Difference between "Physical Fitness Age" Based on Physical Function and Chronological Age Is Associated with Obesity, Hyperglycemia, Depressive Symptoms, and Low Serum Albumin.

OBJECTIVES: This study aimed to (1) develop the physical fitness age, which is the biological age based on physical function, (2) evaluate the validity of the physical fitness age for the assessment of sarcopenia, and (3) examine the factors associated with the difference between physical fitness age and chronological age. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Community-dwelling older adults and outpatients. MEASUREMENTS: A formula for calculating the physical fitness age was created based on the usual walking speed, handgrip strength, one-leg standing time, and chronological age of 4,076 older adults from the pooled data of community-dwelling and outpatients using the principal component analysis. For the validation of the physical fitness age, we also used pooled data from community-dwelling older adults (n = 1929) and outpatients (n = 473). Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia 2019 consensus. The association of D-age (the difference between physical and chronological ages) with cardiovascular risk factors, renal function, and cardiac function was examined. RESULTS: The receiver operating characteristic analysis, with sarcopenia as the outcome, showed that the area under the curve (AUC) of physical fitness age was greater than that of chronological age (AUC 0.87 and 0.77, respectively, p < 0.001). Binomial logistic regression analysis revealed that the D-age was significantly associated with sarcopenia after adjustment for covariates (odds ratio 1.22, 95% confidence interval 1.19-1.26; p <0.001). In multivariate linear regression analysis with D-age as the dependent variable, D-age was independently associated with a history of diabetes mellitus (or hemoglobin A1c as a continuous variable), obesity, depression, and low serum albumin level. D-age was also correlated with estimated glomerular filtration rate derived from serum cystatin C, brain natriuretic peptide, and ankle-brachial index, reflecting some organ function and arteriosclerosis. CONCLUSIONS: Compared to chronological age, physical fitness age calculated from handgrip strength, one-leg standing time, and usual walking speed was a better scale for sarcopenia. D-age, which could be a simple indicator of physical function, was associated with modifiable factors, such as poor glycemic control, obesity, depressive symptoms, and malnutrition.

Genome-wide DNA methylation analysis identifies promoter hypermethylation in canine malignant melanoma.

Canine malignant melanoma is a common cancer with a high mortality rate. Although previous studies have evaluated various aspects of this tumour, the exact mechanism of tumourigenesis remains unknown. Epigenetic mechanisms, such as DNA methylation, have recently gained attention as aetiological factors for neoplasia in humans. This study aimed to analyse genome-wide DNA methylation patterns in canine malignant melanoma based on next-generation sequencing data. A total of 76,213 CpG sites, including 29,482 sites in CpG islands (CGIs), were analysed using next-generation sequencing of methylation-specific signatures, obtained by sequential digestion with enzymes, to compare normal oral mucosal samples from four healthy dogs, four canine melanoma cell lines (3 oral cavity and 1 skin), and five clinical samples of oral canine melanoma. Malignant melanoma showed increased methylation at thousands of normally unmethylated CpG sites in CGIs and decreased methylation at normally methylated CpG sites in non-CGIs. Interestingly, the promoter regions of 81-393 genes were hypermethylated; 23 of these genes were present in all melanoma cell lines and melanoma clinical samples. Among these 23 genes, six genes with "sequence-specific DNA binding" annotation were significantly enriched, including three Homeobox genes-HMX2, TLX2, and HOXA9-that may be involved in the tumourigenesis of canine malignant melanoma. This study revealed widespread alterations in DNA methylation and a large number of hypermethylated genes in canine malignant melanoma.

Factors related to taste sensitivity in elderly: cross-sectional findings from SONIC study.

The sense of taste is important, as it allows for assessment of nutritional value, as well as safety and quality of foods, with several factors suggested to be associated with taste sensitivity. However, comprehensive variables regarding taste and related factors have not been utilised in previous studies for assessments of sensitivity. In the present study, we performed cross-sectional analyses of taste sensitivity and related factors in geriatric individuals who participated in the SONIC Study. We analysed 2 groups divided by age, 69-71 years (young-old, n = 687) and 79-81 years (old-old, n = 621), and performed a general health assessment, an oral examination and determination of taste sensitivity. Contributing variables were selected by univariate analysis and then subjected to multivariate logistic regression analysis. In both groups, females showed significantly better sensitivity for bitter and sour tastes. Additionally, higher cognitive scores for subjects with a fine taste for salty were commonly seen in both groups, while smoking, drinking, hypertension, number of teeth, stimulated salivary flow salt intake and years of education were also shown to be associated with taste sensitivity. We found gender and cognitive status to be major factors affecting taste sensitivity in geriatric individuals.

Increased incidence of osteonecrosis of the jaw after tooth extraction in patients treated with bisphosphonates: a cohort study.

This study estimated the cumulative incidence and risk ratio for osteonecrosis of the jaw (ONJ) after tooth extraction in patients with and without administration of bisphosphonates (BP) and identified potential risk factors for bisphosphonate-induced osteonecrosis of the jaw (BIONJ). A cohort study was conducted in all patients undergoing tooth extraction at a university hospital in Japan from April 2006 to June 2009. Of 3216 patients, 126 had BP administration, of whom 5 (3.9%, 95% confidence interval (CI): 1.2-9.2) developed ONJ, versus 1 (0.032%, 95% CI: 0.00081-0.18) among 3090 patients without BP administration. BP administration was associated with the development of ONJ after tooth extraction, with an unadjusted risk ratio of 122.6 (95% CI: 14.4-1041.8). When stratified by age and route of BP administration, the risk ratio for ONJ patients aged 65 years or older with intravenous BP administration compared to those without was 200.2 (95% CI: 23.8-1679.4, P<0.001). Patients receiving BP showed a significant association between the incidence of BIONJ and alveolar bone loss score. The risk of ONJ is higher in patients with than without BP administration, particularly intravenous administration. Severe periodontitis might be a risk factor for BIONJ.

Changes in HRCT findings in patients with respiratory bronchiolitis-associated interstitial lung disease after smoking cessation.

High-resolution computed tomography (HRCT) findings in patients with respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) are varied and nonspecific. There is no known report of changes in HRCT findings and respiratory function test results for RB-ILD patients following the cessation of smoking. Five patients with RB-ILD, confirmed by surgical lung biopsy, were retrospectively studied. Each stopped cigarette smoking and did not receive corticosteroid therapy after diagnosis. The clinical symptoms, respiratory function test results and HRCT findings obtained at the final observation were compared with those from the time of diagnosis. Ground-glass opacity and centrilobular nodules corresponding to pathological respiratory bronchiolitis, as well as intralobular fine linear-reticular opacity corresponding to fibrosis involving the subpleural alveolar septa, showed computed tomography-pathological correlations. Both clinical symptoms and the diffusing capacity of the lungs for carbon monoxide improved significantly following smoking cessation, as did ground-glass opacity and centrilobular nodules seen during the initial HRCT examination. Centrilobular nodules and ground-glass opacity, which are the main features of high-resolution computed tomography of respiratory bronchiolitis-associated interstitial lung disease patients and represent pathological respiratory bronchiolitis, can be improved by smoking cessation. The diffusing capacity of the lung for carbon monoxide in respiratory function tests can be also improved.

Poor metabolizer genotype status of CYP2C19 is a risk factor for developing gastric cancer in Japanese patients with Helicobacter pylori infection.

BACKGROUND: Cytochrome P450 2C19 (CYP2C19) polymorphism has been associated with the development of lung, liver or oesophageal cancer by detoxification of carcinogen(s) or activation of procarcinogen(s). AIM: To clarify the association between CYP2C19 polymorphisms and gastric cancer development in Japanese. Methods : We determined CYP2C19 genotypes (CYP2C19*1, *2 and *3) in 111 Helicobacter pylori-positive patients with gastric cancer and 315 H. pylori-positive controls without gastric cancer consisting of patients with gastritis only or peptic ulcer. Frequencies of CYP2C19 genotypes and serum pepsinogen I and II levels, a biomarker of gastric atrophy, in the gastric cancers and controls were compared. RESULTS: Frequencies of homozygous extensive metabolizers, heterozygous extensive metabolizers and poor metabolizers were 31.5%, 42.3% and 26.2% in the gastric cancers and 38.1%, 47.0% and 14.9% in the controls, respectively (P = 0.046). Poor metabolizers were associated with an increased risk for developing gastric cancer with the age- and sex-adjusted odds ratio (OR) of 1.975 [95% confidence interval (CI): 1.068-3.649], especially for diffuse type (OR: 3.385, CI: 1.187-9.648). There is no significant association between CYP2C19 genotypes and serum pepsinogen I level or pepsinogen I/II ratios, although serum pepsinogen I level in gastric cancers were significantly decreased. CONCLUSIONS: In H. pylori-positive Japanese, poor metabolizers of CYP2C19 appear to be at an increased risk for developing gastric cancer, especially diffuse type, and may require an intensive follow-up for scrutinizing possible gastric cancer development.

The disposition of oral amodiaquine in Papua New Guinean children with falciparum malaria.

AIMS: We assessed the disposition of oral amodiaquine (AQ) and CYP2C8 polymorphism in 20 children with falciparum malaria. METHODS: AQ and DEAQ concentrations were determined with SPE-HPLC method. CYP2C8 genotypes were assessed by PCR-RFLP method. RESULTS: AQ was not detectable beyond day 3 postdose. Cmax for DEAQ was reached in 3.0 days. The mean values for t1/2, MRT, and AUCtotal were 10.1 days, 15.5 days and 4512.6 microg l(-1) day, respectively. All the children were CYP2C8* homozygous. CONCLUSION: Our data are consistent with those previously reported, and the AQ regimen seems pharmacokinetically adequate in the absence of CYP2C8 polymorphism.

Orthodontic treatment of a case of Becker muscular dystrophy.

Becker muscular dystrophy, similar to Duchenne muscular dystrophy, is a X-chromosomal linked anomaly characterized by progressive muscle wasting and weakness. Duchenne-type is known to have severe openbite with a steep mandibular plane, but there are no studies that describe the occlusal and skeletal patterns of the Becker-type. Here, we report the orthodontic treatment of a Becker muscular dystrophy patient. In the correction of his severe skeletal open bite general anesthesia or orthognathic surgery was not an option. Multiloop edgewise archwires were employed for orthodontic treatment. After 3 years and 8 months the open bite was corrected. During the retention period contact between the anterior teeth was maintained 8 months after active treatment despite a marked relapse tendency.

Effects of CYP2C19 genotypic differences in the metabolism of omeprazole and rabeprazole on intragastric pH.

BACKGROUND: Omeprazole is mainly metabolized in the liver by CYP2C19, a genetically determined enzyme, whereas rabeprazole is mainly reduced non-enzymatically and partially metabolized by CYP2C19. The therapeutic effects of rabeprazole are therefore assumed to be less affected by an individual's CYP2C19 status. AIM: To investigate the acid inhibitory effects and plasma levels of omeprazole and rabeprazole with reference to different CYP2C19 genotypes. METHODS: Fifteen healthy volunteers took a daily dose of 20 mg of omeprazole or rabeprazole for 8 days. On post-dose days 1 and 8, 24-h profiles of intragastric pH were recorded and plasma concentrations of omeprazole, rabeprazole and their metabolites were determined. RESULTS: After single and repeated doses of omeprazole, the intragastric pH values and plasma concentrations of omeprazole and its metabolites were significantly dependent on the CYP2C19 genotype. Significant differences in the same kinetic and dynamic parameters were also observed after single doses of rabeprazole. Although the plasma levels of rabeprazole differed among the different CYP2C19 genotype groups after repeated doses, no significant differences in intragastric pH values were observed. CONCLUSIONS: The acid inhibitory effects of omeprazole and rabeprazole are significantly dependent on the CYP2C19 genotype status, as well as on their intrinsic pharmacokinetic and pharmacodynamic characteristics and dosing schemes.

Comparison of the kinetic disposition of and serum gastrin change by lansoprazole versus rabeprazole during an 8-day dosing scheme in relation to CYP2C19 polymorphism.

BACKGROUND: Little is known about differences in the disposition kinetics and pharmacological effects on gastrin levels between lansoprazole and rabeprazole given in a repeated dosing scheme with respect to the polymorphic CYP2C19. AIM: To provide preliminary information that should be considered when prescribing proton-pump inhibitors (PPIs) for the treatment of acid-related diseases with reference to the CYP2C/9 genotypic status. METHODS: Helicobacter pylori-negative healthy volunteers were divided into the following three groups (n = 5 each) on the basis of genotyping for CYP2C19: homozygous (hmEMs) and heterozygous extensive metabolizers (htEMs), and poor metabolizers (PMs). All received once-daily 30-mg doses of lansoprazole or 10-mg doses of rabeprazole during an 8-day course in a crossover manner. RESULTS: The relative values for the area under the serum concentration-time curve (AUC) of lansoprazole and rabeprazole in the hmEMs, htEMs, and PMs after the final doses were 1:1.7:3.9 and 1:1.7:3.8, respectively. The relative AUCs of gastrin in the hmEMs, htEMs, and PMs were 1.6:2.6:3.1 for lansoprazole and 1.6:2.6:2.9 for rabeprazole, respectively. CONCLUSION: The disposition kinetic behavior of the two PPIs is co-segregated with CYP2C19. The magnitude of CYP2C19-dependent drug availability in the systemic circulation and resulting gastrin response appears to be fairly similar between the two drugs within the same CYP2C19 genotypic groups after a multiple-dosing regimen.

[Acute eosinophilic pneumonia with positive response to smoking challenge test, suggesting the involvement of health food].

A 17-year-old girl was admitted to our hospital because of acute febrile illness, progressive dyspnea and severe hypoxemia. Chest radiography and HRCT showed bilateral diffuse ground-glass opacities, consolidation, Kerley lines and pleural effusion. Analysis of bronchoalveolar lavage fluid showed 41.9% eosinophils, and a transbronchial lung biopsy revealed infiltration of eosinophils into the alveolar septa and mild alveolar septal edema. The patient's condition was improved immediately by corticosteroid therapy. She had begun smoking and taking health food (chitosan) 3 months before the admission. A smoking challenge test was positive and a drug-induced lymphocyte stimulation test for chitosan was positive. These findings suggested acute eosinophilic pneumonia caused by smoking and health food. The concentration of interleukin-5 (IL-5) in the serum and BALF/granulocyte colony-stimulating factor (G-CSF) in the serum on admission were very high, but decreased after the improvement. Therefore, it is likely that IL-5 and G-CSF are important in the onset of acute eosinophilic pneumonia.

Variant transthyretin in blood circulation can transverse the blood-cerebrospinal barrier: qualitative analyses of transthyretin metabolism in sequential liver transplantation.

BACKGROUND: Although the choroid6 plexus of the brain is one of the most important production sites of transthyretin (TTR), the metabolism of TTR secreted in cerebrospinal fluid (CSF) remains to be elucidated. METHODS: To perform qualitative analysis of variant TTR in CSF of patients who underwent a sequential liver transplantation using an explanted familial amyloidotic polyneuropathy (FAP) ATTR Val30 Met patient's liver, levels and forms of TTR of the two patients were analyzed by means of enzyme linked immunosorbent assay (ELISA) and matrix-assisted laser desorption/time-of-flight mass spectrometer (MALDI/TOF-MS), respectively. RESULTS: After the operation, variant TTR levels in serum increased, and in CSF, a significant peak of free form of ATTR Val30 Met was detected in the transplanted patients whose CSF had shown no variant TTR before the operation. CONCLUSIONS: These findings suggest that the variant TTR can cross-the blood-CSF barrier and migrate into CSF from blood circulation. Because leptomeningeal amyloidosis occurs in FAP ATTR Val30 Met as the progression of the disease, this information suggests that in addition to peripheral neuropathy, disorders of the central nervous system (CNS) should be given an attention in patients who underwent sequential liver transplantation using an explanted FAP ATTR Val30 Met patient's liver.

Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism.

The transition of cell-matrix adhesions from the initial punctate focal complexes into the mature elongated form, known as focal contacts, requires GTPase Rho activity. In particular, activation of myosin II-driven contractility by a Rho target known as Rho-associated kinase (ROCK) was shown to be essential for focal contact formation. To dissect the mechanism of Rho-dependent induction of focal contacts and to elucidate the role of cell contractility, we applied mechanical force to vinculin-containing dot-like adhesions at the cell edge using a micropipette. Local centripetal pulling led to local assembly and elongation of these structures and to their development into streak-like focal contacts, as revealed by the dynamics of green fluorescent protein-tagged vinculin or paxillin and interference reflection microscopy. Inhibition of Rho activity by C3 transferase suppressed this force-induced focal contact formation. However, constitutively active mutants of another Rho target, the formin homology protein mDia1 (Watanabe, N., T. Kato, A. Fujita, T. Ishizaki, and S. Narumiya. 1999. Nat. Cell Biol. 1:136-143), were sufficient to restore force-induced focal contact formation in C3 transferase-treated cells. Force-induced formation of the focal contacts still occurred in cells subjected to myosin II and ROCK inhibition. Thus, as long as mDia1 is active, external tension force bypasses the requirement for ROCK-mediated myosin II contractility in the induction of focal contacts. Our experiments show that integrin-containing focal complexes behave as individual mechanosensors exhibiting directional assembly in response to local force.

[A case of radiologically negative small-cell lung carcinoma successfully detected early by whole-body FDG-PET].

A 68-year-old man was referred to our hospital after being treated for early gastric cancer to investigate the causative malignancy, as his serum carcinoembryonic antigen (CEA) level was increased. Chest radiography showed no abnormal opacities. Subsequently, a whole-body FDG-PET was performed, which detected some tiny lesions in the mediastinum and the right lower lung field. A diagnosis of small-cell lung carcinoma was made after mediastinoscopic and bronchoscopic examinations. After chemoradiotherapy, the previously abnormal uptake of FDG was attenuated and the bronchoscopic appearance was improved, while the serum CEA and NSE levels returned to normal. Our findings demonstrated that whole-body scanning by FDG-PET could be useful for early detection of lung cancer, especially in cases of small-cell lung cancer.

[Clinical and bacteriological studies on hospital outbreak of Salmonella enteritidis food poisoning].

We experienced a hospital outbreak of salmonella food poisoning after ingestion of omelet which was the hospital evening meal on August 8, 1999. Total number of patients was sixty-two (Male 25: female 37) and the mean age was 52.1 years old. Salmonella Enteritidis was isolated from the stool in 59 cases. Twenty-one of them were associated with the immunosuppression (12 with malignancy, 6 with DM, one with nephrotic syndrome, one with chronic nephritis and one with allergic purpura). Clinical symptoms of the patients were composed of watery diarrhea (100%), fever (88.7%), abdominal pain (82.3%), nausea (45.2%) and vomiting (25.8%). The laboratory data revealed leukocytosis (15/47 = 31.9%), increased CRP (44/46 = 95.7%), elevated creatinin (1/37 = 2.7%) and hypokalemia (5/42 = 11.9%). MICs of 20 strains isolated in our laboratory almost coincided with each other indicating that the source of bacteria was probably the same. In vitro, S. Enteritidis were sensitive to OFLX, TFLX, FOM, most of PCs, CEPs, AGs but resistant to MPIPC, CAM, CLDM, VCM. Therefore we administered LVFX to 59 cases (alone in 45cases, combination with FOM in 6 cases), NFLX to two children and FMOX to one pregnant woman. Lactobacillus was administered to 28 cases (45.2%) and antidiarrhetics were given to 6 cases (9.7%). Finally all patients improved within two weeks. We suspect that the salmonella food poisoning was due to infected egg. The partially cooked omelet would permit the growth of a sufficient inoculum to cause disease. To prevent food poisoning, we have to be consistent in cooking the food well (at 75 degrees C, for more than 1 minute) and should not have omelets during the hot summer season.