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Biomedical subjects

Mei-Ling Chen

Publications and source records attributed to Mei-Ling Chen.

At least 19 recordsLinked to original sources

The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/- mice.

The tumor suppressor PTEN is frequently inactivated in human cancers. A major downstream effector of PTEN is Akt, which is hyperactivated via PTEN inactivation. It is not known, however, whether diminished Akt activity is sufficient to inhibit tumorigenesis initiated by Pten deficiency. Here we showed that the deficiency of Akt1 is sufficient to dramatically inhibit tumor development in Pten+/- mice. Akt1 deficiency had a profound effect on endometrium and prostate neoplasia, two types of human cancer, in which PTEN is frequently mutated, and also affected thyroid and adrenal medulla tumors and intestinal polyps. Even haplodeficiency of Akt1 was sufficient to markedly attenuate the development of high-grade prostate intraepithelial neoplasia (PIN) and endometrial carcinoma. These results have significant implications for cancer therapy.

Adrenal Gland Neoplasms↗

Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4+ CD25- LAP+ T cells.

A major goal of immunotherapy for autoimmune diseases and transplantation is induction of regulatory T cells that mediate immunologic tolerance. The mucosal immune system is unique, as tolerance is preferentially induced after exposure to antigen, and induction of regulatory T cells is a primary mechanism of oral tolerance. Parenteral administration of CD3-specific monoclonal antibody is an approved therapy for transplantation in humans and is effective in autoimmune diabetes. We found that orally administered CD3-specific antibody is biologically active in the gut and suppresses autoimmune encephalomyelitis both before induction of disease and at the height of disease. Orally administered CD3-specific antibody induces CD4+ CD25- LAP+ regulatory T cells that contain latency-associated peptide (LAP) on their surface and that function in vitro and in vivo through a TGF-beta-dependent mechanism. These findings identify a new immunologic approach that is widely applicable for the treatment of human autoimmune conditions.

Administration, Oral↗

Symptom clusters in cancer patients.

GOALS OF WORK: Cancer patients often experience multiple symptoms, many of which have been reported to correlate with each other. The goals of this study were to understand which cancer-related symptoms cluster together and to test the conceptual meanings of the revealed symptom clusters. PATIENTS AND METHODS: Patients with various cancer diagnoses (N=151) were recruited from a medical center in northern Taiwan. The 13-item M.D. Anderson symptom inventory was used to assess patients' symptom severity. Selected symptoms were factored using principal-axis factoring with oblique rotation. The known-group technique was used to validate the conceptual meanings of revealed factors. MAIN RESULTS: Patients' symptom severity ratings fit a three-factor solution that explained 55% of the variance. These three factors (symptom clusters) were named sickness symptom cluster, gastrointestinal symptom cluster, and emotional symptom cluster. Patients with pain and with advanced diseases had significantly higher mean scores in the sickness symptom cluster than patients without pain and with earlier-stage diseases. The patients' functional status was negatively correlated with mean scores in the sickness symptom cluster. Patients under chemotherapy demonstrated significantly higher mean scores in the gastrointestinal symptom cluster than patients under other treatments. Patients with anxiety or depression also had significantly higher mean scores in the emotional symptom cluster than patients without anxiety or depression. CONCLUSIONS: This study identified three underlying symptom clusters and verified their conceptual meaning in cancer patients. Knowing these symptom clusters may help healthcare professionals understand plausible mechanisms for the aggregation of symptoms.

Activities of Daily Living↗

Validation of the Taiwanese version of the Brief Fatigue Inventory.

We validated the Taiwanese version of the Brief Fatigue Inventory (BFI-T) in a sample of 439 Taiwanese patients with multiple cancer diagnoses. Internal consistency was indicated by Cronbach alphas of 0.96 for fatigue-related severity and 0.95 for interference. Test-retest reliability was 0.89 for fatigue severity and 0.91 for interference. Factor analysis revealed a one-factor structure. Convergent validity was examined by correlating the BFI-T worst fatigue and fatigue severity composite scores with POMS vigor and fatigue subscales scores. Known-group validity was established by comparing BFI-T worst fatigue and severity composite scores between patients with low functional status and high functional status and between inpatients and outpatients. The BFI-T's sensitivity was examined by comparing BFI-T severity and interference composite scores before, during, and after chemotherapy treatment in a subsample of 20 breast cancer patients. The BFI-T is reliable, valid, and sensitive for measuring cancer-related fatigue severity and interference among Taiwanese cancer patients.

Adult↗

Transformation from tubulointerstitial nephritis to crescentic glomerulonephritis: an unusual presentation of ANCA-associated renal vasculitis.

A 44-year-old man with acute renal failure and antineutrophil cytoplasmic antibodies (ANCA) positivity was described. The first renal biopsy specimen showed tubulointerstitial nephritis (TIN) with normal glomeruli. However, delayed recovery of renal function with low-dose steroid treatment for TIN prompted a second renal biopsy 1 month later; and the specimen demonstrated a dramatically different morphology, with necrotizing and crescentic glomerulonephritis. Improvement in renal function occurred, together with reduction of ANCA titers, following intensive immunosuppressive therapy. This case illustrates an unusual presentation of TIN in ANCA-associated renal vasculitis. The possible pathogenetic mechanism are discussed.

Adult↗

Acute renal failure secondary to small cell lung cancer with tumor infiltration of the kidneys.

Acute renal failure secondary to tumor infiltration of the kidneys is uncommon and largely described in patients with lymphoma or leukemia. We report a 64-year-old man previously diagnosed with limited stage small cell lung cancer who presented with acute renal failure (ARF). Renal imaging showed bilateral enlargement with features suggestive of an infiltrative process. A kidney biopsy established the diagnosis of metastatic small cell lung cancer with diffuse renal parenchymal infiltration. This case emphasizes the rare potential for cancers to metastasize to the kidneys, which can result in ARF. Early recognition of this cause of ARF is crucial, in particular, when the tumor is amenable to chemotherapy or irradiation.

Acute Kidney Injury↗

Ethnic or racial differences revisited: impact of dosage regimen and dosage form on pharmacokinetics and pharmacodynamics.

Ethnic or racial differences in pharmacokinetics and pharmacodynamics have been attributed to the distinctions in the genetic, physiological and pathological factors between ethnic/racial groups. These pharmacokinetic/pharmacodynamic differences are also known to be influenced by several extrinsic factors such as socioeconomic background, culture, diet and environment. However, it is noted that other factors related to dosage regimen and dosage form have largely been ignored or overlooked when conducting or analysing pharmacokinetic/pharmacodynamic studies in relation to ethnicity/race. Potential interactions can arise between the characteristics of ethnicity/race and a unique feature of dosage regimen or dosage form used in the study, which may partly account for the observed pharmacokinetic/pharmacodynamic differences between ethnic/racial groups. Ethnic/racial differences in pharmacokinetics/pharmacodynamics can occur from drug administration through a specific route that imparts distinct pattern of absorption, distribution, transport, metabolism or excretion. For example, racial differences in the first-pass metabolism of a drug following oral administration may not be relevant when the drug is applied to the skin. On the other hand, ethnic/racial difference in pharmacokinetics/pharmacodynamics can also happen via two different routes of drug delivery, with varying levels of dissimilarity between routes. For example, greater ethnic/racial differences were observed in oral clearance than in systemic clearance of some drugs, which might be explained by the pre-systemic factors involved in the oral administration as opposed to the intravenous administration. Similarly, changes in the dose frequency and/or duration may have profound impact on the ethnic/racial differences in pharmacokinetic/pharmacodynamic outcome. Saturation of enzymes, transporters or receptors at high drug concentrations is a possible reason for many observed ethnic/racial discrepancies between single- and multiple-dose regimens, or between low- and high-dose administrations. The presence of genetic polymorphism of enzymes and/or transporters can further complicate the analysis of pharmacokinetic/pharmacodynamic data in ethnic/racial populations. Even within the same dosage regimen, the use of different dosage forms may trigger significantly different pharmacokinetic/pharmacodynamic responses in various ethnic/racial groups, given that different dosage forms may exhibit different rates of drug release, may release the drug at different sites, and/or have different retention times at specific sites of the body. It is thus cautioned that the pharmacokinetic/pharmacodynamic data obtained from different ethnic/racial groups cannot be indiscriminately compared or combined for analysis if there is a lack of homogeneity in the apparent 'extrinsic' factors, including dosage regimen and dosage form.

Cross-Cultural Comparison↗

Detection of severe acute respiratory syndrome coronavirus RNA in plasma during the course of infection.

We examined severe acute respiratory syndrome-associated coronavirus (SARS-CoV) RNA in plasma of 32 patients (probable SARS cases) by a quantitative real-time reverse transcription-PCR assay and reported that the highest detection rate, 75%, was found between day 5 and day 7 of illness, followed by rates of 64, 50, and 38% found between day 8 and day 11, day 2 and day 4, and day 12 and day 16, respectively. Analysis of sequential SARS-CoV load in plasma from six cases revealed different patterns of viremia, with the peak between day 4 and day 8. Our findings of the high detection rate of SARS-CoV RNA in plasma before day 11, together with the relative convenience of collecting and handling plasma, suggest that plasma can be used for early diagnosis of SARS.

Adult↗

Development of a new sampling medium for bioaerosols.

OBJECTIVE: To develop a new sampling medium for detecting of bioaerosols. METHODS: The sampling media were tested by using Escherichia coli, Staphylococcus aureus and Serratia marcescens under static and active conditions, preliminary applications were performed using AGI-10 and high volume sampler. RESULTS: The average recovery rates were raised to 24.7%, 58.2%, 40.5%, 44.1%, 20.5%, and 15.4%, respectively in six consecutive experiments under static condition for 60 min at room temperature. Four kinds of sampling media were singled out after static experiments, which were referred to as "samplutions" PD1, PX2, TD1, and TX2, respectively. Under the active condition, the protective efficacy of PD1, PX2, TD1, and TX2 was 226% (153/47), 553% (111/17), 150% (120/48), and 268% (419/114), respectively. CONCLUSION: The samplutions have some effects on the subsequent nucleic acid detection, which could be avoided by employing standard nucleic acid extraction procedure. The newly developed samplution can be applied to the detection of bioaerosols.

Aerosols↗

[Cloning and expression of the Apx IVA gene of Actionbacillus pleuroneumoniae and development of an indirect ApxIVA-ELISA].

Apx IV, a forth RTX toxin indentified in Actionbacillus pleuropneumoniae recently, is expressed by all A. pleuropneumoniae regardless the serotypes and inducible only in vivo toxin, so it is the optimal to develop species-specific and differentiated diagnostic assay. Here the 2445bp DNA fragment of apxIVA gene of A. pleuroneumoniae was amplified and fused in-frame to the downstream of the T7 promoter and 6 His Tag of the prokaryotic expression vector pET-28b. The construct was transformed into E. coli BL21(DE3). After induction by 1.0 mol/L IPTG, a recombinant protein about 90 kD in size, designed as ApxIVAN, was detected, which was present as inclusion bodies and reacted specifically with swine antisera to the APP-serotype-1 by dot-blot. An indirect ELISA (ApxIVA-ELISA) was developed using purified recombinant ApxIVAN from the inclusion bodies as described previously, which had excellent specificity to A. pleuroneunoniae. Using the ApxIVA-ELISA, the ApxIV antibodies were not detected in the inactivated APP bacterins vaccinated pigs, but were detected in A. pleuropneumoniae serotype 1, 2 and 7 infected pigs and mice. These results suggested that ApxIVA-ELISA can be used not only to detect all serotypes of APP, but also to differentiate the naturally infected and inactivated vaccine immunized pigs.

Actinobacillus Infections↗

Pulmonary-renal syndrome in a patient with bacterial endocarditis.

Pulmonary-renal syndrome is defined as a combination of pulmonary hemorrhage and glomerulonephritis. We report an unusual case of bacterial endocarditis presenting with pulmonary hemorrhage and rapidly progressive glomerulonephritis as the initial manifestations of the disease. A 37-year-old man was admitted with fever, hemoptysis, and dyspnea. Admission examinations revealed severe renal failure requiring dialysis therapy. Chest radiograph showed extensive pulmonary reticulonodular infiltrates. Echocardiography revealed ventricular septal defect. Furthermore, blood cultures grew viridians group streptococci. The kidney and lung biopsies demonstrated diffuse cresentic glomerulonephritis and alveolar hemorrhage, respectively. Bacterial endocarditis was diagnosed according to the Duke criteria and the patient was treated with intravenous antibiotic therapy. The pulmonary infiltrates disappeared gradually. However, renal function did not improve, even after trial of a course of immunosuppressive therapy. The patient survived and remained on regular hemodialysis. We conclude that bacterial endocarditis should be included in the differential diagnosis of pulmonary-renal syndrome.

Adult↗

[The positioning of nursing research in the academic studies: the origin and development of qualitative and quantitative studies].

The purpose of this study is to discuss the historical context of qualitative and quantitative research so as to explain the principle of qualitative study and examine the positioning of nursing research within academic study as a whole. This paper guides the readers towards the historical context from empirical science, discusses the influences of qualitative and quantitative research on nursing research, then investigates the nature of research paradigms, examines the positioning of nursing research, which includes the characteristics of fields such as natural science, humanity and social studies, and science, and lastly, presents the research standard proposed by Yardley in 2000. The research paradigms include Positivism, Postpositivism, Criticism, and Constructivism, which can be compared with Ontology, Epistemology, and Methodology. The nature of the paradigm is to determine the assumption of the paradigm on the basis of Ontology, Epistemology, and Methodology. The paradigm determines how the researcher views the world and decides on what to answer, how to research, and how to answer. The difference in academic environment is reflected in the long-term dialogue between qualitative and quantitative studies, as well as the standard for criticism. This paper introduces the method of evaluation of the quality of qualitative study proposed by Yardley in 2002, namely the sensitivity of the context, the promise and conscientiousness, transparency and consistency, influence and significance. The paper is intended to provide a guideline for readers in evaluating the quality of qualitative study.

Humans↗

Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo.

Cancer patients can harbor significant numbers of CD8 and CD4 T cells with specificities to tumor antigens (Ags). Yet, in most cases, such T cells fail to eradicate the tumor in vivo. Here, we investigated the interference of Ag-specific CD4(+)CD25(+) regulatory T cells (Treg) with the tumor-specific CD8 T cell immune response in vivo, by monitoring the homing, expansion, and effector function of both subsets in draining and nondraining lymph nodes. The results show that CD8 cells expand to the same extent and produce similar levels of IFN-gamma in the presence or absence of Ag-specific Treg. Nevertheless, these Treg abrogate CD8 T cell-mediated tumor rejection by specifically suppressing the cytotoxicity of expanded CD8 cells. The molecular mechanism of suppression involves TGF-beta because expression of a dominant-negative TGF-beta receptor by tumor-specific CD8 cells renders them resistant to suppression and is associated with tumor rejection and unimpaired cytotoxicity.

Animals↗

Do men and women differ in proximal small intestinal CYP3A or P-glycoprotein expression?

The higher systemic clearance of some CYP3A4 [whether also P-glycoprotein (P-gp)] drug substrates in women versus men is attributed in part to a higher hepatic CYP3A4 content in women. This, combined with the general paucity of reported sex differences in the apparent oral clearance of CYP3A4 substrates, suggested a sex-dependent expression of CYP3A4 in the intestine, but in a pattern opposite to that in the liver. Accordingly, duodenal biopsies obtained from healthy men (n = 46) and women (n = 45) were analyzed, by Western blot, for relative CYP3A4, as well as for CYP3A5 and P-gp, expression levels. Among all subjects, CYP3A4 and P-gp varied 8- and 10-fold, respectively. CYP3A5, which was readily detected in 27% of these predominantly white individuals, varied 7-fold. For all three proteins, a sex difference was not detected (p >/= 0.55). The lack of a difference remained for CYP3A4 and P-gp when the analysis was restricted to white individuals (n = 74) or to individuals with undetectable CYP3A5. Comparing the 21 premenopausal women (all were aged <45 years) with the 43 men aged <45 years, again no sex differences were detected in CYP3A4 and P-gp. Comparing the pre- with postmenopausal women, mean CYP3A4 content was 20% lower in the postmenopausal individuals (p = 0.01). The lack of a sex-dependent difference in proximal intestinal CYP3A4 could account, in part, for the lack of reported sex differences in the oral, relative to systemic, clearance of some CYP3A4 substrates. Ramifications of lower intestinal CYP3A4 content in post- versus premenopausal women require further investigation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Impact of cancer patients' quality of life on that of spouse caregivers.

GOALS OF WORK: This study aimed to examine the correlation between quality of life (QOL) in cancer patients and that of their spouse caregivers and to identify factors that influence this correlation. PATIENTS AND METHODS: This cross-sectional study collected data from 121 cancer patient/spouse caregiver dyads. The Functional Assessment of Cancer Therapy Scale-General (FACT-G) was used to measure patients' QOL, and the Caregiver Quality of Life Index (CQLI) was used to measure spouse caregivers' QOL. Correlation coefficients between patients' and caregivers' QOL were computed for four dimensions of QOL, as well as a total score for QOL. Correlations between patients' and caregivers' total QOL scores were furthered analyzed by three groups of factors: disease-/treatment-related, caregiving-related, and relationship-related variables. MAIN RESULTS: Only the social/family and functional dimensions of patient QOL and total score for patient QOL were associated with each dimension of their caregivers' QOL and with the total score ( r=0.27-0.44). Physical and emotional dimensions of patients' QOL did not significantly influence spouse caregivers' QOL for any dimension nor for the total score. Factors influencing the association between patients' and caregivers' overall QOL included cancer diagnosis, length of hospitalization, caregiving intensity and duration, marital satisfaction, and caregiving self-esteem. CONCLUSIONS: Social and functional aspects of patients' QOL play a significant role in determining the QOL of their spouse caregivers. The strength of association between patients' and spouse caregivers' overall QOL can be moderated by some factors.

Adaptation, Psychological↗

Assuring quality and performance of sustained and controlled release parenterals: EUFEPS workshop report.

This is a summary report of the workshop, organized by the European Federation of Pharmaceutical Scientists in association with the American Association of Pharmaceutical Scientists, the European Agency for the Evaluation of Medicinal Products, the European Pharmacopoeia, the US Food and Drug Administration and the United States Pharmacopoeia, on "Assuring Quality and Performance of Sustained and Controlled Release Parenterals" held in Basel, Switzerland, February 2003. Experts from the pharmaceutical industry, regulatory authorities and academia participated in this workshop to review, discuss and debate formulation, processing and manufacture of sustained and controlled release parenterals, and identify critical process parameters and their control. This workshop was a follow-up workshop to a previous workshop on Assuring Quality and Performance of Sustained and Controlled Release Parenterals that was held in Washington, DC in April 2001. This report reflects the outcome of the Basel 2003 meeting and the advances in the field since the Washington, DC meeting in 2001. As necessary, the reader is referred to the report on the 2001 meeting. Areas were identified at the 2003 Basel meeting where research is needed in order to understand the performance of these drug delivery systems and to assist in the development of appropriate testing procedures. Recommendations were made for future workshops and meetings.

Biopolymers↗