Suppressive activity of protease inhibitors from buckwheat seeds against human T-acute lymphoblastic leukemia cell lines.

The buckwheat protease inhibitor designated BWI-1, a member of the potato inhibitor I family, inhibits trypsin, chymotrypsin, and subtilisin, whereas the buckwheat protease inhibitor designated BWI-2a, a novel protease inhibitor homologous to the vicilin family, inhibits only trypsin. We examined the suppressive activity of BWI-1 and BWI-2a against T-acute lymphoblastic leukemia (T-ALL) cells, such as JURKAT and CCRF-CEM, and human normal blood lymphocytes. Both inhibitors significantly suppressed the growth of T-ALL cells as judged by the soluble 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (tetrazolium/formazan assay).

Atypical protein-kinase Czeta, but neither conventional Ca2+ -dependent protein-kinase C isoenzymes nor Ca2+ -calmodulin, participates in regulation of telomerase activity in Burkitt's lymphoma cells.

Purpose: To clarify the role of the pathways dependent on protein-kinase C (PK-C) and Ca2+/calmodulin (CaM) in the regulation of telomerase activity in Burkitt's lymphoma cells.

Methods: Burkitt's lymphoma cells (Raji and Daudi) were treated with the PK-C inhibitor, bisindolylmaleimide (BIM), or the CaM inhibitor, trifluoperazine (TFPZ), in a dose-dependent manner and in a time-dependent manner. The activities of PK-C isoenzymes were analyzed fluorimetrically using POLARIS assay kits.

Antisense inhibition of Bcr-Abl/c-Abl synthesis promotes telomerase activity and upregulates tankyrase in human leukemia cells.

Clinical studies in chronic myelogenous leukemia demonstrate that the overexpression of Bcr-Abl tyrosine kinase is usually accompanied by relatively low telomerase activity in the chronic phase, which reverts to a high activity in blast crisis. The present study was designed to investigate the cross-talk between both enzymes, using Bcr-Abl-positive K-562 and Bcr-Abl-negative Jurkat cell lines, treated with antisense oligodeoxyribonucleotides (ODNs) against Bcr-Abl/c-Abl mRNA. The decreased amount and enzyme activity of Bcr-Abl/c-Abl provoked telomerase activation in both cell lines.

Non-stationary convolution subtraction scatter correction with a dual-exponential scatter kernel for the Hamamatsu SHR-7700 animal PET scanner.

A spatially variant convolution subtraction scatter correction was developed for a Hamamatsu SHR-7700 animal PET scanner. This scanner, with retractable septa and a gantry that can be tilted 90 degrees, was designed for studies of conscious monkeys. The implemented dual-exponential scatter kernel takes into account both radiation scattered inside the object and radiation scattered in gantry and detectors.

Sox21 is a repressor of neuronal differentiation and is antagonized by YB-1.

Sox21, a high-mobility group box transcription factor, is expressed throughout the immature neural stem/progenitor population in ventricular zone but not in the cortical plate in embryonic mouse brain and its expression is restricted to the subventricular zone in the adult brain. In undifferentiated PC12 cells, endogenous Sox21 expression is detected but its expression ceases during the nerve growth factor (NGF)-induced neuronal differentiation. Overexpression of Sox21 results in a substantial repression of NGF-induced neurite outgrowth in PC12 cells.

Plant-derived abrin-a induces apoptosis in cultured leukemic cell lines by different mechanisms.

Abrin-a consists of A-chain with N-glycosidase activity, which inhibits protein synthesis, and lectin-like B-chain responsible for binding with cell-surface receptors and penetrating of abrin-a molecule into the cells. As a lectin component, the B-chain can also participate in cell signal transduction. It has been reported that abrin induces apoptosis, but the molecular mechanism(s) of this induction have been obscure and several alternative variants have been discussed.

Changes in serum KL-6 after intravenous fosfomycin administration in idiopathic interstitial pneumonia.

Changes in serum KL-6 levels after intravenous fosfomycin (FOM) administration in idiopathic interstitial pneumonia (IIP) were studied. Seventeen patients who were diagnosed with usual interstitial pneumonia by surgical lung biopsy were selected as subjects. In these patients, FOM was administered intravenously, at a dose of 2 g twice daily, for 14 days, and serum KL-6 was determined before and after its administration.

Effects of acute acetylcholinesterase inhibition on the cerebral cholinergic neuronal system and cognitive function: Functional imaging of the conscious monkey brain using animal PET in combination with microdialysis.

This study demonstrated the effects of acute acetylcholinesterase (AChE) inhibition by donepezil (Aricept) on the cerebral cholinergic neuronal system in the brains of young (5.2 +/- 1.1 years old) and aged (20.

Flavonoids in translucent bracts of the Himalayan Rheum nobile (Polygonaceae) as ultraviolet shields.

UV-absorbing substances were isolated from the translucent bracts of Rheum nobile, which grows in the alpine zone of the eastern Himalayas. Nine kinds of the UV-absorbing substances were found by high performance liquid chromatography (HPLC) and paper chromatography (PC) surveys. All of the five major compounds are flavonoids, and were identified as quercetin 3- O-glucoside, quercetin 3- O-galactoside, quercetin 3- O-rutinoside, quercetin 3- O-arabinoside and quercetin 3- O-[6"-(3-hydroxy-3-methylglutaroyl)-glucoside] by UV, 1H and 13C NMR, mass spectra, and acid hydrolysis of the original glycosides, and direct PC and HPLC comparisons with authentic specimens.

[Clinical features of Q fever pneumonia].

We report four cases of Q fever pneumonia diagnosed using PanBio Coxilla burnetii ELISA. The patients, a 21-year-old woman, a 53-year-old man, a 74-year-old man and a 87-year-old man, were among 284 with community-acquired pneumonia who were treated as inpatients from March 2001 till March 2003. The frequency of Q fever pneumonia in community-acquired pneumonia was 1.

Association between schizophrenia with ocular misalignment and polyalanine length variation in PMX2B.

The increased incidence of minor physical anomalies (MPAs) in schizophrenia is the fundamental basis for the neurodevelopmental hypothesis of schizophrenia etiology. Ocular misalignment, or strabismus, falls into the category of MPAs, but this phenotype has not been assessed in schizophrenia. This study reveals that a subtype of strabismus, constant exotropia, displays marked association with schizophrenia (P=0.

Structural characterization and promoter analysis of human potassium channel Kv8.1 (KCNV1) gene.

The voltage-gated K(+) channel (Kv) family comprises four subfamilies: Kv1, Kv2, Kv3 and Kv4. Kv6, Kv7, Kv8 and Kv9 subfamilies have also recently been reported. The gene for Kv8.

Characterization and distribution of IS8301 in the radioresistant bacterium Deinococcus radiodurans.

The insertion sequence element IS8301 isolated from the radiation resistant bacterium Deinococcus radiodurans strain KD8301 was characterized. IS8301 is comprised of 1,736-bp, lacks terminal inverted repeats and does not duplicate target DNA upon its insertion. The amino acid sequence homology of two open reading frames encoded in IS8301 indicates that this insertion sequence element belongs to the IS200/IS605 group.

Phenothiazines suppress proliferation and induce apoptosis in cultured leukemic cells without any influence on the viability of normal lymphocytes. Phenothiazines and leukemia.

Purpose: The purpose of the present study was to investigate the effects of phenothiazines (at clinically relevant doses) on the viability and proliferation of leukemic cell lines and normal lymphocytes, and to investigate the possibility of specific induction of apoptosis in leukemic cells.

Methods: Phenothiazines with different chemical structure and hydrophobicity were used: chlorpromazine (CPZ); levomepromazine (LVPZ); prometazine (PMZ); trifluoperazine (TFPZ); thioridazine (TRDZ). The leukemic cell lines used were: Daudi and Raji (derived from Burkitt's lymphoma), K-562 (derived from myelogenous leukemia), and BALL-1, MOLT-4, HPB-ALL and CCRF-HSB-2 (derived from acute lymphoblastic leukemia).

Cross-talk between Bcr-Abl tyrosine kinase, protein kinase C and telomerase-a potential reason for resistance to Glivec in chronic myelogenous leukaemia.

To prevent the resistance to Glivec in patients with chronic myelogenous leukaemia (CML), it is necessary to get a good understanding of its potential mechanisms. The present hypothesis accents on the mechanisms whereby Bcr-Abl tyrosine kinase remains inhibited by Glivec, but alternative signalling pathways become activated-the potential reason associates with activation of telomerase after long-term treatment with Glivec and recovery of cell proliferation and immortality. The hypothesis is based on the observations about differences in telomere dynamics and telomerase activity between chronic and blast phases of CML patients, as well as about the potential effect of Glivec on the cross-talk between telomerase, Bcr-Abl tyrosine kinase and protein kinase C family-key enzymes in CML.

Synthesis of DNA conjugates by solid phase fragment condensation.

Development of a novel method for the synthesis of DNA conjugates is described. Oligonucleotides were successfully conjugated with a variety of functional molecules on a solid phase (Solid Phase Fragment Condensation) using an amino, a hydroxyl, a thiol, and a carboxyl group. DNA-peptide conjugate was obtained as a pure from by a single RPHPLC purification approximately in 20% yield.

DNA conjugates as novel functional oligonucleotides.

Oligodeoxynucleotides with RNA cleavage activity 1) were conjugated with amines and peptides by solid phase fragment condensation (SPFC). It was found that 29 mer DNA enzyme conjugated with spermine at its 5'-end showed higher affinity to the target RNA sequence and 40 times higher activity of cleavage than native DNA enzyme. It is also to be noted that conjugate DNA enzymes showed increased resistance against nuclease digestion.

Control of intracellular delivery and inhibition of genetic expression by DNA-peptide conjugates.

Various types of DNA-peptide conjugates were synthesized by solid phase fragment condensation (SPFC). DNA-LNS (nuclear localizing signal) peptide conjugate was proved to be delivered and localized into cellular nucleus and exhibited higher antisense inhibitory effect against telomerase than antisense phosphorothioate DNA. In contrast, DNAzymes conjugated with NES (nuclear export signal) peptide was shown to be taken up and localized in cytoplasm.

Antisense effects of DNA-peptide conjugates.

Antisense conjugate DNA covalently bound to functional amines, sugars or peptides such as nuclear localization signals (NLS), nuclear export signals (NES) and artificial amphiphilic alpha-helical and beta-sheet peptides were synthesized by solid phase fragment condensation (SPFC). Inhibitory effects on human telomerase of synthesized antisense conjugate DNAs were evaluated by TRAP assay. Antisense conjugate DNAs showed several times higher inhibitory effects on telomerase activity compared to native antisense DNA in cell lysis solutions.

Conjugate DNAzymes.

Conjugate DNAzymes were synthesized by solid phase fragment condensation and their biological properties were characterized. They have increased affinity to target RNA, enhanced stability against DNase 1 digestion and comparable or higher RNA cleaving activity compared with native and also phosphorothioate DNA zymes. It was also demonstrated that conjugate DNAzymes could inhibit BCR-ABL tyrosine kinase in cellular lysis of human leukemia cell line.