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1.
Public Health ; 221: 131-134, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37451201

ABSTRACT

OBJECTIVES: Relative deprivation has been linked to various adverse health outcomes. However, the potential mediating factors in the association between relative deprivation and health outcomes remain unclear. This study aimed to (1) examine the association between relative deprivation and self-rated health and health-related quality of life among the working-age population in Taiwan and (2) investigate the mediating effect of subjective social status. STUDY DESIGN: Cross-sectional study using nationally representative data. METHODS: Data were obtained from the 2022 Taiwan Social Change Survey conducted from September 2021 to April 2022. We analyzed 1108 participants aged 25-64 years. Relative deprivation was measured using the Yitzhaki Index based on individual monthly income from all sources. Health-related quality of life was assessed using the 12-item Short Form Health Survey. RESULTS: After adjusting for all covariates and absolute income, least-squares regression models indicated a negative association between the Yitzhaki Index and self-rated health, as well as the physical and mental components of health-related quality of life. Furthermore, subjective social status partially mediates the association between relative income deprivation and poorer self-rated health and health-related quality of life. CONCLUSIONS: The findings support the psychosocial effect of the relative deprivation measure, emphasizing the importance of addressing relative deprivation to improve health-related quality of life among the working-age population.


Subject(s)
Quality of Life , Social Status , Humans , Cross-Sectional Studies , Income , Surveys and Questionnaires , Health Status
2.
Osteoporos Int ; 30(4): 837-843, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30734067

ABSTRACT

Osteoporosis is a well-known bone disorder affecting people worldwide. Patients with osteoporosis have an increased risk of bone fracture. This study provides new information on the risk of developing osteoporosis post burn injury and the risk of fracture among those with osteoporosis developed. INTRODUCTION: The relationship between burn injury and hip fracture risk is unclear. Population-based evaluation on relationships between burn injury and osteoporosis development and subsequent fractures is limited. We conducted a retrospective cohort study as the investigation. METHODS: From the insurance data of Taiwan, we established a cohort of 43,532 patients with a burn injury in 2000-2012 and a comparison cohort of 174,124 individuals without such an injury, frequency matched by sex, age, and diagnosis date. Both cohorts were followed up to the end of 2013 to evaluate the occurrence of osteoporosis and hip fracture. RESULTS: The incidence of osteoporosis was greater in the burn cohort than in the comparison cohort (6.40 vs. 4.75 per 1,000 person-years) with an adjusted IRR of 1.35 (95% confidence interval = 1.32-1.39). The incidence rates in both cohorts were greater in women than in men, increased with age, income, and Charlson comorbidity index. Patients with burns involving 20%-49% of total body surface area and with burns confined to the lower/upper limbs had the greatest incidence rates, 8.32 and 8.58 per 1,000 person-years, respectively. Osteoporosis incidence increased further to 22.7 per 1,000 person-years for burn victims with comorbid diabetes. The risk of fracture was over five-fold greater for burn victims with osteoporosis developed than for comparisons without osteoporosis. CONCLUSION: Patients who have a burn injury deserve prevention intervention to reduce the risk of osteoporosis and fracture.


Subject(s)
Burns/complications , Osteoporosis/etiology , Osteoporotic Fractures/etiology , Adult , Aged , Burns/epidemiology , Comorbidity , Databases, Factual , Female , Humans , Incidence , Male , Middle Aged , Osteoporosis/epidemiology , Osteoporotic Fractures/epidemiology , Retrospective Studies , Risk Assessment/methods , Taiwan/epidemiology
3.
Acta Physiol (Oxf) ; 222(4): e13001, 2018 04.
Article in English | MEDLINE | ID: mdl-29178430

ABSTRACT

AIM: Pregnant women have been recommended to take FA daily to prevent birth defects in the brain and spinal cord. We previously showed that folic acid (FA) exerts an anti-angiogenic activity. As angiogenesis is important for endometrial reorganization and embryonic development, there should be some mechanisms to allow the pregnant mother and the foetus to escape from the FA-induced anti-angiogenesis. This study was designed to investigate the effect of female sex hormones on the FA-induced anti-angiogenic activity. METHODS: The protein levels and protein-protein interaction were examined by Western blot analysis and immunoprecipitation assay respectively. The cell proliferation and migration were examined by MTT assay and wound healing assay respectively. The in vivo angiogenesis was evaluated by Matrigel angiogenesis assay. RESULTS: In human umbilical venous endothelial cells (HUVEC), FA receptor (FR) formed a complex with progesterone receptor (PR), oestradiol receptor (ER) and cSrc. Pregnancy levels of progesterone (P4) or oestradiol (E2) prevented FA-induced inhibitions of proliferation and migration in HUVEC. Both E2 and P4 prevented the FA-induced anti-angiogenesis in vivo. Moreover, cotreatment with FA and P4 or E2 inhibited the signalling pathways involved in FA-induced inhibitions of proliferation and migration in HUVEC. CONCLUSION: Female sex hormones interrupt the FA-induced anti-angiogenic action through receptor-receptor interaction.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Estradiol/pharmacology , Folic Acid/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Neovascularization, Physiologic/drug effects , Progesterone/pharmacology , Animals , Cell Proliferation/drug effects , Female , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Mice , Pregnancy , Receptors, Estradiol/metabolism , Receptors, Progesterone/metabolism
4.
Chem Sci ; 8(10): 7236-7245, 2017 Oct 01.
Article in English | MEDLINE | ID: mdl-29081956

ABSTRACT

One constraint of semiconducting polymer dots (Pdots), especially those with near-IR emission, is their low effective emitter ratio (∼1.5 mole percent), which limits their pH sensing performance. The other critical issue of existing Pdot-based pH sensors is their poor photostability. To address these issues, we developed a series of Pdots by dendronizing the squaraine-based pH responsive near-IR emitter, which is covalently incorporated into the polyfluorene (PFO) backbone. The fluorescence self-quenching of the NIR squaraine emitter was effectively suppressed at a high emitter concentration of 5 mole percent. Through controlling the individually incomplete energy transfer from the amorphous PFO donor to the blue ß-phase PFO and NIR squaraine emitter, we obtained a ratiometric pH sensor with simultaneously improved pH sensitivity, brightness, and photostability. The Pdots showed a fast and reversible pH response over the whole biological pH range of 4.7 to 8.5. Intracellular pH mapping was successfully demonstrated using this ultra-bright and photostable Pdot-based pH indicator.

5.
Osteoporos Int ; 28(12): 3415-3420, 2017 12.
Article in English | MEDLINE | ID: mdl-28875313

ABSTRACT

This work aimed to evaluate the hip fracture risk for patients with burn injury. A total of 16,430 patients with burn injury had an adjusted hazard ratio of 1.54 to encounter a hip fracture, compared with controls without the injury. These results encourage future studies focusing on mechanisms leading to fracture associated with burn injury. INTRODUCTION: The relationship between burn injury and hip fracture risk is unclear. We conducted a retrospective cohort study to investigate this relationship. METHODS: From insurance data of Taiwan, we identified a cohort with 16,430 burn patients in 2000-2010 and a comparison cohort of 65,716 persons without the history of burn, frequency matched by sex, age, and diagnosis date. Both cohorts were followed up to the end of 2011 to evaluate the risk of hip fracture. RESULTS: Patients with burn injury were 1.62-fold more likely than comparisons to encounter a hip fracture (6.95 vs. 4.28 per 1000 person-years), with an adjusted hazard ratio (aHR) of 1.54 (95% confidence interval (CI) = 1.40-1.68). The fracture incidence increased with age and is slightly greater for women than for men in both cohorts. The fracture risk was greater for patients with burn in the eyes, face, and head with an incidence of 7.14 per 1000 person-years, or an aHR of 2.09 (95% CI = 1.53, 2.86). Diabetes and osteoporosis were also associated with an increased hip fracture risk. CONCLUSION: Burn injury is associated with an increased risk of hip fracture. Diabetes and osteoporosis are associated with an enhanced risk.


Subject(s)
Burns/epidemiology , Hip Fractures/epidemiology , Osteoporotic Fractures/epidemiology , Adult , Burns/complications , Comorbidity , Databases, Factual , Female , Hip Fractures/etiology , Humans , Incidence , Male , Middle Aged , Osteoporosis/complications , Osteoporosis/epidemiology , Osteoporotic Fractures/etiology , Retrospective Studies , Risk Assessment/methods , Risk Factors , Taiwan/epidemiology
6.
Sci Rep ; 6: 33184, 2016 09 15.
Article in English | MEDLINE | ID: mdl-27627855

ABSTRACT

The superconductor-to-insulator transition (SIT) induced by means such as external magnetic fields, disorder or spatial confinement is a vivid illustration of a quantum phase transition dramatically affecting the superconducting order parameter. In pursuit of a new realization of the SIT by interfacial charge transfer, we developed extremely thin superlattices composed of high Tc superconductor YBa2Cu3O7 (YBCO) and colossal magnetoresistance ferromagnet La0.67Ca0.33MnO3 (LCMO). By using linearly polarized resonant X-ray absorption spectroscopy and magnetic circular dichroism, combined with hard X-ray photoelectron spectroscopy, we derived a complete picture of the interfacial carrier doping in cuprate and manganite atomic layers, leading to the transition from superconducting to an unusual Mott insulating state emerging with the increase of LCMO layer thickness. In addition, contrary to the common perception that only transition metal ions may respond to the charge transfer process, we found that charge is also actively compensated by rare-earth and alkaline-earth metal ions of the interface. Such deterministic control of Tc by pure electronic doping without any hindering effects of chemical substitution is another promising route to disentangle the role of disorder on the pseudo-gap and charge density wave phases of underdoped cuprates.

7.
Sci Rep ; 6: 23856, 2016 Mar 30.
Article in English | MEDLINE | ID: mdl-27025538

ABSTRACT

We investigate the effect of Rh doping in Sr2IrO4 using X-ray absorption spectroscopy (XAS). We observed appearance of new electron-addition states with increasing Rh concentration (x in Sr2Ir1-xRhxO4) in accordance with the concept of hole doping. The intensity of the hole-induced state is however weak, suggesting weakness of charge transfer (CT) effect and Mott insulating ground states. Also, Ir Jeff = 1/2 upper Hubbard band shifts to lower energy as x increases up to x = 0.23. Combined with optical spectroscopy, these results suggest a hybridisation-related mechanism, in which Rh doping can weaken the (Ir Jeff = 1/2)-(O 2p) orbital hybridisation in the in-planar Rh-O-Ir bond networks.

8.
Biosens Bioelectron ; 26(11): 4301-7, 2011 Jul 15.
Article in English | MEDLINE | ID: mdl-21664119

ABSTRACT

We report a fully integrated, portable, battery-operated electronic nose system comprising a bio-inspired two-layer multiple-walled carbon nanotube (MWNT)-polymer composite sensor array, a bio-inspired fast-adaptive readout circuit, and a microprocessor embedded with a pattern recognition algorithm. The two-layer MWNT-polymer composite sensor is simple to operate, and the membrane quality can be easily controlled. These two-layer membranes have improved sensitivity and stability. The fast-adaptive readout circuit responds to the sensor response, while tuning out the long-term constant background humidity, temperature, and odors. This portable electronic nose system successfully classified four complex alcohol samples 40 times for each sample; these samples were sake, sorghum liquor, medical liquor, and whisky.


Subject(s)
Biomimetic Materials , Biosensing Techniques/instrumentation , Odorants/analysis , Algorithms , Biosensing Techniques/statistics & numerical data , Equipment Design , Ethanol/analysis , Microscopy, Electron, Scanning , Nanotechnology , Nanotubes, Carbon/ultrastructure , Polymers
9.
Opt Express ; 17(15): 12910-21, 2009 Jul 20.
Article in English | MEDLINE | ID: mdl-19654696

ABSTRACT

This work investigates a novel color cone lasing emission (CCLE) based on a one-dimensional photonic crystal-like dye-doped cholesteric liquid crystal (DDCLC) film with a single pitch. The lasing wavelength in the CCLE is distributed continuously at 676.7-595.6 nm, as measured at a continuously increasing oblique angle relative to the helical axis of 0-50 degrees . This work demonstrates that lasing wavelength coincides exactly with the wavelength at the long wavelength edge of the CLC reflection band at oblique angles of 0-50 degrees . Simulation results of dispersion relations at different oblique angles using Berreman's 4X4 matrix method agrees closely with experimental results. Some unique and important features of the CCLE are identified and discussed.


Subject(s)
Cholesterol/chemistry , Liquid Crystals/chemistry , Optics and Photonics , Computer Simulation , Equipment Design , Glass , Lasers , Polyvinyl Alcohol/chemistry , Refractometry
10.
Clin Pharmacol Ther ; 84(1): 83-9, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18183038

ABSTRACT

Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements and could be used to predict warfarin dose. We conducted a prospective study in which warfarin dose was prescribed based on CYP2C9 and VKORC1 polymorphisms in 108 Han-Chinese patients without prior warfarin treatments. Using the genotype-based dosing, 83% of patients reached stable, therapeutic international normalized ratio (INR) within 2 weeks of treatment initiation and none of the patients developed clinical bleeding or thromboembolic event. Ten percent (11) of patients with INR > 4 and no clinical bleeding were detected during this study. At 12 weeks, 69% of the patients' maintenance doses matched the prediction. Dosing algorithms incorporating genetic factors, age, and body surface area were developed, which could explain up to 62% of the total variation (R(2) of 0.62). This study demonstrated that pharmacogenetics-based dosing could improve time to stable, therapeutic INR, reduce adverse events, and achieve high sensitivity.


Subject(s)
Aryl Hydrocarbon Hydroxylases/genetics , Mixed Function Oxygenases/genetics , Warfarin/administration & dosage , Adult , Aged , Aged, 80 and over , Aryl Hydrocarbon Hydroxylases/blood , Cytochrome P-450 CYP2C9 , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Gene Frequency/genetics , Genotype , Humans , Male , Middle Aged , Mixed Function Oxygenases/blood , Polymorphism, Genetic/genetics , Prospective Studies , Vitamin K Epoxide Reductases , Warfarin/blood
13.
Appl Opt ; 46(21): 4555-62, 2007 Jul 20.
Article in English | MEDLINE | ID: mdl-17609700

ABSTRACT

An inverse approach based on an optimization technique is proposed to characterize a fiber Bragg grating (FBG) and the strain gauge factor (GF) when the FBG is bonded on a structure. By bonding an FBG on a substrate and simply straining this FBG into a chirped fiber Bragg grating with a predesignated strain, the proposed method, based on an optimization technique, can be used to reconstruct seven parameters of the FBG from the corresponding reflective spectrum. The parameters identified are the length of an FBG, the grating period, the average refractive index, the index modulation, the apodization coefficient, the starting point bonded on the plate, and the strain GF. The information from the predesignated strain, as well as the measured reflective spectrum, is used as the objective function during the optimal search. As a result, the design sensitivity for the optimal search is much improved compared with the design sensitivity when only the reflective spectrum is used. In particular, the strain GF, which depends on the adhesive, the bonding layer characteristics, etc., can be determined in order to provide a reference for an FBG used as a strain sensor. Results from numerical simulations and experiments show that seven parameters of an FBG can be obtained accurately and efficiently.

14.
Int J Clin Pract ; 61(3): 392-6, 2007 Mar.
Article in English | MEDLINE | ID: mdl-16749916

ABSTRACT

The relationship between QT duration and its dispersion in patients with primary hyperaldosteronism is not clearly known. We studied 26 patients (nine males and 17 females) with primary hyperaldosteronism. The serum potassium levels were low (2.32 +/- 0.52 mmol/l), did not correlate with serum renin or aldosterone levels, or aldosterone/renin ratio (ARR). The maximum QT intervals (QTmax) were prolonged (502 +/- 62 ms), correlated well with ARRs (p = 0.005) and aldosterone levels (p = 0.019), but not to renin (p = 0.517) or potassium levels (p = 0.196). The QT dispersions (QTd) were small (60 +/- 28.8 ms) and did not correlate with potassium, renin or aldosterone levels. QTmax but not QTd correlate with aldosterone levels in patients with primary aldosteronism. The maintenance of repolarisation homogeneity with relatively unchanged QT dispersion may contribute to our understanding of the clinical observation that ventricular tachydysrhythmia is rare among patients with primary aldosteronism.


Subject(s)
Hyperaldosteronism/complications , Long QT Syndrome/complications , Adult , Aldosterone/blood , Electrocardiography , Female , Humans , Hyperaldosteronism/physiopathology , Long QT Syndrome/physiopathology , Male , Middle Aged , Potassium/blood , Regression Analysis , Renin/blood , Retrospective Studies
15.
Int J Clin Pract ; 58(11): 1045-7, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15605669

ABSTRACT

Although cardiac tamponade is an important and emergent complication of systemic lupus erythematosus (SLE), purulent pericarditis is rare despite the high frequency of pericardial effusion in SLE. We describe the first SLE case of Haemophilus influenzae type-f pericarditis with cardiac tamponade with SLE as the initial presentation. The pathophysiology and therapy are discussed.


Subject(s)
Cardiac Tamponade/etiology , Haemophilus Infections , Lupus Erythematosus, Systemic/complications , Pericarditis/etiology , Female , Humans , Middle Aged
16.
J Pharm Pharmacol ; 55(1): 115-23, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12625875

ABSTRACT

We have investigated the role of protein kinase C (PKC) and nuclear factor-kappaB (NF-kappaB) in cyclooxygenase-2 (COX-2) expression caused by Staphylococcus aureus lipoteichoic acid in RAW 264.7 macrophages. A phosphatidylcholine-phospholipase C (PC-PLC) inhibitor (D-609) and a phosphatidylinositol-phospholipase C (PI-PLC) inhibitor (U-73122) attenuated lipoteichoic acid-induced COX-2 expression, while a phosphatidate phosphohydrolase inhibitor (propranolol) had no effect. Two PKC inhibitors (Go 6976 and Ro 31-8220) and the NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), also attenuated lipoteichoic acid-induced COX-2 expression. Lipoteichoic acid resulted in a decrease in PKC activity in the cytosol and an increase in PKC activity in membranes. The lipoteichoic acid-induced translocation of p65 NF-kappaB from the cytosol to the nucleus was inhibited by D-609, U-73122, Go 6976, Ro 31-8220, and PDTC, but not by propranolol. The results suggested that lipoteichoic acid might have activated PC-PLC and PI-PLC to induce PKC activation, which in turn initiated NF-kappaB activation, and finally induced COX-2 expression in RAW 264.7 macrophages.


Subject(s)
Isoenzymes/biosynthesis , Lipopolysaccharides/pharmacology , Macrophages/physiology , NF-kappa B/pharmacology , Prostaglandin-Endoperoxide Synthases/biosynthesis , Protein Kinase C/pharmacology , Teichoic Acids/pharmacology , Animals , Cell Culture Techniques , Cyclooxygenase 2 , Mice , Phosphatidylcholines/chemistry , Phosphatidylinositols/chemistry , Phospholipases/chemistry , Staphylococcus aureus/pathogenicity
17.
Cancer Res ; 61(24): 8845-50, 2001 Dec 15.
Article in English | MEDLINE | ID: mdl-11751407

ABSTRACT

Currently, molecular markers offer the unique opportunity to identify occult metastasis in early stage cancer patients not otherwise detected with conventional staging techniques. To date, well-characterized molecular tumor markers to detect occult breast cancer cells in blood are limited. Because breast tumors are heterogeneous in tumor marker expression, we developed a "multimarker" reverse transcription-PCR assay combined with the highly sensitive electrochemiluminescence automated detection system. Breast cancer cell lines (n = 7), primary breast tumors (n = 25), and blood from normal donors (n = 40) and breast cancer patients [n = 65; American Joint Committee on Cancer (AJCC) stages I-IV] were assessed for four mRNA tumor markers: beta-human chorionic gonadotropin (beta-hCG), oncogene receptor (c-Met), beta 1-->4-N-acetylgalactosaminyl-transferase, and a tumor-associated antigen (MAGE-A3). None of the tumor markers were expressed in any normal donor bloods. Breast cancer cell lines and primary breast tumors expressed beta-hCG, c-Met, beta 1-->4-N-acetylgalactosaminyl-transferase, and MAGE-A3 mRNA. Of the 65 breast cancer patient blood samples assessed, 2, 3, 15, 49, and 31% expressed 4, 3, 2, 1, and 0 of the mRNA tumor markers, respectively. At least two markers were expressed in 20% of the blood specimens. The addition of a combination of markers enhanced detection of systemic metastasis by 32%. In patient blood samples, the MAGE-A3 marker correlated significantly with tumor size (P = 0.0004) and AJCC stage (P = 0.007). The combination of beta-hCG and MAGE-A3 mRNA markers correlated significantly with tumor size (P = 0.04), and the marker combination c-Met and MAGE-A3 showed a significant correlation with tumor size (P = 0.005) as well as AJCC stage (P = 0.018). A multimarker reverse transcription-PCR assay that correlates with known clinicopathological prognostic parameters may have potential clinical utility by monitoring tumor progression with a blood test.


Subject(s)
Biomarkers, Tumor/blood , Breast Neoplasms/blood , Breast Neoplasms/pathology , Neoplasm Proteins , Neoplastic Cells, Circulating/pathology , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/biosynthesis , Antigens, Neoplasm/blood , Antigens, Neoplasm/genetics , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , Choriocarcinoma/genetics , Choriocarcinoma/metabolism , Chorionic Gonadotropin, beta Subunit, Human/biosynthesis , Chorionic Gonadotropin, beta Subunit, Human/blood , Chorionic Gonadotropin, beta Subunit, Human/genetics , Female , Humans , N-Acetylgalactosaminyltransferases/biosynthesis , N-Acetylgalactosaminyltransferases/blood , N-Acetylgalactosaminyltransferases/genetics , Neoplasm Staging , Neoplastic Cells, Circulating/metabolism , Proto-Oncogene Proteins c-met/biosynthesis , Proto-Oncogene Proteins c-met/blood , Proto-Oncogene Proteins c-met/genetics , RNA, Messenger/blood , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Tumor Cells, Cultured
18.
J Invest Dermatol ; 117(2): 375-8, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11511319

ABSTRACT

Melanoma frequently metastasizes to the central nervous system (CNS). The diagnosis of CNS metastases typically is made following the onset of clinical symptoms. Thus, more sensitive diagnostic approaches are needed to identify subclinical CNS metastases. Currently, standard cytologic analysis of the cerebrospinal fluid (CSF) is limited by its poor sensitivity. A more sensitive assay was therefore developed using multiple reverse transcriptase-polymerase chain reaction (RT-PCR) markers. CSF was collected and assessed by RT-PCR for three known melanoma-associated markers (MAGE-3, MART-1, and tyrosinase) to detect occult metastatic melanoma cells in the CSF of 37 American Joint Committee on Cancer (AJCC) stage IV melanoma patients. Cytologic analysis of CSF was performed on all patients, and immunohistochemistry (IHC) analysis was performed on 33 CSF samples using anti-S100 and anti-HMB-45 antibodies. Only one patient (3%) had tumor-positive CSF cytology and IHC upon entry into the study, whereas 12 patients (32%) were positive for at least one RT-PCR marker. The correlation between CSF RT-PCR positivity of MART-1 and/or MAGE-3 and the development of CNS metastases at 3 mo was significant (p = 0.04). Fifteen of 37 patients (41%) had either positive MRI and/or positive RT-PCR results. Multimarker RT-PCR is more informative and sensitive than cytology/IHC in assessing the CSF of melanoma patients.


Subject(s)
Antigens, Neoplasm , Melanoma/cerebrospinal fluid , Melanoma/secondary , Skin Neoplasms/cerebrospinal fluid , Skin Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor , Brain Neoplasms/mortality , Brain Neoplasms/secondary , DNA, Neoplasm/analysis , DNA, Neoplasm/cerebrospinal fluid , Disease-Free Survival , Female , Humans , MART-1 Antigen , Male , Melanoma/mortality , Middle Aged , Monophenol Monooxygenase/genetics , Neoplasm Proteins/genetics , Predictive Value of Tests , Reverse Transcriptase Polymerase Chain Reaction , Skin Neoplasms/mortality
19.
Am J Pathol ; 159(2): 493-500, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11485908

ABSTRACT

GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-4Glcbeta1-Cer (GM2)/GalNAcbeta1-4(NeuAcalpha2-8NeuAcalpha2-3)Galbeta1-4Glcbeta1-1Cer (GD2) synthetase [beta-1,4-N-acetyl-galactosaminyl transferase (GalNAc-T)] mRNA, which encodes a key glycosyltransferase for ganglioside GD2 synthesis, was assessed as a molecular marker for detecting metastatic neuroblastoma cells in bone marrow (BM). GalNAc-T mRNA expression by neuroblastoma cell lines (n = 15), primary untreated neuroblastoma tumors (n = 29), morphologically normal BM (n = 22), peripheral blood stem cells (n = 10) from patients with cancers other than neuroblastoma, and blood mononuclear cells from normal donors (n = 17) was assessed by using reverse transcriptase-polymerase chain reaction (RT-PCR) and electrochemiluminescence detection assay (RT-PCR/ECL). BM harvested from 15 neuroblastoma patients was tested before and after ex vivo immunomagnetic bead purging, and results were compared to immunocytological analysis of the same specimens. All neuroblastoma cell lines (mean, 653 x 10(3) ECL units) and primary tumors (mean, 683 x 10(3) ECL units) were positive for significant expression of GalNAc-T mRNA compared to normal blood and BM cells. The RT-PCR/ECL assay could detect GalNAc-T mRNA in 100 pg of total RNA, and in a mixture of one neuroblastoma cell among 10(7) normal BM or blood cells. Eight of 15 autologous BM cells harvested from patients with neuroblastoma had tumor cells detectable by immunocytology, and all 15 were positive for GalNAc-T mRNA. After ex vivo purging, none of the BM cells was immunocytology-positive, but six remained positive by the RT-PCR/ECL assay. GalNAc-T mRNA provides a specific and sensitive molecular marker for RT-PCR/ECL detection of infrequent neuroblastoma cells in BM.


Subject(s)
Biomarkers, Tumor/genetics , Bone Marrow/pathology , N-Acetylgalactosaminyltransferases/genetics , Neuroblastoma/pathology , RNA, Messenger/analysis , Adolescent , Biomarkers, Tumor/analysis , Bone Marrow Purging , Brain Neoplasms/drug therapy , Brain Neoplasms/enzymology , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Carbohydrate Sequence , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Luminescent Measurements , Molecular Sequence Data , N-Acetylgalactosaminyltransferases/analysis , Neuroblastoma/drug therapy , Neuroblastoma/enzymology , Neuroblastoma/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Tumor Cells, Cultured , Polypeptide N-acetylgalactosaminyltransferase
20.
Nat Immunol ; 2(8): 698-704, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11477405

ABSTRACT

T lymphocytes circulate in a quiescent state until they encounter cognate antigen bound to the surface of an antigen-presenting cell. The molecular pathways that regulate T cell quiescence remain largely unknown. Here we show that forced expression of the lung Krüppel-like transcription factor (LKLF) in Jurkat T cells is sufficient to program a quiescent phenotype characterized by decreased proliferation, reduced cell size and protein synthesis and decreased surface expression of activation markers. Conversely, LKLF-deficient peripheral T cells produced by gene targeting showed increased proliferation, increased cell size and enhanced expression of surface activation markers in vivo. LKLF appeared to function, at least in part, by decreasing expression of the proto-oncogene encoding c-Myc. Forced expression of LKLF was associated with markedly decreased c-Myc expression. In addition, many effects of LKLF expression were mimicked by expression of the dominant-negative MadMyc protein and rescued by overexpression of c-Myc. Thus, LKLF is both necessary and sufficient to program quiescence in T cells and functions, in part, by negatively regulating a c-Myc--dependent pathway.


Subject(s)
Proto-Oncogene Proteins c-myb/immunology , T-Lymphocytes/immunology , Trans-Activators/immunology , Cell Division/immunology , Cellular Senescence/immunology , Humans , Jurkat Cells , Kruppel-Like Transcription Factors , Molecular Sequence Data , Proto-Oncogene Mas , T-Lymphocytes/pathology
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