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Biomedical subjects

S Ruan

Publications and source records attributed to S Ruan.

At least 37 records · Page 2Linked to original sources
PubMed2000

[An experimental study of myocardial injury by hydrofluoric acid in burned rabbits].

OBJECTIVE: To investigate the myocardial injury by hydrofluoric acid in burned rabbits METHODS: New Zealand white rabbits were injured with 2% TBSA III degree skin burn on the back by hydrofluoric acid. The blood and tissue samples were taken from the rabbit after injury for the detection of myocardial and related enzymes and the pathomorphological examination. RESULTS: (1) Postburn myocardial enzymes increased significantly compared to those before burn (P < 0.01). (2) All the myocardial enzymes reached their peak levels within 48 postburn hours and were higher than those before burn (P < 0.01). (3) Among all the enzymes, CPK increased by 97.5% and those of LDH, AST and CK-MB by 81.9%, 76.1% and 60.3%, respectively. (4) Pathomorphological findings with LM were the granular degeneration and focal necrosis of myocardial fibers, interstitial hemorrhage of myocardium accompanied with neutrophil and lymphocyte infiltration. Ultrastructural changes included myofibril decrease or even disappearing, severe cellular and mitochondrial swelling, disappearing of mitochondrial crista, endothelial swelling, decrease of electronic density with the exhibiting of bulla and deformation of myocardial cellular nucleus. CONCLUSION: Myocardial function could be damaged after hydrofluoric acid burn. Therefore, special attention should be paid to the protection of cardiac function after hydrofluoric acid burn by strengthening the monitoring of myocardial enzymes and ECG, etc.

Animals↗
PubMed1999

Relationship of glycosyltransferases and mRNA levels to ganglioside expression in neuroblastoma and melanoma cells.

Most human neuroblastoma tumors are characterized by the high expression of GD2 (or GD2 and/or GM2) gangliosides, whereas melanomas characteristically express GD3 ganglioside. The molecular basis for these patterns was investigated by examining the relationship between ganglioside levels, glycosyltransferase (GM2/GD2 synthase and GD3 synthase) activity, and corresponding mRNA levels in a panel of human neuroblastoma and melanoma cell lines. In general, the ganglioside patterns could be explained by the levels of the transferases and their mRNA, indicating control at the level of transcription. A key role was noted for GD3 synthase. Notably, it was found that neuroblastoma cell lines with high GD2 ganglioside levels had low levels of GD3, its synthase, and mRNA for the enzyme even though this step provides the substrate for GD2 synthesis. The key role for GD3 synthase was also examined by stably transfecting GD3 synthase cDNA into a neuroblastoma cell line (SH-SY5Y) not expressing GD3 and GD2. The resulting cell line had high levels of GD2 ganglioside and altered morphology and growth characteristics.

Blotting, Northern↗
PubMed1999

[Histomorphometry of silicon nitride composite endosteal implant in dogs].

OBJECTIVE: To study the dynamic changes of bone interface with silicon nitride (Si3N4) composite implants. METHODS: 4 Beagle dogs were experimental animals, Si3N4-HA and pure Si3N4 implant were experimental group, and Ti and Ti-HA were used as comparisons. They were implanted into dogs' femurs by stages. Histomorphometry was used to analyse and compare bone growth metabolism of bone interface with implant as well as evaluation of biocompatibility from quantitative and dynamic aspects. RESULTS: Parameters expressing mineralization and speed of deposition at the Si3N4-HA bone interface were higher than comparisions' at the first month. After 6 months, pure Si3N4's bone histomorphometic parameters had no notable difference with others. CONCLUSION: New implant material is useful to the clinic. The histomorphometry is of much value for the study of interface bone metabolism from quantitative and dynamic point of view.

Animals↗
PubMed1999

[Energy dispersive X-ray analysis in studying the permeability of blood-brain barrier caused by lead in rats].

OBJECTIVE: To observe the changes in permeability of blood-brain barrier caused by lead in rats. METHODS: Rats were fed with drinking water containing 10 and 30 mg/L of lead for three months. Electron microscopy lanthanum nitrate-tracing and electron probe-energy dispersive X-ray (EDX) analysis were used to observe the distribution of lead in different cells of bilateral sides of capillaries of cerebral cortex and the changes in their permeability. RESULTS: There was significant difference in blood lead levels between the rats with drinking water of 10 mg/L lead and the controls, but only a peak of lead, L(alpha), could appear in plasmalemma of endotheliaocyte endosurface in capillaries, and no any peak in the basement membrane of endotheliocyte of the outer-side, end feet of astrocytes and axons of neurons. Lanthanum nitrate-tracing showed changes in capillary permeability. But, in those with drinking water of 30 mg/L of lead, peak of lead, L(alpha) and M(alpha) could appear in all cells mentioned above. Meanwhile, lanthanum salt granules, which penetrated the cellular gaps of endothelia and seeped in the basement and its peripheral cells, could be found in certain sites of the capillaries with larger diameters. CONCLUSION: It suggests that the plasmalemma of endotheliocyte endosurface was the initial target in brain, where was affected by lead, and the consecutive endotheliocytes of blood vessels served as a blood-brain barrier to lead, although in a very weak action. A little bit accumulation of lead on the plasmalemma of endotheliocyte endosurface could cause damage in the close junction between endotheliocytes to spread to brain substance, same as the lanthanum tracing showed.

Animals↗
PubMed1999

Attenuation of WAF1/Cip1 expression by an antisense adenovirus expression vector sensitizes glioblastoma cells to apoptosis induced by chemotherapeutic agents 1,3-bis(2-chloroethyl)-1-nitrosourea and cisplatin.

Previous studies have shown that the negative cell cycle regulator WAF1/Cip1 is often overexpressed in human gliomas and that WAF1/Cip1 overexpression renders glioma cells resistant to chemotherapy agents. In this study, we investigated whether down-regulation of WAF1/Cip1 would sensitize gliomas to chemotherapy. An adenoviral vector expressing antisense WAF1/Cip1 was constructed and used to infect D54 glioma cells, which express a high level of endogenous WAF1/Cip1. After D54 cells were infected with antisense WAF1/Cip1 adenovirus, Western blotting revealed a significant decrease in the WAF1/Cip1 protein level. Down-regulation of WAF1/Cip1 alone resulted in the cells rounding up and detaching from plates. Electron microscopy revealed some nuclear fragmentation in antisense WAF1/Cip1-infected cells, indicating the initiation of apoptosis. The antisense WAF1/Cip1-infected cells were then treated with the chemotherapeutic agents 1,3-bis(2-chloroethyl)-1-nitrosourea and cisplatin. Other cells were infected with sense WAF1/Cip1 adenovirus or control virus and served as controls. Trypan blue exclusion assay revealed significant cell death in antisense WAF1/Cip1-infected cells. In situ end-labeling assay by flow cytometry revealed that many cells died of apoptosis. Our results show that the attenuation of WAF1/Cip1 expression initiated glioma cell death and sensitized glioma cells to apoptosis induced by 1,3-bis(2-chloroethyl)-1-nitrosourea and cisplatin. Thus, blocking WAF1/Cip1 production may serve as a useful chemosensitization regimen for treating glioma.

Adenoviridae↗
PubMed1998

Overexpressed WAF1/Cip1 renders glioblastoma cells resistant to chemotherapy agents 1,3-bis(2-chloroethyl)-1-nitrosourea and cisplatin.

Previous studies have shown that the negative cell cycle regulator WAF1/Cip1 is often overexpressed in human gliomas and that WAF1/Cip1 overexpression may be a factor in cancer chemoresistance. We established a doxycycline-inducible WAF1/Cip1 expression system in two glioblastoma cell lines and examined the role of WAF1/Cip1 in their response to the chemotherapy agents 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and cis-diamminedichloroplatinum (cisplatin), in an isogeneic background. Our results showed that the induction of WAF1/Cip1 expression rendered glioma cells resistant to cell death induced by BCNU and cisplatin. Using an in vivo host-cell reactivation DNA repair assay, we demonstrated that WAF1/Cip1 enhances the repair of BCNU-induced DNA damage. We conclude that WAF1/Cip1 allows repair of BCNU- and cisplatin-damaged DNA and protects glioma cells from chemotherapy agent-induced apoptosis. Thus, blocking WAF1/Cip1 production or function may serve as a useful chemosensitization regimen for glioma.

Antineoplastic Agents↗
PubMed1998

Overexpression of Bax gene sensitizes K562 erythroleukemia cells to apoptosis induced by selective chemotherapeutic agents.

Bax and Bcl-2 are a pair of important genes that control programmed cell death, or apoptosis, with Bax being the apoptosis promoter and Bcl-2 the apoptosis protector. Although the detailed mechanism is unknown, the protein products of these two genes form protein dimers with each other and the relative ratio of the two proteins is believed to be a determinant of the balance between life and death. In our preliminary study, we found that K562 erythroleukemia cells have an extremely low level of endogenous Bcl-2 expression and a fairly high level of endogenous Bax expression. We constructed Bax and Bcl-2 expression vectors and transfected them into K562 cells. We found that transfection of Bax vector increased the expression of Bax protein; a shortened form of Bax also appeared. Cell death analysis using the Annexin V assay showed that the Bax vector caused significantly more apoptotic cells that the Bcl-2 or pCI-neo vector did. After selection with G418, Bax, Bcl-2 and pCI-neo stably transfected cells were established. These three cell lines were examined for their response to the chemotherapeutic agents ara-C, doxorubicin, etoposide and SN-38. Bax-K562 cells showed significantly higher fractions of apoptotic cells than pCI-neo-K562 cells when treated with ara-C, doxorubicin or SN-38. No sensitization effect was seen when etoposide was used. In contrast, Bcl-2-K562 cells had fewer apoptotic cells than pCI-neo-K562 cells after treatment with all these agents. Therefore, Bax may sensitize K562 cells to apoptosis induced by a wide range of, but not all, chemotherapeutic agents.

Apoptosis↗
PubMed1998

Potent and specific inhibition of human leukocyte elastase, cathepsin G and proteinase 3 by sulfone derivatives employing the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold.

This paper describes the results of structure-activity relationship studies in a series of heterocyclic mechanism-based inhibitors based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold I and capable of interacting with the Sn and Sn' subsites of a serine proteinase. Sulfone derivatives of I were found to be highly effective, time-dependent inhibitors of human leukocyte elastase (HLE), cathepsin G (Cat G) and proteinase 3 (PR 3). The judicious selection of an R1 group (accommodated at the primary specificity site S1) that is based on the known substrate specificity of a target serine proteinase, was found to yield highly selective inhibitors. The presence of a benzyl group (R2 = benzyl) at the S2 subsite was found to lead to a pronounced enhancement in inhibitory potency. Furthermore, the effective use of computer graphics and modeling has led to the design of potent, water-soluble inhibitors. The results of these studies demonstrate that the 1,2,5-thiadiazolidin-3-one 1,1, dioxide platform provides an effective means for appending recognition elements in a well-defined vector relationship, and in fashioning highly-selective and potent inhibitors of serine proteinases.

Cathepsin G↗
PubMed1998

Detection of p21WAF1/Cip1 in brain metastases.

The p21WAF1/Cip1 (p21) protein, a negative regulator of G1 checkpoint control, was overexpressed in the majority of human gliomas. To investigate whether p21 expression in brain metastases from various systemic origins is similar to that in gliomas and whether p21 expression is regulated differently in brain metastases and in corresponding primary tumors, we used immunohistochemical staining to examine the expression of p21 in paraffin-embedded sections prepared from primary colon and breast carcinomas and from metastatic brain tumors that originated from colon, breast, lung, and kidney cancers and from melanoma. Our results showed that 56% (28 of 50) of the brain metastases samples have more than 1% p21-positive staining cells compared with 87% of primary gliomas reported previously. Among the samples analyzed, p21 expression in brain metastases from breast carcinomas was much higher than in primary breast carcinomas. In contrast, p21 expression in brain metastases from colon carcinomas was less than primary colon carcinomas. The results from this pilot study suggest that p21 expression is regulated differently in metastatic and primary tumors.

Brain Neoplasms↗
PubMed1998

Differential p53 phosphorylation and activation of apoptosis-promoting genes Bax and Fas/APO-1 by irradiation and ara-C treatment.

In this study, we examined the effects of radiation and ara-C on induction of apoptosis and on the apoptosis-promoting genes p53, Bax and Fas/APO-1, in BV173 human leukemia cells, which harbor the wild-type p53 gene. It has been reported that p53 upregulates Fas/APO-1 and Bax expression. Both irradiation and ara-C treatment resulted in apoptosis and induction of p53 proteins within hours. The Bax gene was activated in irradiated and ara-C-treated BV173 cells, but Fas/APO-1 was induced only in irradiated BV173 cells. Radiation and ara-C treatment did not induce Bax or Fas/APO-1 protein expression in p53-null HL60 cells. Radiation weakly induced Fas/APO-1 expression in KBM-7 cells, which harbor a partially defective p53 gene. Both HL60 and KBM-7 cells are more resistant to radiation- and ara-C-induced apoptosis than BV173 cells. These results suggest that functional p53 is necessary for the activation of Bax and Fas/APO-1 expression. However, elevated p53 protein is not sufficient to activate Fas/APO-1 gene expression in ara-C-treated cells. Using two-dimensional gel electrophoresis, we found that the p53 proteins in irradiated and ara-C-treated BV173 cells have different isoelectric points; they converged to a single isoelectric point after in vitro treatment with phosphatase. These results suggest that different genotoxic treatments cause different phosphorylations of p53, which may account for the different levels of activation of Fas/APO-1 expression.

Apoptosis↗
PubMed1998

[Effects of lead on neurone cells and distribution of calcium in rat brain].

OBJECTIVE: To study the relationship between blood lead levels and damage in neurone cells. METHODS: Young rats were fed with water containing 10 and 20 mg/L of lead for three months since the first day of their weaning. Lanthanum nitrate tracing, calcium cytochemical location technique and Golgi's stain were used to observe changes in rat brain tissues. RESULTS: There were no obvious changes in brain tissues of the low-dose group as its blood lead level reached 1.67 times high as that in control one. Permeability of neurone cells changed and distribution of calcium in plasmalemma increased and their cytoplasm disintegrated in part of the microtubule in the dendrites and axons of the neurones as its blood lead level in high-dose group reached 2.46 times high as that in control one. CONCLUSION: It is possible that pathological changes found in this study provide a basis for the decrease in cognitive function caused by lead during their middle brain development in rats.

Animals↗
PubMed1998

[The mechanism of hemorrhage following phosphorus burns and the effect of calcium gluconate].

OBJECTIVE: To investigate the mechanism of hemorrhagic tendency after phosphorus poisoning. METHODS: 45% phosphoric acid and 20 mg/cm2 phosphorus were used to produce burn injury in rabbits. The total content of phosphorus remaining on the wound and 7-day mortality were similar in both groups. RESULTS: The results showed that plasma free calcium contents were significantly lower in both phosphorus groups than healthy and thermal burn controls (0.80 vs 1.40 mol/l, P < 0.01). The free calcium content of platelet was lowered to 116-140 nmol/l, which was significantly lower than that of healthy control (285 nmol/l) and thermal injury group (480-504 nmol/l). Concomitantly, the platelet aggregation rate was lowered to 1.29% and 10.78% in phosphoric acid group and phosphorus group, respectively, while it was 67.01% in healthy control and 82.1%-84.9% in thermal injury group; the difference was statistically significant. CONCLUSION: Calcium therapy brought back intracellular and extracellular free calcium contents to normal in phosphorus burn group. Also platelet aggregation rate approached normal level after calcium therapy. The results suggest that the bleeding tendency after phosphorus burn is due to combination of phosphorus with intracellular and extracellular calcium of platelets, thus inhibiting aggregation of platelets.

Animals↗
PubMed1998

Loss of p21WAF1/Cip1 protein expression accompanies progression of sporadic colorectal neoplasms but not hereditary nonpolyposis colorectal cancers.

p21 (p21WAF1/Cip1), a cyclin-dependent kinase inhibitor, induces G1 arrest and can inhibit the activity of the proliferating cell nuclear antigen (PCNA). We analyzed p21 expression during colorectal tumorigenesis, its association with its transcriptional regulator p53, and its relationship to rates of cell proliferation and apoptosis. p21 and p53 protein expression were examined in sporadic tumors and hereditary nonpolyposis colorectal cancers (HNPCCs) by immunohistochemistry (IHC) and immunoblotting. Apoptosis was examined using a DNA nick end-labeling assay, and cell proliferation was examined by PCNA staining. In normal colorectal epithelia, nuclear p21 staining was uniformly detected in crypt cells of the superficial compartment (upper one-third) that stained negatively for PCNA. p21 and PCNA expression were, therefore, mutually exclusive. In sporadic cases, a decrease in the frequency of p21 expression accompanied adenoma development and progression to carcinoma. Specifically, p21 was detected in 12 of 16 (75%) adenomas and 10 of 32 (31%) carcinomas. In contrast to sporadic cases, HNPCCs with known mutations in DNA mismatch repair genes expressed p21 in 12 of 15 (80%) carcinomas. An inverse relationship between p21 and p53 was observed wherein mutant p53 proteins were detected in 4 of 15 (27%) HNPCCs versus 22 of 32 (69%) sporadic carcinomas. Although p21+ carcinoma cells were generally negative for p53, IHC revealed that some carcinoma cells expressed both p21 and p53 proteins. Furthermore, p53-mutated SW480 colon carcinoma cells were found to coexpress p21 and p53, suggesting that p21 can also be activated by a p53-independent mechanism. No association was found between p21 or PCNA and apoptotic labeling indices in adenomas or carcinomas. In conclusion, a decrease in p21 expression accompanies neoplastic progression in sporadic cases but not in HNPCCs. This finding appears related to p53 status in that the frequency of p53 expression was significantly reduced in HNPCCs compared to sporadic cases, suggesting a difference in their molecular pathways of tumorigenesis.

Colorectal Neoplasms↗
PubMed1997

Induction of p21waf1 expression and growth inhibition by transforming growth factor beta involve the tumor suppressor gene DPC4 in human pancreatic adenocarcinoma cells.

The tumor suppressor gene deleted in pancreatic cancer locus 4 (DPC4) is inactivated in about 50% of pancreatic adenocarcinomas. DPC4 was found to be homologous to Smad4 and may function as a transcription factor in the transforming growth factor beta (TGF-beta) receptor-mediated signal transduction pathway. We have investigated the role of DPC4 in the TGF-beta receptor-mediated signal transduction cascade in five human pancreatic cancer cell lines (Panc-1, MDAPanc-28, HS766T, Capan-1, and MiaPaCa-2). Our results demonstrate that the loss of responsiveness to TGF-beta-induced growth inhibition correlates with the loss of expression of DPC4. We have shown that TGF-beta induces p21waf1 expression in Panc-1 cells, whereas no induction of p21waf1 expression by TGF-beta was detected in the other four cell lines lacking either DPC4 expression or the TGF-beta type II receptor. No increase in p21waf1 mRNA stability was observed after treatment with TGF-beta, which suggests that the induction of p21waf1 in Panc-1 cells is transcriptionally regulated by TGF-beta. Our data also demonstrate that the expression of DPC4 is directly involved in TGF-beta-mediated induction of the 3TP-lux reporter gene, which contains a known TGF-beta-inducible plasminogen activator inhibitor promoter. These data suggest that: (a) TGF-beta-mediated induction of p21waf1 and subsequent growth inhibition require the expression of DPC4; (b) p21waf1 is a downstream target gene of DPC4; and (c) transfection of the DPC4 gene restores the TGF-beta-inducible gene expression. Inactivation of the tumor suppressor gene DPC4 and other components of the TGF-beta signal cascades may abolish one of the key negative controls of cell proliferation in pancreatic adenocarcinomas.

Adenocarcinoma↗
PubMed1997

Structure-based design of a general class of mechanism-based inhibitors of the serine proteinases employing a novel amino acid-derived heterocyclic scaffold.

We describe in this paper the structure-based design of a general class of heterocyclic mechanism-based inhibitors of the serine proteinases that embody in their structure a novel peptidomimetic scaffold (1,2,5-thiadiazolidin-3-one 1,1-dioxide). Sulfone derivatives of this class (I) were found to be time-dependent, potent, and highly efficient irreversible inhibitors of human leukocyte elastase, cathepsin G, and proteinase 3. The partition ratios for a select number of inhibitors were found to range between 0 and 1. We furthermore demonstrate that these inhibitors exhibit remarkable enzyme selectivity that is dictated by the nature of the P1 residue and is consistent with the known substrate specificity reported for these enzymes. Thus, inhibitors with small hydrophobic side chains were found to be effective inhibitors of elastase, those with aromatic side chains of cathepsin G, and those with a basic side chain of bovine trypsin. Taken together, the findings cited herein reveal the emergence of a general class of stable mechanism-based inhibitors of the serine proteinases which can be readily synthesized using amino acid precursors. Biochemical and high-field NMR studies show that the interaction of this class of inhibitors with a serine proteinase results in the formation of a stable acyl complex(es) and the release of benzenesulfinate, formaldehyde, and a low molecular weight heterocycle. The data are consistent with initial formation of a Michaelis-Menten complex, acylation of Ser195, and tandem loss of the leaving group. The initial HLE-inhibitor complex reacts with water generating formaldehyde and a stable HLE-inhibitor complex. Whether the initial HLE-inhibitor complex also reacts with His57 to form a third complex is not known at this point. The desirable salient parameters associated with this class of inhibitors, including the expeditious generation of structurally diverse libraries of inhibitors based on I, suggest that this class of mechanism-based inhibitors is of general applicability and can be used in the development of inhibitors of human and viral serine proteinases of clinical relevance.

Amino Acids↗
PubMed1996

Detection of brain activation signal from functional magnetic resonance imaging data.

An image-processing strategy for functional magnetic resonance imaging (fMRI) data sets consisting of sequential images of the same slice of brain tissue is considered. An algorithm of detection based on the likelihood-ratio test and the noise properties in fMRI is introduced. Since the data have a poor signal-to-noise ratio, and in order to make detection reliable, the algorithm is organized in two steps: (1) pixel detection, which detects all pixels having significant changes, thus building regions of interest (ROIs), and (2) region detection, which selects the most likely activated region from obtained ROIs. The detection method is applied to experimental fMRI data from the motor cortex and compared with the cross-correlation method and Student's t test commonly applied by others. The results obtained using the likelihood-ratio test show improvement in the detection of activated regions.

Algorithms↗