beta 2 subunit isoforms, and the expression of beta 2 was stronger than that of beta 1. Subepithelial cells contained alpha 1 and alpha 2 subunit isoforms and the expression of alpha 1 was stronger than that of alpha 2. No expression of alpha 3 subunit isoform was observed in endolymphatic sac. CONCLUSION: Na, K-ATPase of endolymphatic sac consists of different alpha and beta subunit isoforms which, working in concert, serve to maintain homeostasis in inner ear.

Animals↗

PubMed2000

Coupling of arterial pulse and 10-Hz rhythm in sympathetic nerve discharge.

We used time series analysis to characterize the relationships among the arterial pulse (AP) and the cardiac-related and 10-Hz rhythms in sympathetic nerve discharge (SND) of urethane-anesthetized cats. We found that 10-Hz activity was more tightly coupled to the AP than to the cardiac-related rhythm. These data support the view that the dynamic coupling of AP and the 10-Hz rhythm in SND involves a direct influence of baroreceptor activity on the 10-Hz oscillator.

Animals↗

PubMed2000

The effects of cyclic loading on pull-out strength of sacral screw fixation: an in vitro biomechanical study.

STUDY DESIGN: The pull-out strength of sacral screw fixation after cyclic loading was tested using young human cadaveric specimens. OBJECTIVES: To evaluate the effects of fatigue loading on the pull-out strength of medial and lateral unicortical and bicortical sacral screws and to correlate the pull-out strength with sacral bone density and the screw insertion torque. SUMMARY OF BACKGROUND DATA: The immediate biomechanical effects of depth of penetration, screw orientation, and bone density on sacral screw fixation have been studied in aged cadaveric specimens. The effect of cyclic loading on the pull-out strength of sacral screw fixation is unknown, however, and data from young specimens is rare. METHODS: Eleven fresh specimens of human sacrum were used in this study. Bone mineral density at the vertebral body and the ala were determined by peripheral quantitative computed tomography. Seven-millimeter compact Cotrel-Dubousset sacral screws were inserted into the sacrum anteromedially and anterolaterally, both unicortically and bicortically, and the insertion torque for each screw was measured. Cyclic loading from 40 to 400 N was applied to each screw at a frequency of 2 Hz up to 20,000 cycles. Pull-out tests were conducted after completion of the fatigue tests. RESULTS: The average bone density was 0.38 +/- 0.08 g/mL at the S1 body and 0.24 +/- 0.05 g/mL at the S1 ala. The insertion torque and average pull-out force after cyclic loading were significantly higher for bicortical fixation than for unicortical fixation for a particular screw alignment. The pull-out strength and insertion torque of medially oriented fixation was always higher than that for lateral fixation, however, regardless of whether the insertion was unicortical or bicortical. The pull-out force of unicortical and bicortical medial screw fixations after cyclic loading showed significant linear correlations with both the insertion torque and the bone mineral density of the S1 body. CONCLUSIONS: In a young population, screw orientation (anterolateral or anteromedial) was more important in determining pull-out strength than screw depth (unicortical or bicortical) after fatigue loading, anteromedially directed screws being significantly stronger than laterallyplaced screws. Bone mineral density of the S1 body andinsertion torque were good preoperative and intraoperative indicators of screw pull-out strength.

Adult↗

PubMed2000

Role of SUMO-1-modified PML in nuclear body formation.

The tumor-suppressive promyelocytic leukemia (PML) protein of acute promyelocytic leukemia (APL) has served as one of the defining components of a class of distinctive nuclear bodies (NBs). PML is delocalized from NBs in APL cells and is degraded in cells infected by several viruses. In these cells, NBs are disrupted, leading to the aberrant localization of NB proteins. These results have suggested a critical role for the NB in immune response and tumor suppression and raised the question of whether PML is crucial for the formation or stability of NB. In addition, PML is, among other proteins, covalently modified by SUMO-1. However, the functional relevance of this modification is unclear. Here, we show in primary PML(-/-) cells of various histologic origins, that in the absence of PML, several NB proteins such as Sp100, CBP, ISG20, Daxx, and SUMO-1 fail to accumulate in the NB and acquire aberrant localization patterns. Transfection of PML in PML(-/-) cells causes the relocalization of NB proteins. By contrast, a PML mutant that can no longer be modified by SUMO-1 fails to do so and displays an aberrant nuclear localization pattern. Therefore, PML is required for the proper formation of the NB. Conjugation to SUMO-1 is a prerequisite for PML to exert this function. These data shed new light on both the mechanisms underlying the formation of the NBs and the pathogenesis of APL. (Blood. 2000;95:2748-2752)

Animals↗

PubMed2000

Purification of the newly found selenium-containing proteins in the arterial wall and brain of the rat.

Previously several selenium-containing proteins with different subunit molecular masses (M(r)) were detected in the arterial wall and brain of rats. In continuation of this work, after labeling of rats in vivo with [(75)Se]selenite, the new selenium-containing proteins of interest were purified on a Sephadex G-200 column followed by preparative isoelectric focusing. Nuclear analytical methods (gamma-counter and gamma-detector) were applied in the detection and identification of the (75)Se-labeled proteins. The two (75)Se-containing proteins from the arterial wall migrated as 15.0- and 67.0-kDa species on SDS-PAGE gels with pI values of 4.5 and 5.1, respectively. The three (75)Se-containing proteins from brain purified to homogeneity had M(r) values of 18.0, 30.0, and 42.9 kDa and pI values of 6.3, 6.5, and 6.0, respectively. Of these proteins, the 67.0-, 42.9-, and 30.0-kDa species may be yet not characterized selenoproteins with important biological functions.

Animals↗

PubMed2000

Internal structure and early thermal evolution of Mars from Mars Global Surveyor topography and gravity.

Topography and gravity measured by the Mars Global Surveyor have enabled determination of the global crust and upper mantle structure of Mars. The planet displays two distinct crustal zones that do not correlate globally with the geologic dichotomy: a region of crust that thins progressively from south to north and encompasses much of the southern highlands and Tharsis province and a region of approximately uniform crustal thickness that includes the northern lowlands and Arabia Terra. The strength of the lithosphere beneath the ancient southern highlands suggests that the northern hemisphere was a locus of high heat flow early in martian history. The thickness of the elastic lithosphere increases with time of loading in the northern plains and Tharsis. The northern lowlands contain structures interpreted as large buried channels that are consistent with northward transport of water and sediment to the lowlands before the end of northern hemisphere resurfacing.

Atmosphere↗