Effect of Al concentration on pseudoelasticity in Fe3Al single crystals

Pseudoelasticity in Fe₃Al single crystals with different Al contents was investigated focusing on the dislocation configuration and the ordered domain structure. Giant pseudoelasticity only appeared in the D0₃-ordered Fe₃Al single crystals, while the B2-ordered crystals and those with the disordered phase exhibited small strain recovery. The amount of shape recovery in the D0₃-ordered crystals showed a maximum near 23.0at.%Al and decreased with increasing deviation from this Al concentration. In the D0₃ phase at 22.0–25.0at.%Al, 1/4[1 1 1] superpartial dislocations moved individually dragging the nearest-neighbour antiphase boundaries (NNAPB), while couplets of the superpartials were observed to bow out, dragging the next-nearest-neighbour antiphase boundaries (NNNAPB) in Fe–28.0at.%Al. In Fe–22.0–25.0at.%Al single crystals, the NNAPB pulled back the superpartials to decrease its energy during unloading, resulting in the giant pseudoelasticity. In contrast, the surface tension of the NNNAPB was lower than that of the NNAPB, leading to the small strain recovery in Fe–28.0at.%Al.     

Performance of the first Japanese large-scale facility for radon inhalation experiments with small animals

A radon test facility for small animals was developed in order to increase the statistical validity of differences of the biological response in various radon environments. This paper illustrates the performances of that facility, the first large-scale facility of its kind in Japan. The facility has a capability to conduct approximately 150 mouse-scale tests at the same time. The apparatus for exposing small animals to radon has six animal chamber groups with five independent cages each. Different radon concentrations in each animal chamber group are available. Because the first target of this study is to examine the in vivo behaviour of radon and its effects, the major functions to control radon and to eliminate thoron were examined experimentally. Additionally, radon progeny concentrations and their particle size distributions in the cages were also examined experimentally to be considered in future projects.     

Photocatalytic Inactivation of Legionella Pneumophila and an Aerobic Bacteria Consortium in Water over TiO2/SiO2 Fibres in a Continuous Reactor

A continuous photoreactor, working in a total recycle mode and irradiated by a low-pressure Hg lamp, has been used to study the bactericidal effect of a photocatalyst, formed by TiO₂ embedded in SiO₂ fibres, on Legionella pneumophila and a consortium of common gram-negative aerobic bacteria: (Escherichia coli, Klebsiella sp., Pseudomona sp. and Proteus sp.) in water. The kinetic modeling of the inactivation process, carried out with the measured values of viable bacteria concentration at the outlet of photoreactor, evidenced that for each pass inside the photoreactor the ratio between the outlet and inlet cell concentrations was of order of 0.01 for the inactivation of L. pneumophila. For the other aerobic bacteria, which are usually taken as reference in photocatalytic bacteria inactivation studies, this ratio was of order of 0.3 for the first hour of illumination, while upon prolonged irradiation (up to 9 h) this ratio increased to 0.7. Several factors inducing this latter decrease of efficiency are possible, as e.g. competition for photocatalytic attack between microorganisms and organic compounds released by damaged bacteria or photoinduced alteration of a small fraction of still viable bacteria making them less interactive with the photocatalyst. The inactivation mechanism normally proposed for common bacteria involves an initial attack of the photogenerated radicals to the outer membrane; the consequent membrane dispersion allows the radicals to damage the cytoplasmic membrane. The higher lethality of the photocatalytic method observed towards Legionella: (in comparison to the other aerobic bacteria) is explained considering that the radicals attack the Legionella secretion system, which is adapted for high virulence and would become activated for and through adhesion to the TiO₂ surface. This attack would then be able to inactivate L. pneumophila without dispersing the outer membrane. Apart from this, the water flow through the catalyst fibres can facilitate the bacteria transport towards the anatase surface, and additionally the generated shear stress may help adhesion, at least for some bacteria as E. coli, contributing further to improve the photokilling efficiency; both factors may contribute to the efficiency of this photoreactor configuration.     

Plasma levels of natriuretic peptides and adrenomedullin in elderly hypertensive patients: relationships to 24 h blood pressure

OBJECTIVE: The aim of this study was to investigate the relationships between levels of natriuretic peptides and adrenomedullin and 24 h blood pressure levels in elderly hypertensives. DESIGN AND METHODS: We performed both 24 h ambulatory blood pressure monitoring and measurement of plasma levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and adrenomedullin in 118 asymptomatic hypertensive elderly (> 60 years old) patients. We classified the subjects into groups with isolated clinic hypertension (n = 40) and sustained hypertension (n = 78). We also measured the levels of these peptides in 37 elderly normotensive subjects. RESULTS: Plasma ANP and BNP levels were slightly increased in patients with isolated clinic hypertension compared with elderly normotensives. Among the hypertensives, plasma ANP and BNP levels were more closely related to 24 h blood pressure levels than to office blood pressure levels. Sustained hypertensives showed significantly increased plasma levels of ANP and BNP compared with isolated clinic hypertensives, while adrenomedullin levels were similar in the two groups. Elderly hypertensives with left ventricular hypertrophy detected by electrocardiography had significantly higher levels of ANP and BNP, and higher BNP/ANP ratios than those without left ventricular hypertrophy, while there was no significant difference in adrenomedullin levels between the two groups. CONCLUSIONS: Our results suggest that measurements of ANP and BNP may be useful in detecting left ventricular hypertrophy and in differentiating isolated clinic hypertension from sustained hypertension in elderly hypertensive patients.     

Evidence for the existence of L-dopa-immunoreactive neurons in the human mesencephalic region

Radioactive end labeling can be used to determine the hydrolytic rates of nuclease mimics on moderate to long lengths of RNA or DNA. However, the reliability of end labeling as an assay can vary depending on how well the unincorporated label is removed from the labeled RNA or DNA products. Therefore, gel filtration, acid precipitation, membrane diafiltration, and paper chromatography were tested to determine which technique was the most effective at such separation. The results in order of decreasing contamination by [gamma-32P]ATP were gel filtration (40%), acid precipitation (5%), diafiltration (2%), and paper chromatography (1%); and, in order of decreasing loss of RNA, were acid precipitation (30%), diafiltration (11%), gel filtration (10%), and paper chromatography (1%). In order for the resultant radioactive counts to be linearly proportional to the number of cleavage sites, the total ATP in the end-labeling reaction should be in excess of 5'-hydroxyl ends by a factor of 10 or more. Interference by nuclease mimics in the end-labeling reaction should be accounted for by including the mimics when developing a standard curve based on known concentrations of 5'-hydroxyl ends.     

Strain difference in the induction of T-cell activation-associated, interferon gamma-dependent hepatic injury in mice

A single intravenous injection of concanavalin A (Con A) induces T-cell activation-associated inflammatory injury selectively in the liver. This study investigated the strain difference in the development of Con A-induced hepatic injury. Normal C57BL/6 and BALB/c spleen cells produced comparable levels of T-cell-derived lymphokines (interferon gamma [IFN-gamma], tumor necrosis factor alpha [TNF-alpha], and interleukin-2 [IL-2]) following in vitro stimulation with Con A. A single intravenous injection of Con A to C57BL/6 mice induced the plasma levels of TNF-alpha and IL-2 comparable with or slightly higher than those observed in BALB/c mice, whereas the same treatment resulted in an apparently lower level of IFN-gamma production in C57BL/6 mice. RNA from livers of Con A-treated C57BL/6 mice exhibited lower levels of IFN-gamma mRNA than RNA of BALB/c livers. Unexpectedly, a dramatic difference in the severity of hepatic injury was observed between C57BL/6 and BALB/c. Namely, the peak alanine transaminase (ALT) level was more than 15,000 U/L and inducible as early as 8 hours after injection of 0.2 mg Con A per mouse in the C57BL/6 strain, whereas the peak was approximately 3,000 U/L and induced as late as 24 hours after Con A injection in the BALB/c strain. The increase in plasma ALT levels was limited to less than 10% by injection of anti-IFN-gamma monoclonal antibody (mAb) in both strains. The C57BL/6 strain inducing lower levels of IFN-gamma exhibited higher IFN-gamma responsiveness as exemplified by the intrahepatic expression of an IFN-gamma-inducible gene, an inducible type of nitric oxide (NO) synthase (iNOS). These results indicate that, while IFN-gamma produced in vivo by activated T cells induces hepatic injury, there exists a striking strain difference in the induction of IFN-gamma-dependent hepatic injury.     

Health-related quality of life varies with personality types: a comparison among cancer patients, non-cancer patients and healthy individuals in a Japanese population

In an attempt to examine differential effects of personality on health-related quality of life (HRQoL) without regard to disease type, we used the HRQoL-20, a general questionnaire (Japanese original scale) we developed (comprising 20 questions related to physiological, psychological or social HRQoL) and the Eysenck Personality Questionnaire (EPQ), which measures personality traits of extraversion (E), neuroticism (N) and psychoticism (P). The subjects (399 males and 429 females), stomach cancer patients, non-cancer patients (who had received acupuncture or moxibustion treatment) and healthy controls, were classified into three personality types. The results indicated that the HRQoL score of the tolerable/tolerant type (high E, low N and high P scorers) was greater than the intolerable/intolerant type (low E, high N and low P scorers) and also the unclassified type (neither of above scorers). The HRQoL correlated positively with the E and P scales and negatively with the N scale, in the case of all subjects, with the exception of N in male cancer patients and E in male non-cancer patients. The results supported the hypothesis that the HRQoL varies with personality variables, in that each patient, in different treatment settings, strives for the situation that is congruent with his/her personality to attain a better HRQoL.     

Cloning of two isoforms of mouse DNA helicase Q1/RecQL cDNA; alpha form is expressed ubiquitously and beta form specifically in the testis

We cloned cDNAs encoding mouse homologues for the human DNA helicase Q1/RecQL (human helicase Q1) which has homology with the Escherichia coli RecQ protein and found that they encode two isoforms. The two isoforms are identical over the entire sequence except for the carboxyl terminal sequence spanning less than 30 amino acids. One of the two isoforms, alpha, contains a sequence, KKRK, in the carboxyl terminus, which is also contained in human helicase Q1 and was confirmed to function as the nuclear localization signal. The other form, beta, does not contain such a sequence. Expression of mouse helicase Q1 mRNA is extremely and relatively high in the testis and the thymus, respectively. RT-PCR analysis revealed that helicase Q1alpha was expressed in all tissues tested and the beta form was expressed only in the testis. A survey of expression of Q1alpha and Q1beta mRNA in the testis after birth revealed that Q1alpha mRNA is expressed in all testes of mice aged from 7 days to 8 weeks, and the expression of Q1beta mRNA begins 14 days after birth, corresponding to the appearance of cells in the pachytene stage.     

A new antitumor agent amrubicin induces cell growth inhibition by stabilizing topoisomerase II-DNA complex

Amrubicin is a novel, completely synthetic 9-aminoanthracycline derivative. Amrubicin and its C-13 alcohol metabolite, amrubicinol, inhibited purified human DNA topoisomerase II (topo II). Compared with doxorubicin (DXR), amrubicin and amrubicinol induced extensive DNA-protein complex formation and double-strand DNA breaks in CCRF-CEM cells and KU-2 cells. In this study, we found that ICRF-193, a topo II catalytic inhibitor, antagonized both DNA-protein complex formation and double-strand DNA breaks induced by amrubicin and amrubicinol. Coordinately, cell growth inhibition induced by amrubicin and amrubicinol, but not that induced by DXR, was antagonized by ICRF-193. Taken together, these findings indicate that the cell growth-inhibitory effects of amrubicin and amrubicinol are due to DNA-protein complex formation followed by double-strand DNA breaks, which are mediated by topo II.     

Loss of biological activity due to Glu-->Arg mutation at residue 11 of the B subunit of cholera toxin

PURPOSE: To determine the maximum tolerated dose, toxicities, and potential antitumor activity of edatrexate (E), an antifolate agent with enhanced in vitro antitumor activity as compared with methotrexate (M), when given in combination with vinblastine, doxorubicin, cisplatin, and filgrastim (G-CSF) to patients with advanced malignancies. PATIENTS AND METHODS: Thirty-seven patients with advanced malignancies were treated with escalating doses of edatrexate in combination with vinblastine (V), doxorubicin (A), cisplatin (C), and filgrastim (EVAC/G-CSF) following three different subsequently developed schedules. Schedule 1 was patterned after the MVAC regimen, a combination chemotherapy program with activity against different epithelial malignancies, and consisted of E, 40 mg/m2/day, days 1/15/22; V, 3 mg/m2/day, days 2/15/22; A, 30 mg/m2/ day, day 2; C, 70 mg/m2/day, day 2; repeated every 28 days. Schedules 2 and 3 were designed to avoid observed dose-limiting toxicity on schedule 1 consisting of transient elevation of serum creatinine levels and delayed myelosuppression. Schedule 2 consisted of E, 40 or 60 mg/ m2/day, days 1 and 15; V, 3 mg/m2/day, days 2 and 15; A, 30 mg/m2/day, day 2; C, 30 mg/m2/day, days 1 and 2; cycled every 28 days. Schedule 3 consisted of E, 60 to 120 mg/m2/day, day 1; V, 3 mg/m2/day, day 2; A, 30 mg/m2/day, day 2; C, 30 mg/m2/day, days 1 and 2; cycled every 21 days. Filgrastim 5 micrograms/kg/day was given to all patients subcutaneously until the absolute neutrophil count was greater than 10,000/microL postnadir. Three patients were treated on schedule 1, 10 on schedule 2 (four at an E dose of 40 mg/m2/day and six at an E dose of 60 mg/m2/day), and 24 on schedule 3 (six at each of the following E dosages: 60, 80, 100, and 120 mg/m2/day). RESULTS: Dose-limiting toxicities of grade 3 to 4 leukopenia and transient elevation of serum creatinine values were observed in two of three patients treated on schedule 1. A dose-limiting toxicity of grade 3 to 4 leukopenia was noted in two of six patients treated on schedule 2 at an edatrexate dose of 60 mg/m2/day. Two of six patients treated on schedule 3 at an edatrexate dose of 120 mg/m2/day had a dose-limiting toxicity of grade 3 stomatitis (one patient) and grade 3 cytopenia (one patient). Nineteen of 37 patients with evaluable or measurable disease had a response to treatment (response rate 51%, 95% confidence intervals = 35%-67%). Nine of 15 patients with metastatic non-small cell lung cancer responded, including one complete remission (response rate 60%, confidence intervals = 35%-85%). A median survival of 517 days (confidence interval = 163-808 days) and a 1-year survival rate of 60% (confidence interval = 35%-85%) was seen in patients with advanced non-small cell lung cancer. CONCLUSIONS: The maximum tolerated dose and the recommended phase II dose of edatrexate is 100 mg/m2/day when administered as part of the EVAC/G-CSF program following schedule 3. Promising antineoplastic activity against non-small cell lung carcinomas was observed, and a phase II study is planned.