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Biomedical subjects

I Hara

Publications and source records attributed to I Hara.

At least 163 records · Page 9Linked to original sources

Selenium status in workers handling aromatic nitro-amino compounds in a chemical factory.

The selenium status of workers handling aromatic nitro-amino (ANA) compounds was evaluated by measurement of their blood and urinary selenium concentrations and blood glutathione peroxidase (GSH-Px) activities. Forty-seven healthy Japanese male workers (42.7 +/- 12.1 yr) handling ANA compounds routinely in a chemical factory were studied as exposed workers, and 107 nonindustrial healthy Japanese males (39.3 +/- 10.0 yr) in the same region served as a control group. Urinary diazoreaction-positive metabolites and methemoglobin, both of which have been used as indices of exposure to ANA compounds, were significantly elevated in the exposed workers. Both plasma and erythrocyte selenium in the exposed workers showed 20% lower values compared to the control group. GSH-Px activities in plasma and erythrocytes were also significantly decreased in the exposed workers, but urinary selenium excretions were similar between the two groups. Questionnaire information obtained from each subject regarding intake habits of selenium-rich foods (bread, eggs, meat, and fish) indicated that the average dietary selenium intake was similar for the control group and the exposed workers. These results indicate that (1) the workers handling ANA compounds were surely exposed to these chemicals; (2) their selenium status was lower than that of the nonindustrial controls; and (3) the low selenium status was not associated with any dietary factor.

Adult↗

Biological monitoring for workers exposed to 4,4'-methylenebis(2-chloroaniline).

Absorption of 4,4'-methylenebis (2-chloroaniline) (MBOCA) was assessed for five workers over one week in a polyurethane elastomer factory by measuring urinary MBOCA levels by high performance liquid chromatography (HPLC) using an electrochemical detector. Personal air exposure levels of MBOCA ranged from 0.2 to 8.9 micrograms/m3. The mean urinary MBOCA levels at the beginning and the end of the work shift were 3.1-81.5 and 2.4-96.6 micrograms/g creatinine, respectively. The differences between preshift and postshift urinary MBOCA values were not significant in all workers, according to the paired t-test. The urinary levels after a two-day holiday (on Monday morning) were almost equal to those of preshift levels on other weekdays. Urinary excretion of MBOCA was much higher than the estimated MBOCA levels from personal exposure measurements, suggesting that a significant amount of MBOCA is absorbed by routes other than inhalation. These results lend strong support for the need to monitor exposure control by urinary MBOCA measurement.

Air Pollutants, Occupational↗

Studies on the activity of phospholipase D with alkyl phosphorylcholines.

The activity of phospholipase D from the Savoy cabbage on alkyl phosphorylcholines containing alkyl groups of C14 to C22 was examined. Apparent Km and maximal velocity values in the presence of diethyl ester were 3.6-8.3 mM and 0.14-0.29 mumol/(min.mg protein), respectively. The maximal velocities for alkyl phosphorylcholine homologues were lower than the value for pig phosphatidylcholines, but higher than those for lysophosphatidylcholines and synthetic phosphatidylcholine with saturated acyl chains. Results suggest that solubilities of the substrates in the organic solvent play an important role in activity observed with phospholipase D.

Animals↗

[Effect of administration with chlorpyrifos on electroretinogram in rats].

Changes in electroretinograms (ERG) due to administration of chlorpyrifos were examined in rats. Male Wistar rats were intraperitoneally injected with chlorpyrifos (0.2 mmol/kg body weight), and their cholinesterase (ChE) activities and ERG were measured at various times after the injection. Amplitudes of A and B waves in ERG were more than 50% decreased and latencies of the waves were prolonged 10-20% from 5 h to 2 d after the injection. At the same time, activities of ChE in plasma, erythrocytes, brain and retinochoroid were remarkably decreased. However, the amplitudes and latencies recovered to the control level more rapidly than the ChE activities of the erythrocytes, brain and retinochoroid. Injection into rats of 0, 0.002, 0.01, 0.05 or 0.25 mmol/kg of chlorpyrifos showed that the chlorpyrifos-induced changes of ERG were dose-dependent, and that a level of 0.05 mmol/kg caused a 50% decrease in the A or B wave 5 h after the injection. These results indicate that chlorpyrifos caused abnormal ERG characterized by decreased amplitudes and prolonged latencies of A and B waves and that the abnormal ERG did not always correspond to the decreased retinochoroid or brain ChE activities.

Animals↗

[Cancer mortality of male workers exposed to benzidine and/or beta-naphthylamine].

The risk of cancer was analysed in a cohort of 604 male workers who had been engaged in manufacturing and/or handling benzidine and/or beta-naphthylamine during the period 1945-71 at two factories located in the city of Osaka. The cohort was followed up from 1 January 1970 to the date of death or 31 December 1986. The mean follow-up time was 16.1 years. A total of 84 deaths was found compared with 112.66 expected based on the mortality of the Osaka population. Thirty-six were found to be dead of malignant neoplasms; 9 stomach, 2 colon, 1 rectum, 3 liver, 1 bile duct, 1 pancreas, 1 maxillary sinus, 6 lung, 8 bladder, and 2 ureter neoplasms as well as 1 case of myeloid leukemia. Seven cases were ascertained on death certificates as neoplasms of uncertain behaviour, all of which were tumors of genitourinary organs except for one case of brain tumor. Cancers of genitourinary organs and tumors of uncertain behaviour showed statistically significant increased standardized ratios (SMR = 12.20, 4.89). The mean age of death of those having genitourinary organs including cancer was 59 years old, and the latent period between the first exposure and the occurrence of the disease was 19.7 years on average. Non-significant increased risks of cancers of the colon, rectum, liver and lung were observed among the workers exposed to benzidine. Among the 7 histologically confirmed cases of these cancers, there were 2 adenocarcinomas of the lung, 1 adenocarcinoma of the rectum, 2 hepatocellular carcinoma and 1 adenocarcinoma of the bile duct. Seven patients with genitourinary tumors were found to have died of other primary cancers.

2-Naphthylamine↗

[Twenty years' follow-up study of asbestos workers].

This report describes a cohort study conducted on workers who were employed in a factory mainly manufacturing asbestos yarn and cloth and were followed from 1964 to 1981. A total of 208 workers (73 males and 135 females) could be traced and 15 deaths were observed by the end of 1983. Among them, three had lung cancer and its relative risk was 6.8 (p less than 0.05) computed based on the age, sex and year specific death rates of Osaka Prefecture. One case of peritoneal mesothelioma was also found. The period from first asbestos exposure to death of these four cases of asbestos-related malignancies was more than 25 yr. In the analysis of the employees who had more than 1 yr of exposure to asbestos and those who had already been engaged in this factory at the beginning of the observation, the relative risk of lung cancer was 8.1 and 13.6, respectively.

Adult↗

[An epidemiological study of lung cancer among workers exposed to bis(chloromethyl)ether].

An epidemiological study of lung cancer was carried out in two dyestuff factories (Factory K and U), where bis (chloromethyl) ether, BCME, was manufactured and used in the initial process of dyestuff production in Wakayama Prefecture, Japan. BCME was used from 1955 to 1970 in Factory K, and from 1960 to 1968 in Factory U. Subjects were 35 men who had been exposed to BCME in each factory. In this study 13 lung cancer cases were found (including 5 cases reported by Sakabe (Ind Health 1973]. The main results obtained were as follows: 1) The exposure period of 13 lung cancer cases to BCME was 86.9 +/- 34.9 months (mean +/- SD) and the latent period was 13.5 +/- 6.6 yr. The age at death was 46.1 +/- 9.5 yr and 7 cases died between the age of 40 and 49. 2) The initial symptoms of lung cancer due to BCME were not different from those of non-occupational lung cancer. The identified histological types of eight cancer cases were small cell carcinoma in 5 cases, adenocarcinoma in 3 cases and large cell carcinoma in the remaining case. 3) Standardized mortality ratio (SMR) was 23.5 at Factory K and 17.9 at Factory U. An excess death due to lung cancer among workers exposed to BCME was observed. 4) The shortest exposure period of the 13 lung cancer cases was only 23 months and therefore workers who had been exposed to BCME for under 3 yr must be examined for lung cancer periodically.

Adenocarcinoma↗

Electroretinographic changes induced by organophosphorus pesticides in rats.

Electroretinographic changes induced by organophosphorus pesticides (OPs) were studied in rats. Male Wistar rats were intraperitoneally injected with fenthion, chlorpyrifos, fenitrothion, dichlorvos or chlorfenvinphos at doses of 0.01 mmol/kg and/or 0.05 mmol/kg. The electroretinogram (ERG) was recorded at 5 hours and 2 days after the administration, and brain and retinochoroid cholinesterase (ChE) activities was assayed at 3 days after the injections. The brain and retinochoroid ChE activities were reduced in rats treated with the OPs. Notably, the reduction of ChE activities by fenthion, chlorpyrifos and dichlorvos were similar. The administration of OPs induced a change in the ERG, characterized by alteration of the amplitudes of a- and b-waves. Nevertheless the ChE activities in the brain and retinochoroid were inhibited by all of the OPs, the OPs affected the amplitude of ERG differently. Fenthion and chlorpyrifos decreased the amplitudes; dichlorvos and chlorfenvinphos increased; and fenitrothion transiently decreased at 5 hours but increased 2 days after the injection. These results indicate that a factor or factors other than inhibition of ChE activities contributes to the alteration of ERG induced by OPs.

Animals↗

[Effects of combination chemotherapy with topical application of 5-FU ointment to mice's tongue and UFT].

After oral administration of UFT and lingual topical application of 5-FU ointment to normal mice, the change of the concentration of 5-FU and Uracil in the tongue, liver and blood serum were studied. We compared with UFT only group, 5-FU ointment only group and the both combination chemotherapy group. 1. As for the tongue concentrations, 5-FU levels in both combination chemotherapy group and 5-FU ointment only group were higher compared to UFT only group. There was no difference between combination chemotherapy and 5-FU ointment only group. Uracil at 21-days in combination chemotherapy group were higher than others. 2. The liver concentrations of 5-FU at 21-days was significantly higher. 3. The blood serum concentrations of 5-FU in both combination chemotherapy and 5-FU ointment only groups revealed similar results. Thereafter, combination chemotherapy in oral region with topical application of 5-FU ointment and UFT may be effective.

Administration, Oral↗

[Clinical studies on 9 patients with Heberden's nodes of premenopausal onset].

Nine patients with Heberden's nodes of premenopausal onset were studied for complications in the form of thyroid disorders as well as from the hereditary, roentgenological and immunological aspects. In addition, rheumatoid arthritis, psoriatic arthritis, traumatic arthritis, erosive osteoarthritis or adult Still's disease was excluded in these patients. All patients had thyroid disorder (Basedow's disease in 6 patients, Hashimoto's thyroiditis in 2 patients and granular thyroiditis in one patient). Immunological examinations were positive for anti-thyroglobulin antibody in 5 patients and anti-microsome antibody in 3 patients and anti-nuclear antibody in 2 patients. Roentgenological findings revealed no typical signs of primary generalized osteoarthritis.

Adult↗

Development of multiple necrotizing enteritis induced by a tumor necrosis factor-like cytokine from lipopolysaccharide-stimulated peritoneal macrophages in rats.

We report the development of an animal model of multiple necrotizing enteritis (MNE) in rats. When rats were injected directly with a culture supernatant of lipopolysaccharide (LPS)-stimulated rat peritoneal macrophages into the abdominal aorta, the overt pathologic lesions of MNE developed within 30 minutes after injection. The rats showed an elevated level of blood fibrinogen degradation product content even 30 minutes after injection. Furthermore the rats that were pretreated intravenously with heparin sulfate did not develop MNE, indicating the acute disturbances of blood microcirculation in the intestine. Multiple necrotizing enteritis was developed also by the injection with recombinant tumor necrosis factor (rTNF) but rarely was observed with even a high dose of recombinant interleukin-1 (rIL-1) or platelet-activating factor (PAF). The supernatant was cytotoxic in vitro to TNF-susceptible LM and many other cells but was less cytotoxic to the TNF-resistant LR line. Partial purification of the supernatant suggested that the supernatant contained a cytokine that has biochemical features of TNF. Furthermore polyclonal anti-TNF antibody could inhibit not only the cytotoxicity in vitro but also MNE development in vivo by this factor. These data strongly indicate that MNE possibly could be caused by a TNF-like cytokine produced by macrophages that are stimulated by the endotoxin.

Animals↗

[Clinical and pathological evaluations of methotrexate, vinblastine, adriamycin and cisplatin (M-VAC) chemotherapy for advanced urothelial cancers].

Fifteen patients with advanced transitional cell carcinoma of the urothelial tract were treated with methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy. Eleven patients were treated to metastatic lesions after surgical resection of primary cancers. One out of 15 patients died of chemotherapy. Of the remaining 14 patients, CR was achieved in one and PR was achieved in seven, clinically. The response rate was 57.1% and the median response duration was 12.6 months. In the patients who had been resected their primary lesions, the response rate was 70% and the duration was 14.1 months. Six patients, including five PRs and one NC, underwent surgical resection and re-staging of the residual tumors after chemotherapy. Clinical response coincided with pathological one in all 6 cases. Three patients were observed the decrease of the lung metastasis, which rate was more than 90%. Two out of 3 who did not show any invasion into the lymph channels in the resected residual tumors, have been free of a recurrence through-out the course of at 47 or at 42 months. However, another patient with lymph channel invasion died of metastasis of the mediastinal and paraaortic lymph nodes. Regarding the frequency of side effects, it seemed to be no significant difference between full and 80% doses administration. In the effectual cases, the residual tumors should be resected surgically and re-staged pathologically.

Adult↗

Heat- or stress-inducible transformation-associated cell surface antigen on the activated H-ras oncogene-transfected rat fibroblast.

A WKA rat fetus fibroblast (WFB) was transfected by several oncogenes including EJras (activated H-ras), polyoma middle T (PyMT), v-src, c-myc, and adenovirus type 12 E1A-E1B. We analyzed the expression of the transformation-associated cell surface antigens on WFB by developing monoclonal antibodies. One of the WFB transformation-associated cell surface antigens, recognized by monoclonal antibody 067, was constitutively expressed only on two (W31 and W70) of ten WFB-EJras-transformed clones. This antigen could not be detected on parental WFB cells as well as ten WFB-PyMT transformant clones. Furthermore, it was not expressed on several clones of partially transformed WFB-v-src and WFB-adeno E1 transfectants or nontransformed WFB-c-myc transfectants. Monoclonal antibody 067 could form an immunoprecipitate with an approximate molecular weight of 67,000 which was composed of a single polypeptide chain. It was also shown that the expression of this antigen could be enhanced by cyclic AMP or cholera toxin treatment of W31; treated cells also showed a phenotypic reversion to the nonmalignant growth characteristics of the parental WFB. Moreover, the expression of this antigen could be induced on the WFB-EJras transformants such as W14, which do not constitutively express this antigen, by treatment of these agents. Furthermore, the expression of antigen was enhanced by heat and superoxide treatment on W31. These data suggest that the monoclonal antibody 067-defined molecule is a novel transformation-associated cell surface antigen that could be induced by heat shock or other physiological stress.

Animals↗

Urinary metabolite levels in workers handling p-tert-butylphenol as an index of personal exposure.

Occupational exposure to p-tert-butylphenol (PTBP) was studied in a workplace where workers were engaged in packing this alkylphenol in bags or transporting the bags by fork-lift. The geometrical mean of eight-hour-time-weighted-average (8 h-TWA) value for personal ambient PTBP level of the packers was 0.39 mg/m3 (n = 15), higher than that of the carriers (0.10 mg/m3, n = 5). Amounts of PTBP collected in the respirators used by the workers were in proportion to the 8 h-TWA values but lower than the estimated theoretical amounts; considerable amounts of PTBP were assumed to be absorbed through the respiratory tract. The urine excreted during the latter half of the shift showed the highest levels of PTBP (geometrical mean: packer, 5.07 micrograms/ml, n = 20; carrier, 3.03 micrograms/ml, n = 8). When the workers were away from the workplace, PTBP levels decreased; most was excreted within 24 h. Correlation between the urinary PTBP levels and 8 h-TWA values was significant (r = 0.46, n = 19, P less than 0.05), but its extent was weak. The total amounts of urinary PTBP excreted for 24 h after the start of the shift were two to three times higher than the estimated respiratory absorption of PTBP; PTBP was assumed to be absorbed not only through the respiratory tract but also through intact skin. It was concluded that the personal ambient PTBP level is not a suitable index for personal exposure, and biological monitoring via the PTBP level in the urine excreted at the end of the each shift is useful for the evaluation of personal exposure.

Air Pollutants, Occupational↗

[Metabolism and urinary excretion of chlorpyrifos in rats].

Urinary metabolites and biological half-life of chlorpyrifos (O, O-diethyl-O-3,5,6-trichloro-2-pyridinyl phosphorothioate) were investigated. Male Wistar rats weighing 200 g were intraperitoneally injected with chlorpyrifos at a level of 0.2 mmol/kg body weight. Both chlorpyrifos and 3,5,6-trichloro-2-pyridinol (TCP) levels in blood showed maximum values at 5 h post-injection, and then decreased rapidly. Biological half-lives of the blood chlorpyrifos and TCP were estimated to 8.15 and 24.66 h, respectively. Urine was collected for 96 h post-injection and hydrolyzed with 4 N HCl or beta-glucuronidase with sulfatase, and TCP released was determined. Urinary excretion levels of the acid hydrolysis-released TCP and the enzyme hydrolysis-released TCP accounted for 86 and 54% of chlorpyrifos administered, respectively. Urinary excretion levels of alkylphosphate for 96 h post-injection were analyzed. The excretion levels of diethylthiophosphate (DETP) and diethylphosphate (DEP) accounted for 45 and 15% of chlorpyrifos administered, respectively. These results indicate that 1) about half of the chlorpyrifos administered was directly hydrolyzed to DETP and TCP, 2) 10 to 20% was hydrolyzed to DEP and TCP after the oxidation to chlorpyrifos oxon, and 3) about 30% was dealkylated to TCP-phosphate after the oxidation.

Animals↗

[Urinary alkylphosphate levels as an index of exposure to organophosphorus insecticides in pest control operators].

In pest control operations, organophosphorus compounds (OP) have been sprayed as insecticides, blood cholinesterase (ChE) activities and urinary alkylphosphate levels were measured for both OP-sprayers (n = 102) and non-sprayers (n = 35) in pest control companies, and the relationship between the analytical results and spraying conditions was investigated. Plasma ChE activities of the OP-sprayers and of the non-sprayers, as well as blood cell ChE activities of the OP-sprayers, were significantly lower than those of employees of chemical factories who served as controls (n = 103). Urinary alkylphosphates were not detected in the controls at all but were detected in 83% of the sprayers and in 57% of the non-sprayer employees of pest control companies. A significant negative correlation (r = -0.34, n = 137, p less than 0.01) between the plasma ChE activities and urinary total alkylphosphate levels was observed in employees of pest control companies. In the case of the employees whose urinary total alkylphosphate levels were 0.1 mumol/g creatinine or more, the plasma ChE activities were 25% decreased compared to the control group. The OP-sprayers showed significantly higher urinary total alkylphosphate levels than the non-sprayers. The OP-sprayers were further divided into two groups. One was sprayers engaged in both cockroach- or fly-control and termite-control operations (sprayers I, n = 54) and the other was sprayers engaged in only cockroach- or fly-control operations (sprayer II, n = 48).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗