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2.
Clin Exp Metastasis ; 37(4): 541-549, 2020 08.
Article in English | MEDLINE | ID: mdl-32524317

ABSTRACT

Malignant pleural effusion (MPE) results from primary mesothelioma or the spreading of metastatic cancer. Both talc pleurodesis (TP) and indwelling pleural catheter (IPC) improve MPE symptoms. We performed a meta-analysis of randomized controlled trials to compare the efficacy of TP with that of IPC in patients with MPE. PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov databases were searched for studies published before February 2020. Individual effect sizes were standardized, and a meta-analysis was conducted to calculate a pooled effect size by using random effects models. In total, 4 trials with 500 patients were reviewed. Difference in pleurodesis success rate and change in dyspnea scores at 4 and 6 weeks between MPE patients treated with IPC and those treated with TP for pleurodesis were nonsignificant. The number of hospital inpatient days was significantly lower among patients who were treated with IPC (weight mean difference: 2.19; 95% confidence interval 0.70-3.67) than among those who were treated with TP. No significant difference was shown in adverse event profile between patients treated with IPC and those treated with TP for pleurodesis. In conclusion, both TP and IPC are equally effective in treating patients with MPE. The number of hospitalization days was significantly lower for patients who were treated with IPC, but the magnitude of the difference is of uncertain clinical importance.


Subject(s)
Catheters, Indwelling/adverse effects , Drainage/methods , Pleural Effusion, Malignant/therapy , Pleurodesis/methods , Talc/therapeutic use , Catheterization , Humans , Length of Stay/statistics & numerical data , Mesothelioma/pathology , Quality of Life/psychology , Randomized Controlled Trials as Topic
3.
Nature ; 566(7744): E9, 2019 02.
Article in English | MEDLINE | ID: mdl-30723267

ABSTRACT

In this Letter, the vertical error bars were missing from Fig. 3b and 3c. This figure has been corrected online.

4.
Nature ; 566(7745): 538-542, 2019 02.
Article in English | MEDLINE | ID: mdl-30675058

ABSTRACT

Oligodendrocytes wrap nerve fibres in the central nervous system with layers of specialized cell membrane to form myelin sheaths1. Myelin is destroyed by the immune system in multiple sclerosis, but myelin is thought to regenerate and neurological function can be recovered. In animal models of demyelinating disease, myelin is regenerated by newly generated oligodendrocytes, and remaining mature oligodendrocytes do not seem to contribute to this process2-4. Given the major differences in the dynamics of oligodendrocyte generation and adaptive myelination between rodents and humans5-9, it is not clear how well experimental animal models reflect the situation in multiple sclerosis. Here, by measuring the integration of 14C derived from nuclear testing in genomic DNA10, we assess the dynamics of oligodendrocyte generation in patients with multiple sclerosis. The generation of new oligodendrocytes was increased several-fold in normal-appearing white matter in a subset of individuals with very aggressive multiple sclerosis, but not in most subjects with the disease, demonstrating an inherent potential to substantially increase oligodendrocyte generation that fails in most patients. Oligodendrocytes in shadow plaques-thinly myelinated lesions that are thought to represent remyelinated areas-were old in patients with multiple sclerosis. The absence of new oligodendrocytes in shadow plaques suggests that remyelination of lesions occurs transiently or not at all, or that myelin is regenerated by pre-existing, and not new, oligodendrocytes in multiple sclerosis. We report unexpected oligodendrocyte generation dynamics in multiple sclerosis, and this should guide the use of current, and the development of new, therapies.


Subject(s)
Cell Proliferation , Multiple Sclerosis/pathology , Oligodendroglia/pathology , Adult , Age of Onset , Aging/pathology , Aging/physiology , Case-Control Studies , Cell Differentiation , Cell Separation , Female , Humans , Male , Multiple Sclerosis/genetics , Myelin Sheath/metabolism , Myelin Sheath/pathology , Oligodendroglia/cytology , Oligodendroglia/metabolism , Remyelination , White Matter/cytology , White Matter/metabolism , White Matter/pathology
5.
Stem Cell Reports ; 5(2): 174-84, 2015 Aug 11.
Article in English | MEDLINE | ID: mdl-26235891

ABSTRACT

In this study, we sought evidence for alpha-synuclein (ASYN) expression in oligodendrocytes, as a possible endogenous source of ASYN to explain its presence in glial inclusions found in multiple system atrophy (MSA) and Parkinson's disease (PD). We identified ASYN in oligodendrocyte lineage progenitors isolated from the rodent brain, in oligodendrocytes generated from embryonic stem cells, and in induced pluripotent stem cells produced from fibroblasts of a healthy individual and patients diagnosed with MSA or PD, in cultures in vitro. Notably, we observed a significant decrease in ΑSYN during oligodendrocyte maturation. Additionally, we show the presence of transcripts in PDGFRΑ/CD140a(+) cells and SOX10(+) oligodendrocyte lineage nuclei isolated by FACS from rodent and human healthy and diseased brains, respectively. Our work identifies ASYN in oligodendrocyte lineage cells, and it offers additional in vitro cellular models that should provide significant insights of the functional implication of ASYN during oligodendrocyte development and disease.


Subject(s)
Cell Lineage , Neural Stem Cells/metabolism , Oligodendroglia/metabolism , alpha-Synuclein/metabolism , Animals , Cell Differentiation , Cells, Cultured , Embryonic Stem Cells/cytology , Embryonic Stem Cells/metabolism , Humans , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , Mice , Neural Stem Cells/cytology , Oligodendroglia/cytology , Species Specificity , alpha-Synuclein/genetics
6.
Cell ; 159(4): 766-74, 2014 Nov 06.
Article in English | MEDLINE | ID: mdl-25417154

ABSTRACT

The myelination of axons by oligodendrocytes has been suggested to be modulated by experience, which could mediate neural plasticity by optimizing the performance of the circuitry. We have assessed the dynamics of oligodendrocyte generation and myelination in the human brain. The number of oligodendrocytes in the corpus callosum is established in childhood and remains stable after that. Analysis of the integration of nuclear bomb test-derived (14)C revealed that myelin is exchanged at a high rate, whereas the oligodendrocyte population in white matter is remarkably stable in humans, with an annual exchange of 1/300 oligodendrocytes. We conclude that oligodendrocyte turnover contributes minimally to myelin modulation in human white matter and that this instead may be carried out by mature oligodendrocytes, which may facilitate rapid neural plasticity.


Subject(s)
Aging , Brain/cytology , Brain/growth & development , Myelin Sheath/metabolism , Oligodendroglia/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Brain/physiology , Carbon Isotopes/analysis , Child , Child, Preschool , Corpus Callosum/metabolism , Humans , Infant , Middle Aged , Neuronal Plasticity , Nuclear Weapons , White Matter/chemistry , White Matter/metabolism , Young Adult
7.
Methods Mol Biol ; 1172: 13-25, 2014.
Article in English | MEDLINE | ID: mdl-24908291

ABSTRACT

A ubiquitous nuclear protein, the high-mobility group box 1 (HMGB1), is secreted by activated macrophages/monocytes and leaked passively from injured cells. HMGB1 functions as a mediator of infection- and injury-elicited inflammatory diseases. Here, we describe a semiquantitative immuno-blotting method to measure the released HMGB1 in human serum, in comparison with a commercially available HMGB1 ELISA technique.


Subject(s)
Blotting, Western/standards , HMGB1 Protein/analysis , Macrophages/metabolism , Amino Acid Sequence , Antibodies/chemistry , Blotting, Western/methods , Cell Nucleus/metabolism , Enzyme-Linked Immunosorbent Assay , HMGB1 Protein/metabolism , Humans , Macrophage Activation , Macrophages/cytology , Macrophages/immunology , Molecular Sequence Data , Peptides/chemistry , Peptides/immunology , Peroxidase/chemistry
8.
Neuron ; 74(4): 634-9, 2012 May 24.
Article in English | MEDLINE | ID: mdl-22632721

ABSTRACT

Continuous turnover of neurons in the olfactory bulb is implicated in several key aspects of olfaction. There is a dramatic decline postnatally in the number of migratory neuroblasts en route to the olfactory bulb in humans, and it has been unclear to what extent the small number of neuroblasts at later stages contributes new neurons to the olfactory bulb. We have assessed the age of olfactory bulb neurons in humans by measuring the levels of nuclear bomb test-derived (14)C in genomic DNA. We report that (14)C concentrations correspond to the atmospheric levels at the time of birth of the individuals, establishing that there is very limited, if any, postnatal neurogenesis in the human olfactory bulb. This identifies a fundamental difference in the plasticity of the human brain compared to other mammals.


Subject(s)
Neurogenesis/physiology , Neurons/cytology , Olfactory Bulb/cytology , Smell/physiology , Cell Movement/physiology , Humans , Neurons/physiology , Olfactory Bulb/physiology
9.
Proc Natl Acad Sci U S A ; 107(33): 14657-61, 2010 Aug 17.
Article in English | MEDLINE | ID: mdl-20675585

ABSTRACT

Neural stem cells have a broad differentiation repertoire during embryonic development and can be reprogrammed to pluripotency comparatively easily. We report that adult neural stem cells can be reprogrammed at very high efficiency to monocytes, a differentiated fate of an unrelated somatic lineage, by ectopic expression of the Ets transcription factor PU.1. The reprogrammed cells display a marker profile and functional characteristics of monocytes and integrate into tissues after transplantation. The failure to reprogram lineage-committed neural cells to monocytes with PU.1 suggests that neural stem cells are uniquely amenable to reprogramming.


Subject(s)
Cellular Reprogramming , Monocytes/metabolism , Neurons/metabolism , Proto-Oncogene Proteins/metabolism , Stem Cells/metabolism , Trans-Activators/metabolism , Animals , Calcium-Binding Proteins/metabolism , Cell Line , Cells, Cultured , Embryo, Mammalian/cytology , Embryo, Mammalian/metabolism , Female , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Humans , Immunohistochemistry , Lentivirus/genetics , Male , Mice , Mice, Inbred C57BL , Microfilament Proteins , Microscopy, Confocal , Monocytes/cytology , Neurons/cytology , Pregnancy , Proto-Oncogene Proteins/genetics , Stem Cells/cytology , Time Factors , Trans-Activators/genetics , Transduction, Genetic
10.
Eur J Oncol Nurs ; 14(1): 17-22, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19734087

ABSTRACT

PURPOSE: The aim of the study was to examine anxiety and depression and their effects on the quality of life (QOL) of patients with breast cancer undergoing chemotherapy or radiotherapy. METHODS: A cross-sectional descriptive design was used. Data were collected from a self-report survey derived from the Hospital Anxiety and Depression Scale (HADS)-Cantonese/Chinese version, the Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B)-Chinese version, and from demographic and clinical characteristics. Chi-square tests and the General Linear Model (GLM) were used for secondary data analysis. SAMPLE: The study group consisted of 218 women (> or = 18 years old) who were midway through chemotherapy or radiotherapy for stage I-III breast cancer. All subjects were recruited from the outpatient sections of the Departments of Clinical Oncology or Breast Centers of the four Hong Kong public hospitals. RESULTS: The percentage of participants with anxiety (chi2=6.56, p=0.01) or depression (chi2=7.26, p=0.007) was higher in the chemotherapy group. More participants in the chemotherapy group had both anxiety and depression than those in the radiotherapy group, though no statistically significant difference was reported. Anxiety and depression had detrimental effects on the overall and other domains of QOL of these women undergoing adjuvant therapy for breast cancer. CONCLUSION: This study should increase nurses' awareness of the importance of integrating psychological symptom assessment into nursing assessment procedures, and enhance their clinical sensitivity in identifying high-risk groups of patients undergoing specific cancer treatments.


Subject(s)
Anxiety/diagnosis , Asian People/statistics & numerical data , Breast Neoplasms/psychology , Breast Neoplasms/therapy , Depressive Disorder/diagnosis , Quality of Life , Age Distribution , Aged , Anxiety/epidemiology , Breast Neoplasms/ethnology , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Chi-Square Distribution , China , Cross-Sectional Studies , Depressive Disorder/epidemiology , Female , Follow-Up Studies , Humans , Incidence , Linear Models , Middle Aged , Neoplasm Staging , Probability , Radiotherapy, Adjuvant , Severity of Illness Index
11.
Oncol Nurs Forum ; 36(4): E205-14, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19581224

ABSTRACT

PURPOSE/OBJECTIVES: To examine the symptom cluster of fatigue, pain, anxiety, and depression and its effect on the quality of life (QOL) of women receiving chemotherapy or radiotherapy for breast cancer. DESIGN: Descriptive. SETTING: Oncology outpatient sections of four public hospitals in Hong Kong. SAMPLE: 215 ethnic Chinese women who were midway through treatment for breast cancer. METHODS: Chinese versions of the Brief Fatigue Inventory, Hospital Anxiety and Depression Scale, Brief Pain Inventory, Functional Assessment of Chronic Illness Therapy for Breast Cancer, and Medical Outcomes Study Social Support Survey were used. Spearman rho correlation and structural equation modeling were used to examine the relationships among the study variables. MAIN RESEARCH VARIABLES: Breast cancer, fatigue, pain, anxiety, depression, and QOL. FINDINGS: Most participants reported mild-to-moderate levels of fatigue and pain. Twenty-one percent and 36% of patients might have had an anxiety or depression disorder, respectively. Significant correlations among the four symptoms supported the existence of the symptom cluster. The participants receiving chemotherapy had inadequate social support, experienced higher levels of symptoms, and were more likely to have a poorer QOL. CONCLUSIONS: The findings supported the existence of the symptom cluster that had detrimental effects on QOL. IMPLICATIONS FOR NURSING: This study shed light on a contemporary approach of grouping several related symptoms together. The findings enhance nurses' clinical sensitivity when identifying patients in high-risk groups and provide useful information for designing and prioritizing symptom-management strategies to meet patients' needs.


Subject(s)
Breast Neoplasms/epidemiology , Breast Neoplasms/nursing , Depression/epidemiology , Fatigue/epidemiology , Pain/epidemiology , Quality of Life , Adult , Aged , Aged, 80 and over , Breast Neoplasms/therapy , Cross-Sectional Studies , Depression/nursing , Fatigue/nursing , Female , Health Status , Hong Kong/epidemiology , Humans , Middle Aged , Oncology Nursing , Outpatients/psychology , Pain/nursing , Prevalence , Surveys and Questionnaires
12.
Nat Neurosci ; 12(3): 259-67, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19234458

ABSTRACT

Neurons are continuously generated from stem cells in discrete regions in the adult mammalian brain. We found that ependymal cells lining the lateral ventricles were quiescent and did not contribute to adult neurogenesis under normal conditions in mice but instead gave rise to neuroblasts and astrocytes in response to stroke. Ependymal cell quiescence was actively maintained by canonical Notch signaling. Inhibition of this pathway in uninjured animals allowed ependymal cells to enter the cell cycle and produce olfactory bulb neurons, whereas forced Notch signaling was sufficient to block the ependymal cell response to stroke. Ependymal cells were depleted by stroke and failed to self-renew sufficiently to maintain their own population. Thus, although ependymal cells act as primary cells in the neural lineage to produce neurons and glial cells after stroke, they do not fulfill defining criteria for stem cells under these conditions and instead serve as a reservoir that is recruited by injury.


Subject(s)
Astrocytes/physiology , Cell Differentiation/physiology , Ependyma/physiology , Prosencephalon/physiology , Receptor, Notch1/physiology , Stem Cells/physiology , Stroke/metabolism , Stroke/pathology , Animals , Astrocytes/cytology , Ependyma/cytology , Growth Inhibitors/physiology , Humans , Mice , Mice, Inbred ICR , Mice, Transgenic , Neurons/cytology , Neurons/physiology , Olfactory Bulb/cytology , Olfactory Bulb/physiology , Phenotype , Prosencephalon/cytology , Stem Cells/cytology
13.
J Cell Biol ; 171(3): 549-58, 2005 Nov 07.
Article in English | MEDLINE | ID: mdl-16260500

ABSTRACT

Actin-based protrusions can form prominent structures on the apical surface of epithelial cells, such as microvilli. Several cytoplasmic factors have been identified that control the dynamics of actin filaments in microvilli. However, it remains unclear whether the plasma membrane participates actively in microvillus formation. In this paper, we analyze the function of Drosophila melanogaster cadherin Cad99C in the microvilli of ovarian follicle cells. Cad99C contributes to eggshell formation and female fertility and is expressed in follicle cells, which produce the eggshells. Cad99C specifically localizes to apical microvilli. Loss of Cad99C function results in shortened and disorganized microvilli, whereas overexpression of Cad99C leads to a dramatic increase of microvillus length. Cad99C that lacks most of the cytoplasmic domain, including potential PDZ domain-binding sites, still promotes excessive microvillus outgrowth, suggesting that the amount of the extracellular domain determines microvillus length. This study reveals Cad99C as a critical regulator of microvillus length, the first example of a transmembrane protein that is involved in this process.


Subject(s)
Cadherins/genetics , Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , Protein Precursors/genetics , Animals , Cadherin Related Proteins , Drosophila Proteins/genetics , Drosophila melanogaster/genetics , Female , Humans , Microvilli/physiology , Microvilli/ultrastructure , Oogenesis , Ovarian Follicle/physiology , Ovarian Follicle/ultrastructure , Protein Structure, Tertiary
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