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Biomedical subjects

S Y Chen

Publications and source records attributed to S Y Chen.

At least 73 records · Page 4Linked to original sources

Pemphigus vulgaris: clinicopathologic review of 33 cases in the oral cavity.

A retrospective study was conducted on all cases of pemphigus vulgaris occurring on oral mucosal surfaces in the files of the Oral Pathology Laboratory at Temple University from 1974 to 1996. A total of 35 biopsies from 33 patients were reviewed, 25 female and eight male. Patient ages ranged from 27 to 79 years; the mean age was 56.5. The most common clinical complaint was of painful ulcers that failed to resolve within several weeks. Thirty patients had no known history of pemphigus, while in three patients a history of pemphigus was known. The most common clinical impression was that of mucous membrane pemphigoid, but the differential diagnosis included other vesiculoerosive conditions.

Adult↗

[Influences of melatonin on the growth of HELA cells].

AIM: To investigate the influence of melatonin (MT) on growth of HeLa cells in vitro. METHODS: The antiproliferation activities of MT were evaluated on HeLa cells by means of trypan blue dye exclusion and MTT vital staining. The morphological changes of MT on HeLa cells were observed under transmission electron microscope. Cell division cycle influenced by MT was assessed by a flow cytometer. RESULTS: MT produced a certain inhibition on HeLa cells at the concentration of 2 mmol.L-1 and prolonged the time of double amount (TD). The fraction of cells inhibited was 61.0%. The IC50 of HeLa cells exposed to MT for 96 h was 2.039 mmol.L-1. The flow cytometric analyses showed that exposure to MT for 72 h reduced the number of HeLa cells in phase S. Under electronic microscope, the HeLa cells exposed to MT for 72 h displayed morphological changes of necrosis, apoptosis, more heterochromosome and less somatic chromosome. CONCLUSION: MT showed certain influence on HeLa cells. Its mechanism may probably be attributable to reduction of the number of cells in phase S.

Antineoplastic Agents↗

Induction of vigorous helper and cytotoxic T cell as well as B cell responses by dendritic cells expressing a modified antigen targeting receptor-mediated internalization pathway.

Efficient Ag presentation is essential to induce effective cellular and humoral immune responses. Thus, one central goal of current immunotherapy and vaccine development is to enhance Ag presentation to induce potent and broad immune responses. Here, a novel Ag presentation strategy is developed by transducing dendritic cells (DCs) to produce an Ag for presentation as an exogenous Ag to efficiently induce both humoral and cellular immunity. The principle of this strategy is illustrated by genetically modifying DCs to secrete a model hepatitis B virus Ag fused with a cell-binding domain and to process the fusion Ag as an exogenous Ag after receptor-mediated internalization for MHC class I and II presentation. Vigorous Ag-specific CD4(+) helper and CD8(+) cytotoxic T cell, as well as B cell, responses were induced by the transduced DCs in mouse models. Thus, this novel strategy uses a receptor-mediated internalization process to efficiently induce all arms of the adaptive immunity and may provide a powerful means to develop potent vaccines and immunotherapies.

Animals↗

Vasorelaxant effect of harman.

The in vivo cardiovascular effect and in vitro vasorelaxant effect of harman, one of harmala alkaloids isolated from Peganum harmala, were examined in this study. Harman (1-10 mg/kg, i.v.) dose-dependently produced transient hypotension and long-lasting bradycardia in pentobarbital-anesthetized rats, which were attenuated by N(G)-nitro-L-arginine pretreatment. In isolated rat endothelium-intact thoracic aortic rings, harman concentration dependently relaxed phenylepherine-induced contractions with an IC(50) value around 9 microM. This vasorelaxant effect was attenuated by endothelium removal or N(omega)-nitro-L-arginine methyl ester pretreatment, but not by tetraethylammonium or indomethacin pretreatment. In cultured rat aortic endothelial cells, harman (1-100 microM) concentration dependently increased nitric oxide (NO) release, which was dependent on the presence of external Ca(2+). Harman pretreatment (3-30 microM) also concentration dependently inhibited the contractions induced by phenylephrine, 5-hydroxytryptamine (5-HT), and KCl in endothelium-denuded aortic rings in a non-competitive manner. In addition, harman pretreatment reduced both phasic and tonic phases of phenylephrine-induced contractions. Receptor binding assays further indicated that harman (K(i) values around 5-141 microM) interacted with the cardiac alpha(1)-adrenoceptors, brain 5-HT(2) receptors, and cardiac 1, 4-dihydropyridine binding site of L-type Ca(2+) channels. Therefore, the present results suggested that the vasorelaxant effect of harman was attributed to its actions on the endothelial cells to release NO and on the vascular smooth muscles to inhibit the contractions induced by the activation of receptor-linked and voltage-dependent Ca(2+) channels. The vasorelaxant effect may be involved in the hypotensive effect of harman.

Animals↗

Retroviral immunotoxin gene therapy of acute myelogenous leukemia in mice using cytotoxic T cells transduced with an interleukin 4/diphtheria toxin gene.

The potential benefit of immunotoxin (IT) for cancer therapy has mostly been limited by the fact that only a small portion of injected dose ever reaches the cancer target. Thus, we set out to determine whether antigen-specific CTLs would be suitable vehicles to deliver IT to the site of cancer cells in vivo. A retroviral vector was constructed for gene therapy with (interleukin 4) IL-4 positioned downstream of its 20-amino-acid leader sequence that permitted cotranslational protein synthesis of IT along with truncated diphtheria toxin (DT). IL-4 was chosen as a ligand based on the expression of IL-4 receptor (IL-4R) on most acute myeloid leukemia cases. The first-time expression and secretion of a cytokine/DT fusion toxin was accomplished in mammalian NIH.3T3 cells, and then a retroviral vector was assembled. The retroviral IT was used to transiently transduce T15, a CD8+ CTL T cell line that specifically recognized C1498 (a lethal murine acute myeloid leukemia cell line). Transduced T15 T cells expressed intracellular DT and IL-4 as determined by immunofluorescence. Secreted IT supernatants collected from T15 had enzymatic activity and killed IL-4R+ C1498 cells, but not IL-4R- EL4 cells. Intravenous injection of transduced T15, but not nontransduced T15, into mice with s.c. tumors significantly inhibited tumor growth. In contrast, systemic therapy with a bacterial preparation of the same IL-4 IT given at its maximum tolerated dose did not protect. Retroviral IT-treated mice showed no sign of the renal or hepatic toxicity that is common to this class of IT. Together, these data indicate that retroviral IT may solve problems relating to systemic IT therapy by delivering reagent more directly to the site of cancer in vivo and may impart new anticancer defense mechanisms to antigen-specific T cells.

3T3 Cells↗

Intrakines--evidence for a trans-cellular mechanism of action.

Human CXCR4 is the receptor for the CXC chemokine SDF-1alpha and also acts as a coreceptor for T lymphotropic HIV-1 strains. Blocking the surface expression of this receptor via an intrakine approach has recently been shown to efficiently prevent HIV-1 infection of T cells. The CXC-chemokine gene is fused to an endoplasmic reticulum retention signal (KDEL) that retains the newly synthesized chemokine and its receptor within the cell, where both are subsequently degraded. We constructed MoMuLV-based vectors containing the SDF-KDEL construct driven by the "MND" long terminal repeat, using eGFP as a marker gene (MND-SDF-KDEL-IRES-eGFP) and a control vector (MND-X-IRES-eGFP). CEM human T lymphoblastic leukemia cells were transduced with the intrakine vector or the control vector. We detected a marked downregulation of CXCR4 expression in the cells transduced with the intrakine vectors as opposed to the cells transduced with the control vector. However, the eGFP-negative fraction of the cells transduced with the intrakine vector displayed the same CXCR4 downregulation as the eGFP-positive fraction, suggesting an effect in trans. The possibility of this being due to eGFP being silenced while SDF-KDEL was still expressed was excluded by Southern and Northern blot analyses. Upon cultivating the control cells with supernatant of the cells transduced with the intrakine vector, we observed a downregulation of CXCR4 expression on the control cells. Experiments using rhSDF-1alpha showed downregulation by the supernatant to be comparable to that achieved by the exogenous addition of 30 ng/ml SDF-1alpha. To assess the bioactivity of the secreted substance in the supernatant, a chemotaxis assay was performed. The transmigration observed was, once again, within the range of that achieved by the addition of 30 ng/ml SDF-1alpha. We conclude that the intrakine SDF-KDEL, apart from acting within the cell, is also in part secreted and causes the downregulation of the receptor by acting like a secreted chemokine.

Blotting, Northern↗

Transduction of human PBMC-derived dendritic cells and macrophages by an HIV-1-based lentiviral vector system.

Professional antigen-presenting cells, such as dendritic cells (DCs) and macrophages, are target cells for gene therapy of infectious disease and cancer. However, transduction of DCs and macrophages has proved difficult by most currently available gene transfer methods. Several recent studies have shown that lentiviral vector systems can efficiently transduce many nondividing and differentiated cell types. In this study, we examined the gene transfer to DCs and macrophages using a lentiviral vector system. Human DCs were propagated from the adherent fraction of peripheral blood mononuclear cells (PBMCs) by culture in medium containing GM-CSF, IL-4, and TNF-alpha. Human macrophages were propagated from adherent PBMCs in medium containing GM-CSF. High titers of a replication-defective vesicular stomatitis virus glycoprotein G pseudotyped HIV-1-based vector encoding the enhanced yellow fluorescent protein were produced. In immature DCs (culture days 3 and 5), transduction efficiencies of 25 to 35% were achieved at a multiplicity of infection of 100. However, the transduction efficiency was decreased in more mature DCs (culture day 8 or later). Furthermore, monocyte-derived macrophages were also transduced by the lentiviral vector system. In addition, Alu-LTR PCR demonstrated the integration of the HIV-1 provirus into the cellular genome of the transduced DCs and macrophages. Allogeneic mixed lymphocyte reactions revealed similar antigen-presenting functions of untransduced and lentivirally transduced DCs. Thus, the results of this study demonstrate that both PBMC-derived DCs and macrophages can be transduced by lentiviral vectors.

Alu Elements↗

Tai Chi Chuan to improve muscular strength and endurance in elderly individuals: a pilot study.

OBJECTIVE: To evaluate the training effect of a Tai Chi Chuan (TCC) program on knee extensor muscular strength and endurance in elderly individuals. DESIGN: Before-after trial. SETTING: Community setting. PARTICIPANTS: Forty-one community dwelling subjects aged 61.1 +/- 9.8 years undertook a TCC program. Nine dropped out during the study. Pretraining and posttraining measurements were obtained from 15 men and 17 women. INTERVENTION: Subjects participated in a 6-month TCC program. Each session consisted of 20 minutes of warm-up, 24 minutes of structured TCC training, and 10 minutes of cool-down exercises. MAIN OUTCOME MEASURES: Peak torque of dominant and nondominant knee extensors was tested at speeds of 60 degrees , 180 degrees , and 240 degrees/sec concentrically and eccentrically. Muscular endurance of the knee extensor was tested at the speed of 180 degrees /sec. RESULTS: In the group of men, concentric knee extensor peak torque increased by 15.1% to 20.0% and eccentric peak torque increased by 15.1% to 23.7%. The group of women also showed increases, ranging from 13.5% to 21.8% in concentric peak torque, and 18.3% to 23.8% in eccentric peak torque. In addition, the knee extensor endurance ratio increased by 9.6% to 18.8% in the men and 10.1% to 14.6% in the women. CONCLUSION: TCC training may enhance muscular strength and endurance of knee extensors in elderly individuals.

Aged↗

Differential sensitivity of mouse neural crest cells to ethanol-induced toxicity.

Neural crest cells (NCCs) have been identified as an important target population relative to ethanol-induced teratogenicity in both mouse and avian models. Additionally, whole embryo culture mouse models have shown strain-related differences in sensitivity to ethanol-induced damage following acute exposure during early NCC development. That differential sensitivity of NCCs may contribute to these strain differences has been unexplored. For this purpose, cultured NCCs from an inbred mouse strain (C57BL/6J; C57) that is more sensitive to ethanol-induced teratogenicity than an outbred strain (ICR) were compared. This study showed that the incidence of cell death was significantly higher for the C57 NCCs than those from the ICR strain at all ethanol concentrations tested, and as early as 12 hours after initial exposure to 100 mM ethanol. The lateral mobility of the membrane lipids was faster and the membrane GM1 content was lower in C57 cells than ICR cells both under control conditions and at all doses and times tested. Ethanol exposure resulted in significant increases in the membrane lipid lateral mobility, and decreases in the membrane GM1 content that occurred in a dose and time-dependent manner in the NCCs from both strains. A significant correlation was found between the GM1 content and lateral mobility of the membrane lipids, the lateral mobility of membrane lipids and cell viability, as well as the GM1 content and cell viability in the NCCs from both strains. These results suggest that different strain sensitivities to ethanol-induced teratogencity may lie, at least in part, in the interstrain differential response of the NCC population and that the vulnerability of the NCCs to ethanol-induced death may be related to their endogenous membrane GM1 content.

Animals↗

3D coronary reconstruction from routine single-plane coronary angiograms: clinical validation and quantitative analysis of the right coronary artery in 100 patients.

BACKGROUND: Current coronary angiographic techniques display complex three-dimensional (3D) coronary structures in two dimensions (2D). We have developed a 3D reconstruction (3DR) algorithm using standard single-plane angiographic images that allows for 3D display of coronary structures. The purpose of this study was to validate our 3DR algorithm and quantify anatomic characteristics of the right coronary artery (RCA) in vivo. METHODS: Accuracy and reproducibility studies were performed using 3DRs of a coronary phantom and in vivo following 3DRs in 40 patients. The anatomic features of the RCA were then quantified in 100 patients. RESULTS: Comparison of length and bifurcation angles (BA) from the phantom to the 3DRs revealed good accuracy and correlation for both (r = 0.95 and 0.93 respectively), with diameter error of < 7%. In vivo, the average root mean square (RMS) error in the spatial coordinates of the vessel centerlines was 3.12 +/- 0.77 and 3.16 +/- 0.75 mm in 20 left coronary arteries (LCA) and 20 RCAs respectively. Interobserver average RMS error was 3.47 +/- 1.96 mm and intraobserver average RMS error was 3.02 +/- 1.07 and 3.44 +/- 1.57 mm for two different operators (p = NS). The average RCA length was 10.2 +/- 1.7 cm, average radius of curvature (ROC) was 52 +/- 9 degrees, and the average 3D bifurcation angle of the posterior descending artery (PDA) from the RCA was 55 +/- 22 degrees. Foreshortening (FS) of the segments of the RCA in three 'standard' projections ranged from 0-60, 0-75, and 0-82% respectively. CONCLUSIONS: Using our 3DR algorithm patient-specific anatomic characteristics can be accurately displayed and quantified, expanding the information that can be derived from routine coronary angiography.

Algorithms↗

Role of SGK in mineralocorticoid-regulated sodium transport.

Mineralocorticoids stimulate electrogenic Na+ transport in tight epithelia by altering the transcription of specific genes. Although the earliest mineralocorticoid effect is to increase the activity of the epithelial sodium channel (ENaC), ENaC mRNA and protein levels do not change. Instead, physiologic observations suggest that a mineralocorticoid target gene(s) encodes an ENaC regulator(s). To begin to identify and characterize mineralocorticoid-regulated target genes, we used suppression-subtractive hybridization to generate a cDNA library from A6 cells, a stable cell line of Xenopus laevis of distal nephron origin. A serine-threonine kinase, SGK, was identified from this screen. Sequence comparison revealed that frog, rat, and human SGK are 92% identical and 96% similar at the amino acid level. SGK mRNA was confirmed by Northern blot to be strongly and rapidly corticosteroid stimulated in A6 cells. In situ hybridization revealed that SGK was strongly stimulated by aldosterone in rat collecting duct but not proximal tubule cells. Low levels of SGK were present in rat glomeruli, but SGK was unregulated in this structure. Finally, SGK stimulated ENaC activity approximately sevenfold when coexpressed in Xenopus laevis oocytes. These data suggest that SGK is an important mediator of aldosterone effects on Na+ transport in tight epithelia. In view of the existence of SGK homologues in invertebrates, it is interesting to speculate that SGK is an ancient kinase that was adapted to the control of epithelial Na+ transport by early vertebrates as they made the transition from a marine to a freshwater environment.

Amino Acid Sequence↗

The relation of serum leptin to body mass index and to serum cortisol in men with spinal cord injury.

OBJECTIVE: To investigate the relations among serum leptin, body mass index (BMI), and various hormone levels in men with spinal cord injury (SCI). DESIGN: Cross-sectional. SETTING: University hospital that is a tertiary referral center. PARTICIPANTS: Forty-seven men with traumatic neurologically complete SCI and 47 age- and BMI-matched male controls. MAIN OUTCOME MEASURES: Baseline levels of various hormones were measured in subjects with SCI. Serum leptin and cortisol levels and BMI were measured in both groups. RESULTS: Serum leptin was significantly higher in the group with SCI than in the control group. A linear relation was found between serum leptin and BMI in both groups separately. A polynomial relation was found between serum leptin level and BMI in the group with SCI. A "J" phenomenon is noted at the lowest BMI. Serum cortisol correlated significantly with serum leptin level in the group with SCI. CONCLUSION: Sympathetic denervation, peripheral nerve palsy, recurrent infections, and possible central neurotransmitter alterations after SCI may contribute to the elevation of serum leptin level in men with SCI.

Adult↗

Segmental odontomaxillary dysplasia: a case report and review of the literature.

Segmental odontomaxillary dysplasia (SOD) is a rare, unilateral developmental disorder of the maxilla involving abnormal growth and maturation of the bone, lack of one or both premolars, altered primary molar structure, delayed tooth eruption, and fibrous hyperplasia of the gingiva. In this, the twenty-third reported case of SOD, the literature is reviewed, and the clinical, radiographic, and histopathologic data are described. Computed tomographic scans of this case showed that the involved segment of the maxilla extends mesiodistally from the permanent cuspid to the mesial portion of the first permanent molar, largely limited to the area of the missing premolars. However, the affected bone extends superiorly in the lateral wall of the maxilla to the zygoma and base of the orbit. This article is intended to serve as baseline data for a future article, describing the natural history and possible treatment of SOD, which remain undocumented.

Child↗

Describing shape changes in the human mandible using elliptical Fourier functions.

Elliptical Fourier functions (EFF) were generated for the boundary outline of the mandibular form in 24 non-orthodontic growth study subjects at 9, 11, 13, and 15 years of age. The mean residual fit (observed versus predicted points) of the mandibular form was 0.11 mm, with a range from 0.09 to 0.14 mm, suggesting an accurate fit. The mean plot for each of the four age groups was area standardized and superimposed on the centroid. Shape changes in males and females were found to be similar. No significant shape changes were found between 9 and 11 years. Shape changes were observed in the lower incisor area, the mental region, the body of the mandible, and the gonial angle area between 11 and 15 years. These changes coincided with the onset of the pubertal growth spurt.

Adolescent↗

Upregulation of tyrosine kinase TKT by the Epstein-Barr virus transactivator Zta.

The Zta protein is a key transactivator involved in initiating the Epstein-Barr virus (EBV) lytic cascade. In addition to transactivating many viral genes, Zta has the capacity to influence host cellular signals by binding to promoter regions or by interacting with several important cellular factors. Based on the observation that tyrosine kinases play central roles in determining the fate of cells, a kinase display assay was used to investigate whether cells expressing Zta have an altered pattern of kinase expression. The assay revealed that TRK-related tyrosine kinase (TKT) is expressed at significant levels in Zta transfectants but not in control cells. Additional evidence was obtained from Northern and Western blotting. Importantly, the upregulation of phosphorylated TKT and TKT downstream effector matrix metalloproteinase 1 in Zta transfectants hinted that TKT might initiate a signaling cascade in Zta-expressing cells. In addition, deletion analysis of the Zta protein revealed that the transactivation and dimerization domains were both essential for the upregulation of TKT transcription. Moreover, correlation of expression levels of Zta and TKT transcripts in nasopharyngeal carcinoma biopsy specimens was clearly demonstrated by quantitative PCR (Q-PCR), which provides the first evidence for an effect of Zta on cellular gene expression in vivo. These findings offer insight into the virus-cell interactions and may help us elucidate the role of EBV in tumorigenesis.

Cell Line, Transformed↗

Identification and chromosomal localization of a transcriptionally active retrotransposon of Ty3-gypsy type in rice.

A DNA fragment representing a transcriptionally active retrotransposon of Ty3-gypsy type was isolated and characterized from rice (Oryza sativa L.). The fragment (named RIRE9) includes the coding sequences for the C-terminal part of the RNase H domain and the N-terminal part of the integrase domain in the polyprotein region. Northern blot hybridization indicated that this element was expressed in rice leaves and stems, suggesting that it is potentially active to transpose under normal growth conditions. Using dot-blot hybridization, the copy number of RIRE9 was estimated to be about 1600 copies per haploid rice genome. Five homologous copies of RIRE9 were assigned to five distinct positions of four chromosomes by restriction fragment length polymorphism (RFLP) mapping approach using an indica-japonica rice doubled-haploid (DH) population and its molecular linkage map.

Amino Acid Sequence↗

Honokiol and magnolol increased hippocampal acetylcholine release in freely-moving rats.

Honokiol and magnolol, phenolic compounds isolated from the stem bark of Magnolia officinalis, have been demonstrated to increase choline acetyltransferase activity, inhibit acetylcholinesterase, promote potassium-induced acetylcholine release and exhibit neurotrophic function in in vitro studies. The objective of the present study was to determine the effect of these compounds on hippocampal acetylcholine release in conscious, freely-moving rats. 10(-4) M-10(-6) M of honokiol or magnolol was perfused into rat hippocampus via a dialysis probe. The results showed that at 10(-4) M concentration, honokiol and magnolol markedly increased extracellular acetylcholine release to 165.5+/-5.78% and 237.83+/-9.47% of the basal level, respectively. However, lower concentrations of either compounds failed to elicit significant acetylcholine release. This result suggests that a high dose of honokiol or magnolol may enhance in vivo hippocampal acetylcholine release.

Acetylcholine↗