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Biomedical subjects

C Yeh

Publications and source records attributed to C Yeh.

At least 19 recordsLinked to original sources
PubMed2003

Resveratrol and cancer: chemoprevention, apoptosis, and chemo-immunosensitizing activities.

The polyphenolic compound Resveratrol is a naturally occurring phytochemical and can be found in many plant species, including grapes, peanuts and various herbs. Several studies have established that Resveratrol can exert anti-oxidant and anti-inflammatory activities. It also has activity in the regulation of multiple cellular events associated with carcinogenesis. This review describes the general properties of Resveratrol including its relationship to estrogen, its effect on lipid metabolism, its cardiovascular effects, and its role on gene expression. Resveratrol has also been examined in several model systems for its potential effect against cancer. Its anti-cancer effects include its role as a chemopreventive agent, its ability to inhibit cell proliferation, its direct effect in cytotoxicity by induction of apoptosis and on its potential therapeutic effect in pre-clinical studies. In addition, Resveratrol has been shown to exert sensitization effects on cancer cells that will result in a synergistic cytotoxic activity when Resveratrol is used in combination with cytotoxic drugs in drug-resistant tumor cells. Clearly, the studies with Resveratrol provide support for the use of Resveratrol in human cancer chemoprevention and combination with chemotherapeutic drugs or cytotoxic factors in the treatment of drug refractory tumor cells.

Animals↗
PubMed2001

The stability of cytokeratin 18 in human liver cells during colchicine-induced microtubule disruption.

The cytoskeleton plays important roles in cell function and is therefore implicated in the pathogenesis of many human liver diseases, including malignant tumors. The stability of cytokeratin proteins during tumor transformation in human hepatocellular carcinoma has been studied with a molecular approach previously. The results demonstrate that the cytokeratin is modulated in human hepatocellular carcinoma. Besides this, three low molecular weight cytokeratin molecules (named HCC CK) are found. This indicates that these HCC CKs have undergone modulation from the human hepatocyte cytokeratin 18. We also checked the cytokeratin profile of the human hepatoma cell line PLC/PRF/5 with the same methods to ensure the HCC CK molecules are produced by modulation but not protein degradation. The stability of cytokeratin molecules was studied by a different approach. The cytokeratin compositions of human liver cells (Chang cell line) were analysed under the effects of microtubule-disrupting drug (colchicine) by SDS-PAGE, Western blot, immunoprecipitation using a commercially available monoclonal anti-cytokeratin 18 antibody and immunofluorescent staining. Within 1 h of treatment, the microtubule began to collapse and the filamentous structure was shortening. The microtubule had almost collapsed and became fragmented to form a lattice-like network after 24 h of treatment. The cytokeratin was modulated after long-term (24 h) treatment of colchicine, and the molecular weight became 14 kD and the antigenicity was lost. The stability of cytokeratin molecules was related to the intact microtubule network, after disruption of the microtubule the cytokeratin would be modulated. The intact microtubule network was a stabilizing factor of cytokeratin 18 in human liver cells.

Blotting, Western↗
PubMed2001

The effects of concomitant phenytoin administration on the steady-state pharmacokinetics of quetiapine.

Quetiapine fumarate ('Seroquel') is a newly introduced atypical antipsychotic with demonstrated efficacy in the treatment of positive and negative symptoms of schizophrenia. It is extensively metabolized, predominantly by cytochrome P450 3A4. Therefore, concurrent administration of drugs that induce or inhibit this enzyme may affect quetiapine pharmacokinetics. This study demonstrated that the potent cytochrome P450 enzyme-inducer phenytoin did indeed have a marked effect on the metabolism of quetiapine, resulting in a 5-fold increase in clearance when administered concomitantly to patients with DSM-IV-diagnosed schizophrenia, schizoaffective disorder, or bipolar disorder. These results indicate that dosage adjustment of quetiapine may be necessary when the two drugs are given concurrently and that caution may be required when administering other drugs that inhibit or induce cytochromes, particularly P450 3A4.

Adolescent↗
PubMed2001

The Emergency Medical Treatment and Labor Act as a federal health care safety net program.

Despite the greatest economic expansion in history during the 1990s, the number of uninsured U.S. residents surpassed 44 million in 1998. Although this number declined for the first time in recent years in 1999, to 42.6 million, the current economic slow-down threatens once again to increase the ranks of the uninsured. Many uninsured patients use hospital emergency departments as a vital portal of entry into an access-impoverished health care system. In 1986, Congress mandated access to emergency care when it passed the Emergency Medical Treatment and Labor Act (EMTALA). The EMTALA statute has prevented the unethical denial of emergency care based on inability to pay; however, the financial implications of EMTALA have not yet been adequately appreciated or addressed by Congress or the American public. Cuts in payments from public and private payers, as well as increasing demands from a larger uninsured population, have placed unprecedented financial strains on safety net providers. This paper reviews the financial implications of EMTALA, illustrating how the statute has evolved into a federal health care safety net program. Future actions are proposed, including the pressing need for greater public safety net funding and additional actions to preserve health care access for vulnerable populations.

Delivery of Health Care↗
PubMed2001

The adhesion receptor CD44 promotes atherosclerosis by mediating inflammatory cell recruitment and vascular cell activation.

Atherosclerosis causes most acute coronary syndromes and strokes. The pathogenesis of atherosclerosis includes recruitment of inflammatory cells to the vessel wall and activation of vascular cells. CD44 is an adhesion protein expressed on inflammatory and vascular cells. CD44 supports the adhesion of activated lymphocytes to endothelium and smooth muscle cells. Furthermore, ligation of CD44 induces activation of both inflammatory and vascular cells. To assess the potential contribution of CD44 to atherosclerosis, we bred CD44-null mice to atherosclerosis-prone apoE-deficient mice. We found a 50-70% reduction in aortic lesions in CD44-null mice compared with CD44 heterozygote and wild-type littermates. We demonstrate that CD44 promotes the recruitment of macrophages to atherosclerotic lesions. Furthermore, we show that CD44 is required for phenotypic dedifferentiation of medial smooth muscle cells to the "synthetic" state as measured by expression of VCAM-1. Finally, we demonstrate that hyaluronan, the principal ligand for CD44, is upregulated in atherosclerotic lesions of apoE-deficient mice and that the low-molecular-weight proinflammatory forms of hyaluronan stimulate VCAM-1 expression and proliferation of cultured primary aortic smooth muscle cells, whereas high-molecular-weight forms of hyaluronan inhibit smooth muscle cell proliferation. We conclude that CD44 plays a critical role in the progression of atherosclerosis through multiple mechanisms.

Animals↗
PubMed2000

Translational upregulation of X-linked inhibitor of apoptosis (XIAP) increases resistance to radiation induced cell death.

Inhibitory regulators of apoptosis play a critical role in the responsiveness of tumour cells to cytotoxic agents. The X-linked inhibitor of apoptosis protein (XIAP) is a member of a novel family of Inhibitor of Apoptosis (IAP) proteins. Here we show that acute low dose ionizing irradiation results in the translational upregulation of XIAP that correlates with an increased resistance to radiation in non-small cell lung carcinoma. This upregulation is mediated by an internal ribosome binding mechanism via an IRES element located within a XIAP 5' UTR. Transient overexpression of XIAP rendered human carcinoma cells resistant to low dose gamma-irradiation. By contrast, the antisense targeting of XIAP resulted in increased cell death following irradiation advocating a distinct role for XIAP in radiation resistant phenotype of human cancers. Oncogene (2000) 19, 4174 - 4177

5' Untranslated Regions↗
PubMed2000

Communication at millimetre-submillimetre wavelengths using a ceramic ribbon

Following the discovery by Kao and Hockman that ultra-low-loss optical fibres could be made from pure silica through the elimination of impurities, the ability to guide signals effectively at optical wavelengths has been assured. But there remains an important region of the spectrum--from 30 to 3,000 GHz (the millimetre-submillimetre band)--where low-loss waveguides are unknown. The main problem here in finding low-loss solids is no longer one of eliminating impurities, but is due to the presence of intrinsic vibration absorption bands. And the use of highly conducting materials is also precluded owing to high skin-depth losses in this part of the spectrum. Here we show that a combination of material and waveguide geometry can circumvent these difficulties. We adopt a ribbon-like structure with an aspect ratio of 10:1, fabricated from ceramic alumina (Coors' 998 Alumina), and the resulting waveguide has an attenuation factor of less than 10 dB km(-1) in the millimetre-submillimetre band. This attenuation is more than 100 times smaller than that of a typical ceramic (or other dielectric) circular rod waveguide and is sufficient for immediate application.

Journal Article↗
PubMed2000

Phosphine-induced oxidative damage in rats: attenuation by melatonin.

Phosphine (PH(3)), from hydrolysis of aluminum, magnesium and zinc phosphide, is an insecticide and rodenticide. Earlier observations on PH(3)-poisoned insects, mammals and a mammalian cell line led to the proposed involvement of oxidative damage in the toxic mechanism. This investigation focused on PH(3)-induced oxidative damage in rats and antioxidants as candidate protective agents. Male Wistar rats were treated ip with PH(3) at 2 mg/kg. Thirty min later the brain, liver, and lung were analyzed for glutathione (GSH) levels and lipid peroxidation (as malondialdehyde and 4-hydroxyalkenals) and brain and lung for 8-hydroxydeoxyguanosine (8-OH-dGuo) in DNA. PH(3) caused a significant decrease in GSH concentration and elevation in lipid peroxidation in brain (36-42%), lung (32-38%) and liver (19-25%) and significant increase of 8-OH-dGuo in DNA of brain (70%) and liver (39%). Antioxidants administered ip 30 min before PH(3) were melatonin, vitamin C, and beta-carotene at 10, 30, and 6 mg/kg, respectively. The PH(3)-induced changes were significantly or completely blocked by melatonin while vitamin C and beta-carotene were less effective or inactive. These findings establish that PH(3) induces and melatonin protects against oxidative damage in the brain, lung and liver of rats and suggest the involvement of reactive oxygen species in the genotoxicity of PH(3).

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Single-dose pharmacokinetics of quetiapine in subjects with renal or hepatic impairment.

1. The atypical antipsychotic quetiapine ('Seroquel') provides equivalent efficacy to the typical antipsychotics chlorpromazine and haloperidol in the short-term treatment of schizophrenia. Moreover, the incidence of extrapyramidal symptoms associated with quetiapine treatment is equivalent to that observed with placebo treatment, which may lead to increased patient compliance with quetiapine compared with typical antipsychotics. 2. This report presents the results from two small studies aimed at determining the pharmacokinetics of quetiapine in nonpsychotic subjects with renal or hepatic impairment. Equal numbers of impaired subjects and healthy control subjects were administered a single, 25 mg dose of quetiapine, and plasma concentrations were determined up to 48 hr after dosing. 3. No clinically significant differences were found when the pharmacokinetic parameters for subjects with renal or hepatic impairment were compared with those for healthy control subjects. The results indicate that dosage adjustment of quetiapine may be unnecessary in psychotic patients with decreased renal function. 4. In subjects with hepatic impairment related to alcoholic cirrhosis, the results suggest that no change is needed in the recommended quetiapine starting dose (25 mg). However, because of a noted inter-subject variability in the clearance of quetiapine in the cirrhotic group, it is recommended that dose escalation be performed with caution in patients with hepatic impairment. 5. The single dose of quetiapine 25 mg generally was well tolerated in nonpsychotic subjects in good health or with either renal or hepatic impairments. Quetiapine also had no effect on the endogenous creatinine clearance of renally impaired or healthy control subjects.

Adolescent↗
PubMed2000

Pharmacokinetics, tolerability, and clinical effectiveness of quetiapine fumarate: an open-label trial in adolescents with psychotic disorders.

BACKGROUND: This is the first investigation of the pharmacokinetics, tolerability, and efficacy of quetiapine fumarate in adolescents with chronic or intermittent psychotic disorders. METHOD: Ten patients with DSM-IV chronic or intermittent psychotic disorders (ages 12.3 through 15.9 years) participated in an open-label, rising-dose trial and received oral doses of quetiapine twice daily (b.i.d.), starting at 25 mg b.i.d. and reaching 400 mg b.i.d. by day 20. The trial ended on day 23. Key assessments were pharmacokinetic analysis of plasma quetiapine concentrations and neurologic, safety, and efficacy evaluations. RESULTS: No statistically significant differences were observed between 100-mg b.i.d. and 400-mg b.i.d. quetiapine regimens for total body clearance, dose-normalized area under the plasma concentration-time curve, or dose-normalized premorning- or postmorning-dose trough plasma values obtained under steady-state conditions after multiple-dose regimens. No unexpected side effects occurred with quetiapine therapy, and no statistically significant changes from baseline were observed for the UKU Side Effect Rating Scale items that were rated. No serious adverse events or clinically important changes in hematology or clinical chemistry variables were reported. The most common adverse events were postural tachycardia and insomnia. Extrapyramidal side effects improved, as evidenced by significant (p < .05) decreases from baseline to endpoint in the mean Simpson-Angus Scale total scores and Barnes Akathisia Scale scores. Quetiapine improved positive and negative symptoms, as shown by significant (p < .05) decreases from baseline to endpoint in the mean Brief Psychiatric Rating Scale total score, the Clinical Global Impressions-Severity of Illness scale, and the Modified Scale for the Assessment of Negative Symptoms summary score. CONCLUSION: Quetiapine pharmacokinetics were dose proportional in adolescents and were similar to those previously reported for adults. Quetiapine was well tolerated and effective in the small number of adolescents studied.

Adolescent↗
PubMed1999

NMDA receptor-mediated K+ efflux and neuronal apoptosis.

Neuronal death induced by activating N-methyl-D-aspartate (NMDA) receptors has been linked to Ca2+ and Na+ influx through associated channels. Whole-cell recording from cultured mouse cortical neurons revealed a NMDA-evoked outward current, INMDA-K, carried by K+ efflux at membrane potentials positive to -86 millivolts. Cortical neurons exposed to NMDA in medium containing reduced Na+ and Ca2+ (as found in ischemic brain tissue) lost substantial intracellular K+ and underwent apoptosis. Both K+ loss and apoptosis were attenuated by increasing extracellular K+, even when voltage-gated Ca2+ channels were blocked. Thus NMDA receptor-mediated K+ efflux may contribute to neuronal apoptosis after brain ischemia.

Animals↗
PubMed1999

Molecular characterization of Cyclospora-like organisms from baboons.

Cyclospora organisms are intestinal pathogens of humans that are increasingly recognized in many parts of the world; yet, the reservoirs and host range remain poorly defined. Analysis of 18S ribosomal DNA (rDNA) suggests that the human-associated Cyclospora species (Cyc-hu) is most closely related to the Eimeria species, which are host species-specific. Recently, oocysts identical to those of Cyc-hu were detected in baboon fecal specimens from Tanzania. The 18S rDNA from 3 of these baboon-associated oocyst specimens was amplified and sequenced. Phylogenetic analysis indicated that these baboon-associated Cyclospora-like organisms (Cyc-bab) are nearly identical to each other and are distinct from Cyc-hu (1.6%-1.7% dissimilar); however, these Cyc-bab organisms are the closest known relatives of Cyc-hu. Together, these primate-associated cyclosporans constitute a coherent clade within the diverse group of Eimeria species. These findings raise important questions about the evolutionary relationships of the eimeriids and Cyc-hu host range and should lead to improved polymerase chain reaction-based diagnostics.

Animals↗
PubMed1999

Existence of optical solitons on wavelength division multiplexed beams in a nonlinear fiber.

A simple analytic expression for the initial fundamental optical solitons on wavelength division multiplexed (WDM) beams in a nonlinear fiber has been found. For an ideal fiber with no loss and uniform group-velocity dispersion (GVD) in the anomalous GVD region, the initial form is [1+2(M-1)](-1/2) sech(tau), where M is the number of WDM beams and tau is the normalized time. Computer simulation shows that these initial pulses on WDM beams in this fiber will propagate undistorted without change in their shapes for arbitrarily long distances. The discovery of the existence of solitons on WDM beams presents the ultimate goal for optical fiber communication on multiple wavelength beams in a single fiber.

Journal Article↗
PubMed1999

Screening for asthma in an inner-city elementary school in Minneapolis, Minnesota.

To the extent that the asthma morbidity so prevalent in children today is due to underdiagnosis or lack of appropriate treatment, schools are increasingly faced with the issue of defining their role in the care of children with asthma. This paper describes efforts to conduct schoolwide screening for asthma in an inner-city elementary school over the past two years. Screening methodology adopted for the project resulted in a simple and noninvasive approach for identifying children with current asthma in a school setting. While not as medically comprehensive as would be required to conclusively diagnose asthma, the simple screening approach proved efficient in identifying a population of elementary school children with a significant level of asthma morbidity. The paper discusses the effectiveness and feasibility of the screening efforts and proposes how such a screening program might be incorporated into the routine health activities undertaken at any elementary school.

Asthma↗
PubMed1998

The design and development of a gloveless endoskeletal prosthetic hand.

Current prosthetic hands, although functional, have the potential of being improved significantly. We report here the design and development of a novel prosthetic hand that is lighter in weight, less expensive, and more functional than current hands. The new prosthesis features an endoskeleton embedded in self-skinning foam that provides a realistic look and feel and obviates the need for a separate cosmetic glove. The voluntary-closing mechanism offers variable grip strength. Placement of joints at three locations (metacarpophalangeal and proximal and distal interphalangeal) within each of four fingers affords realistic finger movement. High-strength synthetic cable attached to the distal phalanx of each finger is used to effect flexion. A multiposition passive thumb provides both precision and power grips. The new prosthesis can securely grasp objects with various shapes and sizes. Compared to current hands, weight has been reduced by approximately 50%, and cable excursion required for full finger flexion by more than 50%. The new endoskeletal prosthesis requires approximately 12-24% less force input to grasp a variety of everyday objects, largely due to its adaptive grip. Production cost estimates reveal the new prosthesis to be significantly less expensive than current prosthetic hands.

Activities of Daily Living↗
PubMed1997

Molecular recognition in the HIV-1 capsid/cyclophilin A complex.

The HIV-1 capsid protein (CA) makes an essential interaction with the human peptidyl prolyl isomerase, cyclophilin A (CypA), that results in packaging of CypA into the virion at a CA to CypA stoichiometry of approximately 10:1. The 231 amino acid residue capsid protein is composed of an amino-terminal CypA binding domain (1 to approximately 151; CA151) and a carboxyl-terminal dimerization domain (approximately 151 to 231). We find that CypA binds dimeric CA and monomeric CA151 with identical intrinsic affinities (K[d] = 16(+/-4) microM). This result demonstrates that capsid dimerization and cyclophilin A binding are not thermodynamically coupled and suggests that the substoichiometric ratio of CypA in the HIV-1 virion results from the intrinsic stability of the CA/CypA complex. In the known co-crystal structure of the CA151/CypA complex, CypA binding is mediated exclusively by an exposed capsid loop that spans residues Pro85 to Pro93. The energetic contributions to CypA binding were quantified for each residue in this loop, and the results demonstrate that the Gly89-Pro90 dipeptide is the primary cyclophilin A recognition motif, with Pro85, Val86, His87, Ala88, and Pro93 also making energetically favorable contacts. These studies reveal that the active site of CypA, which can catalyze the isomerization of proline residues in vitro, also functions as a sequence-specific, protein-binding motif in HIV-1 replication.

Amino Acid Isomerases↗