A high signal-to-noise ratio passive near-field microscope equipped with a helium-free cryostat.

We have developed a passive long-wavelength infrared (LWIR) scattering-type scanning near-field optical microscope (s-SNOM) installed in a helium-free mechanically cooled cryostat, which facilitates cooling of an LWIR detector and optical elements to 4.5 K. To reduce mechanical vibration propagation from a compressor unit, we have introduced a metal bellows damper and a helium gas damper. These dampers ensure the performance of the s-SNOM to be free from mechanical vibration. Furthermore, we have introduced a solid immersion lens to improve the confocal microscope performance. To demonstrate the passive s-SNOM capability, we measured thermally excited surface evanescent waves on Au/SiO2 gratings. A near-field signal-to-noise ratio is 4.5 times the improvement with an acquisition time of 1 s/pixel. These improvements have made the passive s-SNOM a more convenient and higher-performance experimental tool with a higher signal-to-noise ratio for a shorter acquisition time of 0.1 s.

Rapid microstructure characterization of polymer thin films with 2D-array multifocus Raman microspectroscopy.

Raman imaging is one of the very informative methods for the characterization of chemically and structurally heterogeneous materials without employing specific molecular labels. Multifocus Raman imaging is one of the fast-imaging alternatives to the conventional single point mapping technique. Since multiple focal points probe the sample simultaneously, this imaging methodology is faster compared to single point mapping. We have further demonstrated the efficiency of this methodology by investigating the morphological features of a porous PMMA film. A Raman image of a 50 × 50 µm(2) area was obtained in less than 4 minutes (with a 10 × 10 multifocus configuration). Importantly, a 100 × 100 µm(2) area could now be analyzed in minutes while a similar Raman image by single point mapping would take hours to days. Optical sectioning using multifocus Raman imaging reveals unique hierarchical features of the porous polymer thin film. Larger pores are limited to the surface and the inner bulk exhibits characteristic small-pores and an interconnected highly porous morphology. The fast multifocal Raman imaging would be advantageous to the diverse field of scientific disciplines where the speed of image acquisition remains a challenge despite the unparalleled specificity and sensitivity of Raman spectroscopy.

Clinical effectiveness of oseltamivir and zanamivir for treatment of influenza A virus subtype H1N1 with the H274Y mutation: a Japanese, multicenter study of the 2007-2008 and 2008-2009 influenza seasons.

BACKGROUND: Influenza A virus subtype H1N1 with the H274Y mutation emerged and spread worldwide. However, the clinical effectiveness of the neuraminidase inhibitors, oseltamivir and zanamivir, has not been adequately reevaluated. METHODS: Data from 164 patients with H1N1 virus infection and 59 patients with H3N2 virus infection during the 2008-2009 influenza season and 68 patients with H1N1 virus infection during the 2007-2008 influenza season who received a neuraminidase inhibitor were analyzed. The duration of fever (body temperature 37.5 degrees C) after the first dose of oseltamivir or zanamivir and from onset of symptoms was calculated from patient reports. The influenza virus was isolated, and its subtype was determined by hemagglutinin inhibition assay and polymerase chain reaction. The H274Y neuraminidase mutation status was determined by sequencing the neuraminidase segment. RESULTS: Of 68 patients with H1N1 virus infection during the 2007-2008 season, 41 were treated with oseltamivir, and 27 were treated with zanamivir. During the 2008-2009 season, 77 patients with H1N1 virus infection were treated with oseltamivir, and 87 were treated with zanamivir; 31 and 28 patients with H3N2 virus infection were treated with oseltamivir and zanamivir, respectively. All 49 analyzed H1N1 virus isolates obtained during the 2008-2009 season, but none of the isolates obtained during the 2007-2008 season, contained the H274Y mutation. The mean +/- standard deviation duration of fever after the start of oseltamivir therapy was significantly longer for patients with H1N1 virus infection (49.1+/-30.2 h) than it was for patients with H3N2 virus infection (33.7+/-20.1 h; P < .01) during the 2008-2009 season and patients with H1N1 virus infection during the 2007-2008 season (32.0+/-18.9 h; P < .001). The duration of fever was significantly longer after the first dose of oseltamivir than it was after the first dose of zanamivir for patients with H1N1 virus infection during the 2008-2009 season (P <.001). The duration of fever from onset of H1N1 virus infection was significantly longer for children 15 years of age during 2008-2009 (70.6+/-34.5 h) than it was for such children during 2007-2008 (48.4+/-21.2). CONCLUSION: The effectiveness of oseltamivir, but not that of zanamivir, decreased significantly for H1N1 virus infection during the 2008-2009 season.

Microglia and astroglia prevent oxidative stress-induced neuronal cell death: implications for aceruloplasminemia.

We partially characterized the transferrin-independent iron uptake (Tf-IU) of neuronal and glial cells in the previous report. In the present study, we further examined a mechanism of which glial cells protect neuronal cells against iron stress using neuron-microglia (N-MG) and neuron-astrocyte (N-AS) co-cultures. When each solely purified cell was treated with iron citrate, cell death occurred in N and MG. However, AS proliferated under the same condition. Both N-MG and N-AS co-cultures were effective in resistance to excessive iron. The total and specific Tf-IU activities of N-MG co-cultures similar to those of N did not increase in a density-dependent manner. Contrarily, the total activity of AS was extremely high and the specific activity was extremely low as a result of proliferation. Regarding of effect of co-cultures on H(2)O(2)-induced cell death, N-MG co-cultures were less effective, but N-AS co-cultures were more effective in protecting N from the oxidative stress. These results suggest that N-MG co-cultures suppress the Tf-IU and N-AS co-cultures stimulate AS proliferation to protect neuronal cells. Brain cells from aceruloplasminemia with mutations in the ceruloplasmin gene take up iron by Tf-IU. Therefore, the different mechanisms of neuronal cell protection by MG and AS may explain the pathophysiological observations in the brains of patient with aceruloplasminemia.

A comparison of the effectiveness of zanamivir and oseltamivir for the treatment of influenza A and B.

OBJECTIVE: To compare the effectiveness of zanamivir with oseltamivir for influenza A and B. METHODS: 1113 patients with influenza A or B were enrolled in the 2006-2007 influenza season. The duration of fever (temperature, >or=37.5 degrees C) and the percentage of patients afebrile at 24 and 48 h after the first dose of zanamivir or oseltamivir were calculated. Virus persistence after zanamivir therapy was also evaluated. RESULTS: There were marginally significant differences between the duration of fever after the first dose of zanamivir (31.8+/-18.4h) and oseltamivir (35.5+/-23.9h) for influenza A (p<0.05). The duration of fever after starting zanamivir therapy (35.8+/-22.4h) was significantly shorter than that of oseltamivir (52.7+/-31.3h) for influenza B (p<0.001). There were no significant differences between influenza A and B in the percentage of patients afebrile at 24 or 48 h after the first inhalation of zanamivir. The reisolation rate after zanamivir therapy showed marginally significant differences between influenza A and B (<0.05). By multiple regression analysis, therapy (zanamivir or oseltamivir) was the major determinant affecting the duration of fever for influenza B. CONCLUSION: Zanamivir therapy is more effective than oseltamivir for the treatment of influenza B infection.

A change in the effectiveness of amantadine for the treatment of influenza over the 2003-2004, 2004-2005, and 2005-2006 influenza seasons in Japan.

A retrospective study of the 2003-2004, 2004-2005, and 2005-2006 influenza seasons was done to investigate the effectiveness of amantadine and oseltamivir for treating influenza A. Commercial antigen detection kits were used for diagnosis and data were collected from 44 clinics throughout Japan, using an Internet-based system. Oseltamivir was administered to 2775 patients and amantadine to 781 patients. The durations of fever, from the time of the first drug administration and from the onset of fever, were calculated for each patient. In the 2005-2006 season, the duration of fever from the first drug administration was longer for patients who received amantadine than for those who received oseltamivir when the patients were grouped by the time from onset of fever to the start of treatment (P < 0.001 for groups administered at 0-12, 13-24, 25-36 h from the onset) and by patient age (P < 0.001 for under 16 years and P < 0.05 for 16-64 years). Mean values of duration of fever from the first drug administration were 31.3 h, 31.3 h, and 31.9 h for oseltamivir therapy, and 33.3 h, 42.7 h, and 53.3 h for amantadine therapy, in the 2003-2004, 2004-2005, and 2005-2006 seasons, respectively. Reduction in the effectiveness of amantadine over the three influenza seasons were also observed in each age group of 0-6, 7-15, and 16-64 years. The studied season was an independent factor associated with the effectiveness of amantadine by multiple regression analysis. In conclusion, the effectiveness of oseltamivir did not change, but the effectiveness of amantadine was progressively reduced over the three influenza seasons.

[A study on preventive effects of mite allergens by specially-fabricated futons with anti-mite treatments].

BACKGROUND: The purpose of this study was to investigate effects of specially-fabricated futons (beds) with anti-mite treatments on reductions of mite allergens (Der p.1 and Der f.1) and serum IgE antibodies against Dp (Dermatophagoides pteronyssinus), Df (Dermatophagoides farinae) and house dust1. METHODS: The futons made by microfibers (Madoromi: M) and phenolic polymer grafted microfine fibers (Madoromi+ALLER BUSTER: M+A) were used. Three groups of student and nurse subjects were asked to use general woolen cotton futons, and the (M) and (M+A) futons for 11 months, respectively. RESULTS: After the 11 months, the ratios of Der p.1+f.1 allergens in the futons (M) and (M+A) to those in the control futon were 1/3.8 and 1/42.0, respectively, on average. The prevalence of serum IgE antibodies against Dp, Df and house dust1 was found to decrease from 46.7 to 6.7% for the group using the (M+A) futon. CONCLUSION: These results suggested the specially-fabricated futons with anti-mite treatments could effectively reduce mite allergens compared to those made from woolen cotton.

Midline prostatic cysts in healthy men: incidence and transabdominal sonographic findings.

OBJECTIVE: The purpose of this study was to use transabdominal sonography to investigate the incidence of midline prostatic cysts in healthy men. CONCLUSION: Midline prostatic cysts represent a common variant in asymptomatic men. In a patient with urologic symptoms, detection of a midline prostatic cyst requires a focused examination to determine whether the cyst represents a normal variant or is the cause of symptoms.

MyD88 is involved in the signalling pathway for Taxol-induced apoptosis and TNF-alpha expression in human myelomonocytic cells.

Taxol is an effective anti-tumour drug against a variety of tumour cells. Taxol directly induces apoptosis in addition to a G2/M cell cycle arrest. However, it remains poorly understood how Taxol induces apoptosis in tumour cells. Taxol induces the secretion of inflammatory cytokines in murine macrophages in a toll-like receptor-4 (TLR-4)-dependent manner in addition to its anti-tumour effects, but the effect of Taxol on human macrophages is controversial. In this study, we demonstrated that low doses (less than 1000 nmol/l) of Taxol induced the expression of tumour necrosis factor (TNF)-alpha in human myelomonocytic cells and that the induction of TNF-alpha mRNA was inhibited by dominant-negative myeloid differentiation protein (dnMyD88). Furthermore, we demonstrated that the same doses of Taxol induced apoptosis of the same myelomonocytic cells and that the Taxol-induced apoptosis was also inhibited by dnMyD88. In accordance with the previous reports, Taxol induced the expression of TNF-alpha and apoptosis in a TLR4-independent manner. These results suggest that TNF-alpha expression and apoptosis, both induced by Taxol in human myelomonocytic cells, share the signal transduction molecule MyD88.

[Preparation and evaluation of press-coated aminophylline tablet using crystalline cellulose and polyethylene glycol in the outer shell for timed-release dosage forms].

In an attempt to achieve chronopharmacotherapy for asthma, press-coated tablets (250 mg), which contained aminophylline in the core tablet in the form of low-substituted hydroxypropylcellulose (L-HPC) and coated with crystalline cellulose (PH-102) and polyethylene glycol (PEG) at various molecular weights and mixing ratios in the amounts of PH-102 and PEG as the outer shell (press-coating material), were prepared (chronopharmaceutics). Their applicability as timed-release (delayed-release) tablets with a lag time of disintegration and a subsequent rapid drug release phase was investigated. Various types of press-coated tablets were prepared using a tableting machine, and their aminophylline dissolution profiles were evaluated by the JP paddle method. Tablets with the timed-release characteristics could be prepared, and the lag time of disintegration was prolonged as the molecular weight and the amount of PEG, for example PEG 500,000, in the outer shell were increased. The lag time of disintegration could be controlled by the above-mentioned method, however, the pH of the medium had no effect on disintegration of the tablet and dissolution behavior of theophylline. The press-coated tablet (core tablet:aminophylline 50 mg, L-HPC and PEG 6000; outer shell:PH-102:PEG = 8:2 200 mg) with the timed-release characteristics was administered orally to rabbits for an in vivo test. Theophylline was first detected in plasma more than 2 h after administration; thus, this tablet showed a timed-release characteristics in the gastrointestinal tract. The time (tmax) required to reach the maximum plasma theophylline concentration (Cmax) observed after administration of the press-coated tablet was significantly (p < 0.05) delayed compared with that observed after administration of aminophylline solution in the control experiment. However, there was no difference in Cmax and area under the plasma theophylline concentration-time curve (AUC0-->24) between the press-coated tablet and aminophylline solution. These results suggest that the press-coated aminophylline tablet (with the timed-release characteristic) offers a promising forms of theophylline chronotherapy for asthma.

Modulation of iron regulatory protein-1 by various metals.

Iron regulatory protein-1 (IRP-1) is known as a cytosolic aconitase and a central regulator of iron (Fe) homeostasis. IRP-1 regulates the expression of Fe metabolism-related proteins by interacting with the Fe-responsive element (IRE) in the untranslated regions of mRNAs of these proteins. However, it is less known whether IRP-1 modulates various non-Fe metals. In the present study, we showed that treatment of homogenously purified IRP-1 with non-Fe metals decreased the affinity to IRE in RNA band shift assays and increased aconitase activity. Non-Fe metals also inhibited (55)Fe incorporation into the fourth labile position of the Fe-S cluster of IRP-1. In PLC hepatoma cells, metal loading inactivated binding activity and activated enzyme activity. It also suppressed transferrin receptor mRNA expression in the cells. These results suggest that various non-Fe metals modulate IRP-1 by conversion of the 3Fe-4S apo-form to a [1 non-Fe metal + 3Fe]-4Fe holo-form.

Fine-pitched microgratings encoded by interference of UV femtosecond laser pulses.

Fine-pitched microgratings are encoded on fused silica surfaces by a two-beam laser interference technique employing UV femtosecond pulses from the third harmonics of a Ti:sapphire laser. A pump and prove method utilizing a laser-induced optical Kerr effect or transient optical absorption change has been developed to achieve the time coincidence of the two pulses. Use of the UV pulses makes it possible to narrow the grating pitches to an opening as small as 290 nm, and the groove width of the gratings is of nanoscale size. The present technique provides a novel opportunity for the fabrication of periodic nanoscale structures in various materials.