A novel real-time PCR method for determination and quantification of each cytomegalovirus glycoprotein H subtype in clinical samples

To investigate reinfection in patients with congenital cytomegalovirus (CMV) infection, we established a CMV subtype-specific real-time quantitative PCR method targeting the CMV gH epitope region that can be used for evaluating pathogenic CMV strains in cases of mixed CMV infection.     

KSRP/FUBP2 Is a Binding Protein of GO-Y086, a Cytotoxic Curcumin Analogue

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A glypican-1-targeted antibody-drug conjugate exhibits potent tumor growth inhibition in glypican-1-positive pancreatic cancer and esophageal squamous cell carcinoma

An antibody-drug conjugate (ADC) is a promising therapeutic modality because selective and effective delivery of an anti-cancer drug is achieved by drug-conjugated antibody-targeting cancer antigen. Glypican 1 (GPC1) is highly expressed in malignant tumors, including pancreatic ductal adenocarcinoma (PDAC) and esophageal squamous cell carcinoma (ESCC). Herein, we describe the usefulness of GPC1-targeting ADC. Humanized anti-GPC1 antibody (clone T2) was developed and conjugated with monomethyl auristatin E (MMAE) via maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (mc-vc-PABC) linkers (humanized GPC1-ADC[MMAE]). Humanized GPC1-ADC(MMAE) inhibited the growth of GPC1-positive PDAC and ESCC cell lines via inducing cycle arrest in the G2/M phase and apoptosis in vitro. The binding activity of humanized GPC1-ADC(MMAE) with GPC1 was comparable with that of the unconjugated anti-GPC1 antibody. The humanized GPC1-ADC(MMAE) was effective in GPC1-positive BxPC-3 subcutaneously xenografted mice but not in GPC1-negative BxPC-3-GPC1-KO xenografted mice. To assess the bystander killing activity of the humanized GPC1-ADC(MMAE), a mixture of GPC1-positive BxPC-3 and GPC1-negative BxPC-3-GPC1-KO-Luc cells were subcutaneously inoculated, and a heterogenous GPC1-expressing tumor model was developed. The humanized GPC1-ADC(MMAE) inhibited the tumor growth and decreased the luciferase signal, measured with an in vivo imaging system (IVIS), which suggests that the suppression of the BxPC-3-GPC1-KO-Luc population. The humanized GPC1-ADC(MMAE) also inhibited the established liver metastases of BxPC-3 cells and significantly improved the overall survival of the mice. It exhibited a potent antitumor effect on the GPC1-positive PDAC and ESCC patient-derived xenograft (PDX) models. Our preclinical data demonstrate that GPC1 is a promising therapeutic target for ADC.     

Identical structural changes in inherited albumin variants from different populations.

Alloalbuminemia is rare and has a cumulative frequency of only approximately 1 in 3,000 in Europeans and Japanese. The worldwide ethnic and geographic distribution of certain albumin genetic variants appears to be nonrandom. Moreover, we have found that structurally identical variants may occur at different frequencies in ethnically distinct populations, presumably owing to independent mutations. In this study, albumin B and two types of proalbumins, which as a group are the most common European albumin variants, have also been found in Asians. We have identified the amino acid substitution characteristic of albumin B (glutamic acid----lysine at position 570) in alloalbumins from six unrelated individuals of five different European descents and also in two Japanese and one Cambodian. The two types of proalbumins most common in Europe (Lille type, arginine----histidine at position -2; Christchurch type, arginine----glutamic acid at position -1) also occur in Japan. These results provide evidence for independent mutations at single sites in the albumin genome. The clustering of these and of several other amino acid exchanges in certain regions of the albumin molecule suggests two possibilities: that certain sites are hypermutable or that mutants involving certain sites are more subject to selection than mutants involving others.     

Amino acid sequence of human plasma alpha 1B-glycoprotein: homology to the immunoglobulin supergene family.

The complete amino acid sequence has been determined for alpha 1B-glycoprotein (alpha 1B), a protein of unknown function present in human plasma. This protein (Mr approximately equal to 63,000) consists of a single polypeptide chain N-linked to four glucosamine oligosaccharides. The polypeptide has five intrachain disulfide bonds and contains 474 amino acid residues. Analysis of the amino acid sequence by several computer programs shows that alpha 1B exhibits internal duplication and consists of five repeating structural domains, each containing about 95 amino acids and one disulfide bond. alpha 1B has a unique amino acid sequence. However, several domains of alpha 1B, especially the third, show statistically significant homology to variable regions of certain immunoglobulin light and heavy chains. alpha 1B also exhibits sequence similarity to other members of the immunoglobulin supergene family such as the receptor for transepithelial transport of IgA and IgM and the secretory component of human IgA. Because of its internal duplication and its sequence homology to immunoglobulin-like proteins, alpha 1B appears to have evolved from an ancestral gene similar to that of the immunoglobulin supergene family.     

Distinct patterns of regional cerebral glucose metabolism in Parkinson's disease with and without mild cognitive impairment

There is no consensus with regard to the clinical and neuroimaging characteristics of prodromal dementia in Parkinson's disease (PD). To delineate functional neuroimaging features of PD with mild cognitive impairment (PDMCI) and with no cognitive impairment (PDNC), we compared regional cerebral glucose metabolism (CMRglc) amongst 13 patients with PDMCI, 27 with PDNC, and 13 healthy controls. The PDNC patients had limited areas of hypometabolism in the frontal and occipital cortices. In the PDMCI patients, there were extensive areas of hypometabolism in the posterior cortical regions, including the temporo‐parieto‐occipital junction, medial parietal, and inferior temporal cortices. The present results suggest that posterior cortical dysfunction is the primary neuroimaging feature of PD patients at risk for dementia. © 2009 Movement Disorder Society