Urine xanthine crystals are remarkably rare but can be observed by routine urine microscopy. We report the results of a 67-year-old man with T-cell-prolymphocytic leukemia whose urine contained ...xanthine crystals after chemotherapy and prophylactic administration of febuxostat. Accumulation of xanthine was due to tumor lysis syndrome causing a massive release of DNA. The metabolized DNA caused an increase of xanthine, which was not readily converted to uric acid by xanthine oxidase because of febuxostat inhibition of this enzyme.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor that regulates not only adipogenesis but also immune reaction. We previously demonstrated that human eosinophils ...expressed functional PPARgamma, although the modulator of PPARgamma expression is less well understood. Because clinical studies have shown that the efficacy of PPARgamma agonists as insulin sensitizers is stronger in women than in men, we investigated whether sex hormones caused any changes in eosinophil PPARgamma expression levels.
First, purified human peripheral blood eosinophils were cultured with 17beta-estradiol for 24 h, followed by PPARgamma measurement using a flow cytometer. Next, eosinophil PPARgamma expression and serum estradiol were studied in 10 healthy women during the menstrual and follicular phases to identify the physiological significance of estradiol. Eosinophil PPARgamma expression was also compared in 22 men, 21 non-pregnant women, and 15 pregnant women.
We observed that PPARgamma protein expression in eosinophils was significantly enhanced by 10(-6)M 17beta-estradiol. Although serum estradiol concentration was increased during the follicular phase, PPARgamma expression levels were not affected by the menstrual cycle. In addition, no significant differences in PPARgamma expression were observed in terms of sex and pregnancy.
These findings suggest that estradiol potentially upregulates eosinophil PPARgamma expression in vitro, although some other mechanisms might be involved in its regulation in vivo.
Abstract
Blood eosinophil count is a useful measure in asthma or COPD management. Recent epidemiological studies revealed that body mass index (BMI) is positively associated with eosinophil counts. ...However, few studies focused on the role of adiposity and fatty acid-related metabolites on eosinophil counts, including the effect of genetic polymorphism. In this community-based study involving 8265 participants (30–74 year old) from Nagahama city, we investigated the relationship between eosinophil counts and serum levels of fatty acid-related metabolites. The role of
MDC1
, a gene that is related to eosinophil counts in our previous study and encodes a protein that is thought to be involved in the repair of deoxyribonucleic acid damage, was also examined taking into account its interaction with adiposity. Serum levels of linoleic acid (LA) and β-hydroxybutyric acid (BHB) were negatively associated with eosinophil counts after adjustment with various confounders; however, there were positive interactions between serum LA and BMI and between serum BHB and BMI/body fat percentages in terms of eosinophil counts. In never-smokers, there was positive interaction for eosinophil counts between the CC genotype of
MDC1
rs4713354 and BMI/body fat percentages. In conclusion, both serum LA and BHB have negative impacts on eosinophil counts, while adiposity shows robust positive effects on eosinophil counts, partly via genetic background in never-smokers.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Asthma in the elderly needs more attention in an aging society. However, it is likely to remain underdiagnosed and undertreated. This study aimed to clarify clinical characteristics of new-onset ...asthma in the elderly, describing the prevalence, predictive factors, and comorbidities after asthma diagnosis of new-onset asthma in the elderly in the general population.
This community-based prospective cohort study enrolled 9804 generally healthy participants (30–74 years old) in Nagahama City, and conducted a follow-up assessment after 5 years. Elderly participants were those aged ≥65 years at baseline. Patients with new-onset asthma were defined as participants without asthma at baseline assessment and with asthma at the follow-up assessment.
Among the 7948 participants analyzed in this study, 28 (1.4%) elderly and 130 (2.2%) non-elderly had new-onset asthma. Multiple logistic regression analysis revealed low forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and high blood eosinophil counts at baseline as predicting factors for new-onset asthma in the elderly. Additionally, subsequent incidence of new-onset asthma was higher in elderly participants with both predictors (high blood eosinophil counts and low FEV1/FVC at baseline) than those with none or one of the predictors before asthma diagnosis. Lastly, elderly patients with new-onset asthma had more frequent comorbidity of moderate to severe sleep disordered breathing than those non-elderly.
Eosinophilic inflammation and airflow obstruction may predict subsequent new-onset asthma after the age of 65 years. Revealing the characteristics of new-onset asthma in the elderly can aid in the prevention of underdiagnosed asthma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Little is known about the association of prolonged cough, a common and troublesome symptom, with metabolic pathways. We aimed to clarify this association using data from the Nagahama cohort, ...a prospective study of participants from the general population. Self-report questionnaires on prolonged cough were collected at baseline and 5-year follow-up assessments. Blood tests at follow-up were used for gas chromatography-mass spectrometry-based metabolomics. The association between metabolites and prolonged cough was examined using the partial least squares discriminant analysis and multiple regression analysis. Among the 7432 participants, 632 had newly developed prolonged cough at follow-up, which was defined as “new-onset prolonged cough”. Low plasma citric acid was significantly associated with new-onset prolonged cough, even after the adjustment of confounding factors including the presence of asthma, upper airway cough syndrome (UACS), and gastroesophageal reflux disease (GERD). A similar association was observed for isocitric acid, 3-hydroxybutyric acid, and 3-hydroxyisobutyric acid. The analysis of these four metabolites revealed that citric acid had the strongest association with new-onset prolonged cough. This significant association remained even when the analysis was confined to participants with UACS or GERD at baseline or follow-up, and these associations were also observed in participants (n = 976) who had prolonged cough at follow-up regardless of baseline status. In conclusion, low blood citric acid may be associated with prolonged cough.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Subjects with subclinical respiratory dysfunction who do not meet the chronic obstructive pulmonary disease (COPD) criteria have attracted attention with regard to early COPD intervention. Our aim ...was to longitudinally investigate the risks for the development of airflow limitation (AFL) and dyspnoea, the main characteristics of COPD, in a large-scale community-based general population study. The Nagahama study included 9789 inhabitants, and a follow-up evaluation was conducted after 5 years. AFL was diagnosed using a fixed ratio (forced expiratory volume in one second (FEV
)/forced vital capacity (FVC) < 0.7). We enrolled normal subjects aged 40-75 years with no AFL, dyspnoea or prior diagnosis of asthma or COPD at baseline. In total, 5865 subjects were analysed, 310 subjects had subclinical respiratory dysfunction (FEV
/FVC < the lower limit of normal; n = 57, and FEV
< 80% of the predicted value (preserved ratio impaired spirometry); n = 256). A total of 5086 subjects attended the follow-up assessment, and 449 and 1021 subjects developed AFL and dyspnoea, respectively. Of these, 100 subjects developed AFL with dyspnoea. Baseline subclinical respiratory dysfunction was independently and significantly associated with AFL with dyspnoea development within 5 years. Subjects with subclinical respiratory dysfunction are at risk of developing COPD-like features and require careful monitoring.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Obesity and increased body mass index (BMI) are the known risk factors for adult-onset asthma. Serum free fatty acid (FFA) and other blood lipid levels are generally elevated in patients with obesity ...and may be involved in the onset of asthma. However, it remains largely unknown. This study aimed to elucidate the relationship between plasma fatty acids and new-onset asthma.
This community-based Nagahama Study in Japan enrolled 9804 residents. We conducted self-reporting questionnaires, lung function tests, and blood tests at baseline and 5 years later as follow-up. At the follow-up, plasma fatty acids were measured using gas chromatography-mass spectrometry. Body composition analysis was also measured at the follow-up. The associations between fatty acids and new-onset asthma were evaluated using a multifaceted approach, including targeted partial least squares discriminant analysis (PLS-DA).
In PLS-DA for new-onset asthma, palmitoleic acid was identified as the fatty acid most associated with asthma onset. In the multivariable analysis, higher levels of FFA, palmitoleic acid, or oleic acid were significantly associated with new-onset asthma, independent of other confounding factors. The high body fat percentage itself was not the relevant factor, but showed a positive interaction with plasma palmitoleic acid for new-onset asthma. When stratified by gender, the impacts of higher levels of FFA or palmitoleic acid on new-onset asthma remained significant in females, but not in males.
Elevated levels of plasma fatty acids, particularly palmitoleic acid, may be a relevant factor for new-onset asthma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The highly sensitive urine glucose meter based on amperometric glucose sensor was developed and commercialized. It shows remarkable performances of wide measurement range in 0–2000
mg
dl
−1, rapid ...response time as 6
s and robustness against influence by interferents like ascorbic acid or acetaminophen. Correlation between the developed urine glucose meter and commercialized clinical-use urine glucose analyzer showed excellent linear relationship. The monitoring of postmeal blood glucose levels by assess of urine glucose of actual subjects was performed with the developed urine glucose meter. The experimental results suggest the urine glucose level 120
min following the meal should be the appropriate index for diabetes or impaired glucose tolerance to control blood glucose level. The new portable meter was developed, and is expected for flexible use at places other than home or office.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Airway microbiota in asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) remains unknown.
This study with ACO-enriched population aimed to clarify airway microbiota in ACO and in mixed ...granulocytic inflammation, often detected in ACO and chronic airway diseases.
This is an observational cross-sectional study. Patients with asthma with airflow limitation, ACO, and COPD were enrolled. Blood tests, pulmonary function, exhaled nitric oxide, and sputum tests were conducted. Sputum microbiota was evaluated using the 16S rRNA gene sequencing technique.
A total of 112 patients (13 asthma, 67 ACO, and 32 COPD) were examined. There were no significant differences in α-diversity among the 3 diseases. The relative abundances of phylum Bacteroidetes, class Bacteroidia, and genus Porphyromonas were associated with decreased eosinophilic inflammation, and were significantly lower in ACO than in COPD. In a comparison of sputum inflammatory subtypes, the proportion of Haemophilus was numerically highest in the mixed granulocytic subtype, followed by the neutrophilic subtype. Likewise, the proportion of Haemophilus was the highest in the intermediate-high (2%-8%) sputum eosinophil group and lowest in the severe (≥8%) eosinophil group. Clinically, Haemophilus proportion was associated with sputum symptoms. Finally, the proportion of Streptococcus was associated with higher blood eosinophil counts and most severe airflow limitation.
Bacteroidia and Porphyromonas abundances in sputum are associated with the eosinophil-low phenotype, and ACO may be characterized by a decrease in these taxa. A mild elevation in sputum eosinophil does not preclude the presence of Haemophilus, which should be noted in the management of obstructive airway diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract A one-year-old boy with neuroblastoma (NBoma)-associated opsoclonus–myoclonus syndrome (OMS) was treated by oral high-dose dexamethasone (DEX) pulses (20 mg/m2 /day of DEX for three ...consecutive days) every 28 days for 6 months after resection of the tumor. All OMS symptoms improved after the first course of DEX pulse therapy and disappeared after the last course. No adverse effects were observed. Minor deterioration of his developmental quotient was noted 33 months after the onset of the disease. NBoma remission has been maintained since treatment. Before DEX pulse therapy, frequency of T lymphocyte, in particular CD4-positive cell decreased markedly resulted in low CD4/8 ratio in the peripheral blood (PB). The frequency of B lymphocyte increased, especially in cerebrospinal fluid. These aberrant values in PB were reversed by DEX pulse therapy and correlated well with the neurological symptoms. A prospective study that assesses the efficacy of this promising and inexpensive treatment for OMS is warranted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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