Immunological evaluation of personalized peptide vaccination in combination with UFT and UZEL for metastatic colorectal carcinoma patients

To investigate the safety and immunological responses of personalized peptide vaccination in combination with oral administration of UFT and UZEL for metastatic colorectal carcinoma (mCRC), fourteen patients were enrolled in the present study. Peptides were determined based on the presence of peptide-specific cytotoxic T lymphocyte precursors and IgG in each patient. A maximum of four peptides were subcutaneously administered weekly with UFT (300 mg/m² day⁻¹) and UZEL (75 mg/day) for 4 weeks, followed by 1 week of rest. This therapy was well-tolerated although there was a grade-3 skin reaction at the vaccination site in one patient. An increase in peptide-specific interferon-γ production or peptide-specific IgG after the tenth vaccination was observed in nine of ten or eight of ten patients tested, respectively. IgG responses were well correlated with overall survival (P = 0.0215). The safety and immunological responsiveness of the present therapy suggest that this combination would be of clinical benefit for mCRC patients, and further trials are merited. T. Hattori and T. Mine equally contributed to this work.     

The Decay of the Chromosomally Encoded ccdO157 Toxin–Antitoxin System in the Escherichia coli Species

The origin and the evolution of toxin–antitoxin (TA) systems remain to be uncovered. TA systems are abundant in bacterial chromosomes and are thought to be part of the flexible genome that originates from horizontal gene transfer. To gain insight into TA system evolution, we analyzed the distribution of the chromosomally encoded ccd_O157 system in 395 natural isolates of Escherichia coli. It was discovered in the E. coli O157:H7 strain in which it constitutes a genomic islet between two core genes (folA and apaH). Our study revealed that the folA–apaH intergenic region is plastic and subject to insertion of foreign DNA. It could be composed (i) of a repetitive extragenic palindromic (REP) sequence, (ii) of the ccd_O157 system or subtle variants of it, (iii) of a large DNA piece that contained a ccdA_O157 antitoxin remnant in association with ORFs of unknown function, or (iv) of a variant of it containing an insertion sequence in the ccdA_O157 remnant. Sequence analysis and functional tests of the ccd_O157 variants revealed that 69% of the variants were composed of an active toxin and antitoxin, 29% were composed of an active antitoxin and an inactive toxin, and in 2% of the cases both ORFs were inactive. Molecular evolution analysis showed that ccdB_O157 is under neutral evolution, suggesting that this system is devoid of any biological role in the E. coli species.     

Specification of phylogenetic interrelations between skate-rays and sharks

There are several hypotheses concerning phylogenetic interrelations of the ray-skate other also called batoid elasmobranches with other orders of elasmobranchs. Most of these studies are based on morphological studies; however, none of them include the skate itself. Without skate the concept of interrelations of the Batoids will be incomplete. This work deals with a molecular study of ribosomal ITS1-2 regions by the maximum parsimony (MP) and neighbor joining (NJ) methods of analysis, including skate. It is important for understanding the phylogenetic interrelations of the Batoids. The complex of all combined ITS1-2 data with use of the both analyses disagrees with the definition of phylogenesis of the recent Elasmobranchs, which has been put forward by Compagno [1]. On the contrary, results of the ITS1 MP analysis confirm the definition of superorders Squalea and Galeomorphii, which was proposed by Compagno [1]. Mine Dosay-Akbulut, 2006, published in Russian in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2006, Vol. 42, No. 2, pp. 105–109.     

Levels of human serum granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor under pathological conditions

Levels of serum granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with various leukocyte disorders were estimated by enzyme linked immunosorbent assay (ELISA). Some cases of acute myelogenous leukemia and aplastic anemia showed elevated serum levels of G-CSF and/or GM-CSF, whereas almost all of 23 healthy controls showed G-CSF and GM-CSF levels lower than 100 pg/ml. High levels of both types of CSF were noted in patients with granulocytosis due to infection. These levels became lower after resolution of the infection. Daily changes in serum CSF levels were also examined in a patient with autoimmune neutropenia, and it was found that the peripheral neutrophilic granulocyte count changed almost in parallel with the serum G-CSF level but not with GM-CSF, following the pattern with a delay of about 4–5 h, suggesting the possibility that G-CSF mainly regulates peripheral neutrophil circulation.     

Cleavage of human big endothelin-1 by Candida albicans aspartic proteinase

Abstract A Candida albicans aspartic proteinase (CAP), one of the secretory proteinases of Candida albicans , is thought to be a possible virulence factor in Candida albicans infection. Whereas endothelin-1 is found as an endothelium-derived strong vasoconstrictive peptide, it is known to have a role in the maintenance of vascular homeostasis and tissue survival. Endothelin-1 is generated from a precursor form of endothelin-1, the so-called big endothelin-1. It has recently been reported that cathepsin D, E and pepsin, which are aspartic proteinases, convert big endothelin-1 to endothelin-1. In this study, the relationship between CAP and big endothelin-1 was studied. High performance liquid chromatography analysis revealed that big endothelin-1 was cleaved into several amino acid sites by CAP, but endothelin-1 was not converted from big endothelin-1. CAP cleaved big endothelin-1 at different sites when compared with that of other known aspartic proteinases, and it suppressed endothelin-1 production through the degradation of big endothelin-1. CAP may break homeostatic mechanism of endothelin-1 in Candida albicans infectious lesion.     

Cytomorphogenesis in cenocytic green algae. V. Segregative cell division and cortical microtubules in Dictyosphaeria cavernosa (Siphonocladales,Chlorophyceae)*

Disassembly and reassembly of cortical microtubules (MT) during and after segregative cell division (SCO) in Dictyosphaeria cavernosa (Forssk.) Børgesen were observed using fluorescence microscopy. Parallel cortical MT in a mother cell were intact just after the initiation of SCD, but soon circular, MT-free patches appeared. Protoplasmic contraction enlarged the patches, and in these areas, the protoplasm eventually became perforated. Long and undulating cortical MT were arranged densely in the reticulate protoplasm. During further protoplasmic contraction, cortical MT appeared to be random and decreased in density. Finally, short and random cortical MT were present in the segregated protoplasts. Parallel cortical MT reassembled in the expanding daughter cells. After the daughter cells came in contact with one another, a radial system of cortical MT was constructed at the side that faced the inside of the mother cell wall. A microtubule inhibitor (amiprophos methyl, APM) had no effect on SCO. Segregative cell division was not induced directly by mechanical wounding. A comparison between SCO and wound-induced protoplasmic contraction was made.