Prevalence and risk factors associated with nonspecific building-related symptoms in office employees in Japan: relationships between work environment, Indoor Air Quality, and occupational stress.

A nationwide cross-sectional study of 3335 employees was conducted in 320 offices in Japan to estimate the prevalence of building-related symptoms (BRSs) and determine the risk factors related to work environment, Indoor Air Quality, and occupational stress. Data were collected through self-administered questionnaires. The prevalences of general symptoms, eye irritation, and upper respiratory symptoms were 14.4%, 12.1%, and 8.9%, respectively. Multiple logistic regression analyses revealed that eye irritation was significantly associated with carpeting [odds ratio (OR), 1.73; 95% confidence interval (CI), 1.24-2.41], coldness perception (OR, 1.28; 95% CI, 1.13-1.45), and air dryness perception (OR, 1.61; 95% CI, 1.42-1.82). General symptoms were significantly associated with unpleasant odors (OR, 1.37; 95% CI, 1.13-1.65), amount of work (OR, 1.24; 95% CI, 1.06-1.45), and interpersonal conflicts (OR, 1.44; 95% CI, 1.23-1.69). Upper respiratory symptoms were significantly associated with crowded workspaces (OR, 1.36; 95% CI, 1.13-1.63), air dryness perception (OR, 2.07; 95% CI, 1.79-2.38), and reported dustiness on the floor (OR, 1.39; 95% CI, 1.16-1.67). Although psychosocial support is important to reduce and control BRSs, maintaining appropriate air-conditioning and a clean and uncrowded workspace is of equal importance.

Salivary Alpha-Amylase Activity and Mild Cognitive Impairment among Japanese Older Adults: The Toon Health Study.

BACKGROUND: There is growing interest in examining objective markers for early identification and behavioral intervention to prevent dementia and mild cognitive impairment in clinical and community settings. OBJECTIVE: To investigate the association between salivary alpha-amylase as an objective measure of psychological stress response and mild cognitive impairment for the implication of psychological stress in the development of mild cognitive impairment. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study involved 865 participants aged ≥ 65 years. A saliva sample was collected in the morning, and the levels of salivary alpha-amylase were assayed. Mild cognitive impairment was evaluated using the Japanese version of the Montreal Cognitive Assessment; a score < 26 was indicative of mild cognitive impairment. A multivariable logistic regression model was used to examine the association of salivary alpha-amylase and mild cognitive impairment after adjusting for age, sex, current drinking status, current smoking status, body mass index, hypertension, diabetes mellitus, physical activity, education, social support, social network, and heart rate variability. RESULTS: Salivary alpha-amylase was associated with mild cognitive impairment (the multivariable-adjusted odds ratio [95% confidence interval] for the 1-standard deviation increment of log-transformed salivary alpha-amylase was 1.24 [1.07-1.44]). This significant association persisted after adjusting for various confounding factors. CONCLUSION: Elevation of salivary alpha-amylase was associated with mild cognitive impairment among Japanese community-dwelling older adults. This suggests that salivary alpha-amylase is a useful objective marker of psychological stress responses associated with mild cognitive impairment.

Administration of group A streptococcal cell walls to rats induces an interleukin 2 deficiency.

Intraperitoneal administration of group A streptococcal cell walls to Lewis rats induces a chronic arthritis, whereas the Fischer strain is resistant to the development of the lesion. Spleen cells from cell wall-treated rats (Lewis and Fischer) are deficient in the synthesis of IL-2. Using an mAb directed against the rat IL-2-R, the present studies indicate that the expression of IL-2-R on spleens of cell wall-treated rats is normal. However, the addition of exogenous IL-2 to spleen cells cultured with Con A does not stimulate the mitogenic response.

Rat lymphoid cell lines producing human T cell leukemia virus. II. Constitutive expression of rat interleukin 2 receptor.

Three rat lymphoid cell lines (TARS-1, TARL-2, and TART-1) (12) transformed by human T cell leukemia/lymphoma virus I (HTLV-I) had rearrangement of the beta chain gene of the T cell antigen receptor, and had integrated proviral DNA from HTLV-I in their genomes. As is the case with adult T cell leukemia (ATL)-derived human T cell lines transformed by HTLV-I, these rat cell lines unequivocally expressed interleukin 2 (IL-2) receptor, as determined by radiolabeled IL-2 binding. By Scatchard plot analysis, one of the cell lines, TART-1, proved to have high affinity receptors (Ka = 1.3 X 10(11)/M and 8.8 X 10(9)/M). Rat IL-2 receptor, not human IL-2 receptor, was expressed on HTLV+ rat cell lines, as demonstrated by the fact that they expressed antigens reactive with monoclonal antibodies (ART-18) against rat IL-2 receptor, but not with anti-Tac antibodies. The collective evidence indicates that the endogenous IL-2 receptor gene is activated in human and rat lymphoid cell lines with HTLV-I production. The mechanism of abnormal IL-2 receptor expression in HTLV infection is discussed.

Differential association of HLA with three subtypes of type 1 diabetes: fulminant, slowly progressive and acute-onset.

AIM/HYPOTHESIS: We sought to clarify similarities and differences in the contribution of HLA to genetic susceptibility to three subtypes of type 1 diabetes: acute-onset, fulminant and slowly progressive. METHODS: We genotyped 545 Japanese patients with type 1 diabetes (338 acute-onset, 80 fulminant, 127 slowly progressive) and 396 control participants at HLA-DRB1, -DQB1, -A, -B and -C, and at 101 candidate single nucleotide polymorphisms (SNPs) in an 8.5 Mb region of the extended HLA. RESULTS: DRB1*0405-DQB1*0401, DRB1*0802-DQB1*0302 and DRB1*0901-DQB1*0303 were associated with acute-onset type 1 diabetes, with the DRB1*0405-DQB1*0401/DRB1*0802-DQB1*0302 genotype achieving the highest odds ratio of 42.7. DRB1*1501-DQB1*0602 and DRB1*1502-DQB1*0601 were negatively associated with acute-onset type 1 diabetes. A similar tendency was observed for slowly progressive type 1 diabetes. In contrast, only DRB1*0405-DQB1*0401 was associated with fulminant type 1 diabetes, with the DRB1*0405-DQB1*0401/DRB1*0405-DQB1*0401 genotype showing the highest odds ratio of 11.2. DRB1*0802-DQB1*0302, DRB1*0405-DQB1*0401/DRB1*0802-DQB1*0302 and DRB1*1501-DQB1*0602 were not associated with fulminant type 1 diabetes. The association of class I alleles and a panel of SNPs in an extended HLA region with fulminant type 1 diabetes was also different from that seen for the acute-onset and slowly progressive forms. The presence of both one and two susceptible haplotypes conferred susceptibility to slowly progressive type 1 diabetes, whereas the presence of two susceptible haplotypes was required to confer susceptibility to acute-onset and fulminant type 1 diabetes. CONCLUSIONS/INTERPRETATION: These data suggest that HLA associations with fulminant type 1 diabetes are qualitatively different from those with other subtypes of type 1 diabetes, whereas the HLA contribution to slowly progressive type 1 diabetes is qualitatively similar to, but quantitatively different from, that in acute-onset type 1 diabetes.

Prognostic significance of FTO genotype in the development of obesity in Japanese: the J-SHIPP study.

OBJECTIVE: Susceptibility of fat mass and obesity-associated (FTO) gene polymorphisms to obesity has been reported in various populations. Polymorphisms in the melanocortin 4 receptor (MC4R) gene were recently explored as another susceptible locus. However, prognostic significance of these genetic variations has not been fully elucidated. Here, we investigated the involvement of FTO rs9939609 and MC4R rs17782313 polymorphisms in the development of obesity. Association with type 2 diabetes mellitus (T2DM) was also investigated. SUBJECTS: We analyzed 2806 community-dwelling middle-aged to elderly subjects (61+/-14 years). Clinical parameters were obtained from the subjects' personal health records, evaluated at their annual medical check-up. RESULTS: FTO genotype was significantly associated with current body mass index (BMI; TT 23.2+/-3.2, TA 23.7+/-3.2, AA 24.4+/-3.2 kg m(-2), P=2.5 x 10(-6)) and frequency of obesity (26.6, 32.0, 43.0% respectively, P=2.0 x 10(-4)). Age- and sex-adjusted odds ratio for obesity was 1.30 (P=0.004) in TA and 2.07 (P=0.002) in AA genotype. During the 9.4 years comprising the follow-up period, 214 new cases of obesity were diagnosed among 1718 subjects whose retrospective data were available. A allele frequency of the FTO genotype was significantly higher in subjects who developed obesity (22.2, 15.8%, P=0.001), Age-, sex- and initial BMI-adjusted odds ratio for the development of obesity was 1.46 (95% confidence interval, 1.04-2.04) (P=0.031). However, association studies and meta-analysis of T2DM did not actively support the involvement of FTO genotype. No significant differences were observed between the MC4R genotype and BMI (P=0.015), and the frequency of obesity (P=0.284). CONCLUSION: FTO genotype is an independent risk factor for future development of obesity.

[Aortic root replacement and pulmonary vein isolation; report of a case].

A 60-year-old female was admitted to our hospital who suffered from palpitation and dyspnea. Echocardiography revealed severe aortic regurgitation and enlargement of ascending aorta. Electrocardiogram showed tachycardia due to atrial fibrillation. We performed the aortic root replacement with Carboseal composite graft and pulmonary vein isolation using Cardioblate BiPolar (BP) system. Histopathologic diagnosis was giant isolated aortitis. The post operative course was uneventful. And the patient was discharged in normal sinus rhythm.

[Traumatic mitral regurgitation with acute pulmonary edema].

A case of a successful surgical treatment for traumatic mitral valve regurgitation is reported. A 44-year-old, small-statured female with cretinism had a traffic accident. Eleven days after the accident, she was admitted to our hospital with severe respiratory distress syndrome by acute pulmonary edema. Echocardiography showed severe mitral regurgitation due to tendon rupture of posterior leaflet. Mitral valve plasty was performed successfully.

[Experience of chest wall reconstruction with newly developed material].

After the chest wall resection, its reconstruction is often needed. A 45-year-old male lung adenocarcinoma patient with chest wall invasion underwent upper lobectomy of the right lung with partial resection of 4-6th ribs. The size of the removed chest wall was 11 x 6.5 cm. We reconstructed the chest wall with Bard Composix E/X Mesh. This prosthesis is consisted of a polypropylene mesh and an expanded polytetrafluoroethylene sheet This material is seems to be useful in the reconstruction of chest wall in both preventing pulmonary adhesion and enabling good wound healing.

Mitogen-activated protein kinase and p70 ribosomal protein S6 kinase are not involved in the insulin-dependent stimulation of cAMP phosphodiesterase kinase in rat adipocytes.

To elucidate the mechanism of anti-lipolytic action of insulin in rat epididymal adipocytes, we explored the potential mechanism that might be involved in the hormone-dependent stimulation of cAMP phosphodiesterase (PDE) kinase. PDE kinase was assayed in a cell-free system. Both wortmannin and LY294002, highly specific inhibitors of phosphatidylinositol 3-kinase, almost completely blocked the hormonal effect not only on PDE kinase but also on mitogen-activated protein (MAP) kinase. Neither PD98059, a specific inhibitor of MAP kinase, nor rapamycin, a potent inhibitor of insulin-dependent stimulation of p70 ribosomal protein S6 kinase (p70S6K), had inhibitory effect on that of PDE kinase. These results are consistent with the view that (i) insulin-activated PDE kinase as well as MAP kinase and p70S6K are localized downstream of phosphatidylinositol 3-kinase, (ii) PDE kinase is distinct from either MAP kinase or p70S6K and (iii) PDE kinase does not exist downstream of either MAP kinase or p70S6K. It is suggested that PDE kinase and MAP kinase or p70S6K may be localized in separate branches of the cascade of insulin action. The branching point of the cascade could be either at or below the level of phosphatidylinositol 3-kinase.

Regulation of hexokinase II gene transcription and glucose phosphorylation by catecholamines, cyclic AMP, and insulin.

The hexokinases, by converting glucose to glucose-6-phosphate, help maintain the downhill gradient that results in movement of glucose into cells through the facilitative glucose transporters. GLUT4 and hexokinase (HK) II are the major transporter and hexokinase isoforms in skeletal muscle, heart, and adipose tissue, wherein insulin promotes glucose utilization. To understand whether hormones influence the contribution of phosphorylation to cellular glucose utilization, we investigated the effects that catecholamines, cyclic AMP (cAMP), and insulin have on HKII gene expression in cells representative of muscle (L6 cells) and brown (BFC-1B cells) and white (3T3-F442A cells) adipose tissues. Isoproterenol or the cAMP analog 8-chlorophenylthio-cAMP selectively increase HKII gene transcription in L6 cells, as does insulin (Printz RL, Koch S, Potter LP, O'Doherty RM, Tiesinga JJ, Moritz S, Granner DK: Hexokinase II mRNA and gene structure, regulation by insulin, and evolution. J Biol Chem 268:5209-5219, 1993), and cause a concentration- and time-dependent increase of HKII mRNA in both muscle and fat cell lines without changing HKI mRNA. Isoproterenol and insulin also increase the rate of synthesis of HKII protein and increase glucose phosphorylation and glucose utilization in L6 cells.

Improvement in insulin resistance and the restoration of reduced phosphodiesterase 3B gene expression by pioglitazone in adipose tissue of obese diabetic KKAy mice.

Phosphodiesterase (PDE) 3B is a key enzyme in the mediation of the antilipolytic action of insulin in adipocytes, and activation of this molecule results in a reduced output of free fatty acids (FFAs). An elevation of serum FFAs is known to cause insulin resistance in skeletal muscle and liver, which could be the primary cause of type 2 diabetes. To elucidate whether PDE3B is involved in this disease, we examined the PDE3B gene expression in epididymal fat tissues of obese insulin-resistant diabetic KKAy mice. We also examined the effect of an insulin-sensitizing drug, pioglitazone, on this gene expression. In adipose tissue of KKAy mice, PDE3B mRNA and its corresponding protein were reduced to 48 and 43% of those in C57BL/6J control mice. Basal and insulin-stimulated membrane-bound PDE activities were also decreased to 50 and 36% of those in the controls, respectively. Pioglitazone increased both PDE3B mRNA and protein levels by 1.8-fold of those in untreated KKAy mice. Basal and insulin-induced membrane-bound PDE activities were also increased by 1.6- and 2.0-fold, respectively. Pioglitazone reduced the elevated levels of serum insulin, glucose, FFAs, and triglyceride in KKAy mice. Thus, the reduced PDE3B gene expression in adipose tissues could be the primary event in the development of insulin resistance in KKAy mice, which was improved by pioglitazone possibly because of the restoration of the reduced PDE3B gene expression.

Histamine-2 receptor expression in gastric mucosa before and after Helicobacter pylori cure.

BACKGROUND: Helicobacter pylori infection prevents the occurrence of the tolerance phenomenon of Histamine-2 (H2) receptor antagonists. Gastro-esophageal reflux disease develops in some cases with the restoration of acid secretion after H. pylori eradication therapy. AIM: To clarify the mechanisms of H2 receptor restoration after the eradication of H. pylori on parietal cells. METHODS: We enrolled 80 consecutive asymptomatic male patients with H. pylori infection, having chronic gastritis with or without the presence of peptic ulcers. Biopsy specimens from the greater curvatures at the mid-corpus of the stomach were obtained endoscopically from all subjects before and 12 weeks after the eradication of H. pylori. Degrees of gastric atrophy were evaluated by serum pepsinogen levels. The amounts of mRNA expression of H2 receptor were evaluated in each subject's gastric mucosa by real time reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: H2 receptor mRNA expression levels significantly correlated with serum pepsinogens I and II ratios. The expression level of H2 receptor mRNA was lower in subjects with hypergastrinemia. The median expression level of H2 receptor after H. pylori eradication was threefold greater than prior to treatment. In addition, its restoration became more pronounced in subjects with severe gastric atrophy. However, a comparatively low restoration of H2 receptor mRNA was found in subjects with hypergastrinemia. CONCLUSIONS: H2 receptor mRNA levels decrease with the progression of gastric atrophy induced by H. pylori infection, and are restored after H. pylori eradication. Such expression levels of H2 receptor may explain a part of the tolerance phenomenon to H2 receptor antagonists.

Comparison of hemostatic effects by route of H2 receptor antagonist administration following endoscopic mucosal resection in patients with neoplastic gastric lesions.

BACKGROUND: To date, there has not been an in-depth investigation to identify differences in the effects of bleeding prevention among different routes of administration of H2 receptor antagonists to treat gastric ulcers following endoscopic mucosal resection (EMR). AIM: To prospectively compare the frequency of bleeding following EMR between patients treated with intravenous (IV) famotidine and those with oral famotidine. METHODS: Fifty-three patients with neoplastic gastric lesions (33 carcinoma and 20 adenoma) treated by EMR were included. Subjects underwent EMR with circumferential mucosal incision assisted by submucosal injection of sodium hyaluronate (EMRSH), followed by IV or oral (PO) administration of famotidine at a dosage of 40 mg/day for 2 days. Patients with odd ID numbers were assigned to IV therapy (30 cases) while even numbers were given PO therapy (23 cases). Frequencies and endoscopic findings of bleeding during the first 2 days after EMR were examined. RESULTS: Frequency of bleeding within 2 days after EMR was 3 and 4% in IV and PO patients, respectively, showing no significant difference. No significant difference was seen in the endoscopic findings of bleeding and therapy, either, with respective IV and PO findings at 23 and 26%. CONCLUSIONS: No significant difference was observed in frequency of bleeding within 2 days after gastric EMR between IV and oral administrations of famotidine.

Studies on the interleukin-2 receptor, its generation and dynamics using monoclonal anti-interleukin-2 receptor antibodies.

There is increasing evidence suggesting that the monoclonal antibodies ART-18, AMT-13 and anti-Tac recognize species-specific antigenic determinants of the interleukin-2 (IL-2) receptors of rat, mouse and human origin, respectively. In order to compare directly the molecules (glycoproteins) recognized by these antibodies, concanavalin A (ConA) activated T-lymphocytes of the respective species were surface labeled with 125I, after which the materials immunoprecipitated by the appropriate anti-IL-2 receptor antibodies were subjected to SDS-PAGE analysis. The noncross-reacting antibodies ART-18 and AMT-13 both precipitated a 50-55-kD molecule. The anti-Tac-reactive material (the putative human IL-2 receptor) is considerably different (60-65 kD) from those precipitated by antibodies ART-18 and AMT-13 (the putative rat and mouse IL-2 receptors). An indirect binding assay using the anti-mouse IL-2 receptor antibody AMT-13 showed that, after addition of ConA to spleen cell cultures, T-lymphocytes expressed IL-2 receptors before the onset of the ConA-induced DNA synthesis. The ConA-induced expression of the IL-2 receptor is apparently a transient event. IL-2 receptor bearing cells progressively lost their receptors (within 6 days) when recultured in the absence of ConA. Cells re-exposed to ConA regained IL-2 receptors. Short exposure of T-cells (thymocytes) to ConA or the nonmitogenic compound phorbol myristate acetate (PMA) is not sufficient to trigger IL-2 receptor expression. Murine thymocytes incubated with PMA for 30 min or with ConA for 4 hr (mitogen-pulsed T-cells) failed to bind the anti-IL-2 receptor antibody AMT-13 and to absorb IL-2 activity present in semipurified IL-2 preparations, but they proliferated vigorously in response to the same IL-2 preparations. The IL-2 preparations, when absorbed with thymocytes, lost: (1) the capacity to generate IL-2 receptors, and (2) the capacity to induce proliferation of mitogen-pulsed cells; but they retained the capacity to induce proliferation of T-lymphoblasts. These results suggest the existence of a factor, IL-2 receptor inducing factor (RIF), present in the IL-2 preparations. It is postulated that RIF is a prerequisite for the acquisition of IL-2 receptors and consequently for IL-2 responsiveness by lectin-activated cells.

Regulation of interleukin-2 receptor expression and receptor release.

The generation and cell surface expression of IL-2 receptors was monitored by: (i) an ELISA that permits quantitative determination of detergent-solubilized or soluble IL-2 receptors; and (ii) detection of the binding of 125I-labelled recombinant IL-2 and of anti-IL-2 receptor antibodies to receptor bearing cells. Upon lectin stimulation both high and low affinity IL-2 receptors became expressed in parallel at the cell surface. Both high and low affinity receptors were upregulated by IL-2. Upon lectin activation the amount of cell-associated receptors increased and on day 2 of the culture period IL-2 receptors were detectable in the culture supernatant. IL-2 upregulated both high and low affinity IL-2R expression on T-lymphoblasts. IL-2R bearing leukemic cells and T lymphoblasts released IL-2R when cultured in vitro. IL-2R release by T lymphoblasts was enhanced dramatically by IL-2. On the other hand, IL-2-receptor positive leukemic cells released receptors in an IL-2 independent manner. Release of receptors could also be detected in serum-free medium. At least a part of the released receptors could be specifically bound to immobilized pure recombinant IL-2 and to monoclonal anti-IL-2-receptor antibodies. Small but significant amounts of soluble IL-2 receptors were detectable in the sera of normal mice. In sera of mice inoculated with IL-2-receptor positive syngeneic leukemic cells, elevated levels of IL-2 receptors were detectable. Release of IL-2 receptors seems to represent one of the major routes by which the receptors are cleared from the cell surface.

[Prevention of acute exacerbation of interstitial pneumonia in the patients operated for lung cancer].

Eight patients with interstitial pneumonia (IP) underwent pulmonary surgery for lung cancer. The first patient died due to postoperative exacerbation, but the subsequent 7 patients had good postoperative course without exacerbation by the following careful management. 1) Avoidance of administration of high concentration of oxygen keeping the PO2 about 100 mmHg during the operation. 2) Short-term administration of low-dose steroid before the operation. 3) Administration of erythromycin, tocopherol acetate, and inhalation of N-acetylcysteine before and after the operation. 4) Long-term drainage of the postoperative thoracic discharge to release the local cytokines. These treatments inhibit secretion of the inflammatory cytokines which influence exacerbation of IP.

[Lung cancer in patients with idiopathic interstitial pneumonia].

The purpose of this study was to determine the outcome of surgical treatment for lung cancer concomitant with idiopathic interstitial pneumonia (IIP). Between 1994 and 2003, 673 patients with primary lung cancer were treated. Forty-four patients (6.54%) of 673 patients were complicated with IIP. Their data were retrospectively reviewed. There were 37 male and 7 female with an average age of 67 years. They underwent 7 wedge resections of the lung, 3 segmentectomies, 32 lobectomies and 2 bi-lobectomies as surgical treatment for lung cancer. Five of these 44 patients died of acute exacerbation of IIP after the operation. The exacerbation occurred in an average postoperative day of 5 (range, 3 to 7) day. Preoperative values of serum CRP, LDH, SP-D and KL-6 failed to predict the occurrence of the exacerbation of IIP after the surgery. The preoperative value of %DLCO was lower in patients with the exacerbation than patients without the exacerbation (42.3+/-9.6% versus 66.8+/-18.8%, p=0.018). The postoperative 5-year survival rate for pathological stage I lung cancer were 84.9% and 70.2% (p=0.134) for patients without IIP and patients with IIP, respectively. Although the acute exacerbation of IIP after the surgery caused catastrophic outcomes, the long-term results in surgical treatment for stage I lung cancer simultaneously concomitant with IIP were not so poor. It is very important to avoid the postoperative exacerbation and further effort and research are required to avoid the exacerbation.

[Off-pump coronary artery bypass for old myocardial infarction associated with jejunotomy for obstructive ileus due to gall bladder stone; report of a case].

In non-cardiac operative cases with inflammatory digestive organ disease, bacterial translocation (BT) often results from non-enteral nutrition postoperatively. If coronary artery bypass grafting (CABG) is performed in the case having old myocardial infarction (OMI) and inflammatory digestive organ disease at first before non-cardiac operation, he seems vulnerable to have severe complications such as multiple organ failure due to systemic inflammatory response syndrome (SIRS) and preexisting BT postoperatively. We performed a off-pump CABG (OPCAB) for OMI associated with jejunotomy for obstructive ileus due to gall bladder stone. No complication was found in the postoperative course. We conclude that combined operation, non-cardiac surgery after OPCAB is worth considering in those cases. And we think OPCAB is better than conventional CABG in such cases, because cardiopulmonary bypass is known to ponder comparable damages to immune system, coagulation system and others.