Trends in incidence and mortality of tuberculosis in Japan: a population-based study, 1997-2016.

Japan is still a medium-burden tuberculosis (TB) country. We aimed to examine trends in newly notified active TB incidence and TB-related mortality in the last two decades in Japan. This is a population-based study using Japanese Vital Statistics and Japan Tuberculosis Surveillance from 1997 to 2016. We determined active TB incidence and mortality rates (per 100 000 population) by sex, age and disease categories. Joinpoint regression was applied to calculate the annual percentage change (APC) in age-adjusted mortality rates and to identify the years showing significant trend changes. Crude and age-adjusted incidence rates reduced from 33.9 to 13.9 and 37.3 to 11.3 per 100 000 population, respectively. Also, crude and age-adjusted mortality rates reduced from 2.2 to 1.5 and 2.8 to 1.0 per 100 000 population, respectively. Average APC in the incidence and mortality rates showed significant decline both in men (-6.2% and -5.4%, respectively) and women (-5.7% and -4.6%, respectively). Age-specific analysis demonstrated decreases in incidence and mortality rates for every age category, except for the incidence trend in the younger population. Although trends in active TB incidence and mortality rates in Japan have favourably decreased, the rate of decline is far from achieving TB elimination by 2035.

Relationship between U83 gene variation in human herpesvirus 6 and secretion of the U83 gene product.

The betaherpesvirus human herpesvirus 6 (HHV-6) has two variants. The U83 gene product of strain HST is a chemoattractant for monocytes. Here, we describe U83 gene variations that accumulated in variants A and B. A gene-variation hot spot was examined in 36 different strains and one donor DNA sample. U83 gene variations accumulated in variant A and in reactivated variant B after transplantation. None of the variant-A viruses encoded the signal peptide found in the B variant. U83 gene sequencing suggested that the variant A and B groups were separate, and that the variant B viruses could be further divided into the HST-Z29 type and another type with a shorter signal peptide. In a eukaryotic expression system, the HST-Z29 type of U83 gene product was secreted into the medium, a frame-shifted HST-Z29 type was partially secreted, and the variant-A type and a first-methionine knockout of the HST-Z29 type were not secreted.

Psychological and behavioral mechanisms influencing the use of complementary and alternative medicine (CAM) in cancer patients.

BACKGROUND: This study explored the psychological and behavioral mechanisms of complementary and alternative medicine (CAM) use in Japanese cancer patients using two applied behavioral models, the transtheoretical model (TTM), and theory of planned behavior (TPB). PATIENTS AND METHODS: Questionnaires were distributed to 1100 patients at three cancer treatment facilities in Japan and data on 521 cancer patients were used in the final analysis. The questionnaire included items based on TTM and TPB variables, as well as three psychological batteries. RESULTS: According to the TTM, 88 patients (17%) were in precontemplation, 226 (43%) in contemplation, 33 (6%) in preparation, 71 (14%) in action, and 103 (20%) in maintenance. The model derived from structural equation modeling revealed that the stage of CAM use was significantly affected by the pros, cons, expectation from family, norms of medical staff, use of chemotherapy, period from diagnosis, and place of treatment. The primary factor for the stage of CAM use was the expectation from family. CONCLUSIONS: The findings revealed the existence of a number of psychologically induced potential CAM users, and psychological variables including positive attitude for CAM use and perceived family expectation greatly influence CAM use in cancer patients.

Anxiety accelerates T-helper 2-tilted immune responses in patients with atopic dermatitis.

BACKGROUND: Stress, which mediates anxiety, worsens skin symptoms in patients with atopic dermatitis (AD). The contribution of anxiety to immune dysfunction, which plays a critical role in the pathogenesis of AD, requires clarification. OBJECTIVES: To examine the relationship between anxiety and atopy-relevant immune function in AD. METHODS: Eighty-five patients with AD and 58 normal individuals without a history of allergic disorders were enrolled in this study. To assess anxiety, the state-trait anxiety inventory was completed for both groups. In the AD group, measurements were made of SCORAD scores, serum IgE levels, itching (visual analogue scale), blood eosinophil count and T-helper (Th) 1/Th2 ratio in the peripheral blood. RESULTS: Anxiety was significantly higher among the subjects with AD than the normal subjects, and trait anxiety (TA) was higher than state anxiety (SA) in the AD group. Serum total IgE levels were correlated positively with TA and the TA/SA ratio and inversely with SA, and the Th1/Th2 ratio was correlated inversely with TA and the TA/SA ratio. CONCLUSIONS: The patients with AD had higher anxiety levels than normal individuals, and those with a stronger perception of TA than SA showed enhanced serum IgE synthesis and Th2 shifting.

Production and characterization of recombinant human anti-HBs Fab antibodies.

Recombinant human Fab antibodies were generated with different reactivities against the hepatitis B virus surface (HBs) antigen. To isolate the antibodies, a method was used that combined transformation of human B cells by Epstein-Barr virus (EBV) infection with a primer-vector system developed for isolating DNA fragments of human Ig Fab portions. With this method, monoclonal and oligoclonal cell lines producing anti-HBs antibodies were established and three anti-HBs Fab antibodies were isolated from two of these cell lines. From analysis of affinity characteristics, immunohistochemical activity, and cytolysis activity, these three Fab antibodies were classified into three different groups. The first group had high affinity for HBs, the second had the ability to kill HBV-infected cells, and the third was applicable to immunohistochemical staining with HBV-infected cells. The combined effect of these antibodies was also investigated by complement-dependent cytotoxicity assay.

Infrasternal mediastinoscopic surgery for anterior mediastinal masses.

BACKGROUND: Infrasternal mediastinoscopic surgery is a new alternative to the thoracoscopic approach for patients with anterior mediastinal masses. METHODS: We applied this technique to 18 thymectomies, one thymomectomy, and one cystectomy in a total of 20 patients with anterior mediastinal masses and then assessed the surgical results. RESULTS: Infrasternal mediastinoscopic surgery was accomplished in 18 of the 20 patients (90%). The pathological diagnoses included 13 Masaoka stage I thymomas, one stage II thymoma, two stage III thymomas, one thymic cyst, one pericardial cyst, one thymic granuloma, and one mature teratoma. Two patients with stage III thymoma required conversion to sternotomy, one for invasion into the innominate vein and the other for invasion into the pericardium. There was no surgically related mortality or complications in any patients. CONCLUSION: Infrasternal mediastinoscopic surgery is safe and feasible for stage I thymoma and other benign tumors in the anterior mediastinum.

Excess accumulation of body fat is related to dyslipidemia in normal-weight subjects.

OBJECTIVE: To assess the relationship of fat mass (FM) and its distribution to hypertension and dyslipidemia in normal-weight Japanese individuals. DESIGN: Cross-sectional study. SUBJECTS: Apparently healthy Japanese subjects with a body mass index (BMI) between 20 and 23.5 kg/m(2) (265 males and 741 females, age 21-69 y). MEASUREMENTS: BMI, waist circumference (WC), waist-hip ratio (WHR), systolic and diastolic blood pressure, serum levels of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) were measured. Low-density lipoprotein-cholesterol (LDL-C) was calculated by the Friedewald formula. Percentage fat mass (%FM) and trunk fat mass-leg fat mass ratio (FM(trunk)/FM(legs)) were obtained by dual-energy X-ray absorptiometry. RESULTS: WC, WHR, %FM and FM(trunk)/FM(legs) were significantly correlated with TC, LDL-C, HDL-C and TG with the tendency of FM(trunk)/FM(legs) to show the strongest correlations. For %FM and FM(trunk)/FM(legs) in both sexes, odds ratios (ORs) of the third tertiles with respect to the first tertiles increased for LDL-C elevation, TG elevation and dyslipidemia. In males, ORs of the third tertiles of WC were significantly high for LDL-C elevation and dyslipidemia whereas those of WHR were high for TG elevation and dyslipidemia. ORs of the third tertiles of WC and WHR were significantly high for TG elevation in females. BMI was not associated with the risk of abnormal lipid levels. ORs for hypertension showed significant increases in none of the variables of obesity. CONCLUSIONS: Excess accumulation of FM, especially to the upper body, was related to dyslipidemia in normal-weight subjects. Simple anthropometric variables, WC and WHR, may be useful for screening and management of dyslipidemia in these subjects.

Detection of cardiovascular risk factors by indices of obesity obtained from anthropometry and dual-energy X-ray absorptiometry in Japanese individuals.

OBJECTIVE: To determine the cut-off points of indices of obesity for detecting hypertension, dyslipidemia and diabetes mellitus in Japanese individuals. DESIGN: Cross-sectional study. SUBJECTS: A total of 2728 Japanese individuals (768 males and 1960 females, aged 20-79 y) who attended the Fukuoka Health Promotion Center, Japan for health check-up. MEASUREMENTS: Body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR) were measured. Percentage fat mass (%FM), trunk fat mass (FM(trunk)) and trunk fat mass-leg fat mass ratio (FM(trunk)/FM(legs)) were obtained by dual-energy X-ray absorptiometry (DXA). Cardiovascular risk factors were determined by blood pressure, serum lipids, fasting blood glucose and hemoglobin A(1C). RESULTS: The cut-off points of BMI, WC and WHR were around 23.5 kg/m(2), 84 cm and 0.9 for males, and 22.5 kg/m(2), 72 cm and 0.8 for females. The cut-off points of %FM, FM(trunk) and FM(trunk)/FM(legs) were around 24%, 8 kg and 1.6 for males, and 35%, 9 kg and 1.4 for females. WHR and FM(trunk)/FM(legs) most accurately detected the risk factors. CONCLUSIONS: For Japanese individuals, the cut-off points for detecting cardiovascular risk factors are lower than the criteria by the World Health Organization. Indices of fat distribution detected the cardiovascular risk factors more accurately than those of overall adiposity. The accuracy of detecting the risk factors was comparable between the anthropometric indices and indices obtained by DXA.

Endoscopic ultrasonography in patients with thyroid cancer: its usefulness and limitations for evaluating esophagopharyngeal invasion.

BACKGROUND AND STUDY AIMS: Although computed tomography (CT) and magnetic resonance imaging (MRI) are useful for detecting esophagopharyngeal invasion by thyroid cancer, they cannot assess the depth of invasion, which is important for the surgical planning. In the present study, endoscopic ultrasonography (EUS) of the esophagus was used to assess esophagopharyngeal invasion by thyroid cancer, and the value of this technique was assessed prospectively. PATIENTS AND METHODS: Between 1 December 1998 and 31 December 2000, EUS examinations were carried out in 59 patients in whom esophagopharyngeal invasion by thyroid cancer was suspected due to large tumors or tumors with poor mobility. The EUS findings were evaluated in 52 patients (10 men, 42 women; mean age 62.4 years; mean tumor size 39.5mm) with complete resections, and compared with the pathological results. RESULTS: The diagnostic specificity and accuracy of EUS in assessing invasion into the muscularis propria (82.9 %, 82.7 %) were greater than those of MRI (60 %; P = 0.034, 65.4 %; P = 0.044) and esophagography (58.8 %; P = 0.034, 60 %; P = 0.028). The accuracy for detecting cancer invasion located in the upper part of the lobe was less than for invasion in the middle and/or lower parts of the lobe ( P = 0.020). Conclusions. EUS is useful for assessing esophagopharyngeal invasion by thyroid cancer, although its effectiveness may be limited in thyroid lesions located in the upper part of the lobe.

"Ordered" structure in ionic dilute solutions: dendrimers with univalent and bivalent counterions.

As an intermediate sample of ionic solutes between colloidal particles (macroions) and simple electrolyte ions, we made small-angle x-ray scattering (SAXS) measurements for aqueous solutions of poly(amido amine) dendrimers of three generations (G4, G7, and G10). The SAXS curves of univalent acid solutions showed a single scattering peak, as observed for synthetic macroions. The peak position was dependent on the dendrimer concentration but independent not only of the acid concentration (degree of protonation) but also of the counterion species. The effective charge density of the dendrimer determined by conductivity measurements was found to be insensitive to the acid concentration and the counterion species. The nearest neighbor interparticle distance 2D(exp) calculated from the peak position of the structure factor of G7 and G10 was obviously smaller, though slightly, than the average interparticle distance 2D(0) calculated from molecular weights and concentrations of dendrimers, implying that acid solutions of dendrimers formed the two-state structures by the attractive force. The ultra-small-angle x-ray scattering curve for the hydrochloric acid solution did not show an upturn, which indicates the existence of large scale structural inhomogeneities such as localized ordered structures, probably due to the weak attraction and hence less clear distinction of the ordered and disordered regions. For sulfuric acid solutions, clear scattering peaks were not observed. The bivalent counterions were more strongly associated with the dendrimer ions than the univalent ones. The resulting low charge number of the dendrimers with the bivalent counterion was confirmed directly by the conductivity measurements. These observations confirm that the counterion-mediated attraction does exist even with the univalent counterions and point out that the frequently advanced claim that the effective potential is essentially repulsive with univalent counterions while attraction appears with bivalent counterions is not necessarily correct. It is noted that the intensity of the counterion-mediated attraction in dendrimer solutions is dictated by both the effective charge density and the effective charge number, in contrast with macroionic solutions or colloidal dispersions in which only the effective charge density appeared to be important.

[Questionnaire research of the participants in a large scale walking event Fukuoka City analysis of walking habits and related factors].

PURPOSE: We examined the walking habits of the participants in the 'AIREF Spring Walk' which was held on March 9, 1997 in the western suburb of Fukuoka City. The aim of this walking event was to motivate the citizens, especially sedentary people, to walk by providing them an opportunity to enjoy walking. METHODS: The participants walked one of three distances (5 km, 10 km or 20 km) and answered anonymously a questionnaire immediately after finishing (100% response rare). The questionnaire items covered sex, age, district of residence, the distance of the walking course, the source of information on the event, experience of participating in other walking events in the past, and walking habits. RESULTS: The participants of this event (n = 1,039, mean age 49.4 +/- 18.9 [SD] years) were characterized by high rates for females (67%), those aged < 50 years (42%), residents of Fukuoka City (89%), those who chose to walk the shorter courses of 5 or 10 km (74%), and those who took part in a walking event for the first time (61%). Information on the event was obtained through other people (32%) such as friends, acquaintances, members of community walking groups or other family members, leaflets (21%) placed in the Fukuoka Health Promotion Center and seven Fukuoka City public health centers; a newspaper published biweekly by the municipal government (13%); and direct mail (11%). For those attending the 5 km course, more participants learned about the event through other family members compared with the other two courses. Participants who answered that they walked regularly constituted 56% of those aged 20 years or older. The rates for regular walkers significantly increased with the older participants (p < 0.01) and those who chose longer courses (p < 0.001). Compared with the regular walkers, those without a walking habit tended to have acquired information on the event from friends, acquaintances or other family members, or at their work sites (35%). The average amount of time spent was 249 +/- 175 min/week (n = 375). As a whole, only 30% of the participants aged 20 years or older walked longer than the amount of time for aerobic exercise recommended by the Health, Labor and Welfare Ministry (HLWM). The rate for those who reached the HLWM recommendations was increased in older subject (p < 0.001). CONCLUSIONS: It is concluded that the aim of the walking event was partly accomplished, which was reflected by the relatively high rates of participation sedentary for people, compared with other large walking events. The sedentary participants tended to choose the relatively short distances and obtain the information about the event through other people. Walking promotion programs should be developed to motivate sedentary citizens to walk. The programs should also support regular walkers, many of whom are 50 years old or older, to maintain walking habits with the HLWM recommendations on aerobic exercise.

Effects of increased physical activity and mild calorie restriction on heart rate variability in obese women.

The effects of exercise and mild calorie restriction on heart rate variability (HRV) were investigated in 12 mildly obese, normotensive Japanese women aged 45.8+/-4.2 (SEM) years with a body mass index (BMI) of 27.3+/-0.4 kg/m2. The subjects participated in a 3-month program aimed at increasing physical activity and modifying eating behavior (intervention group). The control group consisted of 12 women (age 50.1+/-4.8 years, BMI 27.2+/-0.6 kg/m2) who did not attend the program. The frequency domain of HRV was calculated from 5-min Holter recordings while the subjects rested in a supine position. After 3 months, BMI decreased to 25.0+/-0.5 kg/m2 (p<0.001 vs baseline) in the intervention group, which was accompanied by decreases in body fat mass, waist circumference, serum total cholesterol and triglycerides, and improvement in insulin sensitivity. The mean and SD of the RR intervals, total power, and low and high frequency power of HRV significantly increased after the intervention, whereas no significant changes were seen for the controls. The changes in these HRV variables (calculated by subtracting the baseline values from the follow-up values) negatively correlated with the change in waist circumference, with the Pearson correlation coefficients being between -0.50 and -0.62 (p<0.05). A negative correlation was also seen between the changes in high frequency power and insulin resistance estimated by homeostasis model assessment (r=-0.49, p<0.05). The combination of exercise and mild calorie restriction led to changes in HRV indicative of an improvement in parasympathetic modulation.

Usefulness of endoscopic ultrasonography (EUS) in diagnosing esophageal infiltration of thyroid cancer.

Pre-operative evaluation of esophageal infiltration is sometimes difficult in patients with advanced thyroid cancer even with recent imaging modalities. We evaluated the accuracy of endoscopic ultrasonography (EUS) in diagnosing esophageal infiltration of thyroid cancer. Twenty-nine patients with advanced thyroid cancer underwent EUS and other imaging examinations before surgery. The diagnostic accuracy of EUS was compared with that of magnetic resonance imaging (MRI) and esophagography based on pathologic findings in 27 of the 29 cases. EUS clearly demonstrated the 5-layer structure of the esophageal wall. EUS detected cancer invasion into the muscularis propria of the esophagus correctly in 8 of 10 patients diagnosed pathologically with muscular infiltration. EUS was significantly more accurate than MRI and esophagography (88.9% vs 63.0% and 66.7%, respectively). The specificity of EUS was also significantly better than the specificities of MRI or esophagography (94.1% vs 58.8% and 64.7%, respectively). The sensitivity, positive predictive value and negative predictive value of EUS tended to be better than those of MRI and esophagography. EUS is useful in evaluating the esophageal infiltration of thyroid cancer. This method has the further advantage of detecting the exact depth of cancer invasion into the esophageal wall.

Bronchoscopic diagnosis of thyroid cancer with laryngotracheal invasion.

HYPOTHESIS: Some controversy exists concerning the appropriate surgical management for patients with thyroid cancer invading the laryngotracheal wall. We have used shaving of the wall when cancer invasion was confined to the perichondrium, and extensive resection when it invaded further. Preoperative assessment of the depth and length of laryngotracheal invasion is important when choosing an appropriate surgical procedure. DESIGN: Prospective study. SETTING: A Japanese center for thyroid diseases, where about 1400 thyroid operations are performed each year. PATIENTS: Of 171 patients with thyroid cancer who were surgically treated between January 1, 2000, and July 30, 2000, 37 were suspected to have laryngotracheal invasion on preoperative magnetic resonance imaging or ultrasonography. INTERVENTION: We used bronchoscopy to examine the 37 patients suspected to have laryngotracheal invasion. MAIN OUTCOME MEASURE: Bronchoscopic findings (localized mucosal redness, telangiectasia, mucosal elevation, mucosal edema, and mucosal erosion) were compared with pathological results in the 30 patients who underwent curative resections. Seven patients were excluded because of palliative resections. RESULTS: Of the 18 patients without localized mucosal changes, we performed shaving of the laryngotracheal wall in 4 patients because we found laryngotracheal invasion during surgery. Shaving of the laryngotracheal wall was performed successfully in terms of obtaining a cancer-free margin. Twelve patients with localized mucosal redness required extensive resections. Other mucosal changes were found depending on the depth of cancer invasion. CONCLUSION: Surgeons should perform extensive resections when encountering localized mucosal redness on bronchoscopy.

Relationship between upper body obesity and periodontitis.

Upper body obesity, related to visceral fat accumulation, is known to increase the risk of various adult diseases, especially type 2 diabetes and cardiovascular disease. This study was conducted to clarify the relationship between upper body obesity and periodontitis. We studied 643 apparently healthy, dentulous Japanese adults who attended programs at Fukuoka Health Promotion Center. Waist-hip ratio, body-mass index (BMI), and body fat were significant risk indicators for periodontitis after adjustment for known risk factors (p < 0.002). Subjects were divided into four BMI (or body fat) categories. In only the subjects with high waist-hip ratio, higher categories of BMI (or body fat) significantly increased the adjusted risk of periodontitis, compared with subjects with low waist-hip ratios and the lowest category of BMI (or body fat). The reported relationship between cardiovascular disease and periodontitis should be reconsidered, since abdominal adiposity or visceral fat can be related to both diseases.

Multifocal electroretinograms in patients with branch retinal artery occlusion.

PURPOSE: We recorded multifocal electroretinograms (M-ERG) in patients with branch retinal artery occlusion (BRAO) and compared the waveforms in the area of retinal artery occlusion with those in the normal area, to evaluate the influence of the damage to the inner retina shown by M-ERG responses. METHODS: Three patients who had normal visual acuity and visual field loss of more than one quadrant due to BRAO were examined. The central 50 degrees of ocular fundus was stimulated through dilated pupils by an array of 103 hexagonal elements for 4 minutes. The waveforms of the first order and second order kernel responses of M-ERG in the area of the retinal artery occlusion were compared with those of the vertically symmetrical, normally perfused area of the same eye. RESULTS: The amplitude of the averaged tracing decreased in the first negative wave (N1), first positive wave (P1), and second negative wave (N2) in the first order kernel responses in the area of retinal artery occlusion in comparison with the normally perfused area. Furthermore, prolongation of latency was noted for N1, P1, and N2 in the same area. Second order kernel responses were not detected in the area of the retinal artery occlusion. CONCLUSIONS: The damage to the inner retina affected parts of N1, P1, and N2 of the first order kernel responses, with N2 being the most seriously affected. Furthermore, second order kernel responses clearly reflected the condition of the inner retina.

CD8+ cell changes in psoriasis associated with roxithromycin-induced clinical improvement.

We have shown that T cell receptor BV2- and BV8-bearing CD8+ cells are decreased in the peripheral blood of psoriatic patients, while T cells possessing these BVs accumulate in psoriatic lesions. T cells homing to skin express cutaneous lymphocyte-associated antigen (CLA), and bacterial superantigens that trigger psoriasis promote this expression. Roxithromycin has immunomodulatory potency and its effectiveness for psoriasis has been proposed. Therefore, we monitored BV usage and alteration of superantigen-promoted CLA expression in circulating CD8+ cells of psoriatics before and after roxithromycin therapy. After roxithromycin treatment, circulating BV2- and BV8-bearing CD8+ cells were increased and CD8+ cells exhibited reduced expression of CLA when stimulated in vitro with bacterial superantigens. It is suggested that roxithromycin downregulates augmented expression of CLA by CD8+ cells, thereby suppressing their skin-homing and elevating the numbers of circulating BV2- and BV8-positive CD8+ cells. Such events may be included in part in the improvement of psoriasis with roxithromycin.

Relation between body composition and age in healthy Japanese subjects.

OBJECTIVE: To describe the relation between body composition and age measured by dual-energy X-ray absorptiometry (DXA) in healthy Japanese adults. DESIGN: Cross-sectional study. SUBJECTS AND MEASUREMENTS: The subjects were 2411 healthy Japanese adults (males 625, females 1786, age 20--79 y) who attended the Fukuoka Health Promotion Center, Fukuoka, Japan for health check-up. Body composition was determined by DXA (QDR-2000, Hologic) for the whole body and three anatomical regions of arms, legs and trunk. RESULTS: The mean values of body mass index (BMI) and percentage fat mass (%FM) were 23.2+/-3.1 (s.d.) kg/m(2) and 21.8+/-6.8% for males and 22.1+/-3.3 kg/m(2) and 32.0+/-7.5% for females, respectively. For males, curvilinear relations with the peaks in their forties or fifties were seen for the variables associated adiposity, ie BMI, waist and hip circumference, waist-hip ratio, total or regional fat mass (FM), %FM and ratio of trunk FM to leg FM. For females, most of these variables increased linearly in older subjects. Lean mass (LM), bone mineral content (BMC) and bone mineral density (BMD) of the whole body and appendicular LM were relatively constant until the forties and then decreased in both sexes. The rates of decrease in the total or appendicular LM were larger for males than for females, whereas those in BMC or BMD were larger for females than for males. CONCLUSIONS: This study presents the first detailed data on body composition in Japanese, which may be useful when comparing with populations of different racial and ethnic backgrounds and studying ill subjects.