Enhanced UVfemale1 tumor growth in CBF1 mice infected with Schistosoma mansoni due to modulation of Th1-like responses

Effects of Schistosoma mansoni infection on anti-tumor immunity were examined in CBF1 mice with ultraviolet-induced UVfemale1 fibrosarcoma cells. Although many laboratory established tumor cells had rejection mechanisms independent of CD4(+) T cells, we confirmed that CD4(+) cells had significant roles in rejection of UVfemale1 cells in the syngeneic CBF1 mice. When we prepared two CBF1 mouse groups, S. mansoni-infected and schistosome-free, the former group showed up-regulation of Th2-like response to UVfemale1 cells, whereas the latter group mice showed rather type 1-dominant patterns. Cytotoxic activity against UVfemale1 cells tested in vitro, which was attributed to CD8(+) cells, was significantly weaker in S. mansoni-infected mice compared with infection-free mice. In tumor challenge experiments in vivo, we observed that rapid and complete rejection of UVfemale1 cells required the presence of CD8(+) T cells. Under only CD4-depleted situation, survival of tumor cells in schistosome-free mice was prolonged up to 1 month or more. Under the presence of both CD4(+) and CD8(+) cells, S. mansoni infected mice rejected the challenged UVfemale1 cells as was seen in normal mice. However, when CD8(+) cells were depleted from S. mansoni-infected mice, inoculated UVfemale1 cells grew more rapidly than in infection-free mice. Our results suggest that functionally polarized cytokine patterns in schistosome-infected hosts promote rapid tumor growth.     

Stereoselective determination and pharmacokinetics of dihydropyridines: an updated review

All dihydropyridines, except nifedipine, have at least one chiral center, and their pharmacokinetics and clinical effects differ from one enantiomer to another. Chiral separation methods for dihydropyridines using chromatographic techniques are discussed. The stereoselective pharmacokinetics of dihydropyridine calcium antagonists were reviewed in detail in 1995. The present review article updates the methods for the stereoselective determination of dihydropyridines using chromatographic techniques and summarizes the pharmacokinetics of the dihydropyridines, including the newest drugs under development.     

Variation in mitochondrial DNA of Vietnamese pigs: relationships with Asian domestic pigs and Ryukyu wild boars

Mitochondrial DNA (mtDNA) sequences (574 bp) of 30 Vietnamese pigs (large and small) were examined and compared with those of 61 haplotypes from wild boars and domestic pigs from various locations in Asia. The large Vietnamese pigs had genetic links to Ryukyu wild boars in southern Japan. The small Vietnamese pigs were closely related to other East Asian domestic pigs. These results indicate that Vietnamese pigs are genetically diverse and may be descendents of wild and domestic pigs from other regions of Asia.     

4-hydroxynonenal induces glutamate cysteine ligase through JNK in HBE1 cells

Glutathione is the most abundant non-protein thiol in the cell, with roles in cell cycle regulation, detoxification of xenobiotics, and maintaining the redox tone of the cell. The glutathione content is controlled at several levels, the most important being the rate of de novo synthesis, which is mediated by two enzymes, glutamate cysteine ligase (GCL), and glutathione synthetase (GS), with GCL being rate-limiting generally. The GCL holoenzyme consists of a catalytic (GCLC) and a modulatory (GCLM) subunit, which are encoded by separate genes. In the present study, the signaling mechanisms leading to de novo synthesis of GSH in response to physiologically relevant concentrations of 4-hydroxy-2-nonenal (4HNE), an endproduct of lipid peroxidation, were investigated. We demonstrated that exposure to 4HNE resulted in increased content of both Gcl mRNAs, both GCL subunits, phosphorylated JNK1 and c-Jun proteins, as well as Gcl TRE sequence-specific AP-1 binding activity. These increases were attenuated by pretreating the cells with a novel membrane-permeable JNK pathway inhibitor, while chemical inhibitors of the p38 or ERK pathways were ineffective. These data reveal that de novo GSH biosynthesis in response to 4HNE signals through the JNK pathway and suggests a major role for AP-1 driven expression of both Gcl genes in HBE1 cells.     

The peak height ratio of S-sulfonated transthyretin and other oxidized isoforms as a marker for molybdenum cofactor deficiency,measured by electrospray ionization mass spectrometry

Molybdenum cofactor deficiency is a fatal neurological disorder, which follows an autosomal-recessive trait and is characterized by combined deficiency of the enzyme, sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase. Early detection of molybdenum cofactor-deficient patients is essential for their proper care and genetic counseling of families at risk. We demonstrate the use of S-sulfonated transthyretin (TTR) as a marker for molybdenum cofactor deficiency. Plasma or sera obtained from 4 patients with molybdenum cofactor deficiency and 57 controls were studied by electrospray ionization mass spectrometry (ESIMS) following selective enrichment of TTR by immunoprecipitation using protein G/A agarose. The data obtained from molybdenum cofactor deficiency samples indicated a strong increase in the peak height of S-sulfonated TTR. A more significant difference was revealed if the peak height ratio of S-sulfonated TTR and the sum of the other oxidized TTR were determined. By accurate determination of the ratio, the samples of molybdenum cofactor deficiency patients could clearly be distinguished from controls without molybdenum cofactor deficiency.     

Active-dimeric form of lipoprotein lipase increases in the adipose tissue of patients with rheumatoid arthritis treated with prednisolone

A thermodynamic analysis of the interaction of 125I-labeled human chorionic gonadotropin (IhCG) with two of its monoclonal antibodies (MAbs) was carried out. The dissociation profile of IhCG-MAb complex conforms to a two-step model. vant Hoff enthalpies were calculated with the K(A) (equilibrium constant) values obtained from dissociation at different temperatures. Free energy and entropy changes were calculated using the standard equations. DeltaH values for one of the MAbs, viz. VM7 were favorable at temperatures beyond 30 degrees C. Interestingly, the DeltaS values were also favorable at all temperatures. In the case of MAb VM4a, however, the interaction throughout the temperature range was driven by large favorable entropic contributions, indicating the importance of hydrophobic interaction in the binding of this MAb to hCG. The energetics of the interaction of these two monoclonals with hCG is discussed.     

Chloride channel in vanadocytes of a vanadium-rich ascidian Ascidia sydneiensis samea

Ascidians, so-called sea squirts, can accumulate high levels of vanadium in the vacuoles of signet ring cells, which are one type of ascidian blood cell and are also called vanadocytes. In addition to containing high concentrations of vanadium in the +3 oxidation state, the proton concentrations in vanadocyte vacuoles are extremely high. In order to elucidate the entire mechanism of the accumulation and reduction of vanadium by ascidian vanadocytes, it is necessary to clarify the participation of anions, which might be involved as counter ions in the active accumulation of both vanadium and protons. We examined the chloride channel, since chloride ions are necessary for the acidification of intracellular vesicles and coexist with H(+)-ATPase. We cloned a cDNA encoding a chloride channel from blood cells of a vanadium-rich ascidian, Ascidia sydneiensis samea. It encoded a 787-amino-acid protein, which showed striking similarity to mammalian ClC3/4/5-type chloride channels. Using a whole-mount in situ hybridization method that we developed for ascidian blood cells, the chloride channel was revealed to be transcribed in vanadocytes, suggesting its participation in the process of vanadium accumulation.     

Overproduction of highly active trypanosome alternative oxidase in Escherichia coli heme-deficient mutant

Cyanide-insensitive trypanosome alternative oxidase (TAO) is the terminal oxidase of the respiratory chain of long slender bloodstream forms of the African trypanosome, which causes sleeping sickness in humans and nagana in cattle. TAO has been targeted for the development of anti-trypanosomal drugs, because it does not exist in the host. In this study, we established a system for overproduction of highly active TAO in Eschericia coli heme-deficient mutant. Kinetic analysis of recombinant enzyme and TAO in Trypanosoma brucei brucei mitochondria revealed that recombinant TAO retains the properties of native enzyme, indicating that recombinant TAO is quite valuable for further biochemical study of TAO.     

Endocranial cast and morphology of the olfactory bulb of<Emphasis Type="Italic"> Amphipithecus mogaungensis</Emphasis> (latest middle Eocene of Myanmar)

A detailed endocranial cast of the olfactory bulb of Amphipithecus mogaungensis, a latest middle Eocene primate from the Pondaung Formation (Myanmar), was studied in comparison with some Paleogene primates, the olfactory bulb of which has been reported. The olfactory bulb of Amphipithecus is located just anterior to the postorbital constriction, that is, within the interorbital septum. It is relatively large and pedunculate, not overlapped by the frontal lobe, and consists of two parallell aligned bodies. The relative volume of the olfactory bulb shows the same pattern as in adapiforms, but the location and bilobed form are more similar to those of omomyoids than of adapiforms. Electronic Publication