A murine monoclonal antibody, m357, showing the highly neutralizing activities for human tumor necrosis factor (TNF-α) was chosen to be humanized by a variable domain resurfacing approach. The non-conserved surface residues in the framework regions of both the heavy and light chain variable regions were identified via a molecular modeling of m357 built by computer-assisted homology modeling. By replacing these critical surface residues with the human counterparts, a humanized version, h357, was generated. The humanized h357 IgG1 was then stably expressed in a mammalian cell line and the purified antibody maintained the high antigen binding affinity as compared with the parental m357 based on a soluble TNF-α neutralization bioassay. Furthermore, h357 IgG1 possesses the ability to mediate antibody-dependent cell-mediated cytotoxicity and complement dependent cytotoxicity upon binding to cells bearing the transmembrane form of TNF-α. In a mouse model of collagen antibody-induced arthritis, h357 IgG significantly inhibited disease progression by intra-peritoneal injection of 50 µg/mouse once-daily for 9 consecutive days. These results provided a basis for the development of h357 IgG as therapeutic use.

Background:The offspring of women with gestational diabetes mellitus (GDM) are prone to macrosomia. However, birth weight is difficult to be correctly estimated by ultrasound because of fetal asymmetric growth characteristics. This study aimed to investigate the correlations between fetal hemodynamics, fetal growth indices in late pregnancy, and birth weight in GDM.Methods:A total of 147 women with GDM and 124 normal controls (NC) were enrolled in this study. Fetal hemodynamic indices, including the systolic/diastolic ratio (S/D), resistance index (RI), pulsatility index (PI) of umbilical artery (UA), middle cerebral artery (MCA), and renal artery (RA), were collected. Fetal growth indices, including biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length, were also measured by ultrasound. Birth weight, newborn gender, and maternal clinical data were collected.Results:The independent samples t-test showed that BPD, HC, and AC were larger in GDM than in NC (P < 0.05). Fetal hemodynamic indices of the UA and MCA were lower (P < 0.05), but those of the RA were higher (P < 0.001) in GDM than in NC. Birth weight was higher in GDM than in NC (P < 0.001). Pearson's correlation analysis showed that hemodynamic indices of the UA were negatively correlated with birth weight, BPD, HC, and AC in both groups (P < 0.05). MCA (S/D, PI, and RI) was negatively correlated with birth weight, HC, and AC in GDM (r = −0.164, −0.206, −0.200, −0.226, −0.189, −0.179, −0.196, −0.177, and − 0.172, respectively, P < 0.05), but there were no correlations in NC (P > 0.05). RA (S/D, PI, and RI) was positively correlated with birth weight in GDM (r = 0.168, 0.207, and 0.184, respectively, P < 0.05), but there were no correlations in NC (P > 0.05).Conclusion:Fetal hemodynamic indices in late pregnancy might be helpful for estimating newborn birth weight in women with GDM.

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