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Postprandial glucose concentration is dependent on the time of day and its concentration in the morning is lower than in the evening. However, whether it is dependent on mastication at different times of the day has not been studied before. We hypothesized that mastication affects insulin-mediated glucose metabolism differently in the morning and evening in healthy individuals. Firstly, nine healthy male volunteers (22.0 ± 0.7 SEM years, body mass index 22.0 ± 1.0 kg/m2) performed a 75-g oral glucose tolerance test (OGTT). One week after the OGTT, they participated in a high-carbohydrate food (rice) consumption test with 10 or 40 chews per mouthful. Each experiment was conducted in the morning (0800 h) and evening (2000 h) on the same day. Blood samples were collected before and at 30-min intervals for 120 min after glucose or rice consumption. The incremental area under the curve (iAUC) for glucose in the OGTT was significantly lower in the morning than in the evening, whereas the iAUC for insulin was similar at both times. In participants who chewed 40 times, the iAUC for glucose after rice consumption was significantly lower in the morning than in the evening but was similar at both times in individuals who chewed 10 times. Chewing 40 times in the morning (but not the evening) significantly increased insulin secretion at 30 min. This suggests that morning mastication improves early-phase insulin secretion after rice consumption. This novel finding may aid in reducing the incidence of obesity and type 2 diabetes mellitus.

Arc-welders' pneumoconiosis (AWP) is a less fibrogenic pneumoconiosis with radiographic shadows that can improve after isolation from dusty environments. Therefore, early diagnosis is important. However, the exact role of chest radiograph and computed tomography (CT) for diagnosing AWP is not fully understood. This study was performed to assess the CT appearance of AWP using semi-quantitative methods and to compare the findings with those of silicosis. The profusion of pulmonary abnormality on chest radiograph were also compared with the semi-quantitative CT score.Sixty-six patients with clinically diagnosed AWP were included and compared with 33 patients with silicosis. The CT images were interpreted according to the International Classification of HRCT for Occupational and Environmental Respiratory Diseases (ICOERD). Data on the profusion score by chest radiograph were also compared with CT score.Ill-defined centrilobular nodules, ground-glass opacity (GGO) and centrilobular branching opacity were more frequently observed (p = 0.0031) in AWP, whereas well-defined rounded opacity (p 0.0001), progressive massive fibrosis (p 0.0001), and mediastinal lymphadenopathy (p 0.0001) were more frequently observed in silicosis. Regarding lung nodules, there was a high correlation between the ICOERD and CXR profusion scores in silicosis, but CXR underestimated AWP.Ill-defined centrilobular nodules, GGO and centrilobular branching opacity were more frequently observed in AWP than silicosis. Because these findings are difficult to detect by chest radiograph, CT should be considered for the assessment of patients with suspected AWP.

The aim of the present study was to determine the effect of hypercapnia on motor neuromuscular activity of the human triceps surae muscle. Nine subjects participated in trials in a normal breathing condition and a CO2 rebreathing condition. In both conditions, in order to provoke self-sustained muscle activity, percutaneous electrical train stimulation was applied to the tibial nerve while each subject lay on a bed. Self-sustained muscle activity, which is an indirect observation of plateau potentials in spinal motoneurons, was measured for 30 s after the train stimulation by using surface electromyography. The sustained muscle activity was increased by CO2 rebreathing (P < 0.05). This finding suggests that motor neuromuscular activity may be linked to the respiratory system that is activated during hypercapnia.

We reported that external dead space ventilation (EDSV) enhanced self-sustained muscle activity (SSMA) of the human soleus muscle, which is an indirect observation of plateau potentials. However, the main factor for EDSV to enhance SSMA remains unclear. The purpose of the present study was to examine the effects of EDSV-induced hypercapnia, hypoxia, and hyperventilation on SSMA. In Experiment 1 (n = 11; normal breathing [NB], EDSV, hypoxia, and voluntary hyperventilation conditions) and Experiment 2 (n = 9; NB and normoxic hypercapnia [NH] conditions), SSMA was evoked by electrical train stimulations of the right tibial nerve and measured using surface electromyography under each respiratory condition. In Experiment 1, SSMA was significantly higher than that in the NB condition only in the EDSV condition (P < 0.05). In Experiment 2, SSMA was higher in the NH condition than in the NB condition (P < 0.05). These results suggest that the EDSV-enhanced SSMA is due to hypercapnia, not hypoxia or increased ventilation.

Repetitive or sustained simple muscle contractions have been shown to alter corticomotor excitability. The present study investigated the effects of a sustained handgrip contraction with the right hand on motor-evoked potentials (MEPs) in task-unrelated knee extensor muscles and determined whether the effects are influenced by intensity of the handgrip contraction. Subjects performed a 120-s sustained handgrip contraction at 10% or 50% maximal voluntary contraction (MVC) using the right hand. MEPs in vastus lateral (VL) muscles elicited by transcranial magnetic stimulation were measured before, during, and after the handgrip contraction. Both the handgrip contractions at 10 and 50% MVC induced significant greater MEPs in the left VL muscle (121.5 ± 25.7%) than in the right VL muscle (97.9 ± 17.4%) from 10 min after the handgrip contraction (P

Purpose Effort sense has been suggested to be involved in the hyperventilatory response during intense exercise (IE). However, the mechanism by which effort sense induces an increase in ventilation during IE has not been fully elucidated. The aim of this study was to determine the relationship between effort-mediated ventilatory response and corticospinal excitability of lower limb muscle during IE. Eight subjects performed 3 min of cycling exercise at 75-85 % of maximum workload twice (IE1st and IE2nd). IE2nd was performed after 60 min of resting recovery following 45 min of submaximal cycling exercise at the workload corresponding to ventilatory threshold. Vastus lateralis muscle response to transcranial magnetic stimulation of the motor cortex (motor evoked potentials, MEPs), effort sense of legs (ESL, Borg 0-10 scale), and ventilatory response were measured during the two IEs. The slope of ventilation (l/min) against CO2 output (l/min) during IE2nd (28.0 +/- 5.6) was significantly greater than that (25.1 +/- 5.5) during IE1st. Mean ESL during IE was significantly higher in IE2nd (5.25 +/- 0.89) than in IE1st (4.67 +/- 0.62). Mean MEP (normalized to maximal M-wave) during IE was significantly lower in IE2nd (66 +/- 22 %) than in IE1st (77 +/- 24 %). The difference in mean ESL between the two IEs was significantly (p < 0.05, r = -0.82) correlated with the difference in mean MEP between the two IEs. The findings suggest that effort-mediated hyperventilatory response to IE may be associated with a decrease in corticospinal excitability of exercising muscle.

Development of reliable new biomarkers remains crucial to improve diagnosis and assessing disease activity in sarcoidosis. The objective of this study was to seek such markers from the gene expression signature of alveolar macrophages by transcriptome analysis.Pooled RNA extracted from alveolar macrophages from patients with active sarcoidosis and control patients was subjected to transcriptome analysis using microarrays. Expressed gene intensity in sarcoidosis relative to that in control was calculated. We measured serum cathepsin S (CTSS) concentrations in 89 healthy volunteers, 107 patients with sarcoidosis, 26 with interstitial pneumonia, 150 with pneumoconiosis, and 76 with pulmonary mycobacteriosis by the enzyme-linked immunosorbent assay.Among 12 genes with ratios higher than that of a housekeeping gene, we selected CTSS for scrutinizing protein expression in serum because of the feasibility of the protein assay. CTSS concentrations were significantly increased in sarcoidosis compared with not only controls but also all the other lung diseases. Receiver operating characteristics curve for sarcoidosis and parenchymal lung diseases revealed an area under the curve of 0.800 (95% confidence interval, 0.751-0.850; p=1.4 x 10CTSS has the potential to be a useful biomarker in sarcoidosis.

Aim: Precise clinical significance of antigranulocyte-macrophage colony stimulating factor (GM-CSF) autoantibody levels in autoimmune pulmonary alveolar proteinosis (aPAP) has not been well studied. Methods: We obtained sera from 50 healthy controls, 46 aPAP patients, 50 with sarcoidosis, 52 with idiopathic interstitial pneumonia and 75 with pneumoconiosis. The clinical course of aPAP patients was assessed by scoring computed tomography images in 19 patients. Results: The cut-off level of anti-GM-CSF IgG for discrimination between aPAP and other diffuse lung diseases was 2.8 μg/ml with 100% sensitivity and 98% specificity. Antibody levels at baseline were significantly lower in the improved group than in the unimproved group (p = 0.008). Conclusion: Our results indicate the existence of threshold levels of serum anti-GM-CSF IgG for the development and persistence of aPAP.

ストレスを軽減する可能性をもつ食品としてカモミール茶(C茶)およびペパーミント茶(P茶)の午前中の連続摂取効果を検討した。50～70歳代女性13名を対象に、午前中にC茶またはP茶の摂取実験を行い、その後3週間C茶またはP茶を毎朝食後に自宅で摂取させた後に同じ摂取実験を行った。実験時に前頭部脳波、唾液アミラーゼ活性、および感情状態を測定した。標準化された質問紙MCL S.1で快感情、リラックス感および不安感得点を求めた。α波の増加はその部位のリラックスを示す。C茶を摂取した後、およびP茶の1回目の摂取後に、前頭部α波パワー値が有意に高くなった。快刺激で活性が低下する唾液アミラーゼ活性は、C茶を3週間摂取した後、およびP茶の1回目の摂取後に、活性が有意に低下した。感情状態は、P茶の1回目の摂取でリラックス感が有意に増加した。午前中のC茶の連続摂取は、夕方の摂取と同様、ストレスを軽減する可能性が示唆された。一方、P茶の1回目の摂取はストレス軽減効果を示したが、3週間の連続摂取後では効果が消失した。, In this study, we evaluated the stress relieving effect of continuous morning intake of chamomile tea (C tea) and peppermint tea (P tea). Thirteen healthy women aged between 50 70 years drank a cup of C tea or P tea every day after breakfast for 3 weeks at home. On the first day and after 3 consecutive weeks of C tea or P-tea intake, we performed several tests to obtain the frontal electroence phalogram (EEG), salivary amylase activity, and emotional state of the subjects. The emotional states of pleasantness, relaxation, and anxiety were determined using MCL S.1 (Mood Check List Short Form 1), which is a standardized questionnaire. The power value of the frontal alpha wave, wherein an increment indicates a relaxed state in that portion of the brain, increased significantly after the 3 week intake of C tea and first day intake of P tea. The salivary amylase activity, which is known to be lowered by pleasant stimuli, was significantly decreased after the 3 week intake of C tea and first day intake of P tea. With regard to the emotional state, the feelings of relaxation were significantly increased after drinking P tea on the first day. Thus, continuous intake of C tea in the morning was suggested to have a stress relieving effect. Further, P tea intake on the first day had a similar stress relieving effect, but this effect disappeared after 3 weeks.

Background The progression rate of pneumoconiosis in retired coal miners over ten years has not been studied in Japan. Methods A retrospective longitudinal study was undertaken using chest X-rays of 1091 pneumoconiosis subjects in Hokkaido, Japan between 1985 and 2005. Results The final numbers of subjects were 207 (19% of the entry) after 1 decade and 85 (8%) after 2 decades. Sixty-two percent of 207 subjects after 1 decade and 29% of 85 showed progression in 2 decades. Thirty-one percent of ILO category 1 and 55% of category 2 subjects showed progression to complicated pneumoconiosis after 1 decade, and 6% (4 of 64) of category 1 and 6% (5 of 77) of category 2 subjects progressed to complicated pneumoconiosis during 2 decades. Conclusion The progression of pneumoconiosis was observed after the cessation of dust exposure, especially during the first 10 years.

Infection, immunity and genetic factors play roles in the development of coal worker's pneumoconiosis (CWP) and progressive massive fibrosis (PMF). We investigate whether the genetic polymorphisms of mannose-binding lectin (MBL), one of the key molecules of innate immunity, is associated with the susceptibility to CWP. MBL2 polymorphisms (codon54, promoter -221, and -550) were assessed for 197 patients with CWP (119 with nodular CWP and 78 with PMF) and 153 unexposed regional controls. Serum MBL concentrations were measured in 119 CWP patients. Three polymorphisms were in linkage disequilibrium for all study populations. The MBL2 genotype and haplotypes were associated with lower serum MBL levels. The frequency of such MBL2 genotype and haplotypes were significantly higher in patients with CWP compared to controls, whereas these distributions were not different between patients with nodular CWP and those with PMF. MBL2 polymorphisms and haplotypes may be one of the genetic determinants for the susceptibility of CWP.

Background and objectives: The pathogenesis of IPF is unknown and it is hypothesized that immunological responses are involved. The purpose of this study was to detect autoantibodies in IPF patients and to identify the relevant antigens. Methods: Sera from 37 healthy subjects and 22 IPF patients who had no clinical symptoms of collagen vascular disease were examined for immunostaining of A549 human type II cells and human lung tissue. Immunoprecipitation and proteome analysis were performed to identify the antigen. Results: Fifty per cent of the patient sera and none of the control sera exhibited positive staining. Sera from 10 of the 22 IPF patients showed positive immunohistochemistry and immunoprecipitated a 110-kDa protein from the A549 cell lysate. Sera from only two of 41 patients with collagen vascular disease showed positive immunoreactivity. Proteome analysis using tandem mass spectrometry revealed that the protein was alanyl-tRNA synthetase. Transfection of cDNA of this enzyme into CHO-K1 cells conferred positive staining on these cells with the patients' IgG. The 135-kDa fusion protein consisting of 108-kDa enzyme protein and 27-kDa YFP from the cell lysate of the transfected cells was immunoprecipitated by the patient IgG. In addition, sera from IPF patients significantly inhibited the enzyme activity of alanyl-tRNA synthetase. Conclusion: A significant number of IPF patients possess circulating autoantibodies against alanyl-tRNA synthetase, suggesting the involvement of an autoimmune background in the pathogenesis of IPF.

Inter-individual variations in the development of silicosis, even within the same environments, have been reported, which suggest the contribution of genetic factors in silicosis aetiology. The aim of the present study was to determine whether there is any significant genetic influence on the development of silicosis. Furthermore, which genetic loci are responsible for the pulmonary response to silica exposure? Eight strains of inbred mice were used to examine the genetic influence on the lung fibrotic response to silica exposure. After intercross-breeding between the most susceptible and most resistant strains, a genome-wide linkage analysis of quantitative trait loci (QTL) was performed. Hydroxyproline was applied as an index, and genotypes of 167 marker genes were analysed by fragment analysis using a capillary-type sequencer. There was significant inter-strain difference in the mean concentration of hydroxyproline contents among the eight strains of mice. Breeding studies were conducted between the most susceptible, C57BL/6J, and the most resistant strain, CBA/J. A genome-wide linkage analysis of silica-exposed intercrossed cohorts identified significant QTL on chromosome 4 and suggestive QTL on chromosomes 3 and 18. The present study demonstrates that genetic factors may play a significant role in fibrotic-lung responses to silica; one significant and two suggestive quantitative trait loci were identified.

Inter-individual variation in the severity of pneumoconiosis has been described, even with the same environmental exposure. We hypothesized that TNF-alpha promoter polymorphisms associate with lung responses to environmental exposure in coal worker's pneumoconiosis (CWP) patients. We examined polymorphisms at -238, -308, and -376 in 124 patients with CWP who had similar dust exposure history and in 122 non-exposed controls. CWP patients were divided into two groups: (1) nodular CWP (n = 84): (2) progressive massive fibrosis (PMF) (n = 44). The -308 A allele frequency was higher in patients with CWP compared to controls (6.35% and 2.05%, P {lt} 0.01). It was also higher in patients with nodular CWP compared to PMF (P {lt} 0.05). Logistic regression analysis revealed that patients with the -308 A allele were 3.8 times (P = 0.036) and those with smoking habit were 2.3 times (P {lt} 0.002) more likely to have nodular CWP than PMF. Thus TNF-alpha-308 A allele might interact with smoking to enhance susceptibility to nodular CWP.

Exhaled nitric oxide (eNO) levels are increased in airway inflammatory disorders, such as asthma.We sought to determine whether eNO could serve as a noninvasive marker of allergic airway inflammation for an epidemiologic study in schoolchildren.Two hundred seventy-eight schoolchildren aged 10 to 12 years answered a modified American Thoracic Society questionnaire, and eNO levels and pulmonary function were measured. In 246 subjects serum nonspecific IgE levels and levels of IgE specific to house dust mite, cat, cedar, and mold were also measured. Correlation analysis was used to examine eNO levels, nonspecific IgE levels, antigen-specific IgE levels, and pulmonary function. In addition, we compared these variables between subjects with (recurrent wheezers) and without (nonwheezers) recurrent wheeze. Finally, multiple logistic regression analysis was used to find possible predictors for recurrent wheezers.eNO showed significant positive correlations with nonspecific IgE (r=0.62, P.001) and mite-specific IgE (r=0.74, P.001) and weak positive correlations with specific IgE to cat and cedar. Only eNO showed a weak but significant inverse correlation with pulmonary function (%FEV(1), P=.035; FEV(1)/forced vital capacity, P=.018). eNO, nonspecific IgE, and mite-specific IgE levels in recurrent wheezers were greater (P.001), and %FEV(1) was less (P=.06) when compared with values seen in nonwheezers. Finally, eNO was determined by means of multiple logistic regression analysis to be the best predictor for recurrent wheezers compared with other variables (odds ratio, 11.2; 95% CI, 1.33-94.0).eNO can be used in epidemiologic studies as a noninvasive marker of allergic airway inflammation in schoolchildren.

To improve write performance at high frequency, a flattop-type head consisting of a flat upper yoke and sputtered soft magnetic films is proposed. The sputteredFeAlO films used as yoke materials are magnetically soft, and have a resistivityρ of -100 μΩcm, a saturation magnetic flux density Bs of -1.8T, and an anisotropy field Hk of -25 Oe. All of these values for the FeAlO films are higher than those of conventional plated NiFe yoke materials. The yoke thickness and length are 2μm and 18μm, respectively. A flattop-type head containing an FeAlO yoke at a high writing frequency of more than 540 Mfrps has an O/W of around -30 dB and shows good NLTS (≤15%). Consequently, the improvement of the write performance at high frequency is confirmed when plated 45-50 NiFe films are replaced by sputtered FeAlO films as yoke materials.

BACKGROUND The ras oncogene and the p53 tumor suppressor gene play important roles in the carcinogenic process of lung carcinoma. The authors evaluated whether alterations of the ras and p53 proteins may contribute to the development of lung carcinoma in patients with idiopathic pulmonary fibrosis (IPF) and whether such alterations may explain the high incidence of lung carcinoma among patients with IPF. METHODS Lung tissues were obtained from 35 patients who had IPF without complications of lung carcinoma and from 36 patients who had IPF with complications of lung carcinoma. Altered expression of ras and p53 proteins was evaluated by immunohistochemistry, and mutations of both genes were evaluated by polymerase chain reaction-single strand conformation polymorphism and sequencing analyses. RESULTS The frequency of expression of ras protein in type II alveolar pneumocytes was significantly greater in lung tissues from patients with IPF who had lung carcinoma compared with lung tissues from patients with IPF who did not have lung carcinoma (75% vs. 40%, respectively; P < 0.01). K-ras point mutation in codon 12 (GGT to GTT transversion) was detected in lung tissue with interstitial pneumonia, in which ras protein was overexpressed in type II alveolar pneumocytes obtained from 2 of 41 patients with IPF complicated by lung carcinoma, causing amino acid substitution (Gly to Val) in both patients. A p53 mutation was detected in three of six lung tissue samples from patients who had IPF lung with positive p53 immunoreactivity, and multiple mutations were detected in two samples. CONCLUSIONS Expression of ras protein in type II alveolar pneumocytes and mutation in the codon 12 of K-ras gene in lung tissue may contribute to the induction of lung carcinoma in patients with IPF. Furthermore, the presence of multiple mutations in the p53 gene may explain the high incidence lung carcinoma in patients with IPF. Cancer 2002;95:624–33. © 2002 American Cancer Society. DOI 10.1002/cncr.10708

Gangliosides are known as modulators of transmembrane signaling by regulating various receptor functions. We have found that insulin resistance induced by tumor necrosis factor-alpha (TNF-alpha) in 3T3-L1 adipocytes was accompanied by increased GM3 ganglioside expression caused by elevating GM3 synthase activity and its mRNA. We also demonstrated that TNF-alpha simultaneously produced insulin resistance by uncoupling insulin receptor activity toward insulin receptor substrate-1 (IRS-1) and suppressing insulin-sensitive glucose transport. Pharmacological depletion of GM3 in adipocytes by an inhibitor of glucosylceramide synthase prevented the TNF-alpha-induced defect in insulin-dependent tyrosine phosphorylation of IRS-1 and also counteracted the TNF-alpha-induced serine phosphorylation of IRS-1. Moreover, when the adipocytes were incubated with exogenous GM3, suppression of tyrosine phosphorylation of insulin receptor and IRS-1 and glucose uptake in response to insulin stimulation was observed, demonstrating that GM3 itself is able to mimic the effects of TNF on insulin signaling. We used the obese Zucker fa/fa rat and ob/ob mouse, which are known to overproduce TNF-alpha mRNA in adipose tissues, as typical models of insulin resistance. We found that the levels of GM3 synthase mRNA in adipose tissues of these animals were significantly higher than in their lean counterparts. Taken together, the increased synthesis of cellular GM3 by TNF may participate in the pathological conditions of insulin resistance in type 2 diabetes.

Spinal deformities, a condition in which the spine deviates to the left or right from the midline, are on the rise, particularly among elementary and middle-school students. Group diagnoses are being performed at schools for the purpose of early detection, but the burden on physicians is high due to the need to process many images. Automated diagnosis using computers is highly desirable from the standpoint of treatment. In this paper the authors establish a left–right rectangular processing region in a moire image of a human back, then propose a method to automatically detect spinal deformities with the differences in the centroid positions as a feature. Using an approximately symmetrical reference axis which closely follows the midline of a person, and the amount of the feature from the centroid position of the left–right rectangular region as centered on the reference axis, the authors' method discriminates between normal cases and abnormal cases using a linear discrimination function on a two-dimensional surface. If this kind of primary diagnosis of spinal deformities can be automated, group diagnosis in schools would be more efficient and useful. The authors use their method, perform discrimination tests on 120 normal and abnormal cases, and find a recognition rate of 87.9%. © 2001 Scripta Technica, Syst Comp Jpn, 32(7): 20–28, 2001

This paper presents a technique for automating human scoliosis detection by computer based on moiré topographic images of human backs. Scoliosis is a serious disease often suffered by teenagers. For prevention, screening is performed at schools in Japan employing a moiré method in which doctors inspect moiré images of subjects' backs visually. The inspection of a large number of moiré images collected by the school screening causes exhaustion of doctors and leads to misjudgment. Computer-aided diagnosis of scoliosis has, therefore, been requested eagerly by orthopedists. To automate the inspection process, unlike existent three-dimensional techniques, displacement of local centroids is evaluated two-dimensionally between the left-hand side and the right-hand side of the moiré images in the present technique. The technique was applied to real moiré images to draw a distinction between normal and abnormal cases. According to the leave-out method, the entire 120 image data (60 normal and 60 abnormal) were separated into three data sets. The linear discriminant function based on Mahalanobis distance was defined on the two-dimensional feature space employing one of the data sets containing 40 moiré images and classified 80 images in the remaining two sets. The technique finally achieved the average classification rate of 88.3%.

Study objectives: Serum KL-6 (Krebs von den Lungen-6) has been recognized to be a marker for the activity of diffuse interstitial lung diseases. The purpose of the study is to evaluate serum KL-6 measurement as a marker for farmer’s lung disease (FLD). Design: A cross-sectional survey of a cohort of dairy farmers. Retrospective measurement of KL-6 stored serum samples from those dairy farmers previously screened for FLD. Setting: University hospital screening project for FLD within a dairy-farming community in Japan. Participants: Four hundred seventy-two dairy farmers were invited to attend a local clinic. Measurements and results: We examined serum KL-6 concentrations in 272 farmers. Subjects were classified into three groups: (1) 5 farmers with FLD, (2) 30 farmers with positive serum precipitating antibodies to Saccharopolyspora rectivirgula and/or Thermoactinomyces vulgaris without FLD (Ab 1 ), and (3) 237 farmers without these antibodies (Ab 2 ). Serum KL-6 concentrations in the FLD group were significantly higher than those in the Ab 1 and the Ab 2 groups (1,263 6 288 [SEM], 328 6 57, and 207 6 6 U/mL, respectively, p < 0.001). Serum KL-6 concentrations in those with FLD were significantly higher than KL-6 concentrations from stored screening samples from the same individual when FLD was not diagnosed (1,263 6 288 and 419 6 209 U/mL, respectively, p < 0.05). Serum KL-6 concentrations of the Ab 1 group were significantly higher than those of the Ab 2 group (p < 0.001). In the Ab 1 group, farmers with high serum KL-6 concentrations had lower permeability coefficients than farmers with normal serum KL-6 concentrations (p < 0.05). These results may suggest that subclinical FLD can be detected in farmers with high KL-6 concentrations and precipitating antibodies. Conclusion: Serum KL-6 concentration can be a useful marker for assessing the activity of FLD and may be able to be used to detect subclinical disease. (CHEST 2000; 118:445‐ 450)

Particle-induced increases in respiratory morbidity and mortality have been observed worldwide in industrialized cities but the toxicologic mechanisms have not been elucidated. It is hypothesized that subpopulations including the elderly and individuals with cardiopulmonary disease are particularly at risk to the effects of exposure. Genetic background is another important host factor that may contribute to interindividual responsivity to particulate exposure. This study was designed to identify susceptibility loci for alveolar macrophage (AM) immune dysfunction induced by inhalation of sulfate-associated carbon particles in susceptible C57BL/6J and resistant C3H/ HeJ inbred mice. AMs were chosen for study because they represent an important component of host defense, and compromised host defense has been hypothesized to be an important factor in particle-induced respiratory morbidity. The quantitative phenotype for these studies was Fc receptor-mediated phagocytic function, an index of AM integrity. Analyses of macrophage dysfunction phenotypes of segregant and nonsegregant populations derived from these two strains indicate that two unlinked genes control susceptibility. A genome-wide linkage analysis of an intercross (F(2)) cohort identified significant and suggestive quantitative trait loci (QTLs) on chromosomes 17 and 11, respectively. Candidate susceptibility genes were identified for mice and humans by comparative mapping. Importantly, both QTLs overlap previously identified QTLs for susceptibility to another common pollutant, ozone. This is the first demonstration that genetic background is an important determinant of responsiveness to particle-induced immune dysfunction, and it has important implications for understanding the epidemiologic associations between particulates and morbidity and mortality.

A CMOS time-to-digital converter IC with half-nanosecond resolution by inverter-delay-time has been developed for measuring time intervals with a fully digital circuit. A new circuit “ring-gate-delay” system using two revolution counters can make the area of the circuit far smaller than it would be without them. Accuracy is assured through digital processing with a 2 MHz crystal clock reference. A time resolution of 0.5 ns and a measurement range of 0–2200 ns using 1.5 μm CMOS were confirmed.

Effects of balneotherapy on platelet glutathione metabolism were investigated in 12 type II (non-insulin-dependent) diabetic patients. Levels of the reduced form of glutathione (GSH) on admission were well correlated with those of fasting plasma glucose (FPG; r = 0.692, P0.02). After 4 weeks of balneotherapy, the mean level of GSH showed no changes; however, in well-controlled patients (FPG150 mg/dl), the level increased (P0.01) and in poorly controlled patients (FPG150 mg/dl), the value decreased (P0.05). There was a negative correlation between glutathione peroxidase (GPX) activities and the levels of FPG (r = -0.430, P0.05). After balneotherapy, the activity increased in 5 patients, decreased in 3 patients and showed no changes (alteration within +/- 3%) in all the other patients. From these findings in diabetic patients we concluded: (1) platelet GSH synthesis appeared to be induced in response to oxidative stress; (2) lowered GPX activities indicated that the antioxidative defense system was impaired; and (3) platelet glutathione metabolism was partially improved by 4 weeks balneotherapy, an effect thought to be dependent on the control status of plasma glucose levels. It is suggested that balneotherapy is beneficial for patients whose platelet antioxidative defense system is damaged, such as those with diabetes mellitus and coronary heart disease.

A two-dimensional optical scanner suitable for integration in a plane structure has been developed. To make it vibration robust, a torsional vibration system with two degrees of freedom is adopted for the resonator, and the vibration system axis is matched to the center of gravity. Piezoelectric bimorph cells are used as the actuator to excite the torsional vibration. Algorithms of Luh, Walker and Paul, which are usually used for motion analysis of manipulators in robot engineering, were applied for deriving the equations. This optical scanner is capable of optical scanning in two orthogonal directions independently or simultaneously at a scanning angle of ±30 degrees or more. One-dimensional scanning is enabled by driving the bimorph cells with the resonance frequency of either of the two torsional vibrations. Two-dimensional scanning is achieved if the bimorph cells are operated by adding the resonance frequency signals of the two torsional vibrations.

Successful use of a NiFe/Co/sub 90/Fe/sub 10/ bilayer as a soft magnetic free layer in spin-valve films with a GMR enhanced structure comprised of NiFe/Co/sub 90/Fe/sub 10//Cu/Co/sub 90/Fe/sub 10//FeMn is outlined. The GMR ratio of the spin-valve film with Co/sub 90/Fe/sub 10/ is over 7% and the coercivity of the free NiFe/Co/sub 90/Fe/sub 10/ bilayers is less than 5 Oe. A merged inductive/spin-valve head was fabricated with a read track-width of 1.3 /spl mu/m and a read gap-length of 0.26 /spl mu/m using spin-valve film with a Ta(50 /spl Aring/)/NiFe(45 /spl Aring/)/Co/sub 90/Fe/sub 10/(30 /spl Aring/)/Cu(32 /spl Aring/)/Fe/sub 10/(22 /spl Aring/)/FeMn(100 /spl Aring/)/Ta(100 /spl Aring/) structure and 260 /spl Aring/ thick domain control Co/sub 78/Cr/sub 10/Pt/sub 12/ magnet layers. Its read/write performance was tested on a low noise CoCr/sub 17/Pt/sub 5/Ta/sub 4/ thin film disk with an Mr/spl middot/t of 0.41 memu/cm/sup 2/ and a coercivity of 2500 Oe. There is no Barkhausen noise in the readback waveform. The result of the microtrack sensitivity profiles reveals an effective read track-width of 0.8 /spl mu/m. A normalized output for a track-width of 880 /spl mu/Vpp//spl mu/m and D/sub 50/ of 166 kFCI was obtained. Using a PRML channel, a bit error rate of less than 10/sup -8/ was obtained without error correction at a data rate of 3.3 MB/s and at a linear density of 217 kBPI on a thin film disk with an Mr/spl middot/t of 0.72 memu/cm/sup 2/. Thus, 5 Gbit/in/sup 2/ density recording with a linear density of 217 kBPI and a track density of 23 kTPI is possible.

The authors previously have reported on the “ring gate delay” system which digitizes the infinitesimal time interval with the delay time of the inverter as the resolution, without using the high-speed reference clock [1]. A problem then is the improvement of the accuracy since the delay time of the inverter depends on various conditions such as the ambient temperature, the supply voltage, and the fabrication condition. To remedy this point, an LSI is constructed and the delay time of the original circuit is monitored continuously using the quartz oscillation clock of a relatively low frequency as the reference, and the time to be measured is digitized with a high accuracy based on the delay time. In this system, it is not necessary to control the delay time, which makes it possible to utilize the shortest delay time. By a single measurement process using a single input port, up to four pulses can be measured consecutively. If the pulse interval to be measured in less than the specified time, the pulses are combined into a single pulse and an incorrect operation is prevented. In this study, a sample device is constructed by a 1.5-μm CMOS process. The measurement range of 2200 ns (12 bit) with the time resolution 0.5 ns is achieved using the supply voltage of 5 V. The minimum pulse interval that can be measured is 55 ns (at 25°C). The reference clock used is 2 MHz. The number of transistors is 15, 000 and the chip size is 3.5 mm × 3.8 mm. The constructed LSI is composed totally of digital circuits. The operation is robust against the environmental condition, and a stable operation is realized for the ambient temperature of −35 to 140°C.

Increased free radicals and reduced levels of antioxidants have been reported in diabetes mellitus. Since heat-shock protein 70 (HSP70) is a stress-induced protein and is suggested to play a protective role against oxidative stress, we have investigated whether HSP7O acts as one of the defense systems against this stress. We separated mononuclear cells from diabetic patients (N=12) and age- and sex-matched healthy controls (N =12), and detected HSP70 by western blot analysis. The results were expressed by the ratio of the density determined by laser densitometry, to that of 10 mu g of purified HSP70. HSP70 levels in the mononuclear cells of diabetic patients (0.78 + or- 0.56) were significantly high, compared with healthy subjects (0.43 + or - 0.23) (P < 0.05). No correlation was found between HSP7O and hemoglobin A1c, fasting plasma glucose, duration of diabetes or diabetic complications except age. A negative correlation was found between HSP70 and age (r = -0.658, P < 0.05). These results suggest that HSP70 levels in the mononuclear cells are elevated reflecting increased oxidative stress in patients with diabetes.

Viscosity is an important parameter which affects hemodynamics during extracorporeal circulation and long-term cardiac support. In this study, we have aimed to develop a novel viscometer with which we can easily measure blood viscosity by applying the electromagnetically spinning (EMS) method. In the EMS method, we can rotate an aluminum ball 2 mm in diameter indirectly in a test tube with 0.3 ml sample of a liquid by utilizing the moment caused by the Lorentz force as well as separate the test tube from the viscometer body. First, we calibrated the EMS viscometer by means of liquid samples with known viscosities and computational fluid dynamics. Then, when we measured the viscosity of 9.4 mPa s silicone oil in order to evaluate the performance of the EMS viscometer, the mean viscosity was found to be 9.55 ± 0.10 mPa s at available shear rates from 10 to 240 s(-1). Finally, we measured the viscosity of bovine blood. We prepared four blood samples whose hematocrit levels were adjusted to 23, 45, 50, and 70% and a plasma sample without hemocyte components. As a result, the measurements of blood viscosities showed obedience to Casson's equation. We found that the viscosity was approximately constant in Newtonian silicone oil, whereas the viscosity decreased with increasing shear rate in non-Newtonian bovine blood. These results suggest that the EMS viscometer will be useful to measure blood viscosity at the clinical site.

Multiple bullae have often been observed in the lungs of patients with idiopathic interstitial pneumonia (IIP). The etiology of bullae has been considered to be distinct from that of interstitial pneumonia and honeycomb lesions seen in IIP. The incidence of bullae was evaluated in 27 IIP patients (male; 23 cases, female; 4 cases) and clinical factors which are related to the development of bulla were analyzed. Of the 27 patients, 16 (59%) had bullae. All 16 were male smokers, and had higher smoking indices (p

Most squamous cell carcinoma of the lung arises in the large bronchi and causes bronchial obstruction. We report a 74-year-old man with a squamous cell carcinoma of the lung whose roentgenogram revealed a lobar consolidation without collapse. A postmortem examination showed that the tumor cells filled the alveolar spaces completely without destroying the original architecture of the lung. The finding that tumor cells replacing alveolar epithelium, as in bronchioloalveolar cell carcinoma, was not seen throughout the lung. Airway obstruction by the tumor was not observed at any bronchus. These pathological findings seemed to explain the radiological findings.(Internal Medicine 32: 494-497, 1993)