Chronic toxicity of methylmercury chloride in rats: clinical study and chemical analysis.
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Biomedical subjects
Publications and source records attributed to S Goto.
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In order to clarify the relationship between exposure to hard metal dust containing cobalt and bronchopulmonary diseases, cross-sectional medical and occupational hygienic investigations were conducted in a hard metal tool manufacturing factory. As a part of the environmental investigation, general air concentrations and personal exposure to both total dust and cobalt dust were measured. The highest total dust and cobalt concentrations in general atmosphere and personal samples were found in a powder handling room among all departments. The highest personal exposure concentration of cobalt was 1.29 mg/m3 (arithmetic mean value) in the dry grinder using diamond wheels. Powder handlers were exposed to cobalt 0.56 mg/m3, press operators to 0.66 mg/m3, shapers to 0.19 mg/m3, wet grinders to 0.07 mg/m3, and sintering workers to 0.03 mg/m3. In Japan TLV for cobalt has not yet been established. Dust exposure measurement should be carried out in all hard metal industries. TLV for cobalt is discussed by means of literature.
An effective method for removing leukocytes and platelets from red blood cell concentrates (RBC) reconstituted with phosphate buffer solution was investigated in vitro. Reconstituted RBC were warmed at 37 degrees C for 1 hr. Neither leukocyte count nor platelet count was decreased by the treatment. When compared with whole blood, leukocytes present in the fractions below the buffy coat layer were significantly less than those of whole blood, while the distribution of platelets in reconstituted RBC was unchanged. It is suggested that the reduction of leukocytes in red blood cells below the buffy coat layer may contribute to the preparation of RBC with a poor leukocyte.
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The protective effect of an immunoactive peptide, D-lactoyl-L-alanyl-gamma-D-glutamyl-(L)-meso-diaminopimelyl-(L)-glycine (FK-156) and a related compound, heptanoyl-gamma-D-glutamyl-(L)-meso-diaminopimelyl-(D)-alanine (FK-565) was determined in mice with various kinds of microbial infections. FK-156 and FK-565 were given to mice either subcutaneously or orally before challenge. The drugs enhanced significantly the defense of mice against acute systemic infections induced by various extracellular and facultative intracellular organisms, and subcutaneous abscess by Staphylococcus aureus. The protective effect of these drugs against Escherichia coli infection differed considerably depending on the route of administration; FK-156 was only effective by the parenteral route; however, FK-565 was effective by both parenteral and oral routes. After subcutaneous dosing with FK-156, the enhancement of host defense of mice against E. coli infection was more rapid than against Listeria infection. The enhancing effects of FK-156 and FK-565 on host defense of mice against pseudomonal infection was more potent than other immunoactive drugs.
The immunoactive peptides, FK-156 and its analogue, FK-565 were evaluated in various models of mice immunosuppressed with cyclophosphamide, hydrocortisone, mitomycin C, carrageenan and tumor cells. Treatment with FK-156 (subcutaneous) and FK-565 (oral) markedly restored host defense ability against microbial infection. The therapeutic effect of ticarcillin or gentamicin alone against pseudomonal infection in cyclophosphamide- and hydrocortisone-treated mice and tumor-bearing mice was much lower than in normal mice. The therapeutic effect of these antibiotics against pseudomonal infection in immunosuppressed mice was enhanced markedly by combined use with FK-156. The killing ability of macrophages and polymorphonuclear leukocytes of the immunosuppressed mice was also markedly enhanced by dosing with FK-156.
We investigated the effect of immunoactive peptides, FK-156 and FK-565 on host defense mechanisms against microbial invasion. It was shown that these drugs given to normal mice increased the counts of phagocytes in both peripheral blood and peritoneal cavity, and enhanced the chemotactic, phagocytic and killing activities of peritoneal macrophages and polymorphonuclear leukocytes, and stimulated the phagocytic function of the reticuloendothelial system. Enhanced host resistance to microbial infection by these immunoactive peptides might be induced by both increase in counts and enhancement of functions of phagocytes. FK-156 restored decreased counts and functions of phagocytes in mice immunosuppressed by cyclophosphamide, hydrocortisone or tumor. These findings suggest that these immunoactive peptides could be applied to prevent intractable infection in immunocompromised hosts.
A 73-year-old male was admitted with suspected Grawitz tumor. Aspiration cytology from the tumor was diagnosed as Class V with suspected sarcoma. He died 17 days after admission. Autopsy revealed this to be a massive hepatic tumor occupying over half of the right lobe. It showed protrusion into the right retroperitoneum. Histology of the tumor evidenced widespread proliferation of sarcoma-like neoplastic cells besides a minute area of definite liver cell carcinoma in the center of the tumor mass. Definite transitional features between liver cell carcinoma and a sarcomatous pattern, the latter involving a major part of this tumor, were noted. Thus, we diagnosed this tumor to be liver cell carcinoma with a sarcoma-like histological pattern. The possibility of collision tumor or carcinosarcoma could be ruled out.
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We report usefulness of early movements for evaluating the functional development of human fetuses. The movements were classified into seven patterns and named as follows; "rippling", "small twitch", "twitch", "strong twitch", "float", "swim", and "jump". Relationship between classification and the menstrual age, or the distribution of crown-rump length are presented. The results indicate that the characteristic fetal movements are "rippling" at 8 weeks, "small twitch" around 9 weeks, "twitch" at the beginning of 9 weeks, "strong twitch" at 9 1/2 weeks, "float", "swim", and "jump" at 10 weeks or later.
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A simple and sensitive method was developed for detection of antibodies to histones using a modification of the enzyme-linked immunosorbent assay (ELISA) for antibodies to nucleic acids. The antigens used for antibody assay were poly(ADP-ribose), left-handed Z-DNA, double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), and calf thymus histones. These five antigen-antibody systems were used to examine the antibodies in patients with systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS). A positive correlation was found between the antibody titers in patients with PSS. However, weak correlation was found between the titers of antibodies to these nuclear antigens in the SLE patients, except for correlations between the titers of antibodies to left-handed Z-DNA and histones, and those to ssDNA and dsDNA. From these data, it is suggested that presentation of modified chromatin to immune systems is involved in antinuclear antibody formation in PSS patients, whereas spontaneous expansion of clones for antinuclear antibodies may occur in SLE patients under certain conditions.
Using the technique of somatic cell fusion, monoclonal antibodies to human chorionic gonadotropin (hCG) and its beta-subunit were produced. Spleen cells from immunized mice were fused with the myeloma line NS-1 using 50% polyethylene glycol and cultured in a selection medium. A sensitive enzyme immunoassay was performed for antibody screening using immobilized solid-phase antigen and anti-mouse IgG Fab' (rabbit)-beta-D-galactosidase complex. Three double-cloned hybridomas (named 4H10, 4G2 and 1D12) were obtained. Anti-hCG 4H10 antibody reacted with hCG, the alpha-subunit of hCG (alpha-hCG) and human luteinizing hormone (hLH); and anti-hCG 4G2 antibody reacted with hCG and the beta-subunit of hCG (beta-hCG). It was interesting that anti-beta-hCG 1D12 antibody had the capacity to bind with free beta-hCG but not with intact hCG, which suggests that the 1D12 antibody can recognize a determinant site that is unique to beta-hCG. This unique epitope in beta-hCG might be expressed in or near a part which is hidden in the intact hCG molecule which is composed of alpha- and beta-subunits.
Methotrexate (MTX) was covalently bound to rabbit antibodies (IgG) against hCG and placental alkaline phosphatase (PLALP) by two different methods. By carbodiimide method, 16.9 mols of MTX could be coupled to one mol of IgG, but the antibody activity was completely lost. Whereas, 2.6-3.4 mols of MTX were bound to one mol of IgG and a quarter of original antibody activity was preserved by dextran bridge method. Choriocarcinoma cells BeWo and SCH were exposed to the IgG-MTX conjugates prepared by the latter method for 30 minutes, and the cell growth was investigated. To BeWo, which produces much hCG and less PLALP, anti hCG-IgG-MTX showed a considerable growth inhibition compared to the control groups (p less than 0.05). No effect was observed with anti PLALP-IgG-MTX, nonimmunized IgG-MTX, free MTX and anti hCG-IgG. In contrast, to SCH, which produces much PLALP and less hCG, anti PLALP-IgG-MTX exhibited considerable inhibition (p less than 0.05), whereas anti hCG-IgG-MTX showed no inhibition. Neither anti hCG-IgG-MTX nor anti PLALP-IgG-MTX showed any effect to the endometrial carcinoma cell HEC50B. We concluded that MTX bound to anti hCG-IgG and anti PLALP-IgG have specific growth inhibition effects to the choriocarcinoma cells in vitro, and suggested the possibility of specific immunochemotherapy of this disease.
One hundred and sixty-five patients of choriocarcinoma were treated during the period from 1957 to 1979. Pulmonary metastases were found in 111 of the 165 patients. The authors found that surgical intervention for pulmonary metastasis was an extremely effective means for the patients who were not cured by chemotherapy and satisfied the criteria that we newly established for surgery. All patients satisfied the criteria achieved primary complete remission and their three years survival rate was 80%. The timing for surgery was also discussed and it was concluded that pulmonary surgery should be adopted when patient's urinary hCG values persisted at the level below 1000 iu/l for 70-80 days period.
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