Polymerization of room-temperature ionic liquid monomers by electron beam irradiation with the aim of fabricating three-dimensional micropolymer/nanopolymer structures.

A novel method for fabricating microsized and nanosized polymer structures from a room-temperature ionic liquid (RTIL) on a Si substrate was developed by the patterned irradiation of an electron beam (EB). An extremely low vapor pressure of the RTIL, 1-allyl-3-ethylimidazolium bis((trifluoromethane)sulfonyl)amide, allows it to be introduced into the high-vacuum chamber of an electron beam apparatus to conduct a radiation-induced polymerization in the nanoregion. We prepared various three-dimensional (3D) micro/nanopolymer structures having high aspect ratios of up to 5 with a resolution of sub-100 nm. In addition, the effects of the irradiation dose and beam current on the physicochemical properties of the deposited polymers were investigated by recording the FT-IR spectra and Young's modulus. Interestingly, the overall shapes of the obtained structures were different from those prepared in our recent study using a focused ion beam (FIB) even if the samples were irradiated in a similar manner. This may be due to the different transmission between the two types of beams as discussed on the basis of the theoretical calculations of the quantum beam trajectories. Perceptions obtained in this study provide facile preparation procedures for the micro/nanostructures.

Inorganic polyphosphate induces osteoblastic differentiation.

Inorganic polyphosphate [Poly(P)] is especially prevalent in osteoblasts. We tested the hypothesis that Poly(P) stimulates osteoblastic differentiation and polyphosphate metabolism for bone formation. The osteoblast-like cell line, MC 3T3-E1, was cultured with Poly(P), and gene expression was evaluated by real-time reverse-transcription polymerase chain-reaction. Phosphatase activity and extracellular matrix mineralization were also determined. The role of Poly(P) was assessed in a beagle dog alveolar bone regeneration model. Poly(P) increased osteocalcin, osterix, bone sialoprotein, and tissue non-specific alkaline phosphatase gene expression, with a high level of end-polyphosphatase activity, resulting in low-chain-length Poly(P), inorganic pyrophosphate, and inorganic phosphate production. MC3T3-E1 cells differentiated into mature osteoblasts and showed expression of ectonucleotide pyrophosphatase phosphodiesterase 1, while mouse progressive ankylosis gene expression remained unchanged. Promotion of alveolar bone regeneration was observed in Poly(P)-treated beagle dogs. These findings suggest that Poly(P) induces osteoblastic differentiation and bone mineralization, and acts as a resource for mineralization.

Tuning of the fluorescence wavelength of CdTe quantum dots with 2 nm resolution by size-selective photoetching.

Photoetching of CdTe nanocrystals was applied to thiol-capped CdTe quantum dots (QDs) to control their fluorescence wavelength. CdTe QDs with a high quantum yield (49%) were synthesized in aqueous solution, and they were successfully photoetched in strong alkaline (pH = 13.5) conditions. When monochromatic light was used, size-selective photoetching could be conducted; the photoetching proceeded until the band gap energy of the CdTe QDs increased to the energy corresponding to the wavelength of the irradiating light. As a result, a good linear relationship was obtained between the wavelength of the irradiating light and that of the fluorescence peak. The resulting CdTe QDs exhibited a fluorescence peak with an FWHM value as small as 23.5 nm, indicating preparation of highly monodispersed nanocrystals. The high quantum yield (ca. 45%) was maintained after the photoetching. Very fine tuning of the fluorescence wavelength with 2 nm resolution was achieved by changing the wavelength of the irradiating light by 2 nm. Theoretical calculation of the quantum size effects (effective mass approximation) predicts that a difference in the band gap fluorescence wavelength of 2 nm corresponds to a change in particle diameter of ca. 0.02 nm.

Soft-copy reading in digital mammography of mass: diagnostic performance of a 5-megapixel cathode ray tube monitor versus a 3-megapixel liquid crystal display monitor in a diagnostic setting.

BACKGROUND: Liquid crystal display (LCD) monitors and cathode ray tube (CRT) monitors are currently the two most common types used in digital mammography systems. The appropriate selection of a monitor is very important and requires balancing the monitor's performance and its cost. A previous study of soft-copy reading in digital mammography of microcalcifications showed that 3-megapixel (M) LCD monitors were similar in diagnostic performance to 5M CRT monitors in a diagnostic setting. PURPOSE: To compare 5M CRT monitors with 3M LCD monitors for soft-copy reading of digital mammography of a mass in a diagnostic setting. MATERIAL AND METHODS: Seventy mass lesions having undergone either breast biopsies or definitive surgery (46 malignant and 24 benign) and 30 normal cases were recruited into the study. The median size of the lesions was 16 mm (range 7-20 mm). The digital mammograms in the 100-case set were assigned to two blocks, block A (50 cases) and block B (50 cases), for 5M CRT and 3M LCD monitors. A single radiologist read all 100 cases with both types of monitors, starting with the images in block A on the 5M CRT monitors and then the images in block B on the 3M LCD monitors. The radiologist analyzed the soft-copy images on 5M CRT and 3M LCD monitors with 5 months between the interpretations to reduce the effects of learning and memory. Again, the reader started with the images in block A on the 3M LCD monitors and then read the images in block B on the 5M CRT monitors. A five-point rating scale for the probability of malignancy was used for interpreting the soft-copy mammograms. The mass descriptor was scored on a six-point scale. Breast density was scored on a four-point scale. The positive predictive value (PPV) and negative predictive value (NPV) were calculated based on the criteria of the Breast Imaging Reporting and Data System. The interpretation time was also measured. RESULTS: No significant difference was observed in the probability of malignancy (P=1), mass descriptor (P=0.317), and breast density (P=0.739). The PPV and NPV of soft-copy reading on the 5M CRT monitors were 91% (42/46) and 94% (51/54), respectively, identical to the results using 3M LCD monitors. The total interpretation time averaged 62 s for the 5M CRT monitors and 60 s for the 3M LCD monitors (P<0.0001). CONCLUSION: Soft-copy reading of a digital mammography of mass with 3M LCD monitors was similar in diagnostic performance to 5M CRT monitors in this study. On the basis of the results of this and a previous study, 3M LCD monitors can replace 5M CRT monitors without any loss in the ability to diagnose digital mammograms.

Soft-copy reading in digital mammography of microcalcifications: diagnostic performance of a 5-megapixel cathode ray tube monitor versus a 3-megapixel liquid crystal display monitor in a clinical setting.

BACKGROUND: A recent study using dedicated contrast-detail phantoms showed that the image quality of a 3-megapixel (M) monitor can approach that of a 5M monitor in digital mammography. PURPOSE: To compare a 5M cathode ray tube (CRT) monitor with a 3M liquid crystal display (LCD) monitor for soft-copy reading of digital mammography of microcalcifications in a clinical setting. MATERIAL AND METHODS: 100 screen-detected microcalcification lesions (34 malignant and 66 benign) without mass that had been evaluated with 11-gauge stereotactic vacuum-assisted breast biopsy or definitive surgery were recruited into the study. One radiologist analyzed the soft-copy mammograms on a 5M CRT monitor and a 3M LCD monitor with 5 months between interpretations and scored the likelihood of malignancy and calcification distribution on a five-point scale. Calcification morphology and breast density were scored on a four-point scale. Positive predictive value (PPV) and negative predictive value (NPV) were calculated on the basis of a Breast Imaging Reporting and Data System. The interpretation time was also measured. RESULTS: There was no significant difference in the likelihood of malignancy (P = 0.655), calcification morphology (P = 0.168), calcification distribution (P = 0.11), and breast density (P = 0.0608). The PPV and NPV of soft-copy reading on the 5M CRT monitor was 57% (30/53) and 91% (43/47), respectively, identical to the results using the 3M LCD monitor. The total interpretation time averaged 88 s for the 5M CRT monitor and 67 s for the 3M LCD monitor (P<0.0001). CONCLUSION: Soft-copy reading of a digital mammography of microcalcifications with a 3M LCD monitor was similar in diagnostic performance to a 5M CRT monitor in this study.

Inorganic polyphosphate: a possible stimulant of bone formation.

Inorganic polyphosphates [Poly(P)] are often distributed in osteoblasts. We undertook the present study to verify the hypothesis that Poly(P) stimulates osteoblasts and facilitates bone formation. The osteoblast-like cell line MC 3T3-E1 was cultured with Poly(P), and gene expression and potential mineralization were evaluated by reverse-transcription polymerase chain-reaction. Alkaline phosphatase activity, von Kossa staining, and resorption pit formation analyses were also determined. The potential role of Poly(P) in bone formation was assessed in a rat alveolar bone regeneration model. Poly(P) induced osteopontin, osteocalcin, collagen 1alpha, and osteoprotegerin expression and increased alkaline phosphatase activity in MC 3T3-E1 cells. Dentin slice pit formation decreased with mouse osteoblast and bone marrow macrophage co-cultivation in the presence of Poly(P). Promotion of alveolar bone regeneration was observed locally in Poly(P)-treated rats. These findings suggest that Poly(P) plays a role in osteoblastic differentiation, activation, and bone mineralization. Thus, local poly(P) delivery may have a therapeutic benefit in periodontal disease.

Preoperative computed tomography-guided percutaneous hookwire localization of metallic marker clips in the breast with a radial approach: initial experience.

BACKGROUND: Hookwire localization is the current standard technique for radiological marking of nonpalpable breast lesions. Stereotactic directional vacuum-assisted breast biopsy (SVAB) is of sufficient sensitivity and specificity to replace surgical biopsy. Wire localization for metallic marker clips placed after SVAB is needed. PURPOSE: To describe a method for performing computed tomography (CT)-guided hookwire localization using a radial approach for metallic marker clips placed percutaneously after SVAB. MATERIAL AND METHODS: Nineteen women scheduled for SVAB with marker-clip placement, CT-guided wire localization of marker clips, and, eventually, surgical excision were prospectively entered into the study. CT-guided wire localization was performed with a radial approach, followed by placement of a localizing marker-clip surgical excision. Feasibility and reliability of the procedure and the incidence of complications were examined. RESULTS: CT-guided wire localization surgical excision was successfully performed in all 19 women without any complications. The mean total procedure time was 15 min. The median distance on CT image from marker clip to hookwire was 2 mm (range 0-3 mm). CONCLUSION: CT-guided preoperative hookwire localization with a radial approach for marker clips after SVAB is technically feasible.

New class of dynamics in concentrated polymer gels.

We show that concentrated poly(methyl methacrylate) solution exhibits a new class of coupled dynamics, which can be regarded as an intermediate between the collective diffusion of solutions and the structural relaxations of glasses. This class of dynamics have a relaxation rate that is directly proportional to the wave vector. The transition from diffusive to coupled collective dynamics occurs at smaller length scales with increasing polymer concentration and decreasing temperature. The experimental observations can be understood by considering the contributions from physical cross-links interconnected by stiff polymer segments.

Overeruption without root exposure of third molars and periodontal health in the mandible.

Bone formation is seen around the third molar even when the tooth is exposed to the oral environment due to overeruption. To determine if overeruption of the third molar with or without root exposure is related to the status of the exposure of other teeth in the mandible, using orthopantomographs, 424 third molars were studied in 371 patients who were over 41 years of age. The rate of overeruption and root exposure in third molars was measured, and its relationship to the number of teeth lost and the rate of root exposure in other teeth in the mandible was analyzed. Tooth loss in the group of third molars with overeruption without root exposure was greater than in that without overeruption or root exposure in men, whereas the relationship was not seen in women. We found that root exposures of other teeth in the group of third molars with overeruption without root exposure were significantly smaller than in those with root exposure in both genders. Third molars with overeruption without root exposure, in which bone formation was easy to observe for radiographic diagnosis, were correlated with periodontal health in the mandible, suggesting a component of precision determination for predicting resistance to periodontitis.

Induction of calcification in MC3T3-E1 cells by inorganic polyphosphate.

Relatively large amounts of inorganic polyphosphate [poly(P)] (400 microM) have been found in normal osteoblasts. The effect of poly(P) with an average chain length of 65 phosphate residues on cell calcification was therefore investigated with the use of MC3T3-E1 cells. Expression of both osteopontin and osteocalcin was induced by poly(P) (0.1 approximately 1 mM), and cells treated with poly(P) were strongly stained by alizarin red. In addition, the level of alkaline phosphatase activity induced in poly(P)-treated cells was two-fold higher than that in either orthophosphate-treated or control cells but not higher than that in cells treated with beta-glycerophosphate and ascorbic acid. In contrast, however, polyphosphatase activities were activated by poly(P) treatment to levels up to six-fold greater than that in controls. MC3T3-E1 cells may utilize poly(P) as a phosphate source for calcification rather than phosphate sources that are mainly produced by ALPase. Poly(P)-dependent induction of polyphosphatase activities may therefore promote calcification in MC3T3-E1 cells.

Power laws in polymer solution dynamics.

The dynamical screening length xi(h) in semidilute to highly concentrated polymer solutions of poly(methyl methacrylate) in propylene carbonate has been examined using photon correlation spectroscopy and pulsed field gradient nuclear magnetic resonance. A crossover between different concentration dependent regimes, xi(h) approximately phi(-alpha), where alpha is found to be approximately 0.5, approximately 1, and approximately 2, is observed when the local viscosity is taken into account. Here phi is the volume fraction of polymer in the solution. Well-defined crossovers between alpha=0.5 and alpha=1 corresponding to a transition from a marginal solvent to a theta solvent behavior have been predicted to occur due to the reduction of excluded-volume effects between the spatially correlated polymer segments with increasing polymer volume fraction. However, a clear experimental validation of the crossover has never been presented before. The third regime (alpha approximately 2) is observed in the highly concentrated region where the static screening length is comparable to the persistence length of the polymer. The observation indicates that the rigid rod model previously used to describe concentrated solutions is an oversimplification valid only in the very high concentration limit. The obtained results at high concentrations are discussed in the frame of a simple physical model where segments at the persistence length scale are treated as flexible rodlike segments.

Relationship of the hyoid bone and posterior surface of the tongue in prognathism and micrognathia.

In order to study relationship of the hyoid bone and posterior surface of the tongue in prognathism and micrognathia, we focused on the effect of the tongue on the upper airway lumen in 16 patients with Angle's Class II and 51 patients with Angle's Class III, and assessed the position of the hyoid, the depth from the posterior surface of the tongue, from the bottom of the vallecula and from hyoid bone to the posterior pharyngeal wall using lateral cephalograms. We were able to assess significant correlations between the posterior surface of the tongue and hyoid position in Angle's Class III. However, we found no association between them in Angle's Class II. This could be an adaptive feature of the genioglossus in response to hyoid localization to serve a compensatory role to prevent respiratory impairment in micrognathia at risk of apnoea.

Comparison between high-resolution helical CT and pathology in breast examination.

PURPOSE: To determine whether high-resolution helical CT can show the architectural features of breast carcinomas of non-limited extent (non-BCLE) and to establish the CT characteristic morphology of non-BCLE. MATERIAL AND METHODS: We prospectively studied high-resolution helical CT of 136 invasive breast carcinomas before breast-conserving surgery. Non-BCLE were defined as ductal carcinomas in situ and invasive carcinomas beyond 1 cm from the edge of the dominant mass. Non-BCLE were defined as positive if enhanced beyond 1 cm from the edge of the focal enhancement on CT. After surgical resection, specimens were sliced in serial sections at 5-mm intervals, and the gross morphology and histology were correlated with the appearance of the preoperative CT lesion images. RESULTS: Non-BCLE were present in 47 invasive carcinomas. The sensitivity and specificity of non-BCLE evaluation by high-resolution helical CT were 70% and 89%, respectively. The morphology of non-BCLE on CT agreed with histologic findings. The morphological pattern on CT significantly correlated with intraductal tumor density adjacent to invasive tumor. CONCLUSION: Comparison of high-resolution helical CT with histologic data suggests that demonstration of a non-BCLE morphology can make the CT breast carcinoma local staging more accurate.

Interleukin (IL)-17 enhances prostaglandin F(2 alpha)-stimulated IL-6 synthesis in osteoblasts.

We previously showed that prostaglandin F(2alpha) (PGF(2alpha)) and endothelin-1 (ET-1) induce interleukin (IL)-6 through the activation of protein kinase C-dependent p44/p42 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. It has recently been reported that tumor necrosis factor-alpha-induced IL-6 synthesis is amplified by IL-17 in these cells. In the present study, we investigated the effect of IL-17 on the IL-6 synthesis stimulated by PGF(2alpha) in MC3T3-E1 cells. IL-17 significantly enhanced the PGF(2alpha)-induced IL-6 synthesis in a dose-dependent manner in the range between 0.1 and 10 ng/ml. IL-17 also enhanced the IL-6 synthesis stimulated by 12- O -tetradecanoylphorbol-13-acetate, a direct activator of protein kinase C. In addition, IL-17 amplified the IL-6 synthesis induced by ET-1. However, IL-17 hardly affected the phosphorylation of p44/p42 MAP kinase induced by PGF(2alpha) or ET-1. These results strongly suggest that IL-17 enhances the IL-6 synthesis stimulated by PGF(2alpha) as well as ET-1 in osteoblasts, and that the effect is exerted at a point downstream from p44/p42 MAP kinase.

Mechanism of prostaglandin E2-stimulated heat shock protein 27 induction in osteoblast-like MC3T3-E1 cells.

We investigated the effect of prostaglandin E2 (PGE2) on the induction of heat shock protein 27 (HSP27) and HSP70, and the mechanism behind the induction in osteoblast-like MC3T3-E1 cells. PGE2 time-dependently increased the level of HSP27 without affecting the level of HSP70. PGE2 stimulated the accumulation of HSP27 dose-dependently in the range between 10 nM and 10 microM. PGE2 stimulated the increase in the level of the mRNA for HSP27. Staurosporine and calphostin C, inhibitors of protein kinase C (PKC), suppressed the PGE2-induced HSP27 accumulation. The effect of PGE2 on HSP27 accumulation was reduced in the PKC down-regulated cells. BAPTA/AM, a chelator of intracellular Ca2+, or TMB-8, an inhibitor of intracellular Ca2+ mobilization, reduced the accumulation of HSP27 induced by PGE2. Dibutyryl cAMP had little effect on the basal level of HSP27. PGE2 induced the phosphorylation of both p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase. PD98059 and U-0126, inhibitors of the upstream kinase of p44/p42 MAP kinase, reduced the accumulation of HSP27 induced by PGE2. SB203580, a specific inhibitor of p38 MAP kinase, suppressed the HSP27 accumulation induced by PGE2. U-73122, an inhibitor of phospholipase C, and calphostin C reduced the PGE2-induced phosphorylation of both p44/p42 MAP kinase and p38 MAP kinase. These results indicate that PGE2 stimulates the induction of HSP27 through PKC-dependent activations of both p44/p42 MAP kinase and p38 MAP kinase in osteoblasts.

Autoimmune thyroid disease accompanied by recurring episodes of painful thyroid ameliorated by thyroidectomy.

A 71-yr-old female initially presented with clinical and biochemical hyperthyroidism with high TSH binding inhibitory immunoglobulin (TBII) and anti-thyroid peroxidase antibody (TPOAb) titers. Histological findings of the thyroid revealed hyperplasia with a focal germinal center, indicating Graves' disease and mild focal chronic thyroiditis. Four episodes of painful and tender thyroid occurred over the next 2 yr accompanied by acute inflammatory reactions. The first episode that developed while the patient was in a hyperthyroid state was soon followed by hypothyroidism associated with further increases in anti-thyroglobulin antibody (TGAb) and TPOAb titers. The subsequent 3 episodes occurred during the hypothyroid state, when the TGAb titer progressively increased with each episode. We performed subtotal thyroidectomy to prevent further episodes. Specimens obtained at thyroidectomy showed that extreme fibrosis had replaced the thyroid parenchyma with collapsed follicles and moderate lymphocyte infiltration. No further episodes occurred after thyroidectomy, and during a 3-yr follow-up period, TBII and thyroid-stimulating antibody (TSAb) disappeared and TGAb and TPOAb titers decreased. This case report provides further evidence supporting the notion that thyroid epithelial destruction progresses during relatively short periods of recurrent painful thyroid and that thyroidectomy helps patients affected by this condition that are unresponsive to other treatment strategies.

Trifluoromethyl ketone-based inhibitors of apoptosis in cerebellar granule neurons.

A variety of aromatic trifluoromethyl ketone derivatives has been studied as inhibitors of apoptosis in cerebellar granule neurons (CGNs). Among them, alpha-trifluoromethyl diketone (2) and benzyl trifluoromethyl ketone (11) were found to be apoptosis inhibitors which can prevent a neurodegenerative disease. Compounds 2 and 11 showed neuroprotection effect on low K+-induced apoptosis in CGNs. Furthermore, these compounds effectively suppressed DNA fragmentation accompanied with apoptosis. The neuroprotection mode of 2 and 11 was not related to inhibition of caspase-3.

Measurement of flecainide in hair as an index of drug exposure.

We report a method for measuring the concentration of flecainide in hair. An animal study, in which flecainide (1, 5, and 10 mg/kg/day) was orally administered for 1, 2, and 3 weeks to pigmented rats, showed that flecainide concentration in rat hairs newly regrown after administration significantly correlated with both the daily dose and the dosing period. The part of hair containing flecainide continued to grow upward, retaining the drug within the hair structure that had been formed at the time of drug exposure. Flecainide was also determined in human scalp hairs collected from patients treated with flecainide. The drug content of white hairs was much less than that black hairs collected from the same rats and subjects, suggesting the determinant effect of hair pigment on flecainide accumulation in hair. These findings suggest that the analysis of flecainide in hair may be useful for assessing exposure to drug qualitatively.

Contrasting effects of midazolam on induction of heat shock protein 27 by vasopressin and heat in aortic smooth muscle cells.

We previously showed that vasopressin stimulates the induction of heat shock protein (HSP) 27, a low molecular-weight HSP, through protein kinase C activation in aortic smooth muscle A10 cells. In the present study, we examined the effects of midazolam, an intravenous anesthetic, on the HSP27 induction stimulated by vasopressin, heat, or sodium arsenite (arsenite) in A10 cells. Midazolam inhibited the accumulation of HSP27 induced by vasopressin or 12-O-tetradecanoylphorbol 13-acetate (TPA), a direct activator of protein kinase C. Midazolam also reduced the vasopressin-induced level of the mRNA for HSP27. In contrast, midazolam enhanced the HSP27-accumulation induced by heat or arsenite. Midazolam also enhanced the heat-increased level of the mRNA for HSP27. However, midazolam had no effect on the dissociation of the aggregated form of HSP27 following stimulation by vasopressin, heat, or arsenite. These results suggest that midazolam suppresses vasopressin-stimulated HSP27 induction in vascular smooth muscle cells, and that this inhibitory effect is exerted at a point downstream from protein kinase C. In contrast, midazolam enhanced heat- or arsenite-stimulated HSP27 induction. Thus, midazolam has dual effects on the HSP27 induction stimulated by various stresses in vascular smooth muscle cells.

Inhibition by adenylyl cyclase-cAMP system of ET-1-induced HSP27 in osteoblasts.

We have previously reported that endothelin-1 (ET-1) stimulates heat shock protein (HSP) 27 induction in osteoblast-like MC3T3-E1 cells and that p38 mitogen-activated protein (MAP) kinase acts at a point downstream from protein kinase C (PKC) in HSP27 induction. In the present study, we investigated the effect of the adenylyl cyclase-cAMP system on ET-1-stimulated induction of HSP27 in MC3T3-E1 cells. Dibutyryl-cAMP (DBcAMP) dose dependently inhibited the HSP27 accumulation stimulated by ET-1. Forskolin and cholera toxin significantly suppressed the ET-1-stimulated accumulation of HSP27. However, dideoxyforskolin, a forskolin derivative that does not activate cAMP, failed to suppress the ET-1-induced HSP27 accumulation. Forskolin reduced the p38 MAP kinase phosphorylation induced by ET-1 or 12-O-tetradecanoylphorbol-13-acetate (TPA). PGE(1), an extracellular agonist that activates cAMP production, reduced the ET-1-induced HSP27 accumulation. In addition, the phosphorylation of p38 MAP kinase induced by ET-1 or TPA was suppressed by PGE(1). Forskolin, DBcAMP, and PGE(1) suppressed the ET-1-stimulated increase in the mRNA level for HSP27. These results indicate that the adenylyl cyclase-cAMP system has an inhibitory role in ET-1-stimulated HSP27 induction in osteoblasts and that the effect is exerted at the point between PKC and p38 MAP kinase in osteoblasts.