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61.
An Immunotoxicological Evaluation of 4,4'-Thiobis-(6-t-butyl-m77-cresol)in Female B6C3F1 Mice. 1. Body and Organ Weights, Hematology,Serum Chemistries, Bone Marrow Cellularity, and Hepatic MicrosomalParameters. MUNSON, A. E., WHITE, K. L., JR., BARNES, D. W.,MUS-GROVE, D. L., LYSY, H. H., AND HOLSAPPLE, M. P. (1988).Fundam. Appl. Toxicol. 10, 691–700. Adult female B6C3F1mice were gavaged with 4,4'-thiobis-(6-t-butyl-m-cresol) (TBBC)in corn oil at doses of 10, 100, or 200 mg/kg daily for 14 consecutivedays. There was no overt toxicity, as manifested by grosslyobservable behavioral changes, decreased growth rate over theexposure period, or mortality. There were also no marked effectson serum chemistries or hematology, with the exception of asignificant increase (41%) in the number of leukocytes at thehighest dose. Absolute differential counts indicated that significantincreases occurred in the number of lymphocytes (31%) and neutrophils(177%). Studies with bone marrow indicated a significant 30%increase in the number of cells/femur from animals treated withthe highest dose of TBBC. The number of macrophage progenitors(CFU-M)/femur was significantly increased by 28%, while thenumber of granulocyte-monocyte progenitors (CFU-GM)/femur wasnonsig-nificantly increased by 20% in the high dose animals.The weight of both the spleen and liver was increased in a dose-relatedfashion, although the histopathology of the spleen of TBBC-treatedmice was not different from control. The livers of mice receivingthe high dose showed mild focal hydropic degeneration, mildhepatitis, and a slight increase in the number of Kupffer cells.No other organs were affected. Liver microsomal protein andcytochrome P-450 levels were increased in a dose-related fashion.Enzyme activities of aminopyrine demethylase and aniline hydroxylase,but not arylhydrocarbon hydroxylase, were also increased ina dose-related fashion.  相似文献   
62.
The mortality experienced by a cohort of 10,491 United Kingdom steel foundry workers during the period 1946-85 has been investigated. These workers were all male operatives first employed in any one of the 10 participating foundries in 1946-65; all had worked in the industry for a minimum period of one year. Compared with the general population of England and Wales, statistically significant excesses relating to cancer mortality were found for cancer of the stomach (E = 77.4, O = 106, SMR = 137) and cancer of the lung (E = 229.2, O = 441, SMR = 147). A statistically significant deficit was found for cancer of the brain (E = 19.4, O = 10, SMR = 51). Involvement of occupational exposures was assessed by the method of regression models and life tables (RMLT). This method was used to compare the duration of employment in the industry, in "dust exposed" jobs, in "fume exposed" jobs, in foundry area jobs, in fettling shop jobs, and in foundry area or fettling shop jobs, of those dying from cancers of the stomach and lung with those of all matching survivors. The RMLT analyses provided evidence of an occupational involvement in the risk of death from lung cancer from work in the foundry area or fettling shop, and weaker evidence of an occupational involvement in the risk of death from stomach cancer from work in the foundry area.  相似文献   
63.
The mortality experienced by a cohort of 10,491 United Kingdom steel foundry workers during the period 1946-85 has been investigated. These workers were all male operatives first employed in any one of the 10 participating foundries in 1946-65; all had worked in the industry for a minimum period of one year. Compared with the general population of England and Wales, statistically significant excesses relating to cancer mortality were found for cancer of the stomach (E = 77.4, O = 106, SMR = 137) and cancer of the lung (E = 229.2, O = 441, SMR = 147). A statistically significant deficit was found for cancer of the brain (E = 19.4, O = 10, SMR = 51). Involvement of occupational exposures was assessed by the method of regression models and life tables (RMLT). This method was used to compare the duration of employment in the industry, in "dust exposed" jobs, in "fume exposed" jobs, in foundry area jobs, in fettling shop jobs, and in foundry area or fettling shop jobs, of those dying from cancers of the stomach and lung with those of all matching survivors. The RMLT analyses provided evidence of an occupational involvement in the risk of death from lung cancer from work in the foundry area or fettling shop, and weaker evidence of an occupational involvement in the risk of death from stomach cancer from work in the foundry area.  相似文献   
64.
Immunotoxicity of the Semiconductor Gallium Arsenide in Female B6C3F1 Mice   总被引:1,自引:1,他引:0  
The effects of gallium arsenide (GaAs) exposure on immunocompetenceof B6C3F1 female mice were investigated. GaAs was administeredas a single intratracheal instillation at doses of 50, 100,and 200 mg/kg. Fourteen days after exposure, various cellularand humoral immune parameters were assessed. GaAs exposure increasedspleen cellularity in a dose-dependent manner. However, thepercentages of Thy 1.2 positive and 1g positive cells were decreasedand that of F4/80 positive cells was increased dose dependency.The IgM and IgG antibody-forming cell response of the spleento the T-dependent antigen sheep erythrocytes was reduced by66 and 48%, respectively, at 200 mg/kg. Levels of the serumcomplement protein, C3, were increased by as much as 16% withno significant change in CH50 levels. The mitogenic responseof splenic T cells to Con A and PHA was unaffected by GaAs,but that of B cells to LPS was increased by 52%. The delayedhypersensitivity response to keyhole limpet hemocyanin and mixedlymphocyte response were significantly reduced in a dose-dependentmanner by GaAs exposure. Natural killer cell activity againstthe YAC-1 mouse lymphoma was enhanced in treated mice. Analysisof peritoneal exudate cells (PEC) revealed a dose-dependentdecrease in number and a shift in the composition of PECs. Thepercentage of PEC monocytes increased from 53% of the populationto 81%, while the lymphocytes decreased from 46 to 20%. Theadherent PEC population demonstrated decreased phagocytosisof covaspheres and increased phagocytosis of chicken erythrocytes(CRBC). GaAs exposure had no effect on host resistance to Plasmodiumyoelii or Streptococcus pneumoniae, but dose dependency increasedresistance of the mouse to Listeria monocytogenes Treated micedemonstrated a significantly decreased resistance to the B16F10melanoma with a sevenfold increase in tumor burden at 200 mg/kg.GaAs affects both humoral and cellular immune parameters inmice and impairs the ability of the immune system to protectagainst B16F10 tumor challenge.  相似文献   
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67.
The Second International Nonhuman Primate Histocompatibility Workshop permitted comparison of rhesus monkey alloantisera developd in various laboratories on a single common panel of related and unrelated monkeys. Analysis of the data permits the conclusion that at least nine specificities are recognized by more than one laboratory, including six at the first locus and three at the second locus.  相似文献   
68.
Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.   相似文献   
69.
Summary The structure of myosin filaments isolated from skinned toad stomach smooth muscle cells has been examined by electron microscopy as a step toward identifying thein vivo structure. When negatively stained following exposure to relaxing conditions, the filaments exhibited a continuous 14-nm axial repeat of crossbridge projections with no central bare zone. The filaments thus differed from the bipolar filaments found in striated muscle and displayed instead features resembling side-polar and mixed-polarity filament models. By rotation of isolated filaments around their longitudinal axes it was found that cross bridges occurred only along two sides of the filament, an arrangement consistent with the side-polar but not the mixed-polarity model. The polarity is thus similar to that proposed for ribbons (Small & Squire,J. molec. Biol. 67, (1972) 17–149) and for synthetic smooth muscle myosin filaments (Craig and Megerman,J. Cell Biol. 75, (1977) 990–996); their appearance in cross-section, however, shows that these structures are filaments (i.e. with two axes of similar dimensions) and not broad ribbons. As the filaments were derived directly from skinned cells which contracted and relaxed in response to physiological levels of MgATP and Ca2+ at rates comparable to those of native, isolated cells, this unusual arrangement of cross bridges appears to be an effective, functional form of myosin in the contractile apparatus. Side-polar filaments therefore merit consideration as plausible candidates for the native organization of myosin in vertebrate smooth muscle cells.  相似文献   
70.
The Gm-Pi linkage heterogeneity in view of Pi M subtypes   总被引:1,自引:3,他引:1  
In this study linkage between the loci for Gm (γ-type heavy-chain immunoglobulin markers) and Pi (α1-antitrypsin/α1-protease inhibitor) has been shown in families segregating for the Pi M subtypes (Ml, M2, M3 and Msal) as identified by separator isoelectric focusing. The estimate for the Gm-Pi (M-type) recombination is 0-29 (95% limits 0-24-O37) at a peak lod score of 4-31 and with no sex difference. This value is not significantly different from updated recombination frequency estimates for Gm-Pi in Pi MS (0-26) and Pi MZ, SZ and FZ families (0 21). The overall Gm-Pi recombination fraction estimate of 0 26 (95 % limits O23-0-30) at a peak lod score of 20-75 must now be considered as solid. There is a significant heterogeneity within the male Pi MZ families in that the new Finnish families show a higher recombination between Gm and Pi. There is also a possible segregation distortion (Z:M = 23:8). The heterogeneity is discussed in terms of haplotypes, the behaviour of which could be determined by linked genes or chromosomal rearrangements. The possibility that the α1-antitrypsin level influences recombination frequency has not been ruled out, but cannot explain the heterogeneity within Pi MZ families.  相似文献   
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