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S Meng

Publications and source records attributed to S Meng.

At least 19 recordsLinked to original sources
PubMed2005

Methods for isolating circulating epithelial cells and criteria for their classification as carcinoma cells.

Novel assay methods developed for the isolation and characterization of circulating tumor cells (CTC) of epithelial origin offer the potential of markers for the non-invasive gathering of clinical information relevant to the diagnosis, evolution and treatment of carcinoma. Of the numerous techniques currently used to analyze CTC, slide-based assays are perhaps the most common. While traditional combined immunocytochemical/brightfield microscopy systems continue to be the most frequently employed, fluorescence-based analysis is gaining in importance. This is partly because fluorescence microscopy analysis of slide-mounted CTC can provide simultaneously cytogenetic as well as morphologic and multiple phenotypic information. In particular, fluorescence microscopy analysis of slide-mounted CTC can accurately determine genetic changes at the chromosomal level in patients with recurrent disease. More importantly, by identifying genetic aberrations in CTC, it becomes possible to choose those patients most likely to benefit from a given treatment. The potential of this technique has already been demonstrated by employing fluorescence in situ hybridization (FISH) methods to measure expression of the HER2/neu gene in tissue from patients with breast carcinoma for the specific purpose of identifying those patients most likely to respond to Trastuzumab targeted therapy. Here, we review the major methodologies used in the preparation and analysis of the slide-based assays.

Carcinoma↗
PubMed2004

Cerebral blood flow response to a hypoxic-ischemic insult differs in neonatal and juvenile rats.

To compare the cerebral blood flow (CBF) response to a transient episode of hypoxia-ischemia producing damage in neonatal and juvenile rats. One- and four-week-old rats were subjected to unilateral carotid artery occlusion plus hypoxia (8% oxygen). Perfusion MR images were acquired either in sham controls or in hypoxic-ischemic rats before, during, 1 h and 24 h after hypoxia-ischemia. At 24 h post hypoxia-ischemia, T2 maps and histology were used to assess damage. In sham controls, CBF increased twofold between the age of one and four weeks. Reductions in CBF ipsilateral to the occlusion occurred during hypoxia-ischemia followed by a substantial recovery at 1 h post in both age groups. However, contralaterally, hyperemia occurred during hypoxia-ischemia in four-week but not one-week-old rats. Similarly, hyperemia occurred ipsilaterally at 24 h post hypoxia-ischemia in four-week but not one-week-olds, corresponding to the distribution of elevations in T2. Despite CBF differences, extensive cell death occurred ipsilaterally in both age groups. The CBF responses to hypoxia-ischemia and reperfusion differ depending on postnatal age, with hyperemia occurring in juvenile but not neonatal rats. The results suggest a greater CBF responsiveness and differential relationship between post-ischemic vascular perfusion and tissue injury in older compared with immature animals.

Aging↗
PubMed2003

[Morphology and functional anatomy of the growing thorax].

Morphogenesis of most thoracic organs and structures is not finished with birth but perpetuates in postnatal life. The postnatal growth is partly associated with enormous changes in structure, morphology, and function. Our study presents an overview of morphological, topological and functional peculiarities of thoracic anatomy during infancy, childhood and adolescence. It focuses on the development of the mammary gland, osseous structures of the chest wall, thymus, heart, and lungs. Most of the presented data are based on post-mortem studies. Measurements and numerical data are mainly included for illustration of growth-associated changes.

Adolescent↗
PubMed2003

Renal and vascular oxidative stress and salt-sensitivity of arterial pressure.

Oxidative stress occurs in a tissue or in the whole body when the total oxidant production exceeds the antioxidant capacity. Recent studies in human essential hypertension indicate that free radical production is increased and antioxidant levels are decreased, and more than one-half of these hypertensives have a salt-sensitive type of hypertension with progressive renal damage. Increased oxidative stress may also play a critical role in animal models of salt-sensitive hypertension. The stroke-prone spontaneously hypertensive rats (SHRSP) exhibits salt-sensitivity, vascular release of superoxide is increased, and total plasma antioxidant capacity is decreased. The superoxide release in the SHRSP rats inactivates nitric oxide, and superoxide dismutase (SOD) administration returns the bioactive nitric oxide levels to normal. The deoxycorticosterone acetate (DOCA)-salt hypertensive rat is salt-sensitive, aortic superoxide production is increased, and renal inflammation is significant. Treatment of the DOCA-salt rats with apocynin, an NADPH oxidase inhibitor, decreased aortic superoxide production and decreased arterial pressure. The Dahl salt-sensitive (S) rat has increased mesenteric microvascular and renal superoxide production and increased plasma levels of H2O2. The renal protein expression of SOD is decreased in the kidney of Dahl S rats, and long-term administration of Tempol, a superoxide mimetic, significantly decreased arterial pressure and renal damage. In conclusion, both human hypertension and experimental models of salt-sensitive hypertension have increased superoxide release, decreased antioxidant capacity and elevated renal damage.

Animals↗
PubMed2001

Role of abnormal nitric oxide systems in salt-sensitive hypertension.

A large percentage of human hypertensive patients are salt sensitive, referring to the dependence of hypertension on sodium intake, but the cause of the salt sensitivity is not known. Although several mechanisms may contribute to salt-sensitive hypertension, the nitric oxide (NO) system appears to play a major role. Studies in humans and Dahl salt-sensitive (S) rats indicate that NO production is decreased during hypertension. Intravenous L-arginine infusion in Dahl S rats increases NO production and prevents salt-sensitive hypertension. In the Dahl salt-resistant (R) rat, NO production by both inducible NO synthase (iNOS) and neuronal NOS (nNOS) help to prevent salt-sensitive hypertension. Experimental evidence is summarized, indicating that the Dahl S rat has a deficient production of NO by nNOS, although NO production by iNOS appears to moderately decrease salt sensitivity. Other evidence about the importance of NO in salt-sensitive hypertension is reviewed, including the role of the renal NO system.

Animals↗
PubMed2001

Transient vs. prolonged histone hyperacetylation: effects on colon cancer cell growth, differentiation, and apoptosis.

The role of histone hyperacetylation in regard to growth, differentiation, and apoptosis in colon cancer cells was assessed in an in vitro model system. HT-29 cells were grown in +/-10% fetal bovine serum with either 5 mM sodium butyrate or 0.3 microM trichostatin A [single dose (T) or 3 doses 8 h apart (TR)] for 24 h. Serum-starved HT-29 cells were further treated with epidermal growth factor or insulin-like growth factor I for an additional 24 h. Apoptosis was quantified with propidium iodide and characterized by electron microscopy. Northern blot analyses were performed with cDNA probes specific for intestinal alkaline phosphatase, Na-K-2Cl cotransporter, the cell cycle inhibitor p21, and the actin control. Flow cytometric analysis revealed a time-dependent growth suppression along with early induction of p21 mRNA in the butyrate, T, and TR groups. Histone hyperacetylation, assessed by acid-urea-triton gel electrophoresis, was transient in the T group but persisted for up to 24 h in the butyrate and TR groups. Induction of apoptosis, growth factor unresponsiveness, and differentiation occurred in the butyrate- and TR-treated cells but not those treated with a single dose of trichostatin A. Thus transient hyperacetylation of histones is sufficient to induce p21 expression and produce cellular growth arrest, but prolonged histone hyperacetylation is required for induction of the programs of differentiation, apoptosis, and growth factor unresponsiveness.

Acetylation↗
PubMed2001

American ginseng transcriptionally activates p21 mRNA in breast cancer cell lines.

American ginseng (AG) has been demonstrated to inhibit breast cancer cell growth in vitro. p21 protein, a universal cell cycle inhibitor, binds cyclin-CDK complexes, an important mechanism in cell cycle regulation. The purpose of this investigation was to determine if AG induces p21 gene expression in hormone sensitive (MCF-7) and insensitive (MDA-MB-231) breast cancer cell lines. Cells grown in steroid stripped medium (SSM) were treated with AG, 17-beta-estradiol (E2), genistein or cycloheximide (CHX). Northern blot analyses were performed using human p21Cip1 and 36B4 cDNA probes. Cell lines were transiently transfected with select mouse p21 CAT reporter constructs, including those lacking a p53 binding site. Cell cycle analyses was performed by FACScan. The results revealed that AG induced p21 mRNA expression in MCF-7 and MDA-MB-231 cells (p=0.0004; p < or =0.0001, respectively). Neither E2 nor genistein alter p21 mRNA expression. CHX, a protein synthesis inhibitor, did not block p21 mRNA expression induced by AG, indicating that p21 is induced as an immediate early gene. AG activated p21 reporter constructs in transfected cells, independent of p53 binding sites. The cell cycle proliferative phase was significantly decreased by AG and increased by E2 (p < or =0.0001). AG may inhibit breast cancer cell growth by transcriptional activation of the p21 gene, independent of p53.

Animals↗
PubMed2001

[Establishment of detection test for hepatitis C virus antigen].

OBJECTIVE: To establish the enzyme linking immunosorbent assay (ELISA) test with the specific monoclonal antibody (McAb) for detecting the hepatitis C virus (HCV) antigen so as to study the possibility of HCV antigen detection from plasma and serum samples. METHODS: Among the McAbs against HCV core and NS3 region, several kinds of combination models were analyzed to choose the optimal one. 348 samples from volunteer donors were tested by this test to calculate the cutoff value. 371 samples, among which 146 samples were positive to anti-HCV and 225 ones were negative to anti-HCV, were screened. The antigen positive samples were confirmed by HCV nested PCR. RESULTS: The model of detection test was constructed with the C39,C7-6 as capture McAb and C39,C7-57 as HRP Conjugated McAb. This test could detect the C7 antigen to 5 ng/ml, and its cutoff value was determined as the average value of negative control by adding 0.25. Eleven of 146 samples positive to anti-HCV and 16 of 225 ones negative to anti-HCV were positive to HCV antigen. Among these 27 antigen positive samples, there were 23 positive to HCV RNA by PCR detection. CONCLUSIONS: With this HCV antigen detection test, some of samples positive to HCV antigen can be found from plasma positive to and negative to anti-HCV and be confirmed by PCR. It is shown that it is possible to detect HCV antigen directly from plasma samples and it is important for HCV basic research and for control of transmission of HCV.

Antibodies, Monoclonal↗
PubMed2000

Management of tongue cancer in the patient who is systemically immunosuppressed: a preliminary report.

OBJECTIVE: Renal transplantation is being improved, and life expectancy for patients with transplanted kidneys is being prolonged, but the incidence of malignant tumors in other body organs or tissues is increasing progressively. We investigated effective clinical plans for treating lingual cancer in persons who are long-term renal transplant recipients. STUDY DESIGN: The group included 3 cases of lingual cancer after renal transplantation. All were men. The mean age was 47.5 years (range, 40 to 55). The lingual cancer occurred a mean of 9 years after renal transplantation. The lesions of two patients were in the left lingual margins; the other patient had multiple bilateral lesions. All diagnoses were confirmed microscopically to be squamous cell carcinomas stage I to II. RESULTS: The doses of immunosuppressive agents were decreased, and two patients accepted surgery, chemotherapy, and radiotherapy. The third patient died 1 year after the cancer was diagnosed because of metastases. The other 2 patients had regular follow-up for 2 to 3 years and did not have either local recurrence or metastasis. CONCLUSION: Patients who have lingual cancer develop after renal transplantation have received long-term immunosuppressive therapy. We suggest the following clinical protocol: (1) Besides regular evaluation after renal transplantation, physical examination and biopsy of suspicious oral lesions are necessary because of the possibility of postrenal malignancy. (2) Surgery, along with chemotherapy and radiotherapy, is the main treatment of lingual cancer after renal transplantation. (3) The lingual tumor should be comprehensively treated despite the poor immune state of the body, or tumor recurrence can accelerate and metastases can occur. (4) Treating cancer thoroughly and maintaining the function of the transplanted kidney can decrease the patient's immune status. We should continue to observe and to report the patients' protocol, even if the patients' clinical follow-up periods are limited.

Adult↗
PubMed2000

Mechanisms of salt-sensitive hypertension: role of inducible nitric oxide synthase.

The goal of this study was to determine the role of inducible nitric oxide synthase (iNOS) in the arterial pressure, renal hemodynamic, renal excretory, and hormonal changes that occur in Dahl/Rapp salt-resistant (R) and salt-sensitive (S) rats during changes in Na intake. Thirty-two R and S rats, equipped with indwelling arterial and venous catheters, were subjected to low (0.87 mmol/day) or high (20.6 mmol/day) Na intake, and selective iNOS inhibition was achieved with intravenous aminoguanidine (AG, 12.3 mg. kg(-1). h(-1)). After 5 days of AG, mean arterial pressure increased to 121 +/- 3% control in the R-high Na AG rats compared with 98 +/- 1% control (P < 0.05) in the R-high Na alone rats, and S-high Na rats increased their arterial pressure to 123 +/- 3% control compared with 110 +/- 2% control (P < 0.05) in S-high Na alone rats. AG caused no significant changes in renal hemodynamics, urinary Na or H(2)O excretion, plasma renin activity, or cerebellar Ca-dependent NOS activity. The data suggest that nitric oxide produced by iNOS normally helps to prevent salt-sensitive hypertension in the Dahl R rat and decreases salt sensitivity in the Dahl S rat.

Animals↗
PubMed1999

Intimal hyperplasia of the infant parasellar carotid artery: a potential developmental factor in atherosclerosis and SIDS.

Intimal cushions that project into the lumen of arteries are precursors of atherosclerotic plaque formation. The "carotid siphon, " although frequently affected by atherosclerosis, was never analyzed for the occurrence of neonatal intimal hyperplasia. This study provides a topographic and morphometric analysis of intimal cushions in the parasellar internal carotid artery (pICA) of the human infant. A total of 35 specimens were studied in detail, using both standard histological techniques and a new method of computer-aided 3D reconstruction. Intimal hyperplasia occurred at 3 characteristic locations of the pICA: (1) the convex side of the posterior knee (C5 cushion), (2) the bottom of the horizontal segment (C4 cushion), and (3) the concave side of the anterior knee (C3 cushion). The extension of the cushions and the degrees to which they occluded the vessel lumens were measured. The complex shape of the pICA required 3D computer models for exact topographical descriptions and precise measurements. Our results suggest that the occurrence and degree of intimal hyperplasia are related to shape changes of the pICA during postnatal development. We predict that individuals who retain the relatively straight course of the fetal pICA throughout their lives are less prone to develop atherosclerotic lesions at this portion of the carotid artery. A possible contribution of neonatal intimal cushions to the origin of sudden infant death syndrome is discussed.

Arteriosclerosis↗
PubMed1999

A novel Sp1-related cis element involved in intestinal alkaline phosphatase gene transcription.

We have used sodium butyrate-treated HT-29 cells as an in vitro model system to study the molecular mechanisms underlying intestinal alkaline phosphatase (IAP) gene activation. Transient transfection assays using human IAP-CAT reporter genes along with DNase I footprinting were used to localize a critical cis element (IF-III) corresponding to the sequence 5'-GACTGGGCGGGGTCAAGATGGA-3'. Deletion of the IF-III element resulted in a dramatic reduction in reporter gene activity, and IF-III was shown to function in the context of a heterologous (SV40) promoter in a cell type-specific manner, further supporting its functional role in IAP transactivation. Electrophoretic mobility shift assays revealed that IF-III binds Sp1 and Sp3, but these factors comprise only a portion of the total nuclear binding and appear to mediate only a small portion of its transcriptional activity. IF-III does not correspond to any previously characterized regulatory region from other intestine-specific genes. We have thus identified a novel, Sp1-related cis-regulatory element in the human IAP gene that appears to play a role in its transcriptional activation during differentiation in vitro.

Alkaline Phosphatase↗
PubMed1999

Role of neuronal nitric oxide synthase in Dahl salt-sensitive hypertension.

The goal of this study was to determine the role of neuronal nitric oxide synthase (nNOS) in the arterial pressure, renal hemodynamic, and renal excretory changes that occur in Dahl salt-resistant (DR) and salt-sensitive (DS) rats during changes in Na intake. Fifty-three DR and DS rats/Rapp strain of 7 to 8 weeks of age with indwelling arterial and venous catheters were subjected to low (0.87 mmol/d) or high (20.6 mmol/d) Na intake beginning 2 days before the start of the control period. Measurements were made during a 5-day control period followed by a 5-day period of nNOS inhibition with intravenous 7-nitroindazole (7NI, 1.67 mg. kg-1. h-1) or vehicle infusion. After 5 days of 7NI, mean arterial pressure increased to 120+/-6% control in the DR-high Na, 7NI rats compared with 98+/-1% control (P<0.05) in the DR-high Na alone rats. After 5 days of 7NI, DS-high Na rats, which had a control arterial pressure 31 mm Hg higher than the comparable DR rats, increased their arterial pressure to 114+/-3% control, which was not significantly different from the DS-high Na alone pressure of 110+/-2% control. No significant changes occurred in glomerular filtration rate, effective renal plasma flow, urinary Na excretion, or urine volume because of 7NI. However, plasma renin activity decreased significantly in DR and DS rats on low Na intake with 7NI infusion. The data demonstrate that the highly salt-resistant DR rat became salt-sensitive during nNOS inhibition with 7NI. However, the arterial pressure of the DS rat was not affected by 7NI. This suggests that nitric oxide produced by nNOS in the DR rat normally helps to prevent salt-sensitive hypertension and that low functional levels of nNOS in the DS rat may contribute to its salt-sensitivity.

Animals↗
PubMed1999

Short-chain fatty acids and thyroid hormone interact in regulating enterocyte gene transcription.

BACKGROUND: Enterocyte differentiation is known to be regulated by a variety of extracellular compounds, among which are triiodothyronine (T3) and the short-chain fatty acids (SCFAs). Because several SCFAs are known to induce histone hyperacetylation, and T3 action has been recently linked to chromatin structure, we sought to investigate the interplay between SCFAs and T3 in regard to the enterocyte differentiation marker, intestinal alkaline phosphatase (IAP). METHODS: Caco-2 cells were transiently transfected with a reporter construct containing 2.4 kb of the human IAP gene 5' flanking region (IAP2.4CAT). Cotransfections were carried out with and without thyroid hormone receptor-1 (TR beta-1) or histone deacetylase-1 (HDAC-1) expression plasmids. Cells were treated with 5 mmol/L SCFAs (propionic, butyric, valeric, or caproic acids as propionate, butyrate, valerate, or caproate, respectively), with and without 10 nmol/L T3. Reporter gene activity was measured and the level of histone acetylation assessed by means of acid-urea-triton (AUT) gel assays. RESULTS: TR beta-1 cotransfection caused a marked decrease in IAP reporter gene activity, which is consistent with the well-known phenomenon of ligand independent repression (LIR), whereas T3 treatment reversed the LIR and caused further reporter gene activation. Treatment with SCFAs similarly resulted in a complete blockage of LIR, and, in fact, turned the TR beta-1 into a transcriptional activator, even in the absence of T3. Concomitant treatment with T3 and butyric acid produced an additive effect on IAP transactivation. In contrast, cotransfection with HDAC-1 attenuated the effects of SCFAs on IAP gene activation. AUT gel studies demonstrated histone hyperacetylation in response to SCFA treatment. CONCLUSION: One or more DNA cis-elements in the human IAP gene mediate ligand independent repression by the TR beta-1, an effect that can be entirely reversed by those SCFAs that induce histone hyperacetylation. In addition T3 and SCFAs can act in concert to induce IAP gene transcription, demonstrating an important link between triiodothyronine and histone hyperacetylation in regard to enterocyte-specific gene expression.

Alkaline Phosphatase↗
PubMed1998

p21(WAF1) is required for butyrate-mediated growth inhibition of human colon cancer cells.

A diet high in fiber is associated with a decreased incidence and growth of colon cancers. Butyrate, a four-carbon short-chain fatty acid product of fiber fermentation within the colon, appears to mediate these salutary effects. We sought to determine the molecular mechanism by which butyrate mediates growth inhibition of colonic cancer cells and thereby to elucidate the molecular link between a high-fiber diet and the arrest of colon carcinogenesis. We show that concomitant with growth arrest, butyrate induces p21 mRNA expression in an immediate-early fashion, through transactivation of a promoter cis-element(s) located within 1.4 kb of the transcriptional start site, independent of p53 binding. Studies using the specific histone hyperacetylating agent, trichostatin A, and histone deacetylase 1 indicate that growth arrest and p21 induction occur through a mechanism involving histone hyperacetylation. We show the critical importance of p21 in butyrate-mediated growth arrest by first confirming that stable overexpression of the p21 gene is able to cause growth arrest in the human colon carcinoma cell line, HT-29. Furthermore, using p21-deleted HCT116 human colon carcinoma cells, we provide convincing evidence that p21 is required for growth arrest to occur in response to histone hyperacetylation, but not for serum starvation nor postconfluent growth. Thus, p21 appears to be a critical effector of butyrate-induced growth arrest in colonic cancer cells, and may be an important molecular link between a high-fiber diet and the prevention of colon carcinogenesis.

Butyrates↗
PubMed1998

Na-K-2Cl cotransporter gene expression and function during enterocyte differentiation. Modulation of Cl- secretory capacity by butyrate.

The basolateral Na-K-2Cl cotransporter (NKCC1) is a key component of the intestinal crypt cell secretory apparatus. Its fate during the transition to absorptive enterocyte and the potential impact of its altered expression on secretory output have not been addressed. In this report, NKCC1 mRNA was found to be expressed in rat jejunal crypt but not villus cells. Butyrate treatment of intestinal epithelial HT29 cells induced a differentiation pattern that recapitulated the rat intestinal crypt-villus axis, with NKCC1 mRNA levels decreasing in a time- and dose-dependent fashion in parallel with upregulation of apical brush-border markers. Butyrate but not acetate or proprionate decreased basal and cAMP-stimulated bumetanide-sensitive K+ (86Rb) uptake in both HT29 cells and the Cl--secreting T84 line. Butyrate markedly decreased transepithelial Cl- secretion in confluent T84 monolayers without effect on cAMP-regulated apical Cl- efflux. We conclude that NKCC1 regulation during enterocyte differentiation occurs at the level of gene expression, and that selective downregulation of NKCC1 gene expression and function by butyrate leads to a profound decrease in transepithelial Cl- secretion. These data emphasize the importance of NKCC1 in determining epithelial secretory capacity and suggest the possibility of modulation of the enterocytic transport phenotype as therapy for diarrheal disorders.

Animals↗
PubMed1998

A new episcopic method for rapid 3-D reconstruction: applications in anatomy and embryology.

The topographic relations of complex structures and the morphogenesis of organ systems can only be fully understood in their three-dimensional context. Three-dimensional (3-D) reconstruction of physically sectioned specimens has become an indispensable tool in modern anatomical and embryological research. Teaching also makes increasingly use of 3-D representations, in particular in the case of embryonic systems that undergo complicated transformations of form and shape. At present no cheap and simple technique is available that generates accurate 3-D models of sectioned objects. In this study we describe a novel technique that rapidly provides faithful 3-D models of sectioned specimens. The images are captured directly from the cutting surface of the embedding block after each sectioning and "on block" staining step. Automatic image processing generates a stack of binary images of the specimen contour. Binary images of internal structures are obtained both by automatic segmentation and manual tracing. Since these image series are inherently aligned, they can be reconstructed three-dimensionally without time-consuming alignment procedures. The quality and the flexibility of the method are demonstrated by reconstructing three kinds of specimens of different histological composition and staining contrast: a 4 mm mouse embryo together with several of its inner organs, a cavernous sinus region of a human infant, and a segment of a human carotid artery. Very short processing times and the faithful representation of complex structural arrangements recommend this technique for routine use in morphological research and for creating embryologic teaching models or 3-D embryonic staging series.

Anatomy, Cross-Sectional↗