Impulse Oscillometry; Therapeutic Impacts of Transdermal Long-Acting Beta-2 Agonist Patch in Elderly Asthma with Inhaled Corticosteroid Alone

Growing interest had been focused on the involvement of the small airways in asthma, and impulse oscillometry (IOS) has been utilized as pulmonary functions for detecting large and small airways diseases separately. IOS can measure respiratory resistance and reactance at multiple frequencies, not available by spirometry or body plethysmography, is non-invasive techniques and convenient for elderly patients with a low dependency on cooperation during tidal breathing. IOS indices were well correlated with not only predicted FEV1 but also FEF25-75, residual volume/total lung capacity, delta N2 of a single nitrogen washout test which representing air trapping and inhomogeneous ventilation in the distal lung. These parameters and QOL scores were improved by additional transdermal long-acting beta-2 agonist patch even in well-controlled elderly asthma treating with inhaled corticosteoids alone. IOS may have a complementary role of spirometry in detecting subtle airways changes in general practice. However, systemic studies are required to investigate the clinical implication of each IOS index.     

Frequency of consumption of balanced meals,bodyweight gain and incident risk of glucose intolerance in Japanese men and women: A cohort study

Aims/IntroductionThis cohort study assessed the risk for bodyweight gain and development of glucose intolerance based on the frequency of consumption of balanced meals including grain, fish or meat and vegetables.Materials and MethodsThe participants (8,573 men, 3,327 women) were employees of a company in Japan. A self‐administered questionnaire was used to evaluate the frequency of balanced meal consumption. Bodyweight changes and the incidence of glucose intolerance (glycated hemoglobin >6.0%) during the 3‐year follow‐up period were determined through annual health examinations.ResultsThe mean bodyweight change over a period of 3 years was 0.78 kg for men and 0.84 kg for women. A lower frequency of balanced meals was associated with a higher bodyweight gain for men (P for trend = 0.004), but not for women. During the study, 464 men and 115 women developed glucose intolerance. Overall, the frequency of balanced meals was not associated with the risk of glucose intolerance in either sex. However, the interaction between the frequency of balanced meals and degree of obesity had a significant effect on the incidence of glucose intolerance in men (P = 0.005), with less frequent consumption of balanced meals being associated with a higher risk for glucose intolerance among men with a BMI ≥25.0 kg/m² (P for trend = 0.007).ConclusionsA higher frequency of balanced meals, including grain, fish or meat and vegetable dishes – important components of healthy Japanese food – was associated with a lower risk of glucose intolerance in obese men, but not in non‐obese men and women.     

Comparative sequencing of human and chimpanzee MHC class I regions unveils insertions/deletions as the major path to genomic divergence

Despite their high degree of genomic similarity, reminiscent of their relatively recent separation from each other ( approximately 6 million years ago), the molecular basis of traits unique to humans vs. their closest relative, the chimpanzee, is largely unknown. This report describes a large-scale single-contig comparison between human and chimpanzee genomes via the sequence analysis of almost one-half of the immunologically critical MHC. This 1,750,601-bp stretch of DNA, which encompasses the entire class I along with the telomeric part of the MHC class III regions, corresponds to an orthologous 1,870,955 bp of the human HLA region. Sequence analysis confirms the existence of a high degree of sequence similarity between the two species. However, and importantly, this 98.6% sequence identity drops to only 86.7% taking into account the multiple insertions/deletions (indels) dispersed throughout the region. This is functionally exemplified by a large deletion of 95 kb between the virtual locations of human MICA and MICB genes, which results in a single hybrid chimpanzee MIC gene, in a segment of the MHC genetically linked to species-specific handling of several viral infections (HIV/SIV, hepatitis B and C) as well as susceptibility to various autoimmune diseases. Finally, if generalized, these data suggest that evolution may have used the mechanistically more drastic indels instead of the more subtle single-nucleotide substitutions for shaping the recently emerged primate species.     

C-reactive protein and peripheral artery disease among Japanese elderly: the Tsurugaya Project.

We investigated the cross-sectional relationship between ankle brachial index and cardiovascular disease risk factors, including C-reactive protein (CRP), among Japanese elderly, a topic which has had little prior epidemiologic study. Our study population comprised 946 subjects aged at least 70 years in whom both CRP and ankle brachial index were measured. The participants were classified into a low (ankle brachial index<0.9) and normal ankle brachial index group. We found that current smoking, high-density lipoprotein cholesterol <40 mg/dl, a low body mass index (continuous variable), hypertension, diabetes and statin use were all significantly related to a lower ankle brachial index. Higher log-transformed CRP level was significantly related to a lower ankle brachial index after adjustment for the cardiovascular risk factors mentioned above (p <0.01). The odds ratios for low ankle brachial index compared to 0-1 risk factors were 5.79 (95% confidence interval [CI]: 2.99-11.20) for 2 risk factors and 17.45 (95% CI: 6.78-49.91) for 3 or more risk factors; independently of other risk factors, the odds ratio for CRP>1.0 mg/l was 2.10 (95% CI: 1.13-3.88) compared to lower CRP values. Thus, a high level of CRP is related to a low ankle brachial index among Japanese elderly as well as Western subjects. This is the first study to report the relationship between CRP and low ankle brachial index among Japanese elderly.     

Glutamate receptors and the regulation of steroidogenesis in the human adrenal gland: The metabotropic pathway

Background

l-glutamate is a major excitatory neurotransmitter in the mammalian brain. Glutamate receptors have been reported in the rat adrenal cortex and in human aldosterone-producing adenomas (APA). However, details regarding the expression levels and functions of these receptors in human adrenocortical tissues remain unknown.

Methods

The mRNA levels of glutamate receptors were evaluated by qPCR in: 12 normal adrenal cortex (NAC), 11 APA, and 12 cortisol-producing adenoma (CPA) tissues. Protein localization was evaluated by immunohistochemistry for 15 NAC, 5 idiopathic hyperaldosteronism cases, 15 APA and 15 CPA. H295R cells were treated with angiotensin-II or forskolin alone or combined with the GRM2/3 agonist LY354740.

Results

The level of GRM3 mRNA was higher in APA than in CPA (P = 0.0086) or NAC (P = 0.0022). GRM1, IGLUR2, and IGLUR3 were also detected in adrenocortical tissues. When added to angiotensin-II/forskolin treatments, LY354740 decreased aldosterone and cortisol production in H295R cells.

Conclusions

GRM3 is considered to regulate steroidogenesis in adrenocortical tissues.     

Low-risk profile for cardiovascular disease and mortality in Japanese.

BACKGROUND: Some studies focusing on low-risk profiles for cardiovascular disease have been reported in Western countries. Yet, few reports have examined, with substantial longevity, the low-risk profile for cardiovascular disease in the Japanese population. This study examines whether having a favorable risk factor profile yields lower all-cause mortality and whether the proportion of those with a low-risk profile is larger in the Japanese population. METHODS AND RESULTS: A total of 8,339 men and women aged 30-69 years without a history of cardiovascular diseases for 19 years, who had participated in the 1980 National Survey on Circulatory Disorders after being randomly selected from throughout Japan, were followed. Low risk was defined as having all of the following baseline characteristics: blood pressure (BP) <120/80 mmHg; no antihypertensive medication; serum cholesterol 160-240 mg/dl (4.14-6.22 mmol/L); no history of diabetes; and non-smoker. The long-term mortality of the low-risk group was compared with that of others using the Cox proportional hazard model. The prevalence of low risk was 9.4% of all participants. The multivariate-adjusted hazard ratios for low-risk individuals compared with others were as follows: 0.33 (95% confidence intervals (CI), 0.15-0.74) for cardiovascular disease and 0.63 (95% CI, 0.46-0.88) for all-cause mortality. The most attributable risk factor for all-cause mortality was high BP (>or=120/80 mmHg). CONCLUSION: Japanese individuals with favorable cardiovascular disease risk profiles had lower mortality from cardiovascular disease and all-causes than those without.     

Cholinergic and noradrenergic nervous systems in the cynomolgus monkey cochlea

The cholinergic and noradrenergic nervous systems in the cochleas of cynomolgus monkeys were examined by histochemical and immunohistochemical demonstration of acetylcholinesterase (AChE) and tyrosine hydroxylase (TH) and/or dopamine B-hydroxylase (DBH), respectively. AChE activity was demonstrated in the efferent fibers making synaptic contact with the perikarya and the cell processes of type II neurons. Type II neurons also demonstrated AChE activity on the cell surface and their neurites, suggesting that the AChE-positive fibers in the simian cochlear nerve trunk, previously believed to be of efferent origin, are the central processes of type II neurons. TH-like and DBH-like immunoreactivity of beaded unmyelinated fibers demonstrated similar distribution throughout the cochlear nerve trunk, Rosenthal's canal, and osseous spiral lamina. During their course, they came in contact with unmyelinated efferent fibers and neurites of type II neurons and abutted blood vessels. However, their distribution was not restricted to following blood vessels or cochlear nerve fibers. These observations indicate that the sympathetic nerve supply and olivocochlear efferent system in the cochleas of monkeys differ from those of smaller animals.