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The direct numerical simulation of fully developed turbulent channel flow with a sinusoidal riblet surface has been carried out at the friction Reynolds number of 110. Lateral spacing of adjacent walls in a sinusoidal riblet is varied sinusoidally in the streamwise direction. The average lateral spacing of a sinusoidal riblet is larger than the diameter of a quasi-streamwise vortex and its wetted area is smaller than that of ordinary straight-type riblets. We investigate the effect of sinusoidal riblet design parameters on the drag reduction rate and flow statistics in this paper. The parametric study shows that the maximum total drag reduction rate is approximately 9.8% at a friction Reynolds number of 110. The riblet induces downward and upward flows in the expanded and contracted regions, respectively, which contribute to periodic Reynolds shear stress. However, the random Reynolds shear stress decreases drastically as compared with the flat surface case, resulting in the reduction of total drag owing to the sinusoidal riblet. We also performed vortex tracking to discuss the motion of the vortical structure traveling over the sinusoidal riblet surface. Vortex tracking and probability analysis for the core of the vortical structure show that the vortical structure is attenuated owing to the sinusoidal riblet and follows the characteristic flow. These results show that the high skin-friction region on the channel wall is localized at the expanded region of the riblet walls. In consequence, the wetted area of the riblet decreases, resulting in the drag-reduction effect. [ABSTRACT FROM AUTHOR]

A tumor-selective non-lytic retroviral replicating vector (RRV), Toca 511, and an extended-release formulation of 5-fluorocytosine (5-FC), Toca FC, are currently being evaluated in clinical trials in patients with recurrent high-grade glioma (NCT01156584, NCT01470794 and NCT01985256). Tumor-selective propagation of this RRV enables highly efficient transduction of glioma cells with cytosine deaminase (CD), which serves as a prodrug activator for conversion of the anti-fungal prodrug 5-FC to the anti-cancer drug 5-fluorouracil (5-FU) directly within the infected cells. We investigated whether, in addition to its direct cytotoxic effects, 5-FU generated intracellular^ by RRV-mediated CD/5-FC prodrug activator gene therapy could also act as a radiosensitizing agent. Efficient transduction by RRV and expression of CD were confirmed in the highly aggressive, radioresistant human glioblastoma cell line U87EGFRvlll and its parental cell line U87MG (U87). RRV-transduced cells showed significant radiosensitization even after transient exposure to 5-FC. This was confirmed both in vitro by a clonogenic colony survival assay and in vivo by bioluminescence imaging analysis. These results provide a convincing rationale for development of tumor-targeted radiosensitization strategies utilizing the tumor-selective replicative capability of RRV, and incorporation of radiation therapy into future clinical trials evaluating Toca 511 and Toca FC in brain tumor patients. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA; miR) is a class of small regulatory RNA molecules, the aberrant expression of which can lead to the development of cancer. We recently reported that overexpression of miR-21 and/or miR-155 leads to activation of the phosphoinositide 3-kinase (PI3K)-AKT pathway in malignant lymphomas expressing CD3−CD56+ natural killer (NK) cell antigen. Through expression analysis, we show in this study that in both NK/T-cell lymphoma lines and samples of primary lymphoma, levels of miR-150 expression are significantly lower than in normal NK cells. To examine its role in lymphomagenesis, we transduced miR-150 into NK/T-cell lymphoma cells, which increased the incidence of apoptosis and reduced cell proliferation. Moreover, the miR-150 transductants appeared senescent and showed lower telomerase activity, resulting in shortened telomeric DNA. We also found that miR-150 directly downregulated expression of DKC1 and AKT2, reduced levels of phosphorylated AKTser473/4 and increased levels of tumor suppressors such as Bim and p53. Collectively, these results suggest that miR-150 functions as a tumor suppressor, and that its aberrant downregulation induces continuous activation of the PI3K-AKT pathway, leading to telomerase activation and immortalization of cancer cells. These findings provide new insight into the pathogenesis of malignant lymphoma. [ABSTRACT FROM AUTHOR]

The transvenous approach via the superior ophthalmic vein (SOV) is an available approach for carotid cavernous fistula (CCF), especially in the event that there is no other suitable approach route to the fistula. Surgical exposure of the peripheral roots of the SOV is commonly used; however, often, the SOV is often not accessible because of anatomical problems and/or complications. In this paper, we present and discuss our original direct-puncture approach to the extraconal portion of the SOV. An attempt on three patients with traumatic CCF failed with the transarterial approach and the conventional venous approach via the inferior petrosal sinus; therefore, the patients were treated with the direct-puncture approach to the extraconal portion of the SOV using two-dimensional digital subtraction angiography with local anesthesia. All cases that had tortuous and partially stenotic division of the SOV were treated successfully with this approach and without complications. This approach will become an alternate approach, especially when the peripheral roots of the SOV are focally narrowed and tortuous, making it impossible to insert a catheter. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To search DNA methylation difference between monozygotic twins discordant for bipolar disorder, we applied a comprehensive genome scan method, methylation-sensitive representational difference analysis (MS-RDA) to lymphoblastoid cells derived from the twins. MS-RDA isolated 10 DNA fragments derived from 5′ region of known genes/ESTs. Among these 10 regions, four regions showed DNA methylation differences between bipolar twin and control co-twin confirmed by bisulfite sequencing. We performed a case–control study of DNA methylation status of these four regions by pyrosequencing. Two regions, upstream regions of spermine synthase (SMS) and peptidylprolyl isomerase E-like (PPIEL) (CN265253), showed aberrant DNA methylation status in bipolar disorder. SMS, a gene on X chromosome, showed significantly higher DNA methylation level in female patients with bipolar disorder compared with control females. However, there was no difference of mRNA expression. In PPIEL, DNA methylation level was significantly lower in patients with bipolar II disorder than in controls. The expression level of PPIEL was significantly higher in bipolar II disorder than in controls. We found strong inverse correlation between gene expression and DNA methylation levels of PPIEL. These results suggest that altered DNA methylation statuses of PPIEL might have some significance in pathophysiology of bipolar disorder.Molecular Psychiatry (2008) 13, 429–441; doi:10.1038/sj.mp.4002001; published online 1 May 2007 [ABSTRACT FROM AUTHOR]

Various dissociation channels of silver bromide cluster ion Ag2Br+ and silver cluster ion Ag3 + were observed in high-energy collisionally-activated dissociation (CAD) using a Cs target. The fragment patterns of the high-energy CAD were compared with those of the metastable dissociation and low-energy CAD. The difference in the fragment patterns between the high-energy CAD and the other dissociation methods was explained in terms of the internal energy distributions. The dissociation mechanisms of neutral silver bromide cluster Ag2Br and silver cluster Ag3 were also investigated by charge inversion mass spectrometry using the Cs target. While the fragment ions AgBr- and Ag2 - were dominantly observed in the charge inversion spectrum of Ag2Br+, the undissociated ion Ag3 - was observed as a predominant peak in the case of Ag3 +. The dissociation behavior of Ag2Br* can be explained on the basis of the calculated thermochemical data. Contrary to this, the predominant existence of the undissociated Ag3 - cannot be explained by the reported thermochemical data. The existence of undissociated Ag3 - suggests that the dissociation barrier is higher than the internal energy of Ag3 * (theoretical: 1.03 eV, experimental: 2.31 eV) estimated from the ionization potentials of Ag3 and Cs. [ABSTRACT FROM AUTHOR]

Nateglinide is an oral antidiabetic medication that acts through rapid, short-term stimulation of insulin production. This study undertook to identify the nature of any adverse effects of nateglinide and to assess its clinical efficacy in long-term use in clinical practice. Patients (n=1014) were recruited from centers in Japan and were followed over a 15-month treatment period. Pretreatment and posttreatment values were obtained for fasting blood glucose, postprandial blood glucose, hemoglobin A1c (HbA1c), triglycerides, and total cholesterol. All adverse reactions were noted, along with standard laboratory blood variables. The efficacy value was rated as 78.76% by the treating physicians; this was indicated by a postprandial glucose decrease of 53.2 mg/dL (from 223.8+/-61.1 mg/dL to 170.6+/-40.7 mg/dL), a fasting glucose decrease of 9.3 mg/dL (from 155.1+/- 40.0 mg/dL to 145.4+/-35.1 mg/dL), and an HbA1c decrease of 0.68% (from 7.51+/- 1.36% to 6.83+/-1.09%). In patients previously treated with sulfonylurea, a decrease in HbA1c was not observed. Changes in HbA1c had no association with age, body mass index (BMI), duration of diabetes, or concomitant disease. No change in BMI was noted after 15 months of nateglinide treatment. Adverse reactions occurred at an incidence of 10.07% (100/993 cases), with hypoglycemic symptoms being the most prevalent (1.91%). Adverse reactions were sometimes associated with extant renal dysfunction, a condition about which the physician had to be aware. No problems such as increased incidences of adverse reactions or deterioration in severity were detected in this long-term study. This study showed the efficacy and safety of long-term treatment with nateglinide of patients with diabetes from various backgrounds. [ABSTRACT FROM AUTHOR]

We previously reported that expression level of LIM (ENH, PDLIM5) was significantly and commonly increased in the brains of patients with bipolar disorder, schizophrenia, and major depression. Expression of LIM was decreased in the lymphoblastoid cells derived from patients with bipolar disorders and schizophrenia. LIM protein reportedly plays an important role in linking protein kinase C with calcium channel. These findings suggested the role of LIM in the pathophysiology of bipolar disorder and schizophrenia. To further investigate the role of LIM in these mental disorders, we performed a replication study of gene expression analysis and performed genetic association studies. Upregulation of LIM was confirmed in the independent sample set obtained from Stanley Array Collection. No effect of sample pH or medication was observed. Genetic association study revealed the association of single nucleotide polymorphism (SNP)1 (rs10008257) with bipolar disorder. In an independent sample set, SNP2 (rs2433320) close to SNP1 was associated with bipolar disorder. In total samples, haplotype of these two SNPs was associated with bipolar disorder. No association was observed in case–control analysis and family-based association analysis in schizophrenia. These results suggest that SNPs in the upstream region of LIM may confer the genetic risk for bipolar disorder.Molecular Psychiatry (2005) 10, 1045–1055. doi:10.1038/sj.mp.4001719; published online 26 July 2005 [ABSTRACT FROM AUTHOR]

Nateglinide is an oral antidiabetic medication that acts through rapid, short-term stimulation of insulin production. This study was undertaken to identify the incidence and nature of adverse effects of nateglinide and to assess its efficacy in clinical practice. Patients (n = 3254) were recruited from 606 centers in Japan with a 12-week observation period. Pretreatment and posttreatment values were obtained for fasting blood glucose, postprandial blood glucose, hemoglobin A1c (HbA1c), triglycerides, cholesterol, and body mass index. All adverse events were reported, along with standard laboratory blood variables. The incidence of adverse events was 7.40%; hypoglycemia, including hypoglycemic symptoms, was reported as the most prevalent (1.62%). Adverse events were observed more frequently in patients with hepatic or renal dysfunction; no significant findings were noted in the remaining patient population. The efficacy rating determined by the treating physicians was 76.40%. HbA1c decreased by 0.81% from 7.70+/-1.53% to 6.89+/-1.22%, postprandial glucose decreased by 54.05 mg/dL from 228.91+/-73.69 mg/dL to 174.86+/-62.86 mg/dL, and fasting glucose decreased by 23.73 mg/dL from 164.15+/-51.42 mg/dL to 140.43+/-42.63 mg/dL. These effects were most marked in patients who were previously medication naïve or who had been diagnosed with diabetes for a short period. Mean body mass index decreased, and nateglinide was equally effective in obese patients. Nateglinide showed good therapeutic effect when used as the first choice in patients with a short duration of diabetes, and in those with no history of previous treatment. Moreover, nateglinide seemed to be useful for the treatment of elderly patients and obese patients. [ABSTRACT FROM AUTHOR]

Classical twin research focused on differentiating genetic factors from environmental factors by comparing the concordance rate between monozygotic (MZ) and dizygotic twins. On the other hand, recent twin research tries to identify genetic or epigenetic differences between MZ twins discordant for mental disorders. There are a number of reports of MZ twins discordant for genetic disorders caused by genetic or epigenetic differences of known pathogenic genes. In the case of mental disorder research, for which the causative gene has not been established yet, we are trying to identify the ‘pathogenic gene’ by comprehensive analysis of genetic or epigenetic difference between discordant MZ twins. To date, no compelling evidence suggesting such difference between MZ twins has been reported. However, if the genetic or epigenetic difference responsible for the discordant phenotype is found, it will have impact on the biology of mental disorder, in which few conclusive molecular genetic evidences have been obtained.Molecular Psychiatry (2005) 10, 622–630. doi:10.1038/sj.mp.4001662 Published online 19 April 2005 [ABSTRACT FROM AUTHOR]

We performed the oligonucleotide microarray analysis in bipolar disorder, major depression, schizophrenia, and control subjects using postmortem prefrontal cortices provided by the Stanley Foundation Brain Collection. By comparing the gene expression profiles of similar but distinctive mental disorders, we explored the uniqueness of bipolar disorder and its similarity to other mental disorders at the molecular level. Notably, most of the altered gene expressions in each disease were not shared by one another, suggesting the molecular distinctiveness of these mental disorders. We found a tendency of downregulation of the genes encoding receptor, channels or transporters, and upregulation of the genes encoding stress response proteins or molecular chaperons in bipolar disorder. Altered expressions in bipolar disorder shared by other mental disorders mainly consisted of upregulation of the genes encoding proteins for transcription or translation. The genes identified in this study would be useful for the understanding of the pathophysiology of bipolar disorder, as well as the common pathophysiological background in major mental disorders at the molecular level. In addition, we found the altered expression of LIM and HSPF1 both in the brains and lymphoblastoid cells in bipolar disorder. These genes may have pathophysiological importance and would be novel candidate genes for bipolar disorder.Molecular Psychiatry (2004) 9, 406-416. doi:10.1038/sj.mp.4001437 Published online 26 January 2004 [ABSTRACT FROM AUTHOR]

Presents a study which examined the effects of cocaine or reserpine administration in the rat cerebral cortex to test whether the RNA editing of 5-HT[sub2c]R is regulated by serotonergic activity. Association of 5-HT[sub2c]R with mental disorders; Influence of cocaine or reserpine in RNA editing of 5-HT[sub2c]R; Reduction of RNA editing in patients with schizophrenia;

Aims/hypothesis. To understand the transcriptional regulation and to investigate the pathological influence upon Type II (non-insulin-dependent) diabetes mellitus of insulin receptor substrate 2 (IRS2), the 5′ flanking region of the human IRS2 gene was cloned and screened in Japanese diabetic patients. Methods. Luciferase reporter assay and electrophoretic mobility shift assay (EMSA) were combined in HepG2, Fao, RINm5F, and HeLa cells to characterise the human IRS2 promoter region. Single nucleotide polymorphisms (SNPs) were identified in Japanese Type II diabetic patients by sequencing and were genotyped. Results. The proximal 2399 bp of the 5′ flanking region of the human IRS2 gene was cloned. A core promoter region was extended between nucleotide positions –834 and –557 (relative to the translation initiation site). The region [(–758)AGGGGGAGGG(–749)] that appears important in the positive regulation of IRS2 transcription was identified by EMSA with 32P-labelled double-stranded oligonucleotides encompassing regions protected from DNase I digestion by nuclear extract of HepG2 cells. Two SNPs (–765C/T and –2062T/C), identified by screening Japanese Type II diabetic patients, were not associated with Type II diabetes. IRS2-driven reporter activity in the plasmid containing thymine at –765 was not suppressed by insulin when measured in Fao cells. Conclusion/interpretation. The 5′ flanking sequence of the human IRS2 was investigated and two SNPs were identified. The SNP at –765 was suggested to be involved in the insulin-mediated regulation of the transcriptional activity of IRS2. [ABSTRACT FROM AUTHOR]

Self-compatible cultivars of Japanese apricot (Prunus mume Shieb. et Zucc.), a tree species that normally shows S-RNase-based self-incompatiblity, have a horticultural advantage over self-incompatible cultivars. Inheritance of self-compatibility and a common Sf-RNase allele that is observed in self-compatible cultivars was investigated using progenies from controlled crosses. Total DNAs were isolated from the parents and progenies of seven crosses that included at least one self-compatible cultivar as a parent. These DNAs were PCR-amplified with the Pru-C2 and PCE-R primer pair to determine S-haplotypes of the parents and progenies. A novel S-haplotype, S8, was found. In all crosses examined, the Sf-RNase gene was inherited from either the seed or pollen parent as a pistil S-allele in a non-functional S-haplotype. Self-compatibility of about 20 trees each from reciprocal crosses of 'Benisashi (S7Sf)' and 'Shinpeidayu (S3Sf)', and 26 selections from 16 different crosses was tested by pollination and pollen-tube growth studies. Cosegregation of the Sf-RNase allele and self-compatibility was confirmed with all but selection 1K0-26 (S3S7). Selection 1K0-26 (S3S7) that originated from 'Benisashi (S7Sf)' × 'Koshinoume (S3Sf)' appeared to be self-compatible even without the Sf-RNase allele. The possible role of pollen-S, a presumably existing pollen component of gametophytic self-incompatibility, is discussed. [ABSTRACT FROM AUTHOR]

Presents the experimental visualization of the swirl flow pattern in a transparent bubble eliminator. Calculation of velocity profiles and pressure distributions in the bubble eliminator; Performance evaluation of bubble removal effectiveness.

Aims/hypothesis. The cumulative effects of several thrifty factors could contribute to the pathogenesis of Type II (non-insulin-dependent) diabetes mellitus. We screened the human UCP1 gene (UCP1) for polymorphisms associated with susceptibility to Type II diabetes. Methods. By using PCR and single-strand conformation polymorphism analysis, UCP1 were screened for mutations in 25 Type II diabetic subjects and 25 healthy control subjects. The allele frequencies of the detected polymorphisms were determined by PCR and restriction fragment length polymorphism analysis in 320 diabetic subjects and 250 control subjects. Results. An A→C transition in the 5' untranslated region (UTR) of exon 1 (112 bp upstream of the translation initiation codon) and a Met229→Leu variant were detected. The allele frequencies for the C variant and for the Leu229 variant were higher in the Type II diabetic group than in the control group (p = 0.017 and p = 0.038, respectively). These polymorphisms were in linkage disequilibrium (p < 0.00001). Luciferase assay showed that the former variant in the 5' UTR may affect the promoter activity of UCP1. Conclusion/interpretation. Both the A→C polymorphism and the Met229→Leu polymorphism of UCP1 are in linkage disequilibrium and could be one of the diabetes associated single nucleotide polymorphisms (SNPs). [Diabetologia (2001) 44: 373–376] [ABSTRACT FROM AUTHOR]

Ionizing radiation is a well known risk factor of thyroid cancer development, but the mechanism of radiation induced carcinogenesis is not clear. The RETPTC oncogene, an activated form of the RET proto-oncogene, is frequently observed in papillary thyroid carcinoma (PTC); RETPTC1, -2 and -3 are known to be the three major forms. High frequencies of RETPTC rearrangements have been observed in radiation-associated PTC, such as those appearing post-Chernobyl or post-radiotherapy, but the rearrangement types differ between these two populations. We investigated whether a specific type of RETPTC rearrangement was induced by X-rays in vivo and in vitro. In human normal thyroid tissues transplanted in scid mice, the RETPTC1 rearrangement was predominantly detected throughout the observation period (up to 60 days) after X-ray exposure of 50 Gy. On the other hand, RETPTC3 was detected only 7 days after X-irradiation, and no transcript of RETPTC2 was detected. These results are supported by the results of an in vitro study. The RETPTC1 rearrangement was preferentially induced in a dose-dependent manner by X-rays within a high dose range (10, 50 and 100 Gy) in four cell lines. On the other hand, RETPTC3 was induced at a much lower frequency, and no induction of RETPTC2 was observed. These results suggest that the preferential induction of the RETPTC1 rearrangement may play an important role in the early steps of thyroid carcinogenesis induced by acute X-irradiation. Oncogene (2000) 19, 438–443. [ABSTRACT FROM AUTHOR]

We report case of primary volvulus of the small intestine and review 15 cases from the Japanese literature. A 56-year-old woman, with a history of appendectomy 30 years previously, was admitted with abdominal distension and signs of peritonitis. Abdominal computed tomography (CT) demonstrated a whirl-like pattern of the mesentery, showing the tightly twisted mesentery around the point of torsion. An emergency laparotomy revealed strangulation of the small intestine, from 200 cm anal to the Treitz ligament to 5 cm oral to the terminal ileum, caused by 360 degrees clockwise torsion. There was no adhesion caused by the previous operation nor were there any congenital anomalies. The strangulated intestine was removed and jejunocolonostomy was performed. The patient was discharged from hospital on day 39 after the operation. Primary volvulus of the small intestine was reported to be rare in Japan, but the mortality was 26%. Immediate diagnosis and surgical intervention is essential to achieve a good outcome. A whirl-like pattern of the mesentery is a typical sign of this condition on CT. [ABSTRACT FROM AUTHOR]

A tetradentate chelating agent constituting of an iminodiacetic acid group and a nitrogen atom of pyridine, N-(2-pyridylmethyl)iminodiacetic acid (PMIDA), was coordinated with 99mTc and evaluated as a renal functional agent. The complex of PMIDA with 99mTc was prepared by using a stannous chloride solution as a reducing agent. The chelating efficiency was analyzed by thin layer chromatography and electrophoresis. Chelation with 99mTc resulted in a single radiochemical product. Biological studies were performed in mice and rats. 99mTc-PMIDA was removed from the circulation solely by the kidneys. Clearance of 99mTc-PMIDA from the blood and the kidneys was as rapid as that of 99mTc-diethylenetriaminepentaacetic acid. The rate of blood clearance was unaffected by the administration of probenecid (a test for tubular secretion by the weak-acid mechanism), so that the glomerular filtration rate could be estimated by measuring its clearance from the blood. The results in animals with myohemoglobinuric acute renal failure suggested that 99mTc-PMIDA might be a useful renal function radiopharmaceutical. [ABSTRACT FROM AUTHOR]

Although DNA-damaging agents such as ultraviolet (UV) and X-ray can induce apoptosis, the difference in the apoptotic mechanism is not clearly understood. In the present study, we investigated the effects of these two genotoxic agents on the induction of DNA damage and subsequent apoptotic cell death from the viewpoint of cell cycle regulation by using WiDr cells. Transient G1 arrest was observed after UV exposure, whereas G2 but not G1 arrest was induced after X-ray irradiation. UV-exposure could induce G1 arrest in both mutant-type (mt-p53) and wild-type p53 (wt-p53) cells, but obvious G1 arrest was not observed in the cells lacking in p53 expression. An increase in the DNA fragmentation was observed at S phase in UV-irradiated cells and at G2 phase in X-irradiated cells, respectively. UV-irradiated cells showed an increase production of p53 protein and accumulation of p21 protein. On the contrary, both p53 and p21 proteins remained at a low level in X-irradiated cells. Treatment with aphidicolin, an S phase blocking agent, prolonged cell cycle arrest and reduced the rate of apoptotic cell death in both UV-irradiated and X-irradiated cells. From these results, it is suggested that UV-induced apoptosis occurs mainly at S phase and is regulated by increased production of p53 and p21 proteins, while X-ray-induced apoptosis occurs after G2 blockade and may be independent of p53. [ABSTRACT FROM AUTHOR]

Poly (methacrylic acid) gels (PMAA gels) of various degrees of crosslinking were prepared and the dissociation behavior of these gels was examined; the swelling behavior was investigated as a function of the solution pH values. A reentrant phenomenon of swelling was observed and interpreted based on the Flory-Huggins equation and the Donnan equilibrium formula. Moreover, adsorption of L-lysine, oligo(L-lysine)s (Lys- n, n=3, 9, and 19) and poly(L-lysine) onto PMAA gels from aqueous solutions was investigated under different conditions of pH and concentration of adsorbate. The adsorption ratio of L-lysine onto PMAA gel is dependent on both the pH of solution and the degree of crosslinking. In a pH range between 8 and 9, the protonated form of L-lysine is strongly adsorbed on the PMAA gel by electrostatic interactions. Oligomers and polymer of L-lysine are adsorbed in a somewhat different way from the monomeric L-lysine. In addition, the desorption behavior of L-lysine from PMAA gels by a change in pH was also investigated. [ABSTRACT FROM AUTHOR]

The enzymatic activities of horseradish peroxidase solubilized in reversed micelles of bis(2-ethylhexyl)sodium sulfosuccinate formed in octane at various Ω values ( Ω=[HO]/[AOT]) were investigated by studying the catalytic oxidation of hydroquinone and p-cresol. These enzymatic reactions obeyed Michaelis-Menten kinetics. The turnover number of the enzymatic reaction of hydroquinone solubilized in the water pool increased with a decrease in Ω value. On the other hand, the dependence of the turnover number of the enzymatic reaction of p-cresol solubilized in octane on the Ω value was similar to that in the case of hydroquinone, although even at higher Ω values the turnover number was smaller than that in water. Furthermore, it was suggested by spectrophotometric and circular dichroism measurements that the conformational change of enzyme induced the change in enzymatic activity. [ABSTRACT FROM AUTHOR]

The effect of the chain length on the conformation of oligo-L-lysines (Lys-n, n= 9, 12 and 15) was examined in the reversed micelles of bis(2-ethylhexyl)sodium sulfosuccinate (AOT) in octane by the circular dichroism (CD) measurements. These oligomers seem to take a β-structure in these systems. The structure-inducing effect of the reversed micelles is enhanced as the molar ratio of water to AOT (w=[HO]/[AOT]) becomes smaller. On the other hand, in the aqueous solutions the oligomers having 12 and 15 residues show the conformational transition from random coil to α-helical structure by the addition of AOT, but the short oligomer of 9 residues does not show such a conformational transition. [ABSTRACT FROM AUTHOR]

The molecular conformations of poly(N-dihydroxyethylaminopropyl-L-glutamine) and poly(N-dihydroxyethyl-L-glutamine) were investigated in reversed micelles of AOT as well as in aqueous solutions. Both poly( α-amino acid)s assume disordered structures in pure water. The conformation of poly(N-dihydroxyethylaminopropyl-L-glutamine) transits into α-helix in the reversed micelles as the molar ratio of water to AOT (w=[HO]/[AOT]) becomes smaller. A similar conformational transition was also observed in aqueous solutions when a certain amount of AOT was added. Under these conditions, however, poly(N-dihydroxyethyl-L-glutamine) did not undergo a conformational transition into α-helix. [ABSTRACT FROM AUTHOR]

The conformation of various basic poly ( α-amino acid)s was investigated by CD measurements in aqueous solutions containing bis (2-ethylhexyl)sodium sulfosuccinate (AOT) as well as in the AOT reversed micelles. The addition of AOT into an aqueous solution of poly(L-lysine) induces the conformational transition from coil to ordered structure, followed by aggregation. On the other hand, poly(L-lysine) assumes Β-structure in the reversed micelles at low wvalue (w=[HO]/[AOT]). Similarly to poly(L-lysine), poly(L-ornithine) takes an ordered structure in the aqueous solution containing AOT and Β-structure in the reversed micelles. In this case, however, these ordered structures are not so stable, compared with that of poly(L-lysine). Poly(L-arginine) undergoes the conformational transition from coil to helix by addition of AOT into the aqueous solution. Further addition of AOT allows transformation into Β-structure. Copoly(L-lysyl-L-leucine) with 63% leucine residue was shown to take a stable helical conformation even in pure water. In the reversed micelles, however, this ordered structure is significantly changed probably because the hydrophobic interaction among the leucyl residues is lowered in the reversed micelles. [ABSTRACT FROM AUTHOR]

Ionizing radiation is a well-known risk factor of cancer development, but the mechanism of radiation induced carcinogenesis is not clear. Chromosomal rearrangements induced by radiation most likely are one of the principal genetic alterations resulting in malignant transformation. The chimeric BCR-ABL associated with chronic myelogenous leukemia (CML) and H4-RET oncogenes associated with thyroid papillary carcinoma are the result of a translocation and inversion, respectively. In vitro studies showed these genes were induced by high-doses of X-irradiation in cell lines. Studies also show that therapeutic external X-ray doses as high as 60 Gy for treatment of various childhood cancers including Hodgkin's disease significantly increase the risk of thyroid cancer. Therefore, we examined the induction and persistence of these chimeric genes in human thyroid tissues transplanted in scid mice after 50 Gy exposure as a function of time for 2 months to elucidate the early events of thyroid carcinogenesis. The H4-RET genes were detected on day 2 and throughout the 2 month period. On the other hand, BCR-ABL genes were detected on day 2 and were undetectable subsequently. These results suggest that ionizing radiation causes various oncogene activations, but cells with only specific gene alteration uniquely associated with thyroid carcinogenesis are selectively retained demonstrating one of the early events in the beginnings of radiation carcinogenesis in human thyroid tissues. [ABSTRACT FROM AUTHOR]

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Physicochemical properties of two types of adriamycin preparation, suspensions and emulsions prepared for i.a. chemotherapy of hepatocellular carcinoma, were investigated. A suspension was prepared by dispersing adriamycin directly into the lipid contrast medium, Lipiodol, whereas an emulsion was obtained by emulsifying an aqueous solution of adriamycin into Lipiodol. The dispersibility of the drug in each preparation was examined microscopically. The chemical stability of and drug release from the preparation were determined by high-performance liquid chromatography and spectrophotometry, respectively. The suspension was then given to ten patients with primary hepatocellular carcinoma. The suspension maintained good dispersibility without coagulation of drug particles, whereas coalescence of aqueous droplets and the resultant phase separation occurred 4 h after preparation of the emulsion. Both preparations maintained the initial drug content for at least 1 week at room temperature. The release of adriamycin was more prolonged in the suspension than in the emulsion. After i.a. administration of the suspension, a selective accumulation of Lipiodol in the tumor and decrease in serum alpha-fetoprotein (AFP) levels were found in most patients. A significant amount of adriamycin was still detected in hepatic specimens resected from two patients 1 and 2 months after treatment. These findings suggest that the adriamycin-Lipiodol suspension may be a useful preparation for targeting chemotherapy to hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Pre-mRNA of serotonin 2C receptor (HTR2C, 5- hydroxy tryptamine (serotonin) receptor 2C) undergoes A-to-I type RNA editing, which is a post-transcriptional event leading to the change of genomically encoded information. RNA editing generates various HTR2C isoforms, each of which has distinctive receptor activity. Postmortem, animal, and pharmacological studies have suggested that the altered RNA editing of HTR2C is involved in the pathophysiology of mental disorders, although results remain inconsistent. Here we review the techniques used for estimation of RNA editing of HTR2C. Among the techniques reported so far, a high-throughput sequencing-based method would be the most powerful method of choice for the large-scale experiments. Several different methods that were previously developed, such as pyrosequencing and capillary electrophoresis, should be suitable for validation as well as for rapid screening or exploratory purposes. [ABSTRACT FROM AUTHOR]

A letter to the editor discussing the evidence of systematic gene expression changes with postmortem interval is presented.

Reports findings that the optical spectra and the light curve of supernova SN1998bw can be reproduced by an explosion of a star composed mainly of carbon and oxygen. Qualification of supernova as `hypernova' because of high luminosity; Possible association of the hypernova with the gamma ray burst GRB 980425; Explosion mechanism of very massive stars reconsidered; Origin of some classes of gamma ray bursts freshly examined.

Reports on the discovery of afterglows associated with gamma ray bursts at X-ray, optical, and radio wavelengths. Measurement of the redshifts of some of these events; Distances at which gamma ray bursts have been established to lie; Establishment of gamma ray bursts as the most powerful photon-emitters known in the universe; Discovery of transient optical emission in the error box of the gamma ray burst GRB980425.

A new HaeIII polymorphism, which is found in the first intron of the human p53 gene, provides a genetic marker for tumor suppressor p53 gene alterations. [ABSTRACT FROM AUTHOR]