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Biomedical subjects

Wei Li

Publications and source records attributed to Wei Li.

At least 163 records · Page 9Linked to original sources

[Expression of key cell cycle markers in squamous cell carcinoma of the cervix positive in human papillomavirus: a comparative study between Chinese and Australian populations].

OBJECTIVE: To investigate the patterns of expression of key cell cycle proteins targeting on the human papillomavirus (HPV) sites E6 and E7 in cervical carcinoma. METHODS: Semiquantitative immunohistochemistry was used to determine the expression of the cell cycle regulatory factor p53, retinoblastoma gene product pRb, cyclin-dependent kinase inhibitors p21(CIP1/WAF1) (p21), p16(INK4A) (p21), and p27(KIP1) (p21), and cyclin D1 targeting on the HPV sites E6 and E7 in 73 HPV 16-positive specimens of cervical squamous cell carcinoma, 35 from Australia patients and 38 age, lymph node status, and grade of tumor-matched Chinese patients. RESULTS: There were no significant differences in age, lymph node status, and grade of tumor between the Chinese and Australian groups, however, the number of the patients in advanced stage (>Stage IIa) was greater in the Chinese group than in the Australian group (19:7). The positive rate of p53 in the Australian group was 3%, significantly lower than that in the Chinese group (23%, P = 0.028). The upregulation rate of pRb, p21, and p27 in the Australian group were 56%, 63% and 34% respectively, all significantly higher than those in the Chinese group (89%, 97%, and 89% respectively, P = 0.01, P < 0.001, and P < 0.001). There were no significant differences in the upregulation rate of p16 and cyclin D1 expression rate between the Australian group and Chinese group (97% versus 100%, and 3% versus 12%, both P > 0.05). In the combined data of both groups, the positive rate of p53 was 13%; and the upregulation rates of pRb, p16, p21, p27, and cyclin D1 were 74%, 99%, 81%, 63% and 7% respectively. CONCLUSION: Cervical carcinoma overexpresses pRb, p16, p21, and p27. Tumors from Chinese patients are significantly more likely to be positive in p53 and to have upregulated pRb, p21, and p27 than their Australian counterparts. The molecular pathways to human papillomavirus-induced cervical cancer may be influenced by ethnicity and further investigation is necessary.

Australia↗

Identification of a new Neisseria meningitidis serogroup C clone from Anhui province, China.

BACKGROUND: Outbreaks of a new serogroup C meningococcal disease emerged during 2003-04 (five outbreaks with 43 cases) and in 2004-05 (five outbreaks with 29 cases), all in Anhui province, China. We describe the molecular epidemiology and features of the causative bacterial strains. METHODS: We used pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) to analyse the strains. FINDINGS: Of 34 strains of Neisseria meningitidis cultured during 2003-04 from Anhui province, 31 were group C meningococci, 28 of which were associated with three of five outbreaks; one from a patient and 27 from close contacts of eight patients. Of 30 strains isolated from Anhui province during 2004-05, 17 were identified as serogroup C meningococci, ten of which were associated with four of five outbreaks. In a nationwide survey, 542 strains were isolated during 2004-05; 58 were serogroup C meningococci interspersed among 11 other provinces where no serogroup C outbreak occurred. Of the 106 serogroup C strains analysed, 89 had identical PFGE patterns, designated AH1. Of 28 strains selected for MLST analyses, 25 were sequence type 4821 (ST-4821), which did not belong to any of the previously reported sequence types that can form a new hypervirulent lineage. INTERPRETATION: ST-4821 seems to be unique and caused the serogroup C meningitis outbreaks during the two seasons from 2003 to 2005 in Anhui province. The emergence of this sequence type has epidemiological importance that should be monitored for future spread in China and the rest of the world.

Child↗

rmlB and rmlC genes are essential for growth of mycobacteria.

The rhamnose-GlcNAc disaccharide linker is fundamental to the structural integrity of mycobacterial cell wall. The donor dTDP-rhamnose is synthesized by four enzymes (RmlA, B, C, and D) beginning with dTTP and glucose-1-phosphate. We generated M. smegmatis rmlB gene knockout mutant (transcription of downstream rmlC gene was blocked because of a polar effect) by homologous recombination. When the Mycobacterium tuberculosis (Tb) rmlB rescue plasmid carrying a temperature-sensitive replication origin and Tb rmlC bearing plasmid with a normal replication origin were present in the mc(2)155 rmlB knockout mutant, the mutant was unable to grow at non-permissive temperature (42 degrees C) where the Tb rmlB rescue plasmid is lost. While the Tb rmlC rescue plasmid carrying a temperature-sensitive replication origin and Tb rmlB bearing plasmid with a normal replication origin were present in the mc(2)155 rmlB knock out mutant, this mutant was also unable to grow at the non-permissive temperature where the Tb rmlC rescue plasmid is lost. These results demonstrate that rmlB and rmlC genes are essential for mycobacterial growth, therefore, RmlB and RmlC are essential targets to develop new anti-tuberculosis drugs.

Cell Proliferation↗

Multiple signaling pathways are involved in endothelin-1-induced brain endothelial cell migration.

We have observed that the vasoactive peptide endothelin-1 is a potent inducer of migration of primary human brain-derived microvascular endothelial cells. By blocking signal transduction pathways with specific inhibitors, and using dominant negative mutant infections, we have demonstrated that multiple pathways are involved in endothelin-1-induced migration. Absolutely required for migration are protein tyrosine kinase Src, Ras, protein kinase C (PKC), phosphatidylinositol 3-kinase, ERK, and JNK; partial requirements were exhibited by cAMP-activated protein kinase and p38 kinase. Partial elucidation of the signal transduction sequences showed that the MAPKs ERK, JNK, and p38 are positioned downstream of both PKC and cAMP-activated protein kinase in the signal transduction scheme. The results show that human brain endothelial cell migration has distinct characteristics, different from cells derived from other vascular beds, or from other species, often used as model systems. Furthermore, the results indicate that endothelin-1, secreted by many tumors, is an important contributor to tumor-produced proangiogenic microenvironment. This growth factor has been associated with increased microvessel density in tumors and is responsible for endothelial cell proliferation, migration, invasion, and tubule formation. Because many signal transduction pathways investigated in this study are potential or current targets for anti-angiogenesis therapy, these results are of critical importance for designing physiological antiangiogenic protocols.

Brain↗

[Role of urinary basic fibroblast growth factor in differentiating hemangiomas from vascular malformation].

OBJECTIVE: To investigate a novel method to differentiate hemangioma from vascular malformation, to stage hemangiomas and to monitor the efficacy of management for hemangioma. METHODS: The urinary basic fibroblast growth factor (bFGF) concentration of 144 cases (including 69 cases of proliferating hemangiomas, 41 cases of involuting hemangiomas, 23 cases of vascular malformations and 11 negative controls) was examined using enzyme linked immunosorbent assay (ELISA). RESULTS: The differences of urinary bFGF concentration among proliferating hemangiomas, involuting hemangiomas, vascular malformations and negative control were all significant, while the differences between the latter three groups were not significant. CONCLUSIONS: Our findings suggest that examination of urinary bFGF concentration using ELISA technique is helpful in differentiating hemangioma from vascular malformation, staging hemangiomas and dynamically monitoring the efficacy of treatment for hemangiomas. Our results probably shed new light on the potential pathogenesis of hemangiomas and vascular malformation.

Arteriovenous Malformations↗

Yeast AMID homologue Ndi1p displays respiration-restricted apoptotic activity and is involved in chronological aging.

Apoptosis-inducing factor (AIF) and AIF-homologous mitochondrion-associated inducer of death (AMID) are both mitochondrial flavoproteins that trigger caspase-independent apoptosis. Phylogenetic analysis suggests that these two proteins evolutionarily diverge back from their common prokaryote ancestor. Compared with AIF, the proapoptotic nature of AMID and its mode of action are much less clarified. Here, we show that overexpression of yeast AMID homologue internal NADH dehydrogenase (NDI1), but not external NADH dehydrogenase (NDE1), can cause apoptosis-like cell death, and this effect can be repressed by increased respiration on glucose-limited media. This result indicates that the regulatory network of energy metabolism, in particular the cross-talk between mitochondria and the rest of the cell, is involved in Ndi1p-induced yeast cell apoptosis. The apoptotic effect of NDI1 overexpression is associated with increased production of reactive oxygen species (ROS) in mitochondria. In addition, NDI1 overexpression in sod2 background causes cell lethality in both fermentable and semifermentable media. Interruption of certain components in the electron transport chain can suppress the growth inhibition from Ndi1p overexpression. We finally show that disruption of NDI1 or NDE1 decreases ROS production and elongates the chronological life span of yeast, accompanied by the loss of survival fitness. Implication of these findings for Ndi1p-induced apoptosis is discussed.

Apoptosis↗

Ventricular fibrosis suggested by cardiovascular magnetic resonance in adults with repaired tetralogy of fallot and its relationship to adverse markers of clinical outcome.

BACKGROUND: Late morbidity and mortality remain problematic after repair of tetralogy of Fallot (TOF). We hypothesized that fibrosis detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) would be present in adults with repaired TOF and would be related to adverse markers of outcome. METHOD AND RESULTS: LGE was scored in the right and left ventricles (RV and LV) of 92 adult patients who had undergone TOF repair. RV LGE was seen in all patients at surgical sites located in the outflow tract (99%) or the site of ventricular septal defect patching (98%) and in the inferior RV insertion point (79%) and trabeculated myocardium (24%). LV LGE (53%) was located at the apex consistent with apical vent insertion (49%), in the inferior or lateral wall consistent with infarction (5%), or in other areas (8%). Patients with supramedian RV LGE score were older (38 versus 27 years, P<0.001) and more symptomatic (38% versus 8% in New York Heart Association class II or greater, P=0.001), had increased levels of atrial natriuretic peptide (7.3 versus 4.9 pmol/L, P=0.041), and had a trend to higher brain natriuretic peptide (12.3 versus 7.2 pmol/L, P=0.086), exercise intolerance (maximum VO2 24 versus 28 mL.min(-1).kg(-1), P=0.021), RV dysfunction (RV end-systolic volume 61 versus 55 mL/m2, P=0.018; RV ejection fraction 50% versus 56%, P=0.007), and clinical arrhythmia (26% versus 10%, P=0.039). Non-apical vent LV LGE also correlated with markers of adverse outcome. In a multivariate model, RV LGE remained a predictor of arrhythmia. CONCLUSIONS: RV and LV LGE were common after TOF repair and were related to adverse clinical markers, including ventricular dysfunction, exercise intolerance, and neurohormonal activation. Furthermore, RV LGE was significantly associated with clinical arrhythmia.

Adolescent↗

Investigation of the binding mode of (-)-meptazinol and bis-meptazinol derivatives on acetylcholinesterase using a molecular docking method.

Molecular docking has been performed to investigate the binding mode of (-)-meptazinol (MEP) with acetylcholinesterase (AChE) and to screen bis-meptazinol (bis-MEP) derivatives for preferable synthetic candidates virtually. A reliable and practical docking method for investigation of AChE ligands was established by the comparison of two widely used docking programs, FlexX and GOLD. In our hands, we had more luck using GOLD than FlexX in reproducing the experimental poses of known ligands (RMSD<1.5 A). GOLD fitness values of known ligands were also in good agreement with their activities. In the present GOLD docking protocol, (-)-MEP seemed to bind with the enzyme catalytic site in an open-gate conformation through strong hydrophobic interactions and a hydrogen bond. Virtual screening of a potential candidate compound library suggested that the most promising 15 bis-MEP derivatives on the list were mainly derived from (-)-MEP with conformations of (S,S) and (SR,RS) and with a 2- to 7-carbon linkage. Although there are still no biological results to confirm the predictive power of this method, the current study could provide an alternate tool for structural optimization of (-)-MEP as new AChE inhibitors. [Figure: see text].

Acetylcholinesterase↗

Determination of coenzyme Q10 in human seminal plasma by high-performance liquid chromatography and its clinical application.

A high-performance liquid chromatographic (HPLC) method for the analysis of coenzyme Q10 (CoQ10) in human seminal plasma was developed and applied to investigate its clinical significance as a reference index relating to oxidative stress and infertile status of spermatozoa. After precipitation of proteins in seminal plasma with methanol, CoQ10 and coenzyme Q9 (CoQ9; internal standard) were extracted with hexane. The supernatant after centrifugation was evaporated to dryness with nitrogen at 45 degrees C. The residue was re-dissolved in isopropanol. HPLC separation of the sample solution was performed on a Lichrospher C(18) column with a mobile phase composed of isopropanol-methanol-tetrahydrofuran in the ratio of 55:39:6 (v/v/v) at a flow rate of 1.0 mL/min. Under the chromatographic conditions described, the CoQ10 and CoQ9 had retention times of approximately 5.83 and 4.97 min, respectively. The peaks were detected at UV 275 nm. Good separation and detectability of CoQ10 in human seminal plasma were obtained. The method was linear in the range 0.01-10.00 microg/mL. The relative standard deviations within- and between-assay for CoQ10 analysis were 0.85 and 1.86%, respectively. The average recoveries were 94.1-99.0% for the human seminal plasma samples. The CoQ10 levels in seminal plasma of 195 patients and 23 control subjects were studied. CoQ10 concentrations in the two populations were: 37.1 +/- 12.2 ng/mL in the fertile group and 48.5 +/- 20.4 ng/mL in the infertile group. The large difference (p < 0.01) between the fertile and infertile populations is evident.

Adult↗

An important role of Tyk2 in APC function of dendritic cells for priming CD8+ T cells producing IFN-gamma.

Tyrosine kinase 2 (Tyk2) contributes to the signals triggered by IL-12 for IFN-gamma production by NK cells and T cells. We found in this study that Tyk2-deficient (-/-) mice showed increased susceptibility at the early stage after an i.p. infection with Listeria monocytogenes, accompanied by impaired IFN-gamma production. The numbers of both MHC class Ib (H2-M3)- or MHC class Ia (Kb)-restricted CD8+ T cells producing IFN-gamma and exhibiting cytotoxicity were significantly decreased in Tyk2-/- mice after infection with L. monocytogenes. Using an adoptive transfer system of OT-I cells expressing OVA(257-264)/Kb-specific TCR into Tyk2-/- mice followed by challenge with recombinant L. monocytogenes expressing OVA, we found that the defective Tyk2 signaling in the host environment was at least partially responsible for the impaired CD8+ T cytotoxic-1 (Tc1) cell responses in Tyk2-/- mice following the infection. Adoptive transfer with MHC class Ib- or MHC class Ia-binding peptide-pulsed BM-derived DC from Tyk2-/- mice induced lower levels of the Ag-specific CD8+ Tc1 cells producing IFN-gamma. These results suggest that Tyk2 signaling is also important for DC function in the induction of MHC class Ia- and class Ib-restricted CD8+ Tc1 cells following L. monocytogenes infection.

Adoptive Transfer↗

Study on separation of aristolochic acid I and II by micellar electrokinetic capillary chromatography and competition mechanism between SDS and beta-cyclodextrin.

In this study, a rapid MEKC method using 40 mM sodium borate buffer containing 50 mM SDS as surfactant was developed for the analysis of aristolochic acid (AA) in Aristolochia plants. Baseline separation of AA-I and AA-II was achieved within 3 min with high separation efficiency, satisfactory sensitivity, repeatability, and recovery. Resolution between AA-I and AA-II is above 5 and great performance with higher than 200,000 theoretical plate numbers was obtained. The detection limits (based on 3 S/N) were both 1.0 microg/mL. Two kinds of AA in 35 herbal samples of Aristolochia plants were successfully determined. The competition mechanism between beta-CD and SDS was also investigated by changing the content ratio of beta-CD and SDS.

Antiviral Agents↗

Mutational data integration in gene-oriented files of the Hermansky-Pudlak Syndrome database.

Hermansky-Pudlak Syndrome (HPS) is a genetically heterogeneous disorder characterized by oculocutaneous albinism and prolonged bleeding due to abnormal vesicle trafficking to lysosomes and related organelles such as melanosomes and platelet dense granules. This HPS database (HPSD; http://liweilab.genetics.ac.cn/HPSD/) provides integrated, annotatory, and curative data that is distributed in a variety of public databases or predicted by bioinformatics servers for the recently cloned human and mouse HPS genes, as well as for the genes responsible for HPSrelated syndromes, such as ChediakHigashi Syndrome (CHS), Griscelli syndrome (GS), oculocutaneous albinism (OCA), Usher syndrome type 1B (USH1B), and ocular albinism (OA). The HPSD is designed by using a unique GeneOriented File (GOF) format. Seven blocks (genomic, transcript, protein, function, mutation, phenotype, and reference) are carefully annotated in each userfriendly GOF entry. The HPSD emphasizes paired human and mouse GOF entries. The genes included in this database (currently 58 in total) are arbitrarily divided into four categories: 1) Human and Mouse HPS, 2) Mouse HPS Only, 3) Putative Mouse or Human HPS, and 4) HPS Related Syndromes. All the mutations in these genes are integrated in the GOFs. We expect that these very informative and peerreviewed GOFs will be shortcuts to utilize the webbased information for the emerging interdisciplinary studies of HPS.

Animals↗

Use of polylactic acid/polytrimethylene carbonate blends membrane to prevent postoperative adhesions.

The objective of the study was to evaluate the effect of a novel biodegradable membrane on the prevention of postoperative adhesion formation. The membrane was prepared by blending 50% PLA (polylactic acid) with 50% PTMC (polytrimethylene carbonate). The prepared blends polymer membrane was more flexible than pure PLA membrane, as measured by glass-transition temperature and tensile study. Cytotoxicity study revealed that PLA/PTMC blends membrane showed good biocompatibility. The membrane elicited slight tissue reaction based on the results of histological study. Thirty adult Japanese rabbits were used for the intestine adhesion model. The treatment group had PLA/PTMC membrane, the control group had chitosan, and the blank control group was not operated. The animals were housed for two weeks and sacrificed to investigate adhesion of intestine. Compared with the blank control group, the treatment group and the control group lowered the extent of adhesions (p < 0.01), but the treatment group was better than the control group (p < 0.05). The in-vivo studies confirmed that PLA/PTMC blends membrane could prevent postoperative adhesions.

Animals↗

RepairNET: a bioinformatics toolbox for functional exploration of DNA damage response.

DNA damage response is one of the essential cellular mechanisms to maintaining the genomic integrity of the cell. Aberrations in the mechanism of DNA damage response often result in cancer. We describe here RepairNET, a protein-protein interaction network associated with the DNA damage response. RepairNET is assembled from the published literature by using a protocol that involved computational data mining of the MEDLINE and manual curation. This network represents the current knowledge on the intrinsic signaling pathways related to the DNA damage response process. RepairNET currently contains more than 1,200 proteins with over 2,300 functional interactions. A number of web-interface tools have been implemented to facilitate a user-friendly environment. The users can navigate through the cellular network associated with the DNA damage response via a Java-based interactive graphical interface. In order to help users explore the functional relationships between the interacting proteins, we have assigned functional domains to the proteins in RepairNET based on their sequences. A total of 365 unique functional domains are assigned. RepairNET is available online at http://guanyin.chem.temple.edu/RepairNET.html. It could become an essential resource center for cancer research, providing clues to understanding the functional relationship between proteins in the network, and to building scientific models for the mechanism of DNA damage response and cancer proliferation.

Adaptor Proteins, Signal Transducing↗

Scoutless stepping-table peripheral contrast-enhanced MR angiography.

PURPOSE: To evaluate the feasibility of a scoutless method, termed EZ-STEP, for stepping-table peripheral contrast-enhanced magnetic resonance angiography (CE-MRA). MATERIALS AND METHODS: This scoutless method involves the use of a stepping-table, fast 3D MRA acquisition that incorporates spatially nonselective radiofrequency (RF) pulses for excitation to reduce the repetition time (TR). The sequence was tested in a phantom. The EZ-STEP protocol was optimized in four healthy volunteers and used in 15 subjects. The image quality was scored in a blinded fashion and compared with conventional MRA in eight patients. RESULTS: The acquisition speed of the EZ-STEP sequence was approximately 30% faster in the phantom study compared to the conventional MRA sequence. The total examination time for EZ-STEP was 6 minutes, compared to an average of 23 minutes for conventional MRA. The average image quality scores for EZ-STEP and conventional MRA for stations 1-3 were 3.50 vs. 3.06 (P = 0.087), 3.53 vs. 3.00 (P = 0.033), and 2.97 vs. 2.50 (P = 0.090), respectively. CONCLUSION: EZ-STEP is a more efficient method than the conventional approach for stepping-table peripheral CE-MRA, and provides comparable or better image quality. This method shortens the examination time substantially and eliminates the risk of failing to image a vessel because of improper positioning of the scan volume.

Adult↗

Magnetic resonance imaging of myocardial infarction using a manganese-based contrast agent (EVP 1001-1): preliminary results in a dog model.

PURPOSE: To investigate the MRI characteristics of an intracellular manganese-based contrast agent, EVP 1001-1 (Eagle Vision Pharmaceutical Corp.), in a canine model of myocardial infarction. MATERIALS AND METHODS: Three dogs were imaged 14-37 days following permanent ligation of the left anterior descending coronary artery (LAD). Measurements of the longitudinal relaxation rate R(1) were made prior to EVP 1001-1 administration (20 micromol/kg i.v.) and for one hour thereafter. Triphenyl tetrazolium chloride (TTC) staining was used to document infarction. RESULTS: In normal myocardium, EVP 1001-1 produced a substantial increase in the longitudinal relaxation rate, which remained fairly constant over the postcontrast imaging period (DeltaR1= 1.47 +/- 0.58 sec(-1) (mean +/- SD) at 35 minutes, P < 0.05). In the infarct, the response to EVP 1001-1 was small or negligible (DeltaR1= 0.27 +/- 0.28 sec(-1)). This resulted in a significant postcontrast difference in relaxation rate between normal and infarcted tissue (R1(normal) - R1(infarct) = 1.08 +/- 0.26 sec(-1), P < 0.05). The infarct remained clearly delineated in all animals throughout the steady-state imaging period, and qualitatively matched TTC results. CONCLUSION: The persistent enhancement pattern revealed by MRI following EVP 1001-1 administration may be beneficial for identifying and characterizing myocardial infarction.

Animals↗

Reduction of fat storage in mice fed a high-fat diet long term by treatment with saponins prepared from Kochia scoparia fruit.

The fresh fruit (Japanese name, Tonburi) of Kochia scoparia has been used as a food garnish in Japanese-style dishes from ancient times, and may prevent metabolic syndromes such as hyperlipidemia, hypertension, obesity and atherosclerosis. This study was performed to clarify whether an ethanol extract of K. scoparia fruit prevented obesity induced in mice by a high-fat diet for 9 weeks. The ethanol extract of K. scoparia fruit prevented the increases in body weight and parametrial adipose tissue weight induced by the high-fat diet. Furthermore, consumption of a high-fat diet containing 1% or 3% K. scoparia extract significantly increased the fecal content and the fecal triacylglycerol level at day 3 compared with those in the high-fat diet group. The ethanol extract (250 mg/kg) and total saponins (100 mg/kg) of K. scoparia inhibited the elevation of the plasma triacylglyccerol level 2 or 3 h after the oral administration of the lipid emulsion. Total saponins, momordin Ic, 2'-O-beta-d-glucopyranosyl momordin Ic and 2'-O-beta-d-glucopyranosyl momordin IIc isolated from K. scoparia fruit inhibited the pancreatic lipase activity (in vitro). These findings suggest that the anti-obesity actions of K. scoparia extract in mice fed a high-fat diet may be partly mediated through delaying the intestinal absorption of dietary fat by inhibiting pancreatic lipase activity.

Animals↗

Fragmentation study of hexanitrostilbene by ion trap multiple mass spectrometry and analysis by liquid chromatography/mass spectrometry.

The fragmentation pathways of three explosive compounds with similar structures, hexanitrostilbene (HNS), cyclotrimethylene trinitramine (RDX), and 2,4,6-trinitrotoluene (TNT), have been investigated by multiple mass spectrometry (MSn, n = 1, 2, 3) with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) sources. The electron capture mechanism for these compounds in negative ion APCI and ESI mode differs from the usual negative ion mechanism, deprotonation or addition of other species. This was shown for HNS and TNT, which both gave a [M]- anion but not a [M-H]- ion in APCI, and the [M]- anion of HNS was observed in ESI. The quantitative analysis of HNS was performed by liquid chromatography (LC)/ESI-MS, and the results obtained by the internal standard (ISTD) method were compared with those from the external standard (ESTD) method, demonstrating that both quantitation approaches are useful, with good sensitivity, reproducibility and linearity, and ESTD is preferable in routine applications.

Chromatography, High Pressure Liquid↗