Effects of oxytocin microinjected into the central amygdaloid nucleus and bed nucleus of stria terminalis on maternal aggressive behavior in rats

The central effect of oxytocin (OT) on the aggressive behavior of lactating rats was studied. Female rats are more aggressive than nonlactating resident females, vigorously attacking conspecific intruder male or females. This behavior is considered important for pup protection against infanticide. The present work aimed to test the effects on maternal aggressive behavior of OT infused into the central amygdaloid nucleus (CeM) or bed nucleus of stria terminalis (BNST). The surgeries for bilateral cannula implantation were performed between the 2nd and 4th postpartum day. Three days after the surgery, saline or OT was infused and 5 min later a male intruder was placed in the home-cage and the behaviors were videotaped for 10 min. The frequency of the aggressive behaviors and the duration of locomotion during the aggressive behavior test were measured. The latency to retrieve the pups was also evaluated. The results showed that OT injected into CeM (10 and 20 ng/nucleus) decreased frequency of biting and frontal attack while in the BNST (10 and 20 ng/nucleus) decreased the frequency of biting. No significant change on retrieval activity was detected. OT in CeM and BNST has an inhibitory effect on the aggressive behavior of lactating female rats.     

Transmission of human cytomegalovirus from infected uterine microvascular endothelial cells to differentiating/invasive placental cytotrophoblasts

Analysis of placentas infected with human cytomegalovirus (CMV) suggested that viral transmission could involve differentiating/invasive cytotrophoblasts in villi that attach the placenta to the uterine wall. To parse the cellular components in this process, we developed a coculture system of polarized uterine microvascular endothelial cell (UtMVEC) infection with an endothelial cell-tropic pathogenic strain of CMV. Then we evaluated the potential role of neutrophils and endothelial cells in the spread of infection to differentiating cytotrophoblasts. As shown by immunocytochemistry and analysis of viral replication, CMV preferentially infected endothelial cells via apical membranes and disrupted cell junction proteins, thereby altering paracellular permeability and cell polarity. Neutralizing antibodies to CMV glycoprotein B, an envelope component that facilitates virion penetration, blocked plaque formation in polarized UtMVEC. Neutrophils transmitted CMV infection to UtMVEC, which in turn infected cytotrophoblasts. However, neutrophils did not directly infect cytotrophoblasts. These findings implicate endothelial cells from the uterine microvasculature as a potential source for CMV infection of endovascular cytotrophoblasts of the anchoring villi. Possibly the cytokine/chemokine milieu in the pregnant uterus could attract immune cells that infect endothelial cells in hybrid fetal-maternal vessels. In turn, these cells could infect endovascular cytotrophoblasts, one possible initiation point of a cascade that results in retrograde placental CMV infection.     

Conservation of receptor antagonist anti-tumor activity by epidermal growth factor receptor antibody expressed in transgenic corn seed

Recombinant protein production in plants such as corn is a promising means to generate high product yields at low comparable production cost. The anti-EGFR monoclonal antibody C225, cetuximab, is a well-characterized receptor antagonist antibody recently approved for the treatment of refractory colorectal cancer. We initiated a study to test and compare the functional activity of glycosylated and aglycosylated C225 produced in stable transgenic corn seed. Both corn antibodies were shown to be functionally indistinguishable from mammalian-derived C225 in demonstrating high-affinity binding to the EGF receptor, blocking of ligand-dependent signaling, and inhibiting cell proliferation. In addition, consistent with cetuximab, both corn antibodies possessed strong anti-tumor activity in vivo. Acute dose primate pharmacokinetic studies, however, revealed a marked increase in clearance for the glycosylated corn antibody, while the aglycosylated antibody possessed in vivo kinetics similar to cetuximab. This experimentation established that corn-derived receptor blocking monoclonal antibodies possess comparable efficacy to mammalian cell culture-derived antibody, and offer a cost effective alternative to large-scale mammalian cell culture production.     

<Emphasis Type="Italic">TCF7L2</Emphasis>variant genotypes and type 2 diabetes risk in Brazil: significant association,but not a significant tool for risk stratification in the general population

Background  

Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population.     

Use of specific ELISA for the detection of antibodies directed against p53 protein in patients with hepatocellular carcinoma.

AIMS: To analyse the significance of antibodies to p53 protein as a serological marker for changes in p53 gene expression in patients with hepatocellular carcinoma. METHODS: Thirty eight patients with hepatocellular carcinoma, 19 showing accumulation of p53 protein by immunohistochemistry and 19 having no accumulation, were studied. The presence of anti-p53 was tested using a novel ELISA utilising a recombinant p53 protein as a capture system and verified by western blotting. p53 gene mutations were sought by single strand conformational polymorphism and DNA sequencing analyses. RESULTS: Of 19 patients with p53 protein accumulation in tumour tissue, 10 (52%) had antibodies to p53 in serum by ELISA. Four patients with p53 negative immunohistochemistry also had detectable anti-p53. Western blot analysis confirmed the specificity of the ELISA positive serum samples. The presence of anti-p53 was independent of serum alpha-fetoprotein and was detected in 50% of small tumours while only 8% were alpha-fetoprotein positive. Mutations affecting exons 5 and 6 seem to be more frequently associated with development of anti-p53, than mutations in exons 7 or 8. CONCLUSIONS: The ELISA for anti-p53 is a convenient and specific tet for the detection of humoral response to alterations in p53 gene expression and could be of value in the diagnosis and characterisation of patients with hepatocellular carcinoma.     

A novel glycoprotein for detection of herpes simplex virus type 1-specific antibodies

A novel herpes simplex virus type 1 (HSV-1)-specific glycoprotein reactive with monoclonal antibody H1379 was purified by affinity chromatography. This glycoprotein, provisionally designated as gG-1, forms two sets of bands with molecular weights of 40-44,000 and 60-88,000. When used in an immunodot enzymatic assay, gG-1 reacted strongly with rabbit antisera to HSV-1, but not with sera hyperimmune to HSV-2. Specificity of the assay was further established by the lack of reactivity of convalescent sera collected from 20 patients with primary genital HSV-2 infections, and from 100 sero-negative individuals. In contrast, antibodies to gG-1 were detected in 9 of 10 patients with primary HSV-1 infection, and in 63/67 patients with culture-positive, recurrent oral or genital HSV-1 infection. Reproducibility of the gG-1 immunodot assay for HSV-1 antibody detection was 96%. Serological assay with purified gG-1, done in parallel with the assay using purified gG-2 described in an earlier report, provides simple and reliable methods to detect type-specific HSV-1 and HSV-2 antibodies for seroepidemiological studies.     

In situ immunogold labeling analysis of the rice hoja blanca virus nucleoprotein and major noncapsid protein.

Ribonucleoprotein particles (RNPs) of rice hoja blanca virus (RHBV) were purified and used for electron microscopic analysis and antibody production. Antibodies made to RNPs specifically decorated purified RNPs. The RNPs typically showed characteristic tenuivirus morphologies. They were approximately 8 nm in diameter, mostly circular in nature, and exhibited branching and a high degree of superhelicity. When the RNP antibodies were used for in situ immunogold labeling analysis of RHBV-infected tissues, no specific structures were identified, but gold particles were distributed throughout the cytosol of RHBV-infected but not healthy plants. However, amorphous semi-electron opaque inclusion bodies (ASO-IBs) were abundant in cells of RHBV-infected plants. While the ASO-IBs were not labeled with the anti-RNP antiserum, they were specifically labeled with antibodies to the RHBV major noncapsid protein (NCP) and with antibodies to the NCP of another tenuivirus, maize stripe virus.