Involvement of regional lymph nodes after penetration of Schistosoma mansoni cercariae in naive and infected mice

The very low density lipoprotein receptor (VLDL-r) is a cell-surface molecule specialized for the internalization of multiple diverse ligands, including apolipoprotein E (apoE)-containing lipoprotein particles, via clathrin-coated pits. Its structure is similar to the low-density lipoprotein receptor (LDL-r), although the two have substantially different systemic distributions and regulatory pathways. The present work examines the distribution of VLDL-r in the central nervous system (CNS) and in relation to senile plaques in Alzheimer disease (AD). VLDL-r is present on resting and activated microglia, particularly those associated with senile plaques (SPs). VLDL-r immunoreactivity is also found in cortical neurons. Two exons of VLDL-r mRNA are differentially spliced in the mature receptor mRNA. One set of splice forms gives rise to receptors containing (or lacking) an extracellular O-linked glycosylation domain near the transmembrane portion of the molecule. The other set of splice forms appears to be brain-specific, and is responsible for the presence or absence of one of the cysteine-rich repeat regions in the binding region of the molecule. Ratios of the receptor variants generated from these splice forms do not differ substantially across different cortical areas or in AD. We hypothesize that VLDL-r might contribute to metabolism of apoE and apoE/A beta complexes in the brain. Further characterizations of apoE receptors in Alzheimer brain may help lay the groundwork for understanding the role of apoE in the CNS and in the pathophysiology of AD.     

Function morphemes in young children's speech perception and production.

Function morphemes or functors (e.g., articles and verb inflections) potentially provide children with cues for segmenting speech into constituents, as well as for labeling these constituents (e.g., noun phrase [NP] and verb phrase [VP]). However, the fact that young children often fail to produce functors may indicate that they ignore these cues in early language acquisition. Alternatively, children may be sensitive to functors in perception, but omit them in production. In 3 experiments, 2-year-olds imitated sentences that contained English or non-English functors and that were controlled for both suprasegmental and segmental factors. Children omitted English functors more frequently than non-English functors, indicating perceptual sensitivity to familiar vs unfamiliar elements. The results suggest that children may be able to use functors early in language acquisition to solve the segmentation and labeling problems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interplay of function morphemes and prosody in early language.

Previous studies have demonstrated that children are aware of the function morphemes in their language despite their failure to produce them. However, none of these studies tested whether children are aware of the linguistic contexts in which particular function morphemes occur. Only if children are aware of such co-occurrence patterns could they use function morphemes to determine the linguistic categories of words and phrases. Young 2-yr-olds demonstrated their awareness of function morpheme co-occurrence patterns by performing better in a picture identification task when the target word was preceded by a grammatical article than an ungrammatical auxiliary. Children who heard the sentences produced in a female voice performed better than those who heard a male voice, and this was especially true for sentences exhibiting the most regular co-occurrence patterns. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The quantitative humoral immune response to the hepatitis C virus is correlated with disease activity and response to interferon-alpha

BACKGROUND/AIM: Virus-host interactions may have pathogenetic significance in chronic hepatitis. Thus the humoral immune response was evaluated during the clinical course of HCV-infected patients. METHODS: Eighteen selected chronic HCV patients received three doses of 3 or 6 MU interferon-alpha 2a weekly for 6 to 12 months and were followed up for 6 to 60 months. Anti-HCV antibody levels were serially measured either in end-point diluted sera with the Matrix-Assay or with quantitative anti-HC34-IgG and -IgM ELISA. Circulating immune complexes were assessed by flow cytometry and the results were correlated with histology, quantitative HCV-RNA levels and genotypes. RESULTS: Nine complete responders (CR; genotypes 1a n = 4; 1b n = 1; 2a n = 1; 3a n = 3) showing sustained virus elimination and ALT normalisation had low HCV-RNA pretreatment levels (mean 14 x 10(3) copies/ml) compared to six nonresponders and three partial responders (NR/PR; genotypes 1a n = 2; 1b n = 7) who had significantly higher HCV-RNA pretreatment levels (mean 254 x 10(3) copies/ml; p < 0.01). In untreated NR/PR the HC34 core-antigen was most immunogenic, in CR the NS3-derived HC29-antigen. Pre-treatment levels of anti-HC 34-IgG and -IgM antibody levels in NR/PR were higher than in CR (IgM/IgG p = 0.05, n.s.) and these differences became significant during or after therapy (3 months therapy: IgM p < 0.02/IgG p < 0.07; end of therapy: IgM 0.006/IgG p < 0.04; 6 months post-therapy: IgM p < 0.002/IgG p < 0.004). The PR patients showed recurrent anti-HC34 antibody levels that preceded disease reactivation and detectable HCV-RNA in serum. Immune complex formation increased in some patients during treatment but did not correlate with disease activity, quantitative viraemia, antibody levels or therapy outcome. CONCLUSION: Anti-HC34 antibodies, i.e. of the IgM-subtype, correlated quantitatively with viraemia and disease activity. Monitoring the antibody levels may predict the long-term therapy outcome during interferon-alpha treatment.     

Giant Magnetoelectric Effect in Thin‐Film Composites

Highly sensitive AC magnetic field sensors are presented using magnetoelectric composites consisting of magnetostrictive and piezoelectric phases. They are offering passive nature, high sensitivity, large effect enhancement at mechanical resonance, and large linear dynamic range. Thin‐film magnetoelectric 2‐2 composites benefit from perfect coupling between the piezoelectric and magnetostrictive phases and from the reduction in size which is essential for high spatial resolution. Their design uses AlN and a plate capacitor or PZT with interdigital electrodes and magnetostrictive amorphous FeCoSiB single layers or exchanged biased multilayers. At mechanical resonance and depending on the geometry, extremely high ME coefficients of up to 9.7 kV/cm Oe in air and up to 19 kV/cm Oe under vacuum were obtained. To avoid external DC magnetic bias fields, composites consisting of exchanged biased multilayers serving as the magnetostrictive component with a maximum magnetoelectric coefficient at zero magnetic bias field are employed. Furthermore, the anisotropic response of these exchanged biased composites can be utilized for three‐dimensional vector field sensing. Sensitivity and noise of the sensors revealed limits of detection as good as to 2.3 pT/Hz^1/2 at mechanical resonance. Sensitivity between 0.1 and 1000 Hz outside resonance can be enhanced through frequency conversion using AC magnetic bias fields.     

Prodrugs of anthracyclines for use in antibody-directed enzyme prodrug therapy

A series of new prodrugs of daunorubicin and doxorubicin which are candidates for antibody-directed enzyme prodrug therapy (ADEPT) is reported. These compounds (25a,b,c and 32a,b,c) have been designed to generate cytotoxic drugs after activation with beta-glucuronidase. As expected, recovery of the active drug was observed after enzymatic cleavage by Escherichia coli beta-glucuronidase as well as by a fusion protein which has been obtained from human beta-glucuronidase and humanized CEA-specific binding region. The six prodrugs are highly stable and are more than 100-fold less cytotoxic than doxorubicin against murine L1210 cell lines. The ortho-substituted phenyl carbamates 25a,b,c are better substrates for beta-glucuronidase than the corresponding para-substituted analogues. After taking into account additional factors such as stability in plasma and kinetics of enzymatic cleavage, we selected the o-nitro prodrug 25c for clinical trials.     

HIV and pregnancy: risks of transmission and therapeutic possibilities

In Europe, transmission of HIV-1 during pregnancy occurs in 14% of children born to HIV-infected women. Risk factors for transmission are (1) virus load measured by p-24 antigenemia and HIV RNA level, (2) low CD4+ lymphocyte counts (below 600/microliter, (3) placental membrane inflammation and (4) time interval between membrane rupture and delivery. Breast feeding and vaginal delivery increase the risk of transmission of HIV infection. Antiretroviral therapy with zidovudine (Retrovir) at a dose of 500 mg/day reduces the transmission of HIV infection by two thirds. No malformation of the newborn due to zidovudine has been reported so far, but the possibility of unknown long-term adverse effects on children exposed to zidovudine must be weighed against the benefit of a considerable decrease in HIV transmission. Pregnancy is not associated with a higher rate of progression to AIDS, and HIV infection has no adverse effect on the pregnancy outcome in asymptomatic women.