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Studies on prodrugs. 10. Possible mechanism of N-dealkylation of N-masked norfloxacins having several active methylene groups.

As a prodrug approach to norfloxacin (NFLX, 2), we have prepared several N-masked NFLXs (1a-f) and studied the cleavage mechanism of the C-N bond of N-masked NFLXs utilizing the following experiments: (1) the oxidation of N-masked NFLXs (1a-f) with m-chloroperbenzoic acid (MCPBA) and their subsequent cleavage to 2 in chloroform at room temperature or at 50 degrees C; (2) the liberation of NFLX from N-masked NFLXs after oral administration in mice. It was found that the chemical oxidative dealkylation of N-masked NFLXs proceeded when anion-stabilizing groups (e.g., CN, COR, COOR) are present on the alpha carbon of the nitrogen atom. In in vivo experiments, N-masked NFLXs having acidic hydrogens on the alpha carbon to the nitrogen atom also liberated NFLX (2) after oral administration.

Animals↗

Combined optical tweezers/ion beam technique to tune colloidal masks for nanolithography.

A method is presented to control the in-plane ordering, size, and interparticle distance of nanoparticles fabricated by evaporation through a mask of colloidal particles. The use of optical tweezers combined with critical point drying gives single-particle position control over the colloidal particles in the mask. This extends the geometry of the colloidal masks from (self-organized) hexagonal to any desired symmetry and spacing. Control over the mask's hole size is achieved by MeV ion irradiation, which causes the colloids to expand in the in-plane direction, thus shrinking the size of the holes. After modification of the mask, evaporation at different angles with respect to the mask gives additional control over structure and interparticle distance, allowing nanoparticles of different materials to be deposited next to each other. We demonstrate large arrays of metal nanoparticles with dimensions in the 15-30 nm range, with control over the interparticle distance and in-plane ordering.

Colloids↗

Recognition of small stimulus screen masks using the multifocal ERG.

To evaluate the ability of the multifocal ERG (mfERG) to detect small defects in the stimulus array was the objective of this paper. Seven normal subjects had mfERGs recorded with a VERIS system. Stimulus arrays composed of 61, 103 or 241 hexagons were covered in part by small masks of different light transmittance properties. Only masks that covered at least one-half of a single 103 hexagon stimulus cell caused a significant reduction in signal. Different-shaped masks of about 5 degrees diameter were detectable using a 61-hexagon array only when they fully covered a stimulus cell. Detection was better, but marginal for some of the masks, with the 103 hexagon array. The 241 hexagon array showed sharp defects for all masks. Masking the stimulus screen is not equivalent to having a pathologic scotoma, but it demonstrates the greatest possible spatial sensitivity of the mfERG system. Thus, the mfERG appears to be able to detect small retinal lesions if they reduce local retinal function by at least 50% and correspond to at least half the area of one stimulus hexagon. Scotomas 5 degrees or smaller would be best detected using a fine (241 hexagon) stimulus array. With coarser stimulus arrays (e.g. 103 or 61 hexagons), the effect of a small scotoma depends on its location relative to the stimulus cells. These issues should be considered when selecting mfERG recording conditions.

Adult↗

Effects of a circumferentially vented mask on breathing patterns of women as measured by respiratory kinematic techniques.

Since pneumotachograph masks are commonly used in studies of speech breathing, the purpose of this study was to measure the differences in respiratory volumetric and frequency measures during speech under two conditions: with and without a circumferentially vented pneumotachograph mask coupled to the face. Thus we sought to identify whether changes in breathing patterns occur with the use of a specific face mask, because these patterns are accepted as representative of normal speech breathing. Subjects were 10 normal-speaking women, each of whom produced a syllable train and a connected speech task, both at comfortable intensity levels. Respiratory measures were made using linearized magnetometers during speech production. The measurements included lung volume, rib cage volume, and abdominal volume at utterance initiation and termination, volume excursions during the utterance, and the number of breath groups during the speech task. There were no significant differences between the mask-on and mask-off conditions in volumetric and frequency measures. A significant task difference for abdominal initiation was found. It was concluded that the use of a circumferentially vented pneumotachograph mask does not alter the reliability of respiratory volume and frequency measures for studies of voice.

Adult↗

Evidence that intramolecular interactions are involved in masking the activation domain of transcriptional activator Leu3p.

The Leu3 protein of Saccharomyces cerevisiae regulates the expression of genes involved in branched chain amino acid biosynthesis and in ammonia assimilation. It is modulated by alpha-isopropylmalate, an intermediate in leucine biosynthesis. In the presence of alpha-isopropylmalate, Leu3p is a transcriptional activator. In the absence of the signal molecule, the activation domain is masked, and Leu3p acts as a repressor. The recent discovery that Leu3p retains its regulatory properties when expressed in mammalian cells (Guo, H., and Kohlhaw, G. B. (1996) FEBS Lett. 390, 191-195) suggests that masking and unmasking of the activation domain occur without the participation of auxiliary proteins. Here we present experimental support for this notion and address the mechanism of masking. We show that modulation of Leu3p is exceedingly sensitive to mutations in the activation domain. An activation domain double mutant (D872N/D874N; designated Leu3-dd) was constructed that has the characteristics of a permanently masked activator. Using separately expressed segments containing either the DNA binding domain-middle region or the activation domain of wild type Leu3p (or Leu3-dd) in a modified yeast two-hybrid system, we provide direct evidence for alpha-isopropylmalate-dependent interaction between these segments. Finally, we use the phenotype of Leu3-dd-containing cells (slow growth in the absence of added leucine) to select for suppressor mutations that map to the middle region of Leu3-dd. The properties of nine such suppressors further support the idea that masking is an intramolecular process and suggest a means for mapping the surface involved in masking.

Amino Acid Sequence↗

Gene fusion and overlapping reading frames in the mammalian genes for 4E-BP3 and MASK.

4E-BP3 is a member of the eukaryotic initiation factor (eIF) 4F-binding protein family of translational repressors. eIF4E-binding proteins (4E-BPs) inhibit translation initiation by sequestering eIF4E, the cap-binding protein, from eIF4G thus preventing ribosome recruitment to the mRNA. Previous analysis of 4E-BP3 expression uncovered an 8.5-kb mRNA variant of unknown origin. To study this splice variant, we determined the structure of the genomic locus encoding human 4E-BP3 (EIF4EBP3). EIF4EBP3 is located on human chromosome 5q31.3 and comprises three exons (A, B, and C) and two introns. Exon B contains the region of the open reading frame responsible for eIF4E binding. GenBank searches revealed multiple expressed sequence tags originating from the alternative splicing of exon B with unidentified upstream exons. Further studies revealed that the 8.5-kb transcript arises from the fusion of EIF4EBP3 with the mammalian homologue of Drosophila MASK (multiple ankyrin repeats, single KH domain), which is crucial for photoreceptor differentiation, cell survival, and proliferation. Surprisingly, the open reading frame of the MASK-BP3 transcript is different from that of 4E-BP3, which indicates that exon B is translated using an alternative reading frame. A gene fusion similar to that of MASK and EIF4EBP3 has been reported only once in mammals for the UEV1-Kua transcript. The use of an alternative reading frame is also very rare, having been described for two loci, INK4a/ARF and XLalphas/ALEX. The simultaneous exploitation of both mechanisms underscores the flexibility of mammalian genomes and has important implications for the functional analysis of 4E-BP3 and MASK. Interestingly, both eIF4E and MASK are downstream effectors of the Ras/MAPK pathway, which provides a rationale for the MASK-BP3 fusion in mammals.

Alternative Splicing↗

Natural ligands of the B cell adhesion molecule CD22 beta can be masked by 9-O-acetylation of sialic acids.

CD22 beta is a B cell-restricted phosphoprotein expressed on the surface of mature resting B cells. It mediates interactions with other cells partly or exclusively via recognition of alpha 2-6-linked sialic acids on glycoconjugates. The sialylated N-linked oligosaccharides recognized best by CD22 beta are common to many glycoproteins, suggesting that additional regulatory mechanisms may exist. Since the exocyclic side chain of sialic acid is required for recognition, we explored the effects of a naturally occurring modification of the side chain, 9-O-acetylation. Semisynthetic N-linked oligosaccharides terminating with 9-O-acetylated, alpha 2-6-linked sialic acids showed markedly reduced binding to CD22 beta relative to their non-O-acetylated counterparts. Murine lymphoid cells were probed for natural CD22 beta ligands that might be O-acetylated using recombinant soluble forms of CD22 beta (CD22 beta Rg) and influenza C esterase (CHE-Fc, which specifically removes 9-O-acetyl esters from sialic acids). By flow cytometry analysis, CD22 beta Rg binding to splenic B cells and a subset of T cells was increased by pretreatment with CHE-Fc, indicating that some potential CD22 beta ligands are naturally "masked" by 9-O-acetylation. Unmasking of these CD22 beta ligands by removal of 9-O-acetyl esters from intact splenocytes substantially increases their CD22 beta-dependent adhesion in an in vitro adhesion assay. Probing of murine lymphoid tissue sections by CD22 beta Rg and CHE-Fc treatment demonstrates regionally restricted and differentially expressed patterns of distribution between masked and unmasked ligands. For example, lymph node-associated follicular B cells express high levels of CD22 beta ligands, none of which are masked by 9-O-acetylation. In contrast, the ligands on lymph node-associated dendritic cells are almost completely masked by 9-O-acetylation, suggesting that masking may regulate interactions between CD22 beta-positive B cells and dendritic cells. In the thymus, only medullary cells express CD22 beta ligands, and a significant portion of these are masked by 9-O-acetylation, particularly at the cortical-medullary junction. Thus, 9-O-acetylation of sialic acids on immune cells is in a position to negatively regulate CD22 beta adhesion events in a manner depending on both cell type and tissue localization.

Acetylation↗

Masking the cryptodeterminant on the 54-kilodalton mouse sperm surface antigen.

Previously, we reported that the epitope of a 54-kDa sperm surface sialoglycoprotein on the flagellum is masked by sialic acid residues. The epitope is referred to as a hidden determinant or cryptodeterminant. This paper reports the manner in which the epitope is masked as evaluated qualitatively and quantitatively by means of SDS-PAGE/immunoblots (Western blot) and ELISA. Immunoblotting with four specific monoclonal antibodies to the 54-kDa sialoglycoprotein--T21 (IgM), MC71 (IgG1), MC81 (IgM), and MC91 (IgM)--demonstrated that not only IgM but also IgG antibody MC71 and the Fab fragment MC71 are masked. Quantitative evaluation with ELISA to compare the antibody titration curves of the masked and unmasked antigens on sialidase-treated and untreated sperm, respectively, indicated that sialidase caused the antibody-binding ability of the epitopes to increase to a different level for each antibody. There were 32-256-, 8-16-, 16-, and 2-4-fold increases in binding to T21, MC71, MC81, and MC91 antibodies, respectively. These results suggest that the antigen-masking through the cryptodeterminant does not depend upon the subtype or the molecular mass of the antibody, but upon the biochemical nature of the epitope region that is closely related to the sialic acid. The mechanism and physiological roles of the antigen-masking are discussed.

Animals↗

Effect of firefighter masks on monocular and binocular peripheral vision.

Peripheral vision can impact essential job functions of firefighters and other workers who use Self-Contained Breathing Apparatus and other full face masks. It is important for physicians to know how these masks alter peripheral vision. Also, one must understand the effect of monocular vision on peripheral vision. Using the Goldman Perimeter Machine we measured peripheral vision in the monocular and binocular state, with and without two different types of masks. The results show that monocularity causes an average loss of 23 degrees in the nasal meridian. The use of the masks did not affect this difference. Also, the masks caused an average loss of 28 degrees of peripheral vision in the inferior meridian. How these losses affect the ability of the users of the masks to perform their essential job functions still needs to be researched.

Adult↗

Headaches and the N95 face-mask amongst healthcare providers.

BACKGROUND: During the 2003 severe acute respiratory distress syndrome epidemic, healthcare workers mandatorily wore the protective N95 face-mask. METHODS: We administered a survey to healthcare workers to determine risk factors associated with development of headaches (frequency, headache subtypes and duration of face-mask wear) and the impact of headaches (sick days, headache frequency and use of abortive/preventive headache medications). RESULTS: In the survey, 212 (47 male, 165 female) healthcare workers of mean age 31 years (range, 21-58) participated. Of the 79 (37.3%) respondents who reported face-mask-associated headaches, 26 (32.9%) reported headache frequency exceeding six times per month. Six (7.6%) had taken sick leave from March 2003 to June 2004 (mean 2 days; range 1-4 days) and 47 (59.5%) required use of abortive analgesics because of headache. Four (2.1%) took preventive medications for headaches during this period. Multivariate logistic regression showed that pre-existing headaches [P = 0.041, OR = 1.97 (95% CI 1.03-3.77)] and continuous use of the N95 face-mask exceeding 4 h [P = 0.053, OR = 1.85 (95% CI 0.99-3.43)] were associated with development of headaches. CONCLUSIONS: Healthcare providers may develop headaches following the use of the N95 face-mask. Shorter duration of face-mask wear may reduce the frequency and severity of these headaches.

Adult↗

Investigation of basic imaging properties in digital radiography. 4. Effect of unsharp masking on the detectability of simple patterns.

The signal-to-noise ratios (SNRs) of simple radiologic patterns processed by the unsharp-masking technique were calculated on the basis of a statistical decision theory model that includes both the observer's visual transfer function and a noise component internal to his eye-brain system. For a variety of processing parameters, the contrast-detail diagrams predicted from this SNR agreed qualitatively with experimental results obtained in observer performance studies. Unsharp masking with a large mask and a large weighting factor improved the detection of square objects to a level comparable with that achieved by the overall contrast enhancement technique using a factor of 4. However, unsharp masking with a small mask and a large weighting factor can substantially degrade the detectability of these objects. The potential practical utility of the unsharp-masking technique is discussed.

Humans↗

Suppression in simultaneous masking.

Suppression, i.e., the decrease of masked threshold caused by the addition of a second masker M2 to a first masker M1, is measured for the case of simultaneous masking. The magnitude of suppression decreases with increasing test tone duration; pulsed maskers elicit somewhat more suppression than continuous maskers. In comparison to suppression effects obtained in nonsimultaneous masking (post-masking, pulsation threshold) suppression in simultaneous masking is considerably smaller and was found only at the lower slopes of the two maskers. Suppression in simultaneous masking would not be predicted by those models of suppression which require nonsimultaneous presentation of maskers and test sound.

Acoustics↗

Comparison of a face-mask and a mouthpiece for measuring resting energy expenditure with the 'Oxylog'.

Resting energy expenditure measurements were made simultaneously with an Oxylog and a ventilated hood indirect calorimeter, using (a) the Oxylog with the original oronasal face-mask and (b) the Oxylog with a mouthpiece and a noseclip, both in 15 subjects. The mean difference between Oxylog energy expenditure, when used with the mouthpiece, and ventilated hood measurements was very small: -0.4% (p less than 0.4; n = 15). When used with the face-mask, the Oxylog tended to underestimate energy expenditure relative to the ventilated hood, the mean difference being -2.4% (p = 0.054; n = 13). In 2 subjects, the Oxylog face-mask showed obvious leaks. The subjects did not find the mouthpiece less comfortable than the face-mask, and there was no evidence that the mouthpiece disturbed respiration more than the face-mask. The Oxylog is therefore suitable for measurements of resting energy expenditure, but the use of a mouthpiece and noseclip is preferable to the use of the original Oxylog face-mask.

Adult↗

Football equipment design affects face mask removal efficiency.

BACKGROUND: Researchers have investigated the performance of face mask removal tools for spine injury management in football but not the effects of football equipment design. HYPOTHESES: Various styles or designs of football helmet equipment (helmets, face masks, loop straps) affect face mask removal efficiency. A cordless screwdriver performs more efficiently than do cutting tools. STUDY DESIGN: Controlled laboratory study. METHODS: Nineteen certified athletic trainers were randomly assigned to group 1 (cordless screwdriver and the FM Extractor) or group 2 (cordless screwdriver and the Trainer's Angel). Subjects randomly performed face mask removal for 6 conditions composed of helmet (3), face mask (3), and loop strap (5) combinations. Time, head movement, perceived difficulty, and success rates were measured. RESULTS: Multiple significant differences were found in time, movement, and perceived difficulty between the 6 helmet equipment conditions. The Shockblocker loop strap was consistently superior in all variables regardless of the tool used or the helmet it was attached to. The cordless screwdriver created less movement (mean range from any one plane, 2.8 degrees -13.3 degrees ), was faster (mean range, 42.1-68.8 seconds), and was less difficult (mean rating of perceived exertion range, 1.4-2.9) compared to cutting tools (ranges, 4.4 degrees -18.4 degrees in any one plane, 71-174 seconds, rating of perceived exertion, 2.8-7.7). Trial failure was more common with cutting tools than with the screwdriver. CONCLUSION: Differences in football helmet equipment affect face mask removal. The cordless screwdriver is more efficient than the FM Extractor and Trainer's Angel. CLINICAL RELEVANCE: Professionals responsible for the care of football athletes must be knowledgeable in the types of equipment used and the best option available for effective airway access.

Adult↗

Grading choroidal neovascular membrane regression after strontium plaque radiotherapy; masked subjective evaluation vs planimetry.

PURPOSE: To analyze angiographic changes in choroidal neovascular membranes (CNVM) after strontium-plaque (90Sr) irradiation for exudative age-related macular degeneration (AMD) using masked measurement of the CNVM areas and a masked subjective comparison of CNVM size and leakage. METHODS: We studied the baseline, 3, 6, and 12-month angiograms of 19 eyes treated with 90Sr-plaque irradiation for exudative AMD. The area of CNVM-related hyperfluorescence was measured quantitatively, and the angiograms were subjectively evaluated by a masked grader. RESULTS: In 7 of the 19 eyes the CNVM-related hyperfluorescence was too scattered to be analyzed by planimetry but masked subjective grading correlated with the clinical response to irradiation. In the remaining 12 eyes, the CNVM decreased in size in 67% of the eyes and showed leakage in 67%. Planimetry and subjective assessment of the size and leakage of the CNVMs similarly reflected the regression after irradiation. CONCLUSIONS: CNVM size and leakage frequently diminish after 90Sr-plaque irradiation. Quantitative measurement of the CNVM areas, or a grading system based on masked subjective assessment, give similar results for evaluating these changes. Masked subjective grading can be used even in cases where the CNVM is too scattered to be outlined for planimetry.

Aged↗

Facial dimensions and predictors of fit for half-mask respirators in Koreans.

This study investigated the relationship between facial dimensions and the fit of half-mask respirators using fit factors and selected good facial dimension predictor(s) of fit for designing respirators for Korean workers. Three different brands of half-mask respirators-YS, SG, and 3M-were fit-tested on 112 men and 38 women using TSI Portacount 8020, and fit factors were determined. Before fit-testing, 10 facial dimensions were measured. Data were analyzed by descriptive statistics, Pearson's correlation analysis, and quadratic polynomial regression analysis with log-transformed fit factors (LNFF). However, some of the relationships between LNFF and facial dimensions in brand/gender subgroups were found to be curvilinear rather than linear. Because this result indicated that a multiple polynomial regression model including quadratic terms might be more appropriate than a multiple linear regression, data were also analyzed with a quadratic term by examination of the coefficient of partial correlation. No common facial dimension variables were found to be significant for all nine brand/gender subgroups, but the coefficient of regression for the linear term of the bitragion-menton arc was significant in five of nine brand/gender subgroups including male subjects of all three respirator brands. The 3M mask had the highest coefficient of determination values compared with other brands. Using the quadratic term for the 3M mask, face width (bizygomatic breadth) and nose protrusion were good predictors of half-mask fit. In four of nine brand/gender subgroups, nose protrusion was a good predictor of fit through analysis using a quadratic term. Results indicate that face width, bitragion-menton arc, and nose protrusion should be preferentially considered when designing a half-mask respirator for Korean workers.

Adult↗

Comparison of face mask, head hood, and canopy for breath sampling in flow-through indirect calorimetry to measure oxygen consumption and carbon dioxide production of preterm infants < 1500 grams.

Complete sampling of expired air is essential for accurate O2 consumption(CO2 production) [VO2(VCO2)] measurements with flow-through indirect calorimetry. In preterm infants complete sampling is critical, because only low sampling flows can be used. The accuracy of the various breath sampling systems at low flows and their patient compatibility is untested. We therefore measured 1) the accuracy of VO2(VCO2) measurements with a face mask, a head hood, and a canopy in vitro at low sampling flows; 2) the effect of breathing on measurements with the face mask; and 3) the effect of breath sampling systems on activity and body temperature of preterm infants. VO2(VCO2) were measured with a Deltatrac II. In vitro we used a methanol miniburner incorporated into a doll, which could simulate low VO2(VCO2) and tidal breathing. In vivo we studied seven preterm infants < 1500 g. With the face mask VO2(VCO2) measurements were accurate at a flow of 3 L/min (error -1 +/- 0.8%), when tidal volume was < 15 mL/breath and the distance between mask and manikin < 1 cm. With hood and canopy VO2(VCO2) were underestimated at a flow of 3 L/min (error -13 +/- 1% and -14 +/- 5%), and results were markedly influenced by body position. For accurate measurements, the hood needed a flow of 4.5 L/min, the canopy 8.3 L/min. In vivo the face mask did not increase heart rate, respiration, activity, or rectal temperature, but hood and canopy increased rectal temperature by 0.3-0.4 degree C. For VO2(VCO2) measurements in infants < 1500 g, a face mask should be used, which is accurate at low flows and does not change body temperature. Accuracy at low flows and patient compatibility of breath sampling systems should be evaluated and reported for VO2(VCO2) measurements in preterm infants.

Body Temperature↗

Preparation and evaluation of tablets rapidly disintegrating in saliva containing bitter-taste-masked granules by the compression method.

The aim of this study was to prepare, using taste-masked granules, tablets which can rapidly disintegrate in saliva (rapidly disintegrating tablet), of drugs with bitter taste (pirenzepine HCl or oxybutynin HCl). The taste-masked granules were prepared using aminoalkyl methacrylate copolymers (Eudragit E-100) by the extrusion method. None of the drugs dissolved from the granules (% of dissolved, < 5%) even at 480 min at pH 6.8 in the dissolution test. However, the drugs dissolved rapidly in the medium at pH 1.2 in the dissolution test. Rapidly disintegrating tablets were prepared using the prepared taste-masked granules, and a mixture of excipients consisting of crystalline cellulose (Avicel PH-102) and low-substituted hydroxypropylcellulose (L-HPC, LH-11). The granules and excipients were mixed well (mixing ratio by weight, crystalline cellulose: L-HPC = 8:2) with 1% magnesium stearate, and subsequently compressed at 500-1500 kgf in a single-punch tableting machine. The prepared tablets (compressed at 500 kgf) containing the taste-masked granules have sufficient strength (the crushing strength: oxybutynin tablet, 3.5 kg; pirenzepine tablet, 2.2 kg), and a rapid disintegration time (within 20 s) was observed in the saliva of healthy volunteers. None of the volunteers felt any bitter taste after the disintegration of the tablet which contained the taste-masked granules. We confirmed that the rapidly disintegrating tablets can be prepared using these taste-masked granules and excipients which are commonly used in tablet preparation.

Cholinergic Antagonists↗