Periodontitis Is Associated with Chronic Obstructive Pulmonary Disease.

Although they are known to share pathophysiological processes, the relationship between periodontitis and chronic obstructive pulmonary disease (COPD) is not fully understood. The aim of the present study was to test the hypothesis that periodontitis is associated with a greater risk of development of COPD, when smoking is taken into account. The analysis in a 5-y follow-up population-based cohort study was based on 900 community-dwelling Japanese adults (age: 68.8 ± 6.3 [mean ± SD], 46.0% male) without COPD aged 60 or older with at least 1 tooth. Participants were classified into 3 categories according to baseline periodontitis severity (no/mild, moderate, and severe). COPD was spirometrically determined by a fixed ratio of <0.7 for forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and by FEV1/FVC below the lower limit of normal. Poisson regression was used to calculate the relative risk (RR) of developing COPD according to the severity of periodontitis. The population attributable fraction (PAF) was also calculated. During follow-up, 22 (2.4%) subjects developed COPD. Compared with no/mild periodontitis subjects, a significantly increased risk of COPD occurred among severe periodontitis subjects (RR = 3.55; 95% confidence interval [CI], 1.18 to 10.67), but no significant differences were observed between the no/mild and moderate categories (RR = 1.48; 95% CI, 0.56 to 3.90). After adjustment for potential confounders, including smoking intensity, the relationship between severe periodontitis and risk of COPD remained significant (RR = 3.51; 95% CI, 1.15 to 10.74). Likewise, there was a positive association of periodontitis severity with risk of COPD ( P for trend = 0.043). The PAF for COPD due to periodontitis was 22.6%. These data highlight the potential importance of periodontitis as a risk factor for COPD.

A single administration of human adipose tissue-derived mesenchymal stromal cells (MSC) induces durable and sustained long-term regulation of inflammatory response in experimental colitis.

Current therapies for inflammatory bowel diseases (IBD) are aimed at controlling the exacerbated response in the gut, but no treatment is fully effective for many refractory patients. Mesenchymal stromal cells (MSC) are multi-potent cells with regulatory immunosuppressive activity that may control inflammatory diseases. In this study, we investigated the short- and especially the long-term protective effects of MSC on experimental colitis. We show that MSC elicited protection to acute intestinal inflammation with gain of weight, improvement in the clinical disease score and expressive reduction in the mortality rate of treated mice. MSC changed the population of neutrophils, eosinophils and augmented the frequency of CD4 T lymphocytes in the gut-draining lymph nodes, together with reduced accumulation of these cells in the colon intraepithelial compartment. Interestingly, there were increased levels of programmed death 1 (PD-1) and glucocorticoid-induced tumour necrosis factor receptor family-related receptor (GITR) in the spleen regulatory T cells of mice that received MSC treatment, which also presented a reversal in the pattern of immune response in the gut, with diminished inflammatory, T helper type 1 (Th1) and Th17 profile, in contrast to augmented Th2 responses. Most strikingly, this balanced response elicited by a single administration of MSC during the acute colitis persisted long-term, with restored goblet cells, eosinophils and maintenance of elevated gut interleukin (IL)-4, besides increased CD4+ CD25+ PD-1+ cells in the spleen and reduced Th17 response in mesenteric lymph nodes (MLN) of treated mice on day 60. Taken together, our findings provided a significant contribution to translational immunology by pointing human adipose tissue-derived MSC as a novel therapeutic approach with long-term beneficial regulatory effects in experimental colitis.

Next-generation sequencing for patients with non-obstructive azoospermia: implications for significant roles of monogenic/oligogenic mutations.

Azoospermia affects up to 1% of adult men. Non-obstructive azoospermia is a multifactorial disorder whose molecular basis remains largely unknown. To date, mutations in several genes and multiple submicroscopic copy-number variations (CNVs) have been identified in patients with non-obstructive azoospermia. The aim of this study was to clarify the contribution of nucleotide substitutions in known causative genes and submicroscopic CNVs in the genome to the development of non-obstructive azoospermia. To this end, we conducted sequence analysis of 25 known disease-associated genes using next-generation sequencing and genome-wide copy-number analysis using array-based comparative genomic hybridization. We studied 40 Japanese patients with idiopathic non-obstructive azoospermia. Functional significance of molecular alterations was assessed by in silico analyses. As a result, we identified four putative pathogenic mutations, four rare polymorphisms possibly associated with disease risk, and four probable neutral variants in 10 patients. These sequence alterations included a heterozygous splice site mutation in SOHLH1 and a hemizygous missense substitution in TEX11, which have been reported as causes of non-obstructive azoospermia. Copy-number analysis detected five X chromosomal or autosomal CNVs of unknown clinical significance, in addition to one known pathogenic Y chromosomal microduplication. Five patients carried multiple molecular alterations. The results indicate that monogenic and oligogenic mutations, including those in SOHLH1 and TEX11, account for more than 10% of cases of idiopathic non-obstructive azoospermia. Furthermore, this study suggests possible contributions of substitutions in various genes as well as submicroscopic CNVs on the X chromosome and autosomes to non-obstructive azoospermia, which require further validation.

The Beneficial Effect of Carboxylated Poly-L-Lysine on Cryosurvival of Vitrified Early Stage Embryos.

BACKGROUND: In the vitrification of embryos, dimethyl sulfoxide (DMSO) is one of the most effective cryoprotectant agents (CPAs), but cytotoxic effects of DMSO on embryos are well known. Carboxylated poly-L-lysine (CPLL) has been identified as an effective cryoprotectant of cultured cell lines and mammalian oocytes. OBJECTIVE: To evaluate the efficacy and safety of CPLL as a CPA for developmental stage embryos. MATERIALS AND METHODS: Mouse 8-cell embryos and blastocysts were vitrified with ethylene glycol (EG), DMSO/EG, or CPLL/EG and the developmental potency assessed in vitro. RESULTS: In 8-cell embryos, there were no differences between the levels of survival and developmental progress into the blastocyst stage in each solution. At the blastocyst stage, the proportion of dead cells was significantly higher in the EG compared with other solutions. In contrast, there were no differences between the DMSO/EG and CPLL/EG. CONCLUSION: These results indicate that CPLL can be used as a replacement for DMSO in the vitrification of mouse embryos.

A cryogenic receiver for EPR.

Cryogenic probes have significantly increased the sensitivity of NMR. Here, we present a compact EPR receiver design capable of cryogenic operation. Compared to room temperature operation, it reduces the noise by a factor of ≈2.5. We discuss in detail the design and analyze the resulting noise performance. At low microwave power, the input noise density closely follows the emission of a cooled 50Ω resistor over the whole measurement range from 20K up to room temperature. To minimize the influence of the microwave source noise, we use high microwave efficiency (≈1.1-1.7mTW(-1/2)) planar microresonators. Their efficient conversion of microwave power to magnetic field permits EPR measurements with very low power levels, typically ranging from a few µW down to fractions of nW.

Validation study of the Japanese version of the Faecal Incontinence Quality of Life Scale.

AIM: The aim of the present study was to conduct a psychometric validation of the Japanese version of the FIQL (JFIQL). METHOD: A retrospective analysis of data from the JFIQL was conducted. Wexner scores and Faecal Incontinence Severity Index (FISI) scores were collected prospectively in patients with faecal incontinence who visited our centre between 2008 and 2009. For convergent validity, the JFIQL scores were compared with stages on the Wexner scale for lifestyle alteration. To evaluate reliability, Cronbach's alpha was calculated for internal consistency, whereas a test-retest study was performed to evaluate reproducibility. In assessing responsiveness, JFIQL scores before and after treatments were compared in patients whose FISI scores decreased by ≥ 50%. RESULTS: Convergent validity and internal consistency were determined in 70 patients (49 women; median age 68.5 years). The JFIQL scores were significantly associated with lifestyle alteration stages on the Wexner scale, demonstrating convergent validity in all four domains and the generic score. Cronbach's alpha was > 0.7 for generic scores and all domains except Embarrassment. The intraclass correlations for the 27 patients available for the test-retest study were > 0.7 for generic scores and all domains except Embarrassment. The median JFIQL score improved significantly after treatment in the 23 patients whose FISI scores decreased ≥ 50%, indicating good responsiveness in all four domains and the generic score. CONCLUSION: The JFIQL has been validated and is now ready for use in evaluating the symptom-specific quality of life in Japanese patients with faecal incontinence.

Correlation between ischaemia-modified albumin and intermediate-density lipoprotein in haemodialysis patients with end-stage renal disease.

This study investigated the association between ischaemia-modified albumin (IMA), a biomarker of cardiac ischaemia, and increases in the levels of intermediate-density lipoprotein (IDL), an atherogenic particle that can cause oxidative stress, in haemodialysis patients with end-stage renal disease (ESRD). Fasting levels of serum IMA and lipids/lipoproteins were analysed in 15 patients and 15 healthy control subjects. There was a close positive correlation between IMA and IDL levels in ESRD patients but no significant correlation between IMA and lipids/lipoproteins in control subjects. This suggests a possible link between the characteristic dyslipoproteinaemia found in ESRD and levels of IMA and, if confirmed in studies with larger sample sizes, may lead to further studies on the potential of the relationship between IMA and IDL as a biomarker in haemodialysis patients with ESRD.

Evaluation of a simple loop-mediated isothermal amplification test kit for the diagnosis of tuberculosis.

OBJECTIVE: A new loop-mediated isothermal amplification (LAMP) test kit, including a simple DNA extraction device for the detection of Mycobacterium tuberculosis complex, was developed for commercial use and evaluated for its usefulness in diagnosing tuberculosis (TB). DESIGN: The LAMP test was performed using untreated and N-acetyl-L-cysteine (NALC) NaOH-treated sputum specimen. The efficiency of the kit was compared with other conventional laboratory examinations, including other nucleic acid amplification (NAA) tests. RESULTS: The sensitivity of LAMP using raw sputum (direct LAMP) in smear- and culture-positive specimens was 98.2% (95%CI 94.9-99.4), while the sensitivity in smear-negative, culture-positive specimens was 55.6% (95%CI 43.4-68.0). The diagnostic sensitivity of direct LAMP for the diagnosis of individuals with TB was 88.2% (95%CI 81.4-92.7). The sensitivity values of direct LAMP were slightly, but not statistically significantly lower than those of Cobas Amplicor MTB and TRC Rapid MTB, while the sensitivity of the LAMP test using NALC-NaOH treated sputum was significantly lower than other NAA tests (P < 0.05) for smear-negative, culture-positive specimens. The new commercial version of the LAMP kit was easy to handle and yielded results within 1 h of receiving sputum specimens. CONCLUSIONS: This test is considered a promising diagnostic tool for TB, even for peripheral laboratories with limited equipment, such as those in developing countries.

Effects of surgery and chronic disease states on the concentrations and phenotype distribution of α1-acid glycoprotein: studies in patients with breast cancer and patients with chronic inflammatory disease.

OBJECTIVE: Although the concentration of α1-acid glycoprotein (AGP) in serum increases under some conditions, the behavior of the individual genetic variants is not well understood. Therefore, we studied the relative changes in AGP variants pre- and postoperatively in patients with cancer and patients with chronic inflammatory disease states, as well as the distribution of AGP phenotypes in a Japanese population. METHODS: Serum samples were taken before and after surgery from 25 female patients with early breast cancer. Serum samples were also obtained from 134 patients with rheumatoid arthritis (RA) and 33 with systemic lupus erythematosus (SLE), and from 103 healthy subjects. The relative concentrations of the individual genetic variants in the serum samples were determined by isoelectric focusing after desialylation with neuraminidase. RESULTS: The postoperative AGP concentrations in patients with early breast cancer were 2-fold higher than before surgery. The relative concentrations of the F1 and S variants were significantly increased, whereas that of the A variant was not changed significantly. The relative concentrations of all the AGP variants in patients with RA and SLE were significantly higher than those in healthy subjects. The distribution of the AGP phenotypes did not differ significantly among the groups examined in this study. CONCLUSIONS: The F1/S variants of AGP, but not the A variant, were significantly increased after early breast cancer surgery, but all the variants were increased in patients with chronic inflammatory states such as RA and SLE. The distribution of the AGP phenotypes did not differ significantly among the disease groups studied.

Effect of spinal cord injury and its lesion level on stretch reflex modulation by cold stimulation in humans.

OBJECTIVE: To determine how short-latency stretch reflex amplitude in the soleus muscle is modulated by cold stimulation in able-bodied individuals and individuals with complete spinal cord injury. METHODS: An initial 100-s baseline period was followed by 50-s cold stimulation periods. Stretch reflex of the right soleus muscle was elicited for 10-s intervals, while cold stimulation was applied to the left thigh. RESULTS: Peak-to-peak amplitude of the stretch reflex increased significantly during cold stimulation up to 127 ± 21% of the baseline in the able-bodied group (n=9, P<0.01). Similarly, stretch reflex increased up to 125 ± 11% in a group with injury level at or below thoracic 10 (n=4), although this increase was not significant. On the other hand, stretch reflex decreased significantly down to 78 ± 20% in a group with injury level at or above thoracic 6 (n=8, P<0.05). CONCLUSIONS: Effect of afferent inputs induced by cold stimulation on stretch reflex modulation is different depending on the extent of central nervous systems participating in the modulation. SIGNIFICANCE: Our findings provide a better understanding of some basic changes in afferent-efferent spinal reflex pathways which are probably not monosynaptic in nature.

Feasibility of stomach exploration with a guided capsule endoscope.

BACKGROUND AND STUDY AIMS: Video capsule endoscopy has been established in diagnosis of small-bowel disease and has been evaluated for esophageal pathology and recently for colorectal diagnostics. Gastric capsule endoscopy has not hitherto been feasible due to the stomach's large surface area and volume. We present the first application of a magnetically navigated capsule in the human stomach. PATIENTS AND METHODS: 29 volunteers and 24 patients (men 42, women 11; mean age 47.5 years) were included in a feasibility study. Low-level magnetic fields were used to maneuver the double-sensor video capsule within the human stomach with an air-water interface provided by ingestion of 1300 ml water within 1 hour before examination. Visualization of all parts of the stomach was attempted; time for visualization was recorded, and a subjective assessment of completeness of visualization was documented. RESULTS: There was technical failure in one individual; thus technical success rate was 98 %. In the 52 remaining cases, examiners assessed that the antrum, body, fundus, and cardia were fully visualized in 98 %, 96 %, 73 % and 75 %, respectively. Mean duration of examinations was 30 minutes (range 8 - 50), with a longer time (mean 37 minutes) for volunteers for study reasons. In total, 30 findings were identified: 14 were detected by both gastroscopy and capsule, 10 lesions were identified by guided capsule examination only, 6 by gastroscopy only. No significant capsule-related adverse events occurred. CONCLUSION: Magnetically navigated video capsule endoscopy appears to be feasible and sufficiently accurate for gastric examination. It may permit endoscopic examinations that are more patient-friendly and without sedation. Comparative studies are under way.

Estimation of incidence of tuberculosis infection in health-care workers using repeated interferon-gamma assays.

The aim was to estimate the incidence of Mycobacterium tuberculosis (Mtb) infection in health-care workers (HCWs) in Japan. We repeated cross-sectional surveys of HCWs with QuantiFERON-TB Gold (QFT-G) in 2003, 2005 and 2007 at a hospital with tuberculosis (TB) wards, and 311 HCWs who underwent QFT-G testing two or three times were included in the study. Five HCWs (1.8%) converted from negative to positive. Incidence of new TB infection was estimated to be 0.6/100 person-years by the CDC's definition. Thirteen positive persons (41%) reverted from positive to negative. Multivariable logistic regression analysis identified a significant association between QFT-G conversion and working in TB wards. The IFN-gamma levels of all but two subjects with reverting or converting QFT-G results were close to the test's cut-off. The incidence of Mtb infection in HCWs at our hospital was higher than that estimated for the general population in Japan. Criteria for defining QFT-G conversion and reversion need further investigation considering the high proportion of reversion, as the incidence of infection would have changed if we had applied other definitions.

Comparison of oral falecalcitriol and intravenous calcitriol in hemodialysis patients with secondary hyperparathyroidism: a randomized, crossover trial.

BACKGROUND: Falecalcitriol is a novel vitamin D analog, which has a greater potential to suppress parathyroid hormone (PTH) and a longer half-life. There are few studies to compare clinical effects of oral falecalcitriol treatment with those of intravenous calcitriol treatment. METHODS: Twenty-one patients with moderate to severe SHPT were included in a random 2 x 2 crossover trial with the two vitamin D analogs (12 weeks for each treatment). The primary endpoint measure was a decrease in serum intact PTH (iPTH) level, and the secondary outcome measures included changes in serum calcium (Ca), phosphate (P), and metabolic bone marker levels. RESULTS: Both treatments decreased iPTH and whole PTH (wPTH) levels by similar degrees (iPTH, -200.1 +/- 107.0 with falecalcitriol vs. -200.8 +/- 114.9 pg/ml with calcitriol, p = 0.9895; wPTH, -137.1 +/- 73.1 with falecalcitriol vs. -120.4 +/- 81.1 pg/ml with calcitriol, p = 0.5603). Serum Ca, P, and Ca x P product levels at the end of each treatment were comparable and the frequencies of hypercalcemia and hyperphosphatemia were also similar during each treatment period. Although intravenous calcitriol treatment significantly changed intact osteocalcin and cross-linked N-telopeptide of type I collagen after 12 weeks, oral falecalcitriol treatment did not change any bone metabolic marker level. CONCLUSION: The present study showed that oral falecalcitriol treatment is effective for PTH suppression, and Ca and P metabolism in hemodialysis patients with moderate to severe SHPT, as well as intravenous calcitriol administration.

Mimivirus.

Acanthamoeba polyphaga Mimivirus, the first representative and prototype member of the Mimiviridae, is the latest addition to the menagerie of lesser-known big DNA viruses. Due to the size of its particle--a fiber-covered icosahedral protein capsid with a diameter of 0.7 microm--Mimivirus was initially mistaken for an intracellular parasitic bacteria. Its 1.2-Mb genome sequence was then found to encode more than 900 proteins, many of them associated with functions never before encountered in a virus, such as four aminoacyl-tRNA synthetases. The finding of Mimivirus-encoded central components of the protein translation apparatus thought to be the signature of cellular organisms revived the debate about the origin of DNA viruses and their possible role in the emergence of the eukaryotic cell. Despite the many features making it unique in the viral world, Mimivirus is nevertheless phylogenetically close to other large DNA viruses, such as phycodnaviruses and iridoviruses, and most likely share a common ancestry with all nucleocytoplasmic large DNA viruses. Postgenomic studies have now started in various laboratories, slowly shedding some light on the physiology of the largest and most complex virus isolated to date. This chapter summarizes our present knowledge on Mimivirus.

Alar groove plasty using a subcutaneous flap technique in bulbous nose repair after cleft lip plasty.

BACKGROUND: Bulbous nose is a ball-like nasal deformity, frequently seen in postoperative cleft lip patients, that is hard to prevent despite numerous techniques available for nasal tip plasty. Here we describe a new method for correcting bulbous nose in cleft lip patients by creating an ideal alar groove. METHODS: A subcutaneous flap with the pedicle of the overlying skin connected circumferentially is made just beneath the position for the ideal alar groove. The subcutaneous flap is fixed to the septum cartilage to create the alar groove depression on the nasal tip. This method is generally performed in conjunction with other rhinoplasty using the open nasal approach. RESULTS: Three postoperative cleft lip and nose patients underwent alar groove plasty combined with rhinoplasty. All retained good contour after the operation. CONCLUSION: Alar groove plasty using the subcutaneous flap technique improves bulbous nose deformities of cleft lip patients and can retain good postoperative contour.

Combined treatment using CEA and CAS for carotid arterial stenosis.

In this study we report our surgical results of CAS and CEA for carotid stenosis and suggest an appropriate treatment strategy for patients with high risks such as bilateral carotid stenosis or medical risk factors. From January 2001 to December 2005 we surgically treated 182 patients with carotid stenosis. Seventy-nine lesions were treated by CEA and 145 by CAS, respectively. Although CEA was considered the first choice for severe carotid stenosis, CAS was chosen for treatment when CEA was considered a higher risk for patients. Stenosis of carotid arteries was relieved in all cases after CEA or CAS. Surgical mortality of CEA was 1.1% (1/94). Surgical mortality of CAS was 0.7% (1/145). Carotid stenotic lesions can be treated with comparably low morbidity and mortality rates using CEA or/and CAS considering each characteristic of carotid stenosis of patients even with medically high risk or bilateral carotid stenosis.

Long-range correlated glucose fluctuations in diabetes.

OBJECTIVES: Our objective is to investigate diabetes-related alteration of glucose control in diurnal fluctuations in normal daily life by detrended fluctuation analysis (DFA). METHODS: The fluctuations of glucose of 12 non-diabetic subjects and 15 diabetic patients were measured using a continuous glucose monitoring system (CGMS) over a period of one day. The glucose data was calculated by the DFA method, which is capable of revealing the presence of long-range correlations in time series with inherent non-stationarity. RESULTS: Compared with the non-diabetic subjects, the mean glucose level and the standard deviation are significantly higher in the diabetic group. The DFA exponent alpha is calculated, and glucose time series are searched for the presence of negatively (0.5 < alpha < 1.5) or positively (1.5 < alpha) correlated fluctuations. A crossover phenomenon, i.e. a change in the level of correlations, is observed in the non-diabetic subjects at about two hours; the net effects of glucose flux/reflux causing temporal changes in glucose concentration are negatively correlated in a "long-range" (> two hours) regime. However, for diabetic patients, the DFA exponent alpha = 1.65 +/- 0.30, and in the same regime positively correlated fluctuations are observed, suggesting that the net effects of the flux and reflux persist for many hours. CONCLUSIONS: Such long-range positive correlation in glucose homeostasis may reflect pathogenic mechanisms of diabetes, i.e., the lack of the tight control in blood glucose regulation. Using modern time series analysis methods such as DFA, continuous evaluation of glucose dynamics could promote better diagnoses and prognoses of diabetes and a better understanding of the fundamental mechanism of glucose dysregulation in diabetes.