Search PubMed⌕ Search

Biomedical subjects

Y Shen

Publications and source records attributed to Y Shen.

At least 325 records · Page 18Linked to original sources
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↗
PubMed1998

[A trial to reduce cardiac motion artifact on HR-CT images of the lung with the use of subsecond scan and special cine reconstruction algorithm].

We describe our trial to reduce cardiac motion artifacts on HR-CT images caused by cardiac pulsation by combining use of subsecond CT (scan time 0.8 s) and a special cine reconstruction algorithm (cine reconstruction algorithm with 180-degree helical interpolation). Eleven to 51 HR-CT images were reconstructed with the special cine reconstruction algorithm at the pitch of 0.1 (0.08 s) from the data obtained by two to six contagious rotation scans at the same level. Images with the fewest cardiac motion artifacts were selected for evaluation. These images were compared with those reconstructed with a conventional cine reconstruction algorithm and step-by-step scan. In spite of its increased radiation exposure, technical complexity and slight degradation of spatial resolution, our method was useful in reducing cardiac motion artifacts on HR-CT images in regions adjacent to the heart.

Algorithms↗
PubMed1998

[A trial to reduce cardiac motion artifacts on HR-CT images of lung with combined use of subsecond scan and a high temporal resolution reconstruction algorithm].

PURPOSE: To reduce cardiac motion artifacts with combined use of subsecond CT scanning and a high temporal resolution algorithm. SUBJECTS AND METHODS: Scan data were obtained with step-by-step scanning (scan time, 0.8 seconds). Two sets of images were reconstructed, with and without high temporal resolution reconstruction algorithm (HTRR), from the same set of scan data. HTRR, derived from modification of 180-degree linear helical interpolation, reduces full width at half maximum (FWHM) to half of the scan time. Motion artifacts of two sets of images were compared. RESULTS: The use of HTRR seemed to be useful in reducing cardiac motion artifacts owing to the improvement of effective time resolution. However, there were some images without significant reduction of cardiac motion artifacts. CONCLUSION: Our technique is useful in reducing cardiac motion artifacts without an increase in radiation exposure.

Algorithms↗
PubMed1998

[Reduction of helical artifact using SmartHelical algorithm].

Stair-step artifact is a serious problem in reconstructed images of multiplanar reformation (MPR), surface rendering and maximum-intensity projection (MIP). We developed a new algorithm, SmartHelical Algorithm (SHA), to reduce helical artifacts. SmartHelical Algorithm reduced helical artifacts significantly with slight worsening of longitudinal resolution. Noise was reduced and SNR was increased. SHA reduced stair-step artifact in reconstructed images of MPR, surface rendering and MIP, and improved image quality.

Adult↗
PubMed1997

Neuronal expression of mRNAs for complement proteins of the classical pathway in Alzheimer brain.

To determine possible sources of complement proteins in the brain, we investigated by in situ hybridization expression of the mRNAs of C1q, C2, C3, C4, C5, C6, C7, C8 and C9 in postmortem Alzheimer disease (AD) and control brain tissue. We found detectable hybridization for all these components in the temporal cortex and hippocampus, with significantly higher levels being found in AD tissue. Hybridization signals were strongest over pyramidal neurons. Low or absent hybridization was seen in the visual cortex or cerebellum. These results suggest that the activated complement components found in association with AD lesions may be, in part, derived from neurons.

Aged↗
PubMed1997

Essential role of the first intron in the transcription of hsp90beta gene.

The human HSP90 gene family contains introns. There are two typical heat shock elements (HSE) in the first intron of human hsp90beta gene. As detected by chloramphenicol acetyl transferase (CAT) reporter activity assays, the HSE-containing intron is essential in maintaining high constitutive expression and is critical for heat shock inducibility of the human hsp90beta gene. Cellular heat shock factor 1 (HSF 1) shows much higher binding affinity toward the intronic HSEs in comparison to an atypical HSE in the 5' flanking sequence. Novel initiation sites found in the first intron probably also contribute to constitutive and heat-inducible expression of the hsp90beta gene in Jurkat cells.

Chloramphenicol O-Acetyltransferase↗
PubMed1997

Gene identification and DNA sequence analysis in the GC-poor 20 megabase region of human chromosome 21.

In contrast to the distal half of the long arm of chromosome 21, the proximal half of approximately 20 megabases of DNA, including 21q11-21 bands, is low in GC content, CpG islands, and identified genes. Despite intensive searches, very few genes and cDNAs have been found in this region. Since the 21q11-21 region is associated with certain Down syndrome pathologies like mental retardation, the identification of relevant genes in this region is important. We used a different approach by constructing microdissection libraries specifically for this region and isolating unique sequence microclones for detailed molecular analysis. We found that this region is enriched with middle and low-copy repetitive sequences, and is also heavily methylated. By sequencing and homology analysis, we identified a significant number of genes/cDNAs, most of which appear to belong to gene families. In addition, we used unique sequence microclones in direct screening of cDNA libraries and isolated 12 cDNAs for this region. Thus, although the 21q11-21 region is gene poor, it is not completely devoid of genes/cDNAs. The presence of high proportions of middle and low-copy repetitive sequences in this region may have evolutionary significance in the genome organization and function of this region. Since 21q11-21 is heavily methylated, the expression of genes in this region may be regulated by a delicate balance of methylation and demethylation, and the presence of an additional copy of chromosome 21 may seriously disturb this balance and cause specific Down syndrome anomalies including mental retardation.

Chromosomes, Human, Pair 21↗
PubMed1997

Human cytomagalovirus IE1 and IE2 proteins are mutagenic and mediate "hit-and-run" oncogenic transformation in cooperation with the adenovirus E1A proteins.

Some epidemiological studies have suggested a possible link between human cytomegalovirus (HCMV) infection and various malignancies, and HCMV has been shown to transform cultured cells. However, viral DNA is not detected in most transformants, and the mechanism by which HCMV might contribute to oncogenesis has remained obscure. Here we show that the HCMV immediate early 1 and 2 genes can cooperate with the adenovirus E1A gene to generate transformed foci of primary baby rat kidney cells. HCMV gene expression is transient and viral DNA is not present in clonal cell lines derived from the transformed foci. We find that the HCMV immediate early proteins are mutagenic, and we propose that HCMV has the potential to contribute to oncogenesis through a "hit-and-run" mechanism, by inducing mutations in cellular genes.

Adenovirus E1A Proteins↗
PubMed1997

Estimating asymptomatic duration in cancer: the AIDS connection.

Many chronic diseases, including AIDS and cancer, do not manifest themselves clinically until some time after their inception. In studies of disease natural history, the duration of the asymptomatic period is of interest-in AIDS, to predict the epidemic's course, and in cancer, to develop efficient screening strategies. This article provides a bridge between the two fields with respect to estimation of the asymptomatic period. By adapting AIDS methodology to cancer, the article identifies a non-parametric method for estimating the duration of the asymptomatic period in cancer. The method is similar to one developed by Louis et al. (Mathematical Biosciences, 40, 111-144 (1978)), and is designed to apply to data from a cohort of individuals, screened periodically. After reviewing the similarities and differences between the AIDS and cancer contexts, we develop an EM algorithm that, at convergence, yields a maximum or saddle point of the likelihood. We investigate the performance of the algorithm by means of a simulation study, explore the effect of adding a smoothing step to the estimation procedure, and adapt the method for use with a data set in which disease prevalence is low. We apply the method to data from the HIP breast cancer screening trial.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Integrin-mediated activation of MAP kinase is independent of FAK: evidence for dual integrin signaling pathways in fibroblasts.

Integrin-mediated cell adhesion causes activation of MAP kinases and increased tyrosine phosphorylation of focal adhesion kinase (FAK). Autophosphorylation of FAK leads to the binding of SH2-domain proteins including Src-family kinases and the Grb2-Sos complex. Since Grb2-Sos is a key regulator of the Ras signal transduction pathway, one plausible hypothesis has been that integrin-mediated tyrosine phosphorylation of FAK leads to activation of the Ras cascade and ultimately to mitogen activated protein (MAP) kinase activation. Thus, in this scenario FAK would serve as an upstream regulator of MAP kinase activity. However, in this report we present several lines of evidence showing that integrin-mediated MAP kinase activity in fibroblasts is independent of FAK. First, a beta1 integrin subunit deletion mutant affecting the putative FAK binding site supports activation of MAP kinase in adhering fibroblasts but not tyrosine phosphorylation of FAK. Second, fibroblast adhesion to bacterially expressed fragments of fibronectin demonstrates that robust activation of MAP kinase can precede tyrosine phosphorylation of FAK. Finally, we have used FRNK, the noncatalytic COOH-terminal domain of FAK, as a dominant negative inhibitor of FAK autophosphorylation and of tyrosine phosphorylation of focal contacts. Using retroviral infection, we demonstrate that levels of FRNK expression sufficient to completely block FAK tyrosine phosphorylation were without effect on integrin-mediated activation of MAP kinase. These results strongly suggest that integrin-mediated activation of MAP kinase is independent of FAK and indicate the probable existence of at least two distinct integrin signaling pathways in fibroblasts.

3T3 Cells↗
PubMed1997

Inhibition of p75 tumor necrosis factor receptor by antisense oligonucleotides increases hypoxic injury and beta-amyloid toxicity in human neuronal cell line.

Recent evidence indicates that tumor necrosis factor-alpha (TNF-alpha) is up-regulated following brain injury and in neurodegenerative disorders such as stroke, multiple sclerosis, Parkinson's disease, and Alzheimer's disease. TNF-alpha elicits its biological effects through two distinct TNF receptor (TNFR) subtypes: p55 TNFR (TNFR1) and p75 TNFR (TNFR2). Studies have demonstrated that the p55 TNFR contributes to cell death, whereas the role of the p75 TNFR in neuronal viability is unclear. To better understand the role of p75 TNFR, we treated human neuronal SH-SY5Y cells with phosphorothioate-modified antisense oligonucleotides (ASO) for p75 TNFR and established that ASO inhibited p75 TNFR expression. Treatment of SH-SY5Y cells with ASO alone did not affect cell viability, whereas treatment with both ASO and human TNF-alpha significantly increased cell death relative to treatment with TNF-alpha alone. Moreover, addition of ASO significantly increased the level of cell injury observed following hypoxic conditions or exposure of beta-amyloid peptide. These results indicate that inhibition of p75 TNFR using ASO increases the vulnerability of neurotypic cells to insults and suggest that the p75 TNFR may not be required for normal neuronal cell viability but rather plays a protective role following injury.

Amyloid beta-Peptides↗
PubMed1997

Modified Sihler's technique for studying the distribution of intramuscular nerve branches in mammalian skeletal muscle.

BACKGROUND: A largely forgotten technique initially designed by Sihler for staining nerve tissue has not been fully explored for staining intramuscular nerve branches in skeletal muscles. METHODS: Fresh, long heads of triceps from locally bred New Zealand white rabbits were used for this study. Immediately after their removal, the muscles with their motor nerve branches from the radial nerve were fixed in 10% unneutralized formalin, followed by maceration and depigmentation in 3% aqueous potassium hydroxide, decalcification in Sihler's solution I, micro-dissection, staining in Sihler's solution II, destaining in Sihler's solution I, neutralization in 0.05% lithium carbonate, and clearance in increasing concentrations of glycerin. RESULTS: A clear three-dimensional orientation of the distribution of the intramuscular nerve branches within the muscle belly was visualized. It was found in all specimens that the long head of triceps in the rabbit was constantly innervated by three main intramuscular nerve branches and each of them supplied different amounts of muscle fibers with some variation. CONCLUSION: The Sihler's neural staining technique can be applied to the study of the distribution of intramuscular nerve branches in limb skeletal muscles. Extension of the technique may be utilised in the identification of neuromuscular compartments in skeletal muscles. Such information may be usefully applied in free muscle transfer of segments of skeletal muscle.

Animals↗
PubMed1997

Intracoronary stent implantation using a single high-pressure perfusion balloon catheter.

Currently, the recommended strategy for Palmaz-Schatz intracoronary stent implantation is to use two balloons: an undersized balloon for predilation to facilitate a channel for the stent and a high pressure balloon for postdilation to obtain good apposition of the struts into the vessel wall. We reported our experience using the perfusion balloon as the initial balloon to dilate intracoronary lesions and demonstrated a reduction in the total number of balloons used per angioplasty procedure. The objective of this study was to examine whether a single balloon could effectively be used for stent implantation. The study population included 95 patients who underwent elective intracoronary stent placement to 100 lesions using 110 Palmaz-Schatz stents by nine individual operators. Lesions were predilated with an ACS RX LIFESTREAM balloon at a low pressure of 4-6 atm (mean 5.7 +/- 2.6). After stent deployment, the same balloon was used at a high pressure (mean 16.2 +/- 1.2). Mean balloon size, which was chosen as the stent size, was 3.4 +/- 0.4 mm. Comparison of this strategy with the recommended strategy of 68 consecutive elective stent deployments at a single center during the same time was performed. Stent implantation using a single balloon strategy was angiographically successful in 99 of 100 (99.0%) lesions. The single balloon strategy was associated with a balloon burst rate of 9.1%. The number of balloons used per stent deployment was 1.2 vs. 2.4 using the recommended strategy (P < 0.0001). There was no evidence of stent thrombosis, any MI, or target lesion revascularization during the procedure and hospitalization. One in-hospital death as a result of nonhemorrhagic stroke was documented in the treated group. We concluded that using a single high pressure perfusion balloon for pre and postdilation in patients undergoing elective stent placement is safe and reduces the number of balloons used per procedure.

Aged↗
PubMed1997

Analysis of domains affecting intracellular localization of the FMRP protein.

Fragile X syndrome is the most frequent form of inherited mental retardation and it is caused by deficiency of FMRP, the protein encoded by the FMR1 gene. FMRP is a RNA binding protein of unknown function which is associated with ribosomes. FMRP is found in the cytoplasm, but it is endowed with a nuclear export signal (NES), encoded by exon 14, and a nuclear localization signal (NLS). Characterization of the FMRP NES and NLS domains is presented here. We show by site-directed mutagenesis that three leucine residues in exon 14 are functionally important for the cytoplasmic localization of FMRP. Changing these leucines to serine resulted in a nuclear localization, while another nonconservative change (leucine to tyrosine) did not show such an effect. We also show that the NLS activity is localized between residues 115 and 150, a region that lacks stretches of basic residues. Such stretches are typical of nuclear localization signals that act through the important alpha pathway. The region between residues 151 and 196 can reinforce the NLS activity. A truncated construct containing the N-terminal region of FMRP (residues 1-114) is strikingly concentrated in the nucleus. This suggests that it may contain a domain of strong affinity with a nuclear component.

Cell Nucleus↗
PubMed1997

Prospective study of early detection for primary liver cancer.

PURPOSE: To determine whether repeated screening can lead to early detection of primary liver cancer (PLC) and in turn to an improved clinical result. METHODS: In this randomized controlled study, Shanghai urban residents aged 35-55 years and with serum evidence of HBV infection or chronic liver disease were eligible for recruitment. Using cluster sampling, these subjects were allocated into two groups-the screening group and the control group: there were 8109 subjects in the screening group and 9711 in the control group. Subjects in the screening group were tested with serum AFP and real-time ultrasound every 6 months. One to four rounds of screening were completed. Liver cancer was treated according to stage at diagnosis. RESULTS: All subjects enrolled were followed up and classed at the end-point as alive without liver cancer, alive with liver cancer, dead from liver cancer, or dead from another cause. The mean follow-up was 1.2 years; total follow-up was 12,038 person-years in the screening group and 9,573 person-years in the control group. We detected 38 patients with PLC in the screening group and 18 patients with PLC in the control group. In the patients in the screening group 76.8% of patients were at a subclinical stage, and 70.6% of them underwent resection, the 1- and 2-year survival rates being 88.1% and 77.5%, respectively. However, in the control group, none of the patients was at a subclinical stage when diagnosed, none of them underwent resection, and none of them survived over 1 year. The lead time was estimated at 0.45 years. The cost of detecting PLC at an early stage was RMB 12,600 (US$1,500). CONCLUSION: The study proved that screening the high-risk population for PLC with a serum AFP test and real-time ultrasound examination can detect patients in the early stages, increase the resection rate and prolong the survival time. It is therefore recommended that screening for PLC be advocated in any high-risk area.

Adult↗
PubMed1997

Babesiasis in Nanjing area, China.

This article discusses the tick-borne babesiases which harm dairy cattle, buffaloes and dogs. In addition, the pathogen, vector, seasonal occurrence, hosts, symptoms, pathological changes and treatment are summarized and analysed. The pathogens in this area were identified as Babesia bigemina, B. bovis and B. gibsoni; the vectors as Boophilus microplus, Rhipicephalus haemaphysaloides, Haemaphysalis longicornis. Affected buffaloes were found from April to September, peak numbers occurred between May and July. Affected dairy cattle were most numerous in July and August. Hunting dogs were the most affected dogs. Infected dogs were found from February until the beginning of December; peak numbers occurred from September to November. Affected animals were acute cases. Symptoms and pathological changes were obvious, but jaundice was rare in dogs. Acaprin, acriflavine, imidocarb and berenil were used early and late. Their effect was ideal but resistance has developed to these drugs.

Acriflavine↗
PubMed1997

Assignment of three human markers in chromosome 21q11 to mouse chromosome 16.

Three unique sequence microclones from human chromosome region 21q11 were assigned to mouse chromosome 16 using a mouse/Chinese hamster cell hybrid 96Az2 containing a single mouse chromosome 16. This comparative mapping provides further homology between human chromosome 21 and mouse chromosome 16 to include the very proximal portion of the long arm of human chromosome 21. Since this part of human chromosome 21 is associated with mental retardation in Down syndrome individuals, its homologous mouse region should also be included in the construction of mouse models for studying Down syndrome phenotypes including mental retardation.

Animals↗