Ultrastructural findings in the wound healing of the colonic mucosa of rabbits

The wound healing of the rabbit colonic mucosa after experimental excision was observed with the electron microscope. Between 5 and 7 days, considerable numbers of undifferentiated mesenchymal cells (group I), differentiating muscle cells (group II) and histiocyte-like cells (group III) appear in the regions where the muscularis mucosae is re-establishing. Our electron micrographs indicate that group I cells are stem cells which differentiate to group II cells involved in muscle regeneration or to group III cells involved in phagocytosis. The mitotic proliferation of pre-existing smooth-muscle cells at the ulcer margin does not seem to be the major reason for the re-establishment of the muscular layer. Multinucleated cells occurring in this healing mucosa are considered to be formed by successive fusions between the group III cells and to play a role in enclosure of cell debris such as fragments of elastin.     

Prognostic Relevance of Cytokine Receptor Expression in Acute Myeloid Leukemia: Interleukin-2 Receptor α-Chain (CD25) Expression Predicts a Poor Prognosis

A variety of cytokine/cytokine receptor systems affect the biological behavior of acute leukemia cells. However, little is known about the clinical relevance of cytokine receptor expression in acute myeloid leukemia (AML). We quantitatively examined the expression of interleukin-2 receptor α-chain (IL-2Rα, also known as CD25), IL-2Rβ, IL-3Rα, IL-4Rα, IL-5Rα, IL-6Rα, IL-7Rα, the common β-chain (βc), γc, granulocyte-macrophage colony-stimulating factor (GM-CSF)Rα, G-CSFR, c-fms, c-mpl, c-kit, FLT3, and GP130 in leukemia cells from 767 adult patients with AML by flow cytometry and determined their prevalence and clinical significance. All cytokine receptors examined were expressed at varying levels, whereas the levels of IL-3Rα, GM-CSFRα, IL-2Rα, γc, c-kit, and G-CSFR exhibited a wide spectrum of ≥10,000 sites/cell. In terms of their French-American-British classification types, GM-CSFRα and c-fms were preferentially expressed in M4/M5 patients, G-CSF in M3 patients, and IL-2Rα in non-M3 patients. Elevated levels of IL-3Rα, GM-CSFRα, and IL-2Rα correlated with leukocytosis. In patients ≤60 years old, higher levels of these 3 receptors correlated with poor responses to conventional chemotherapy, but only IL-2Rα was associated with a shorter overall survival. By incorporating IL-2Rα status into cytogenetic risk stratification, we could sort out a significantly adverse-risk cohort from the cytogenetically intermediate-risk group. Analyses with various phenotypical risk markers revealed the expression of IL-2Rα as an independent prognostic indicator in patients with intermediate-risk cytogenetics. These findings were not observed in patients >60 years old. Our results indicate that several cytokine receptors were associated with certain cellular and clinical features, but IL-2Rα alone had prognostic value that provides an additional marker to improve current risk evaluation in AML patients ≤60 years old.     

Constructing an improved pyrroloquinoline quinone glucose dehydrogenase binding aptamer for enzyme labeling

Motif analysis of PGa4 indicated that eight consecutive guanine residues were most important for pyrroloquinoline quinine glucose dehydrogenase (PQQGDH) recognition. Because the truncated mutants minimized unexpected interactions between PGa4 and the target-binding aptamer, they will now facilitate the construction of a highly sensitive detection system using a PQQGDH-labeled diagnostic marker-binding aptamer.     

Improvement of compactin (ML-236B) production by genetic engineering in compactin high-producing <Emphasis Type="Italic">Penicillium citrinum</Emphasis>

An increase in compactin (ML-236B) production was achieved by introducing a whole compactin biosynthetic gene cluster or the regulatory gene mlcR into compactin high-producing Penicillium citrinum. In the previous report, we introduced mlcR encoding the positive regulator of compactin biosynthetic genes into compactin high-producing strain no. 41520, and most of the transformants produced higher amounts of compactin. Here, we characterize one of the resulting high producers (strain TIR-35, which produced 50% more compactin) and reveal that TIR-35 contained five copies of mlcR and that early, enhanced expression of mlcR caused compactin overproduction. Similarly, the introduction of mlcR into strain T48.19, which was created previously from strain no. 41520 by introducing a partial compactin biosynthetic gene cluster, enhanced compactin production further. Our results indicated that genetic engineering is an effective tool to improve compactin production, even in compactin high producers.     

Effect of hydroxystilbamidine on the kinetoplast of Trypanosoma gambiense in mice.

Hydroxystilbamidine (OHSA), an inhibitor of DNA synthesis, was shown to induce the dyskinetoplastic forms (akinetoplastic forms, AK forms) of Trypanosoma gambiense. The mode of appearance of the AK forms after injection of various doses of OHSA into infected mice was examined. The results suggested that production of the AK form is due to the selective inhibition of kinetoplast duplication of the drug without any effect on nuclear and cytoplasmic multiplication. When the parasites were treated with moderate doses of OHSA, segmenting forms without stainable kinetoplasts, were occasionally seen but attempts to establish a clone of akinetoplastic parasite were unsuccessful. Electron microscopy of parasites obtained after OHSA treatment showed not only irregular division of the kinetoplast but also the disorganization of kinetonucleus with disappearance of its envelope. Therefore, it was concluded that the AK forms were also produced by OHSA through disappearance of the kinetoplast.     

The Correlation between Antiesterase Activities and Chemical Structure of Saligenin Cyclic Phosphates

The effect of substituents on phosphorus of saligenin cyclic phosphorus esters on inhibitory activities toward cholinesterases and ali-esterases in vitro and in vivo was studied. The most insecticidal methyl derivative was the strongest inhibitor of insect cholinesterase both in vitro and in vivo. When the size of the substituent increased, the specificity toward ali-esterase increased, while decreased toward cholinesterase. The inhibitor ratio (I₅₀ ChE/I₅₀ AliE) appears to relate closely with insecticidal activity. Non-insecticidal aryl derivatives are very specific to inhibit insect ali-esterase. They are very weak inhibitors of insect cholinesterase in vivo. Their thiono analogs are stronger in vivo than corresponding oxo analogs.     

Dietary intake of the citrus flavonoid hesperidin affects stress-resilience and brain kynurenine levels in a subchronic and mild social defeat stress model in mice

ABSTRACT

Depressive disorders are partly caused by chronic inflammation through the kynurenine (KYN) pathway. Preventive intervention using anti-inflammatory reagents may be beneficial for alleviating the risk of depression. In this study, we focused on the Japanese local citrus plant, Citrus tumida hort. ex Tanaka (C. tumida; CT), which contains flavonoids such as hesperidin that have anti-inflammatory actions. The dietary intake of 5% immature peels of CT fruits slightly increased stress resilience in a subchronic and mild social defeat (sCSDS) model in mice. Moreover, the dietary intake of 0.1% hesperidin significantly increased stress resilience and suppressed KYN levels in the hippocampus and prefrontal cortex in these mice. In addition, KYN levels in the hippocampus and prefrontal cortex were significantly correlated with the susceptibility to stress. In conclusion, these results suggest that dietary hesperidin increases stress resilience by suppressing the augmentation of KYN signaling under sCSDS.