A proposal for guideline for prevention of allergic occupational asthma in conformity with the globally harmonized system of classification and labelling of chemicals (GHS).

The use of chemical products to enhance and improve life is a widespread worldwide practice. Alongside the benefits of these products, there is also the potential of chemicals for adverse effects to people or the environment. As a result, a number of countries or organizations have developed laws or regulations over the years that require information to be prepared and transmitted to those using chemicals, through labels or Safety Data Sheets (SDS). Their differences are significant enough to result in different labels or SDS for the same product in different countries. In July 2003, United Nations (UN) recommended the globally harmonized system of classification and labelling of chemicals (GHS). We, special committee of Japanese Society of Occupational and Environmental Allergy proposed a guideline for prevention of allergic occupational asthma and sensitizers (n=60) causing occupational asthma or contact dermatitis in conformity with respiratory and skin sensitization criteria of GHS. We should propose these 60 sensitizers to the chemical industry association and governments to control, regulate and label them in each country.

Chemical characterization of milk oligosaccharides of the brown bear, Ursus arctos yesoensis.

Two tri-, two hexa- and two deca-saccharides were isolated from bear milk by chloroform/methanol extraction and gel filtration. The oligosaccharides were characterized, mainly by 1H-NMR, as follows: [structures: see text]. Both trisaccharides were present in bear milk at a higher concentration than lactose.

Relationship between polyamine contents and protease activity in the rat submaxillary gland.

The effect of polyamines on the protease activity in the submaxillary gland of castrated rats has been investigated in vivo. The protease activity, which is increased by testosterone, is also increased to a lesser degree by the subcutaneous administration of spermidine. The administration of putrescine was less effective than that of spermidine. The increase of polyamine contents in the submaxillary gland of the castrated rats administered either testosterone or spermidine was nearly parallel to the increase of the enzymatic activity. The administration of methylglyoxal bis(guanylhydrazone), a potent inhibitor of spermidine synthesis, with testosterone inhibited slightly the increase of the protease activity by testosterone, while the administration of the inhibitor with spermidine had essentially no effect on the increase of the enzymatic activity by spermidine. The administration of testosteorne also caused a slight increase of S-adenosyl-L-menthionine decarboxylase activity. These results suggest that spermidine synthesis may be necessary for the stimulation by testosterone of protease synthesis in the rat submaxillary gland.

Urocortin expression in synovium of patients with rheumatoid arthritis and osteoarthritis: relation to inflammatory activity.

Peripherally produced CRH acts as a local auto/paracrine proinflammatory agent. Urocortin is a new member of the CRH family that acts through the family of CRH receptors. In this study, we demonstrated that the expression of urocortin mRNA in synovia of patients with rheumatoid arthritis was greater than that of patients with osteoarthritis. Also, we detected urocortin and CRH receptor immunoreactivity in the synovial lining cell layer, subsynovial stromal cells, blood vessel endothelial cells, and mononuclear inflammatory cells from the joints of rheumatoid arthritis and osteoarthritis patients. The expression of immunoreactive urocortin was significantly greater in rheumatoid arthritis than osteoarthritis (P < 0.0001) and correlated with the extent of inflammatory infiltrate. CRH receptor immunoreactivity was strong in mononuclear inflammatory cells of rheumatoid arthritis synovia. Urocortin stimulated IL-1beta and IL-6 secretion by human peripheral blood mononuclear cells in vitro. These findings suggest that, like CRH, urocortin is present in peripheral inflammatory sites, such as rheumatoid synovium, and acts as an immune-inflammatory mediator.

Relative contributions of age and menopause to the vertebral bone density of healthy Japanese women.

The relative contributions of age and menopause to vertebral bone mineral density were evaluated based on the estimated weights for age- and menopause-related bone loss components using a mathematical model in 177 healthy female volunteers ages 35-81 years, living in a community in Fukui, Japan. Bone mineral density was determined by dual X-ray absorptiometry. The model used was that which afforded the best fit among the eight possible models to the data observed. Each model was composed of a linear function for the age-related component and a different type of function for the menopausal component, without interaction between them. The weights for these components in each model were estimated by the least-squares method. The coefficient of determination and Akaike information criterion disclosed that among the eight models tested, the model affording the best fit was composed of a logarithmic decrease in bone density with an increase in years since menopause, up to 10 years postmenopausal, with no further decline thereafter. In this model, the weights for both components were statistically significant and the type III sum of squares of the menopausal component was greater than that of the age-related component. We suggest that both age and menopause made significant contributions to the decline in vertebral bone mineral density, with the contribution of menopause being greater than that of age.

Combined effect of smoking habits and occupational exposure to hard metal on total IgE antibodies.

A survey was made within a population of workers (n = 706) exposed to hard metal dust (an alloy including cobalt), an agent known to cause occupational allergy. Twenty-seven (4 percent) of 733 workers were eliminated from consideration in this study because of atopic status identified prior to starting work in the plant. Using a Phadebas PRIST, the subjects' total IgE levels were determined and related to their smoking and exposure status. Nonexposed male smokers (n = 135) had a higher geometric mean IgE level (39.7 IU/ml) than did nonexposed subjects who had never smoked (33.1 IU/ml; n = 99); those with a higher Brinkman index (greater than 300), a smoking index obtained by multiplying the number of cigarettes per day by the duration of smoking in years, had significantly (p less than 0.05) decreased IgE levels. Although ex-smokers (n = 72) had a higher geometric mean IgE level (73.3 IU/ml) than did those who had never smoked, their serum IgE level declined with age since the time they quit smoking, regardless of their hard metal exposure status. Hard metal (cobalt) exposure may play a significant role as an adjuvant in the production of total IgE. A multivariate analysis demonstrated that hard metal exposure and a smoking habit together arithmetically (p less than 0.05) increased total IgE levels. These two factors may be preventable risk factors for occupational allergy in hard metal workers.

Occupational asthma from cobalt sensitivity in workers exposed to hard metal dust.

Eight asthmatic patients who had no history of asthma before starting work in a hard-metal plant and eight control subjects (three atopic, three nonatopic asthmatic, and two normal volunteers) without a history of exposure to hard metal dust were subjected to provocation tests, skin tests, radioallergosorbent tests (RAST) and Farr test with cobalt. Four of the eight patients were atopic, and seven showed bronchial hyperresponsiveness to methacholine (BHR). Patch and intradermal skin tests with cobalt chloride (CoCl2) could not discriminate the patients from control subjects. All patients had positive reactions to CoCl2 in the provocation tests; two developed immediate asthmatic reaction (IAR), four late asthmatic reaction (LAR), and two dual asthmatic reaction (DAR), while the control subjects showed no reaction. Evidence of specific IgE antibodies to cobalt-conjugated human serum albumin (Co-HSA) was presented by four patients (RAST score greater than 2) based on comparison of serum samples from 60 asthmatic patients and 25 asymptomatic workers in the same plant. Positive serum samples selectively bound 57Co, and the test was blocked by nonlabled cobalt sulfate (CoSO4). These findings suggest the development of hard metal-induced asthma from cobalt sensitivity.

Preferential inhibition of cyclooxygenase-2 by meloxicam in human rheumatoid synoviocytes.

The aim of this study was to evaluate the anti-inflammatory effect of 4-hydroxy-2-methyl-N-[5-methyl-2-thiazolyl]-2H-1, 2-benzothiazine-3-carboxamide-1,1-dioxide (meloxicam) using cultured rheumatoid synovial fibroblast-like cells (synoviocytes). Synoviocytes were treated with meloxicam in the presence or absence of interleukin-1beta. Meloxicam had no effect on both cyclooxygenase-1 and -2 expression as determined by Western blot analysis, immunohistochemical staining, and reverse transcription polymerase chain reaction (RT-PCR). Even the lower doses of meloxicam inhibited cyclooxygenase-2 activity, but only the higher doses of meloxicam inhibited cyclooxygenase-1 activity as determined by prostaglandin E(2) synthesis assay. So meloxicam had a preferential inhibitory effect of cyclooxygenase-2 relative to cyclooxygenase-1 on cultured rheumatoid synoviocytes without affecting cyclooxygenase expression. On the other hand, indomethacin had no selectivity and dexamethasone inhibited the expression of cyclooxygenase-2. Our data indicate that clinical efficacy and safety of meloxicam for rheumatoid arthritis may result from its preferential inhibition of cyclooxygenase-2 activity relative to cyclooxygenase-1 on rheumatoid synoviocytes.

Auranofin inhibits interleukin-1beta-induced transcript of cyclooxygenase-2 on cultured human synoviocytes.

The aim of this study was to characterize the effects of auranofin (2,3,4,6-tetra-O-acetyl-l-thio-beta-D-gluco-pyranosato-S) on cyclooxygenase expression and prostaglandin E(2) synthesis on cultured human synovial fibroblast-like cells (synoviocytes). Synoviocytes were treated with auranofin in the presence or absence of interleukin-1beta. Cultured supernatants were harvested for prostaglandin E(2) synthesis. Cyclooxygenase-1 and -2 expression was analyzed with Western and Northern blotting. Translocation of nuclear factor-kappa B p65 was determined by immunostaining. Cytotoxicity was measured with 51Cr release assay. Auranofin attenuated interleukin-1beta-induced prostaglandin E(2) production of the cells in a dose-dependent fashion. Auranofin selectively suppressed interleukin-1beta-induced cyclooxygenase-2 mRNA and protein expression of the cells without alteration of cyclooxygenase-1 expression. Also, auranofin interfered with interleukin-1beta-induced translocation of nuclear factor-kappa B. These inhibitory effects did not originate in the cytotoxicity of the agent. Our data indicate that auranofin inhibits interleukin-1beta-induced prostaglandin E(2) synthesis and cyclooxygenase-2 expression via suppression of nuclear factor-kappa B activation on synoviocytes.

Vital immunostaining of human gastric and colorectal cancers grafted into nude mice: a preclinical assessment of a potential adjunct to videoendoscopy.

Videoendoscopy has not significantly advanced diagnostic accuracy beyond that attainable by conventional fiberscopy, with respect to microcarcinomas of the digestive tract. We suspected that after the labeling of these lesions with an agent detectable by videoendoscope, digital processing of the images could facilitate endoscopic diagnosis of microcarcinomas. We have developed a novel antibody labeled with an indocyanine green (ICG) derivative that is evident by videoendoscope. However, the binding of such an exogenous antibody in vivo to tumor surfaces has not been described. In this preliminary study, after transplanting human gastric cancer or colorectal cancer into nude mice, we successfully bound the tumors in vivo with an anti-MUC1 mucin antibody, as subsequently confirmed by the performing of immunohistochemistry with a secondary antibody. The antibody labeled with an ICG derivative may therefore be clinically useful in detecting gastrointestinal microcarcinoma by videoendoscopy.

Further characterization of the binding of substance P to a fraction from rabbit brain enriched in synaptic membranes.

1. The present experiments were designed to further characterize the specific [3H]substance P (SP) binding to membrane fractions from rabbit brain. 2. The specific binding was resistant to treatment with proteolytic enzymes whereas phospholipase A(0.7 unit/ml), C(0.025 unit/ml) and D(6.2 unit/ml) reduced the specific binding without decreasing total binding. Neuraminidase (0.01 unit/ml) decreased total binding as well as the specific binding. 3. High concentration of Triton X-100 reduced the specific binding whereas deoxycholate, at 0.05%, reduced both total and the specific binding. 4. Na+ (50--200 mM) reduced the specific binding, depending on the concentrations employed, whereas K+ decreased the specific binding at 10 and 100 mM. The binding was reduced considerably by 100 mmol/l of CaCl2. 5. From these results it is suggested that the specific [3H]SP binding sites in membrane fractions from rabbit brain could be phospholipids.

Relationship between radiographic classification and arthroscopic findings of articular cartilage lesions in osteoarthritis of the knee.

OBJECTIVE: To examine the relationship between radiographic abnormalities and arthroscopic findings of the cartilage lesions in patients with osteoarthritis (OA) of the knee. METHODS: Arthroscopy was performed in 190 patients with primary medial compartment (MC) OA of the knee to assess the severity of the cartilage lesion. Standing radiographs of all patients were graded according to the joint space narrowing (JSN) and Kellgren-Lawrence (K/L) scales. In addition to evaluating the correlation between arthroscopic articular cartilage lesions and the radiographic scale, multiple regression analysis was used to identify the arthroscopic findings and clinical factors that influenced the cartilage lesions. RESULTS: The positive predictive values of the JSN and K/L scales of the MC for the presence of essentially abnormal articular cartilage in the MC by arthroscopy were high (0.98, 0.96, respectively). The sensitivity and specificity of the JSN scale and the sensitivity and negative predictive value of the K/L scale were also high in the MC. In contrast, the positive predictive values of these radiographic scales for the presence of arthroscopic lesions in the lateral compartment (LC) were poor (0.20 and 0.19). In this study population with severe OA, there were more patients with a high K/L score than with a high JSN score in the MC. CONCLUSION: In MC-OA of the knee, the JSN and K/L scores for the MC correlated highly with cartilage lesions of the MC by arthroscopy. However, the cartilage lesion of the LC correlated poorly with both of these radiographic scales.

Asymptomatic case of congenital absence of the gallbladder.

Congenital absence of the gallbladder is rare among biliary abnormalities, and its preoperative diagnosis has been considered very difficult. We encountered a patient with congenital absence of the gallbladder and suggest a possible preoperative diagnosis of the abnormality, as well as reviewing the literature.

Effects of abstinence from cigarette smoking on the cardiorespiratory capacity.

PURPOSE: The purpose of this study was to determine the effect of 6 or 7 d of abstinence from cigarette smoking on the cardiorespiratory capacity of young men. METHODS: The subjects were 11 male volunteers, mean age 20.5 yr. Their mean smoking duration and cigarettes smoked per day were about 3.5 yr and 20.5 cigarettes, respectively. On the first day of the study, the subjects' physical characteristics, pulmonary functions, and maximal oxygen debt predicted by bicycle ergometer exercise were measured. The subjects' heart rate at rest (HRrest), blood pressure, venous blood analysis and maximal oxygen intake (VO2max) in a treadmill exercise test were measured on the second day. From the time of the second-day measurements, the subjects abstained from cigarette smoking. On the eighth and ninth days of the study, the same measurements were taken as the measurements of the first and second days, respectively. RESULTS: The changes between before and after abstinence from smoking were as follows. The plasma cotinine had almost disappeared after the 7 d of abstinence from smoking. Pulmonary functions did not show a significant improvement. Although there were no significant changes in the HRrest or systolic or diastolic blood pressure, the pulse pressure was significantly increased (P < 0.05). Although the blood components were not changed significantly, the PO2, O2 saturation, HCO3, and CO2 concentration were significantly increased. The predicted maximal oxygen debt was not significantly decreased. Although the VO2max and maximal ventilation volume were not changed, the exercise time was significantly prolonged (P < 0.001). The heart rate during the treadmill exercise at almost all stages decreased significantly; however, the maximal heart rate did not change. CONCLUSION: In conclusion, exercise performance was improved by the 7 d of abstinence from smoking.

Basic study of an agent for reinforcement of near-infrared fluorescence on tumor tissue.

BACKGROUND AND AIMS: An indocyanine green derivative (ICG-sulfo-OSu) and agents for reinforcement of infrared fluorescence, which can be used as an infrared fluorescent labeling substance suitable for detection of microlesions by an IR fluorescence endoscope, have been developed. The study aims were to confirm the ability of a reinforcement agent, as well as imaging processing, to intensify fluorescence from the labeled antibody on immunohistochemical staining. SUBJECTS AND METHODS: ICG-sulfo-OSu-labeled MUC1 antibody and an IR fluorescence imaging system were employed in the present study. Paraffin sections of gastric cancer were stained with anti-MUC1 antibody by the avidin-biotinylated peroxidase complex method. Among the positive specimens, three cases were used for IR imaging analysis. Octylglucoside was used as a reinforcement agent. RESULTS: The incubation of paraffin sections with ICG-sulfo-OSu-labeled MUC1 antibody resulted in positive staining of the tumor sites by an IR fluorescence imaging system, and the intensity of fluorescence was increased depending on the concentration of octylglucoside and grade of imaging processing. CONCLUSION: A reinforcement agent, and image processing, intensify a labeled antibody excitable by infrared fluorescence in tumor sections and can generate a strong enough fluorescent signal to detect small cancers when examined with an infrared fluorescence endoscope.

Human heart-type cytoplasmic fatty acid-binding protein in serum and urine during hyperacute myocardial infarction.

We have previously reported that serum and/or urinary human heart-type cytoplasmic fatty acid-binding protein (HH-FABPc) can be used as an early indicator of myocardial injury (Clin Biochem 1991; 24: 195-201). To confirm the usefulness of HH-FABPc as an early diagnostic indicator of acute myocardial infarction (AMI), its serum and urinary levels were measured in samples obtained within 6 h after the onset of acute coronary syndrome related symptoms. Samples were collected from 97 patients, who were composed of 63 with AMI, 24 with unstable angina and 10 with chest pain syndrome. The positivity of serum and urinary HH-FABPc and cardiac creatine kinase isozyme MB (CK-MB) was analyzed in these samples. Serum HH-FABPc levels in AMI were above normal in 91.4% (64/70) of the samples tested within 3 h of the onset of symptoms and in 100% (111/111) of those tested at 3-6 h. Elevated urinary HH-FABPc levels in AMI were obtained in 88.9% (8/9) of samples at 0-3 h and in 75% (6/8) at 3-6 h. CK-MB activity in AMI was positive in 20% (8/40) and 66.3% (53/80) of serum samples at 0-3 h and 3-6 h, respectively. HH-FABPc was always positive when a serum sample was positive for CK-MB. Serum HH-FABPc at 0-6 h in chest pain syndrome and in unstable angina were positive in 17.8% (5/28) and 56.7% (34/60), respectively. The elevated HH-FABPc in serum and urine was noted much earlier than that of CK-MB during the hyperacute phase of AMI. HH-FABPc showed high positive value in unstable angina, but it was low in normal coronary patients having chest pain. However, HH-FABPc level in unstable angina and chest pain syndrome was lower than that of AMI. Thus, HH-FABPc may be a valuable indicator for the diagnosis of hyperacute myocardial infarction.

Direct effect of cadmium on citrate uptake by isolated rat renal brush border membrane vesicles.

High incidence of multiple kidney stone formation has been observed among workers exposed to cadmium (Cd). Citrate is known to be a protective factor against renal stone formation. To study the direct effect of cadmium on citrate uptake by the renal brush border membrane, we exposed isolated rat renal brush border membrane vesicles (BBMV) to cadmium and determined their citrate uptake characteristics. BBMV were prepared by the divalent cation precipitation method. Citrate uptake was measured by the Millipore rapid membrane filtration technique. Preincubation of BBMV with 2 and 10 mM CdCl2 for 1 min significantly inhibited citrate uptake compared with that of BBMV without Cd. Analysis of the time course of citrate uptake during 30-min preincubation of BBMV with 0.5 mM Cd also revealed significant reduction of the uptake compared with that of the control BBMV without preincubation. These findings indicate that preincubation of BBMV with cadmium results in time-dependent and concentration-dependent inhibition of citrate uptake.

Age, menopause, bone turnover markers and lumbar bone loss in healthy Japanese women.

The change in lumbar vertebral bone mineral density (BMD) during a 2-year study period was examined in 167 healthy middle-aged and elderly Japanese women with reference to age, menopausal status and bone turnover markers at baseline. The perimenopausal and postmenopausal groups of the subjects showed a significant loss of BMD during the study period but the premenopausal women did not. The annual percent decrease of BMD (delta BMD) in the perimenopausal women (-2.40% in average) was significantly greater than that in either of the premenopausal (-0.01%) or over-all postmenopausal women (-0.85%). The subjects who had been postmenopausal for less than 10 years showed a significant bone loss. delta BMD in the postmenopausal women became less marked as the postmenopausal duration increased. The bone loss was accelerated for about 10 years after menopause. The pattern and magnitude of bone loss of Japanese women seemed to be similar to those of Caucasian women. The regression equation for delta BMD based on the bone turnover markers at baseline was shown to be significant in the postmenopausal women and the serum level of bone-specific alkaline phosphatase isoenzyme had a significant relation to delta BMD. However, this equation accounted for only 17.3% of the total variance of delta BMD and, hence, its validity was not sufficiently high for the prediction of bone loss in clinical settings.

(1)H double-quantum filtered MR imaging of joints tissues: bound water specific imaging of tendons, ligaments and cartilage.

The (1)H double-quantum filtered (DQF) NMR and DQF MRI is applied to the joint tissues of rabbits for selective visualization of tendons, menisci and articular cartilage. The (1)H DQF NMR selectively filters double-quantum coherence arising from the (1)H dipolar interaction of the "bound" water in these tissues. The double-quantum creation time dependency of the DQF signal intensity is determined by the molecular environment of the "bound" water. Therefore, each tissue has a unique creation time at which the DQF signal reaches its maximum intensity, tau(max) (Achilles tendon: 0.46 +/- 0.02 ms, patella: 0.55 +/- 0.8 ms, anterior cruciate ligament: 0.60 +/- 0.05 ms, meniscus: 0.78 +/- 0.02 ms, skin: 0.81 +/- 0.07 ms). We have presented the creation-time-contrasted DQF images of the meniscus, patella, foot, and knee joint. Compared with conventional T(2)*-weighted gradient-echo (GRE) MR images, tendons, ligaments, menisci, and articular cartilage were more clearly seen in the DQF MR images. All these tissues were distinctly discriminated from each other by their creation times. DQF MR images of foot and knee joints can selectively demonstrated tendons, ligaments, and cartilage, which make it easier to understand the complicated anatomic structure of joints. Because the DQF NMR signal intensity and tau(max) are sensitive to the order structure of the "bound" water, it might be possible to introduce the creation-time dependent-contrast of (1)H DQF MR images as a new tool for analyzing the changes in the ordered structure of the tissue.