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Biomedical subjects

Y Kusaka

Publications and source records attributed to Y Kusaka.

At least 55 records · Page 3Linked to original sources

Labeled carcinoembryonic antigen antibodies excitable by infrared rays: a novel diagnostic method for micro cancers in the digestive tract.

OBJECT: An indocyanine green derivative (ICG-sulfo-OSu) was used as the labeling substance for monoclonal antibody, and a fluorescence imaging system appropriate for ICG-sulfo-OSu excitable by infrared rays (IR) was developed. The goal of this study was to demonstrate antibody labeling at the tissue level using this new imaging system. MATERIALS AND METHODS: ICG-sulfo-OSu labeled mouse anti-human carcinoembryonic antigen (CEA) monoclonal antibody, a newly developed imaging system, and an infrared ray microscope were employed in this experiment. Paraffin sections of human colon cancer previously proven to have cross-reactivity to anti-CEA antibody were examined. RESULTS: Positive staining was seen as a brownish discoloration of oxidized 3,3'-diaminobenzidine tetrahydrochloride (DAB) in sections that reacted with ICG-sulfo-OSu-labeled anti-CEA antibody, and the fluorescence was well-matched with the oxidized DAB-positive sites. CONCLUSION: Specific antibodies labeled with ICG-sulfo-OSu have significant affinity to cancer cells and seem to reflect sufficient amounts of fluorescence by IR to be useful in a system for the endoscopic detection of micro cancers using the immunohistochemical staining method.

Adenocarcinoma↗

Differences in the extent of inflammation caused by intratracheal exposure to three ultrafine metals: role of free radicals.

Nickel and cobalt, which belong to the same elemental group, are known to cause interstitial lung disease and bronchial asthma. The ability of these metals to injure lung cells and cause inflammation is likely to be important in their pathogenicity but comparative studies are rare. Additionally, ultrafine (uf) forms of these metals are used increasingly and there is little available information on their toxicity. Thus the inflammatory response following intratracheal instillation of ultrafine particles of Co, Ni, and TiO2 was compared. Physiological saline (PS) was used as a vehicle control and DQ12 quartz as a positive control. Male Wistar rats were intratracheally instilled with the 3 particle types at a dose of 1 mg suspended in physiological saline. At 1, 3, 7, 15, and 30 d after the injection, lung weight and the cellular and biochemical changes in bronchoalveolar lavage fluid (BALF) were determined. By all of the indices, Uf-Ni appeared to be the most injurious to the lung, causing severe and sustained inflammation, cytotoxicity and increased epithelial permeability. The next most toxic material was DQ12 quartz, with Uf-Co being closely similar in ability to cause inflammation. Uf-TiO2 was more active than the saline control in all of the indices, but was the least toxic of the particles studied. The present study reveals that three ultrafine particles of the same diameter are dramatically different in their ability to cause inflammation. The three ultrafines were compared as to their ability to cause free-radical damage to supercoiled plasmid DNA, and the result of free-radical activity was found to be Uf-TiO2 << Uf-Co = Uf-Ni. Difference in free-radical-generation activity therefore could underlie the difference in inflammation of these three ultrafine particle types.

Animals↗

A case of sarcoidosis that developed three years after the onset of hard metal asthma.

A 23-year-old man who worked at a hard metal factory from 1988 had developed bronchial asthma in 1990. He was diagnosed as having bronchial asthma by inhalation challenge with cobalt. He never developed a severe attack after that by avoiding inhalation of cobalt. In 1993, he developed iridocyclitis, and his chest radiograph showed bilateral hilar lymph node swelling. He was diagnosed as having sarcoidosis with pathological certainty and an increased serum angiotensin-converting enzyme (ACE) level. On second admission, an inhalational challenge with cobalt resulted in no significant decrease of FEV1. Cobalt is well known to cause occupational asthma and other interstitial lung diseases. Although we could not get clear evidence suggesting an association between the sarcoidosis and his history of cobalt exposure, there is a possibility that changes in the immune reaction to cobalt might explain the improvement of asthma followed by sarcoidosis in this case.

Adult↗

[Mercury sensitization induced by environmental exposure].

We investigated mercury sensitization in relation to urinary and hair mercury concentrations. Patch tests were performed on 215 medical students and these tests demonstrated that 28 students were mercury-sensitized (13.0%). Life-styles were studied by questionnaire in 26 of the mercury sensitized students and 46 of the non-sensitized subjects. Urinary mercury concentrations were measured in 25 sensitized and 46 non-sensitized and hair mercury concentrations were measured in 19 sensitized and 22 non-sensitized subjects. The eating of fish was not significantly associated with mercury sensitization (one-tailed t-test). The number of teeth treated with metals in the sensitized group was significantly higher than in the control group (6.8 +/- 4.3 in sensitized vs. 4.8 +/- 4.1 in non-sensitized, one-tailed t-test. p < 0.05). The usage of mercurochrome was not significantly associated with mercury sensitization (chi-squared test). Urinary mercury concentrations were not significantly higher in sensitized subjects. Hair mercury concentrations were significantly higher in sensitized subjects (1.98 +/- 0.91 micrograms/g in sensitized vs. 1.23 +/- 0.53 in non-sensitized, one-tailed t-test p < 0.05). These results suggest that mercury sensitization is associated with increased hair mercury concentrations but not with urinary mercury concentrations. In this study it is confirmed that dental amalgam for treating teeth may be an important factor relating to mercury sensitization.

Adult↗

Log-normality of distribution of occupational exposure concentrations to cobalt.

In evaluating occupational exposures, the daily exposure levels of a worker are generally assumed to be distributed log-normally between days. When there are many workers in a job group, the individual worker's arithmetic means are assumed to be distributed log-normally. Using the cobalt exposure data in a hard metal factory, these assumptions were examined with the Shapiro-Wilk W test. The hypothesis of log-normality was accepted in all cases, while the hypothesis of normality was rejected in some cases.

Cobalt↗

Association of natural killer cell activity with serum IgE.

Association of natural killer (NK) cell activity (NKCA) or NK cell subsets with total IgE or antigen-specific IgE in serum were studied among 66 healthy non-allergic males. NKCA was determined by using 61Cr release assay and NK subsets were counted usings surface antigens (CD16, CD57) in peripheral blood mononuclear cells. NKCA was associated mainly with the frequency of a CD16+,CD57- subset. When the subjects were classified into three groups according to total IgE values in serum (grade 0: IgE < 10 IU/ml; grade 1: IgE 10-400 IU/ml; grade 2: IgE > 400 IU/ml), one-way analysis of variance of NKCA showed that the grades of total IgE were significantly associated with increasing NKCA. In addition, NKCA in the grade 0 group was significantly lower than that in the grade 2 group and than a mixture of grade 1 group and grade 2 group. A similar finding was not observed between NKCA and RAST for specific IgE against mites. Therefore, NKCA may be related to total IgE level in serum.

Adult↗

Citrate uptake by isolated rat renal brush border membrane vesicles in cadmium-intoxicated rats.

Epidemiological Studies have reported that the formation of renal stones is often observed in workers exposed to cadmium (Cd). Citrate is known to be a protective factor against renal stone formation. We previously reported that direct exposure to high-level cadmium impaired the citrate uptake by the brush border membrane vesicles (BBMV), which may mean that the formation of renal stones from exposure to Cd could be prevented. In the present study, to clarify the mechanism of Cd-induced renal stone formation, the characteristics of BBMV-induced citrate uptake were determined in Cd-intoxicated rats. Cd intoxication was induced by daily subcutaneous injections of CdCl2 at a dose of 2 mg Cd/kg body wt per day for 17 to 20 days. The BBMV were prepared by the divalent cation precipitation method. Citrate uptake was measured by the Millipore rapid membrane filtration technique. The citrate uptake per mg protein was not significantly different between the two groups. The volume of BBMV was significantly reduced (50%) in Cd-intoxicated rats compared with that of control rats. Percentages of the equilibrium value were also significantly inhibited in Cd-intoxicated rats.

Animals↗

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

Occupational exposure to mercury has long been associated with renal proximal injury and an increased incidence of proteinuria, as has such exposure to cadmium. Renal citrate excretion is very important with respect to acid-base balance since the metabolism of citrate generates three bicarbonate ions. In this study, we exposed isolated rat renal brush border membrane vesicles (BBMV) to mercury (Hg2+) and examined their citrate uptake characteristics. BBMV were prepared by the divalent cation precipitation method. Citrate uptake was measured by the Millipore rapid membrane filtration method. The preincubation of BBMV with 0.5 and 2 mM HgCl2 for 1 min significantly inhibited citrate uptake compared with that of BBMV without Hg preincubation. The analysis of the time course of citrate uptake during a 30-min preincubation of BBMV with 0.1 mM Hg2+ also revealed a significant reduction in the uptake compared with that of the control BBMV without preincubation. These findings indicate that the preincubation of BBMV with mercury results in a time- and concentration-dependent inhibition of citrate uptake.

Animals↗

Technegas ventilation SPECT for evaluating silicosis in comparison with computed tomography.

To compare the subtle pulmonary parenchymal morphologic changes with ventilation function in patients with silicosis, the conventional CT, high resolution CT and technegas ventilation SPECT were performed. In 25 silicotic patients and six controls, the pulmonary ventilation state was evaluated by an index called the coefficient of variation (CV), which expresses the subliminal heterogeneous distribution of technegas in the lungs. The results showed that with silicosis the CV value is significantly higher than that without silicosis. The CV value was proved by multifactorial analysis to independently reflect the extent of the appearance of small scattered interstitial findings such as nodules, septal thickening and bulla, which were typical findings for silicosis. The CV value calculated from the technegas SPECT correlated well with the severity of silicosis. It is considered that the CV value can also express the functional state of the silicotic lung.

Adult↗

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.

Adult↗

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.

Absorptiometry, Photon↗

Cobalt exposure level and variability in the hard metal industry of Japan.

Cobalt, used as a binder for tungsten carbide, has been demonstrated to be toxic to the lung and to be a sensitizer of the bronchial airways among hard metal workers. To determine cobalt exposure levels in 9 job groups at a hard metal factory, 935 samples were collected from 356 workers. The arithmetic means of 8-hr time-weighted averages were more than 50 micrograms/m3 (American Conference of Governmental Industrial Hygienists' threshold limit value) in the powder preparation, rubber press, and shaping groups. The within-worker and between-worker components of exposure variation were estimated for each job group using the random effects analysis-of-variance model. The geometric standard deviations indicating the within-worker and between-worker components ranged from 1.88 to 2.77 and 1.00 to 2.31, respectively.

Air Pollutants, Occupational↗

Epidemiological study of hard metal asthma.

OBJECTIVES: To elucidate factors contributing to hard metal asthma, the entire workforce of a corporation producing hard metal tools (n = 703) was examined. METHODS: The variables evaluated were the atopy reflected by immunoglobulin E (IgE) antibody against mite allergen, history of exposure to hard metal, smoking, concentration of airborne cobalt, specific IgE antibody reaction against cobalt, and the respiratory symptom of attacks of reversible dyspnoea with wheeze (asthmatic symptoms). RESULTS: Univariate analysis showed that the prevalence of the asthmatic symptoms was significantly higher in formerly and currently exposed male workers than in non-exposed male workers. Positive IgE reaction against cobalt was found in seven men (2.0%), all of whom had asthmatic symptoms. Furthermore, it was found that atopy, positive IgE antibody against cobalt, and age of 40 or older were significantly correlated with asthmatic symptoms. Multilogistic analysis on the same factors and smoking in all of the workers showed that the age, experience of hard metal exposure, and atopy were significant risk factors associated with the asthmatic symptoms. Multilogistic analysis of data for currently exposed and non-exposed workers also showed that age and atopy were risk factors, and that the exposure to cobalt at the low concentration (at or below 50 micrograms/m3) but not at the higher concentration was a significant risk factor. Exposure to mist of coolants containing ionic cobalt, used during grinding, was not found to be any more hazardous in terms of onset of asthmatic symptoms than exposure to hard metal dust containing metallic cobalt. CONCLUSIONS: Accordingly, it is concluded that both environmental factors and individual susceptibility should be taken into consideration in efforts to reduce the prevalence of hard metal asthma.

Adolescent↗

Decreased ventilatory function in hard metal workers.

OBJECTIVES: To study individual effects on pulmonary function of exposure to hard metal including cobalt. METHODS: All of the workers in a hard metal company (583 men and 120 women) were examined for smoking, respiratory symptoms, ventilatory function, occupational history of exposure to hard metal, and present exposure to airborne cobalt. The ventilatory function indices (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory volume in one second per cent (FEV1%), peak expiratory flow (PEF), mid-maximal flow (MMF), forced expiratory flow at 50% vital capacity (V50), forced expiratory flow at 25% vital capacity (V25)) were standardised for height and age and expressed as a percentage of predicted values. RESULTS: Two way analysis of variance of indices of ventilatory function showed that an interaction of hard metal exposure and smoking decreased %V50 for both men and women. Among the currently exposed men, those with asthmatic symptoms (defined as reversible dispnoea with wheeze) had significantly lower %FVC, %FEV1%, %PEF, %MMF, %V50, and %V25 than did workers without asthma. The ventilatory disfunction did not differ between exposed and non-exposed workers with asthmatic symptoms. Even among the men without asthmatic symptoms, %V50 was significantly lowered by the interaction of hard metal exposure and smoking. The multilinear regression analysis of indices of ventilatory function for all of the subjects on sex, smoking (Brinkman index), exposure to hard metal, and asthmatic symptoms showed that asthmatic symptoms and smoking had significant effects on all variables and that the decrease in %V25 was associated with hard metal exposure. In the currently exposed and non-exposed workers, multilinear regression analysis applying indices for cobalt exposure (mean cobalt concentration, duration of exposure, and cumulative dose) showed that not only asthmatic symptoms or smoking but also duration of exposure had significant decreasing effects on %FVC, %MMF, and %V25. CONCLUSIONS: Occupational exposure to hard metal probably causes impairment of ventilatory function in a dose dependent manner.

Adolescent↗

Urinary selenium excretion in infancy: comparison between term and preterm infants.

We evaluated the urinary excretion of selenium (Se), an essential component of glutathione peroxidase, in infants aged 1 week and 1, 4, and 7 months and examined the relationship between urinary Se and renal function. Daytime spot urine samples from a total of 80 infants were analyzed. The Se concentration in urine was measured by fluorometry, while the beta 2-microglobulin content, an index of renal tubular function, was determined by radioimmunoassay. In healthy term infants, the urinary Se excretion showed a peak level at 1 month of age. In contrast, the urinary Se concentration rapidly decreased in preterm infants from 1 week to 7 months postnatally. The level at 1 week in preterm infants was significantly higher than that in term infants, although the mean levels at 1, 4, and 7 months were lower in preterm infants. The level of urinary Se did not correlate significantly with the beta 2-micro-globulin concentration, either in term or preterm infants at any age investigated. Our results suggest that the renal excretion of Se probably reflects the body stores of Se and is not related directly to the renal function in infants. Urinary Se, a noninvasive marker of the Se status, may be used for diagnosis and follow-up of Se deficiency in infants.

Aging↗