PURPOSE: Our objective was to investigate the role of CD8+T cells in pathogenesis of wheezing in children with atopic nature. METHODS: Twelve atopic wheezers, 8 nonatopic wheezers, 8 disease controls and 8 healthy controls were enrolled in the study. We isolated CD8+ T cells from peripheral blood samples, incubated them for 72 hours either in the absence or presence of phytohemagglutinin (PHA) and compared the concentrations of interleukin (IL)-5, IL-13, and interferon (IFN)-gamma in the cell culture supernatants. RESULTS: In the atopic wheezer group, the IL-5 concentration was significantly higher after PHA stimulation than after non-stimulated incubation. This difference was not observed in the nonatopic wheezer, disease control and healthy control groups. IL-13 was undetectable in all of the cell culture supernatants. There was no significant difference in the IFN-gamma concentration between the PHA-stimulated and non-stimulated conditions in all 4 groups. CONCLUSION: The results of this study suggest that CD8+ T cells may play a role in the pathogenesis of wheezing in children with atopic nature through the production of IL-5.
Cell Culture Techniques ; Child ; Humans ; Interferon-gamma ; Interferons ; Interleukin-13 ; Interleukin-5 ; Interleukins ; Respiratory Sounds ; T-Lymphocytes

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a familial syndrome characterized by the parathyroid, pancreas and pituitary tumors. Parathyroid tumors are the most common clinical manifestations, occurring in more than 90% of MEN1 patients. Heterozygous germline mutations of the MENIN gene underlie the tumorigenesis in MEN1 and epigenetic alterations along with germline mutations may contribute to tumorigenesis. Here, we investigated the associations between genotype and phenotype in Korean MEN1 patients. METHODS: We analyzed medical records from 14 unrelated MEN1 patients who had newly confirmed MENIN germline mutations, together with 14 previous reports in Korea. Aberrant DNA methylations were also examined in MEN1-related parathyroid tumors using the Infinium HumanMethylation 450 BeadChip. RESULTS: Total 28 germline mutations of MENIN were relatively highly concentrated in exons 7 and 8 compared to previous reports from Western countries. Six mutations (c.111dupT/p.S38Ffs*79, c.225_226insT/p.T76Yfs*41, c.383_398del16/p.S128Tfs*52, c.746dupT/p.H250Afs*20, c.1150G>T/p.E384*, and c.1508G>A/p.G503N) were newly found in the present study. Of interest, four patients (15%) showed unusual initial presentations and three patients were diagnosed incidentally at the general medical checkup. We also found three distinct sites in exon 2 of MENIN were significantly hypomethylated in the MEN1 parathyroid tumors, comparing correspondent blood samples. CONCLUSION: We also have found a lack of genotype/phenotype correlation in Korean MEN1 patients. There were not a few unusual initial manifestations in MEN1 patients, thus, genetic testing for the MENIN germline mutations can provide important information for the better prognosis. Further studies are warranted to investigate altered DNA methylations in the MENIN gene involved in tumorigenesis.
Carcinogenesis ; DNA Methylation ; Epigenomics* ; Exons ; Genetic Testing ; Genotype ; Germ-Line Mutation ; Humans ; Korea ; Medical Records ; Multiple Endocrine Neoplasia Type 1* ; Pancreas ; Phenotype ; Pituitary Neoplasms ; Prognosis

BACKGROUND AND OBJECTIVES: Cardiovascular complications are the leading cause of morbidity and mortality in childhood cancer survivors. Hematopoietic stem cell transplantation (HSCT) is a curable therapy for pediatric cancer. However, changes in cardiac function in children after HSCT are not well known. We assessed left ventricular (LV) function in children after HSCT using speckle tracking echocardiography (STE). SUBJECTS AND METHODS: Forty consecutive patients with median age of 11.9 years (range, 1.5-16 years) who received HSCT for acute leukemia and had comprehensive echocardiography before and after (median 9.2 month) HSCT were included in this study. The LV function parameters including conventional tissue Doppler imaging (TDI) and STE data were collected from pre- and post-HSCT echocardiography. These data were compared to those of 39 age-matched normal controls. RESULTS: Compared to normal controls, post HSCT patients had similar (p=0.06) LV ejection fraction. However, the following three LV function parameters were significantly decreased in post HSCT patients: rate-corrected velocity of circumferential fiber shortening (p=0.04), mitral inflow E velocity (p<0.001), and mitral septal annular E' velocity (p=0.03). The following four STE parameters were also significantly decreased in post HSCT patients: LV global circumferential systolic strain (p<0.01), strain rate (SR, p=0.01), circumferential diastolic SR (p<0.01), and longitudinal diastolic SR (p<0.001). There was no significant change in TDI or STE parameters after HSCT compared to pre-HSCT. Patients with anthracycline cumulative dose >400 mg/m2 showed significantly (p<0.05) lower circumferential systolic strain and circumferential diastolic SR. CONCLUSION: Subclinical cardiac dysfunction is evident in children after HSCT. It might be associated with pre-HSCT anthracycline exposure with little effect of conditioning regimens. Serial monitoring of cardiac function is mandatory for all children following HSCT.
Case-Control Studies* ; Child* ; Echocardiography* ; Hematopoietic Stem Cell Transplantation* ; Humans ; Leukemia* ; Mortality ; Stem Cell Transplantation ; Survivors ; Ventricular Dysfunction, Left*

BACKGROUND AND OBJECTIVES: Survivors of pediatric hematopoietic stem cell transplantation (HSCT) are at risk for developing hypertension. The objectives of this study are to evaluate the prevalence and risk factors of early onset hypertension during the engraftment period after HSCT. SUBJECTS AND METHODS: This is a retrospective study of 157 consecutive patients (mean age at HSCT: 9.1+/-5.1 years) who underwent HSCT for acute myeloid leukemia (n=47), acute lymphoblastic leukemia (n=43), severe aplastic anemia (n=41), and other reasons (n=26). Blood pressure data were collected at five time points: 0, 7, 14, 21, and 28 days after HSCT. Hypertension was defined as having systolic and/or diastolic blood pressure > or =95th percentile according to age, gender, and height. To analyze the risk factors related to hypertension, data, including patients' demographic and transplant characteristics, were reviewed. RESULTS: Hypertension developed in 59 patients (38%), among whom 12 (7.6%) required long term therapy. Thirty-two (54%) patients had systolic and diastolic, 8 (14%) had only systolic, and 19 (32%) had only diastolic hypertension. Younger age, acute graft-versus-host disease, sinusoidal obstruction syndrome, treatment with antifungal agent, and greater increase in serum creatinine (Cr) levels were associated with hypertension. Multivariate analysis showed that younger age at HSCT and greater increase in serum Cr level were independent risk factors for hypertension. CONCLUSION: Prevalence of hypertension during immediate post-HSCT period is high, especially in younger children. A greater increase in Cr after HSCT was significantly associated with hypertension. Further study is needed to elucidate long-term cardiovascular complications in pediatric HSCT survivors.
Anemia, Aplastic ; Blood Pressure ; Child ; Creatinine ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Hepatic Veno-Occlusive Disease ; Humans ; Hypertension* ; Incidence* ; Leukemia, Myeloid, Acute ; Multivariate Analysis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prevalence ; Retrospective Studies ; Risk Factors* ; Survivors

BACKGROUND: Skeletal muscle is the most important tissue contributing to insulin resistance. Several studies have shown that accumulation of intramyocellular lipid is associated with the development of insulin resistance. Thus, proteins involved in lipid transport, storage and metabolism might also be involved in insulin action in skeletal muscle. Adipose differentiation-related protein (ADRP), which is localized at the surface of lipid droplets, is known to be regulated by peroxisome proliferator activated receptor gamma (PPARgamma). However, it is not known whether ADRP plays a role in regulating glucose uptake and insulin action in skeletal muscle. METHODS: ADRP expression in skeletal muscle was measured by RT-PCR and western blot in db/db mice with and without PPARgamma agonist. The effect of PPARgamma agonist or high lipid concentration (0.4% intralipos) on ADRP expression was also obtained in cultured human skeletal muscle cells. Glucose uptake was measured when ADRP was down-regulated with siRNA or when ADRP was overexpressed with adenovirus. RESULTS: ADRP expression increased in the skeletal muscle of db/db mice in comparison with normal controls and tended to increase with the treatment of PPARgamma agonist. In cultured human skeletal muscle cells, the treatment of PPARgamma agonist or high lipid concentration increased ADRP expression. siADRP treatment decreased both basal and insulin-stimulated glucose uptake whereas ADRP overexpression increased glucose uptake in cultured human skeletal muscle cells. CONCLUSION: ADRP expression in skeletal muscle is increased by PPARgamma agonist or exposure to high lipid concentration. In these conditions, increased ADRP contributed to increase glucose uptake. These results suggest that insulin-sensitizing effects of PPARgamma are at least partially achieved by the increase of ADRP expression, and ADRP has a protective effect against intramyocellular lipid-induced insulin resistance.
Adenoviridae ; Animals ; Blotting, Western ; Glucose ; Humans ; Insulin ; Insulin Resistance ; Membrane Proteins ; Mice ; Muscle, Skeletal ; PPAR gamma ; Proteins ; RNA, Small Interfering

Dental primary afferent (DPA) neurons and proprioceptive mesencephalic trigeminal nucleus (MTN) neurons, located in the trigeminal ganglion and the brainstem, respectively, are essential for controlling masticatory functions. Despite extensive transcriptomic studies on various somatosensory neurons, there is still a lack of knowledge about the molecular identities of these populations due to technical challenges in their circuit-validated isolation. Here, we employed high-depth single-cell RNA sequencing (scRNA-seq) in combination with retrograde tracing in mice to identify intrinsic transcriptional features of DPA and MTN neurons. Our transcriptome analysis revealed five major types of DPA neurons with cell type-specific gene enrichment, some of which exhibit unique mechano-nociceptive properties capable of transmitting nociception in response to innocuous mechanical stimuli in the teeth. Furthermore, we discovered cellular heterogeneity within MTN neurons that potentially contribute to their responsiveness to mechanical stretch in the masseter muscle spindles. Additionally, DPA and MTN neurons represented sensory compartments with distinct molecular profiles characterized by various ion channels, receptors, neuropeptides, and mechanoreceptors. Together, our study provides new biological insights regarding the highly specialized mechanosensory functions of DPA and MTN neurons in pain and proprioception.
Animals ; Mice ; Neurons ; Proprioception ; Gene Expression Profiling ; Pain ; Sequence Analysis, RNA