The ability of human gd T cells from healthy donors to kill pancreatic ductal adenocarcinoma (PDAC) in vitro and in vivo in immunocompromised mice requires the addition of gd T-cell-stimulating antigens. In this study, we demonstrate that gd T cells isolated from patients with PDAC tumor infiltrates lyse pancreatic tumor cells after selective stimulation with phosphorylated antigens. We determined the absolute numbers of gd T-cell subsets in patient whole blood and applied a real-time cell analyzer to measure their cytotoxic effector function over prolonged time periods. Because phosphorylated antigens did not optimally enhance gd T-cell cytotoxicity, we designed bispecific antibodies that bind CD3 or Vg9 on gd T cells and Her2/neu (ERBB2) expressed by pancreatic tumor cells. Both antibodies enhanced gd T-cell cytotoxicity with the Her2/Vg9 antibody also selectively enhancing release of granzyme B and perforin. Supporting these observations, adoptive transfer of gd T cells with the Her2/Vg9 antibody reduced growth of pancreatic tumors grafted into SCID-Beige immunocompromised mice. Taken together, our results show how bispecific antibodies that selectively recruit gd T cells to tumor antigens expressed by cancer cells illustrate the tractable use of endogenous gd T cells for immunotherapy.

Biologically active corticotrophin-releasing-hormone (CRH) is produced by the placenta in large amounts and can be measured in the maternal circulation during third trimester of pregnancy. Its physiological significance is unknown. To further investigate the action of CRH in pregnancy, we performed a standard CRH-test (1 micrograms/kg synthetic human CRH) in seven pregnant women 1 week prior to their calculated delivery data and 4-5 weeks post-partum. No response of plasma ACTH to CRH administration could be measured in any of the third trimester pregnant women. Post-partum, basal ACTH levels were significantly lower (1.6 +/- 0.3 vs 5.3 +/- 0.2 pmol/l) and reacted promptly to CRH administration (1.6 +/- 0.3-4.2 +/- 0.5 pmol/l; P less than 0.05). Concentration of cortisol in plasma and salivary cortisol paralleled the ACTH response to administration of CRH. However, one pregnant woman experienced physical and emotional stress during the CRH-test and reacted with a sharp rise in cortisol secretion. The lack of the ACTH and cortisol response in this study to exogenously administered CRH in third trimester pregnancy may be due to high circulating glucocorticoid concentrations, desensitization of the pituitary corticotroph and/or in part due to circulating specific CRH-carrier protein.

Short rib-polydactyly syndrome (SRPS; types I–IV) is an autosomal recessive, lethal skeletal dysplasia characterized by short-limb dysplasia, narrow thorax, and polydactyly. This syndrome is invariable and can be detected by 2-trimester ultrasound. The underlying gene has not been discovered yet. We report a case of SRPS subtype III Verma-Naumoff-Le Marec that was sonographically detected at 20 weeks’ gestation and compare prenatal ultrasound with postmortem findings from pathology and radiology. Since the risk of recurrence is 25%, early ultrasound for consecutive pregnancies was advised and performed at 11+6 weeks’ gestation in the following pregnancy without any findings. Ultrasound diagnosis in this rare case of SRPS is a valuable tool for identification and early management, since there are no specific biochemical or histopathological markers for this syndrome. Radiological and pathological findings confirmed SRPS type III and assisted in the differential diagnosis of the subtype.

The aim of our work was to study the specificity of MRI in comparison with transvaginal US for differentiation of malignant from benign adnexal lesions. A total of 67 patients with clinically suspicious adnexal lesions were evaluated by MRI. Transaxial and coronal images were acquired using T1-weighted sequences before and following IV contrast and T2-weighted sequences. In all patients transvaginal ultrasound examinations (TVUS) were performed. For both imaging modalities each lesion was classified separately as either benign or malignant according to previously published criteria. Pathologic findings were available in 65 cases. Both MRI and TVUS correctly classified the 12 malignant lesions (sensitivity 100 %). Specificity (MRI: 78.2 %, TVUS: 65.5 %) and accuracy (MRI: 82 %, TVUS: 71.6 %) were higher with MRI than with TVUS, but differences were statistically not significant (p = 0.18 and p = 0.20, chi-square test). There was agreement/disagreement between findings of MRI and US in 52/15 lesions. The macroscopic criteria for malignancy are unspecific and result in a limitation of the specificity of both MRI and TVUS. The MRI technique is a valuable adjunct to TVUS by enabling further clarification of adnexal tumors with equivocal complex or solid vaginal sonographic findings.