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Acrylamide (AA) is an important industrial chemical used mainly in the production of polymers. It can be absorbed through the skin. AA was shown to be a germ cell clastogen that entails a genetic risk for exposed workers. The genetic risk calculation was based on mouse heritable translocation test data obtained after acute intraperitoneal (ip) exposure (Adler et al., 1994). To obtain a correction factor between ip and dermal exposure, dominant lethal and heritable translocation tests were carried out with dermal exposure of male mice to AA. In the dominant lethal test, male (102/El × C3H/El)F1 mice were exposed by dermal application to the shaved backs of 50 mg/kg AA per day on five consecutive days or to five daily ip injections of 50 mg/kg AA. One day after the end of exposure, the males were mated to untreated females of the same hybrid stock for four days and females were changed every four days for a total of five matings. Dominant lethal effects were found during matings 1–3. For ip exposure, these values were 81.7, 85.7 and 45.4%, respectively; for dermal exposure the corresponding values were 22.1, 30.6 and 16.5%, respectively. In the heritable translocation assay, male C3H/El mice were treated with five dermal exposures of 50 mg/kg AA and mated 1.5–8.5 days after the end of exposure to untreated female 102/El mice. Pregnant females were allowed to come to term and all offspring were raised to maturity. Translocation carriers among the F1 progeny were selected by a sequential fertility testing and cytogenetic analysis including G-band karyotyping and M-FISH. A total of 475 offspring were screened and 41 translocation carriers were identified. The observed translocation frequency after dermal exposure was 8.6% as compared to 21.9% after similar ip exposure (Adler, 1990). The calculated ratio of ip vs. dermal exposure of 0.39 can be applied to obtain a more realistic calculation of genetic risk for dermally exposed workers. Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In this study, we describe the ability of hybrid mouse monoclonal antibody (mAb) to induce monocyte-mediated cytotoxicity towards human IgA1-coated E (HuIgAl-E), and the effect of mAb binding valency on FcγRI-mediated ADCC. All hybrid monospecific (ms) anti-HulgAl and bispecific (bs) anti-HuIgA1/HRP mAb were capable of inducing monocyte-mediated lysis of HuIgAl-E, in spite of differences in mAb densities essential for optimal lysis. The cytotoxicity induced by hybrid mAb which consist of one or more mlgG2a H chains was predominantly mediated via FcγRI, as shown by inhibition studies on monocytes with FcγRI-blocking mAb TB-3 (≈80% inhibition). However, partial inhibition of mtgGl-2a and mlgG2a-2b-induced cytotoxicity (20-50%) was observed by using FcγRll-blocking mAb IV.3 or CIKM5. For hybrid mIgGl-l mAb the opposite was true; the cytotoxicity was predominantly mediated via FcαRlI (70-80%) and less via FcγRl (20-30%). Comparing the hybrid ms anti-HulgA 1 mAb-induced cytotoxicity with the cytotoxicity induced by hybrid bs anti-HuIgAl/HRP mAb of the same isotype, we observed a decrease in cytotoxicity towards HuIgAl-E sensitized with univalently bound bs anti-HuIgAl/HRP mAb. This decrease was only found for FcγRI-mediated ADCC (mlgG2ae2a, mlgGl -2a and mIgG2a-2b). This diminished recognition of univalently bound IgG relative to bivalently bound IgC by FcγRI was also observed with U937 effector cells. In conclusion, this work shows that hybrid mAb are able to induce monocyte-mediated cytotoxicity towards E-HuIgA1 and that there appears to be an effect of Ag-IgG binding valency on FcγRI-mediated cytotoxicity. [ABSTRACT FROM AUTHOR]

Study Design: Diffusion tensor magnetic resonance imaging (DT-MRI) reconstruction of lumbar erector spinae (ES) compared with cadaver dissection., Objective: The aim of this study was to reconstruct the human lumbar ES from in vivo DT-MRI measurements and to compare the results with literature and cadaver dissection., Summary of Background Data: DT-MRI enables 3-dimensional in vivo reconstruction of muscle architecture. Insight in ES architecture may improve the understanding of low back function. Furthermore, DT-MRI reconstructions allow individualized biomechanical modeling, which may serve as a clinical tool in injury evaluation and in improvement of understanding of pathologies like scoliosis., Materials and Methods: The lumbar spine of 1 healthy male volunteer was scanned using a 3.0 T clinical MRI scanner. MRI data acquisition consisted of 3 parts: (1) high-resolution T1-weighted turbo spin echo for anatomical reference; (2) DT-MRI measurements for fiber tractography; (3) dual echo gradient echo sequence for signal correction purposes. After processing, DT-MRI data were exported to a custom-built software program for fiber tractography. The resulting reconstructions were anatomically validated by comparison with cadaver dissection and literature., Results: DT-MRI reconstruction of 4 parts of the lumbar ES (thoracic part of iliocostalis lumborum, lumbar part of iliocostalis lumborum, thoracic part of longissimus thoracis, and lumbar part of longissimus thoracis) adequately reflected its complex geometry. Some inaccuracies were found in reconstruction details. DT-MRI reconstructions were generally in agreement with anatomical descriptions from literature and with findings in a dissected cadaver specimen., Conclusions: DT-MRI enables anatomically valid reconstruction of ES architecture. However, for reliable reconstruction of the smallest fascicles and attachments a higher resolution or application of higher-order models is needed. Reconstructions can be used as input for estimation of muscle architecture parameters in individualized biomechanical modeling. Such models are promising as a tool in clinical evaluation and in research of low back pain mechanisms.

Background: There is a lack of standardized mobility measures specific to the long-term care (LTC) population. Therefore, the Continuing Care Activity Measure (CCAM) was developed., Objective: This study determined levels of reliability, validity for clinical utilization, and sensitivity to change of this measure., Design: This was a prospective longitudinal cohort study among elderly people with primarily physical or medical impairments who were residing in LTC institutions that provide nursing home and more-complex care, with access to physical therapy services., Method: The CCAM, the Clinical Outcome Variables Scale (COVS), the Social Engagement Scale (SES) of the Resident Assessment Instrument-Minimum Data Set (RAI-MDS) 2.0 instrument, and the Resource Utilization Groups, version 3, (RUG-III) were administered by clinical and research physical therapists, with timing dictated by the study purpose., Results: The participants were 136 residents of LTC institutions and 21 physical therapists. The CCAM interrater reliability (intraclass correlation coefficient [ICC]) was .97 (95% confidence interval=.91-1.00), and test-retest reliability (ICC) over a period of 1 week was .99 (95% confidence interval=.93-1.00). Over 6 months, the absolute change in total score was 5.88 for the CCAM and 4.26 for the COVS; the CCAM was 28% more responsive across all participants (n=105) and 68% more responsive for those scoring in the lower half (n=49). The minimal detectable difference of the CCAM was 8.6 across all participants. The CCAM correlated with the COVS, nursing care hours inferred from the RUG-III, and the SES., Limitations: Some participants were lost to follow-up., Conclusions: The CCAM is a reliable and valid tool to measure gross motor function and physical mobility for elderly people in LTC institutions. It discriminates among functional levels, measures individual functional change, and can contribute to clinical decision making.

In this study, we describe the ability of hybrid mouse monoclonal antibody (mAb) to induce monocyte-mediated cytotoxicity towards human IgA1-coated E (HuIgA1-E), and the effect of mAb binding valency on Fc gamma RI-mediated ADCC. All hybrid monospecific (ms) anti-HuIgA1 and bispecific (bs) anti-HuIgA1/HRP mAb were capable of inducing monocyte-mediated lysis of HuIgA1-E, in spite of differences in mAb densities essential for optimal lysis. The cytotoxicity induced by hybrid mAb which consist of one or more mIgG2a H chains was predominantly mediated via Fc gamma RI, as shown by inhibition studies on monocytes with Fc gamma RI-blocking mAb TB-3 (approximately 80% inhibition). However, partial inhibition of mIgG1-2a and mIgG2a-2b-induced cytotoxicity (20-50%) was observed by using Fc gamma RII-blocking mAb IV.3 or CIKM5. For hybrid mIgG1-1 mAb the opposite was true; the cytotoxicity was predominantly mediated via Fc gamma RII (70-80%) and less via Fc gamma RI (20-30%). Comparing the hybrid ms anti-HuIgA1 mAb-induced cytotoxicity with the cytotoxicity induced by hybrid bs anti-HuIgA1/HRP mAb of the same isotype, we observed a decrease in cytotoxicity towards HuIgA1-E sensitized with univalently bound bs anti-HuIgA1/HRP mAb. This decrease was only found for Fc gamma RI-mediated ADCC (mIgG2a-2a, mIgG1-2a and mIgG2a-2b). This diminished recognition of univalently bound IgG relative to bivalently bound IgG by Fc gamma RI was also observed with U937 effector cells. In conclusion, this work shows that hybrid mAb are able to induce monocyte-mediated cytotoxicity towards E-HuIgA1 and that there appears to be an effect of Ag-IgG binding valency on Fc gamma RI-mediated cytotoxicity.

We studied the interaction of bispecific mouse mAb with human IgG Fc receptors, and assessed their ability to activate the monocytic cell line U937. Binding of monomeric hybrid anti-HuIgA1/HRP mAb to the high-affinity IgG receptor, Fc gamma RI, on U937 cells was only observed when mAb with one or more mIgG2a H chains (hybrid mIgG1-2a, mIgG2a-2b, and mIgG2a-2a) were used. These Fc gamma RI-bound hybrid mAb were capable of enhancing the internal free cytosolic Ca2+ concentration ([Ca2+]i) in U937 cells only when bound mIgG were cross-linked using F(ab')2 fragments of goat anti-mIg antibody. A hybrid mIgG1-2a mAb were cross-linked using goat anti-mIgG1 antibody, showing that the hybrid mAb themselves mediate the induction of Ca2+ increase. Remarkably, anti-Fc gamma RII mAb IV.3 was able to inhibit the Ca2+ increase induced via mIgG2a-1 or mIgG1-2a hybrid mAb completely, despite the fact that we could not detect any effect of IV.3 on binding of monomeric hybrid mIgG1-2a or mIgG2a-1 mAb to U937. The hybrid mAb were also able to induce lysis of HuIgA1-coated E using U937 effector cells. This lysis was completely inhibited by preincubation of U937 cells with mIgG2a mAb TB-3, which blocks Fc gamma RI via its Fc-part ("Kurlander phenomenon"). In contrast, Fc gamma RII-blocking mAb IV.3 and CIKM5 caused a significant enhancement of the antibody-dependent cellular cytotoxicity (ADCC) activity mediated by hybrid mIgG1-2a and mIgG2a-2b mAb. This enhancement did not occur when the parental anti-HuIgA1/2a or the hybrid anti-HuIgA1/HRP/2a-2a mAb were evaluated for ADCC activity. These findings suggest that hybrid mAb not only can bind to Fc gamma RI, but can mediate functional activation of myeloid cells. Given the effect of mAb IV.3 on [Ca2+]i changes and ADCC triggered through IgG1-2a mAb, we suggest that Fc gamma RII may have a role in the regulation of Fc gamma RI-triggered functions or signaling.