Contact urticaria to phosphorus sesquisulphide.
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Patch testing was performed with phosphorus sesquisulfide P4S3 in 2 groups containing equal numbers of patients using different concentrations (0.5% P4S3 in pet. and 1% P4S3 in pet., the usual suggested test concentration as recommended by the International Contact Dermatitis Research Group). We found that there was a statistically significant increase in the number of clinically irrelevant irritant reactions in the group tested with the concentration (chi 2 = 16, p < 0.0004). We recommend that patch testing with phosphorous sesquisulfide should be at a reduced concentration of 0.5% pet.
The results of patch testing with a series containing components of cigarettes and matches were reviewed. 2 years were reviewed, 1987 and 1997. 314 patients were patch tested to this series, 203 in 1987 and 111 in 1997. 31 patients had clinically relevant positive reactions to the series, 25 in 1987 and 6 in 1997. 26 patients had relevant positive tests to cigarette components in the series. There were 14 relevant positive reactions to phosphorus sesquisulfide in 1987 and one in 1997. All patients with relevant positive reactions to red match tips also had reactions to phosphorus sesquisulfide. There was a significant association between cigarette and fragrance hypersensitivity. The eczema in 3 of 4 patients who stopped smoking improved. A series containing match heads, smoked cigarette filters and remnants of tobacco from smoked cigarettes may be useful in smokers with eczema of the face, neck or hands.
Current electronic portal imaging devices (EPIDs) based on active matrix flat panel imager (AMFPI) technology use a metal plate+phosphor screen combination for x-ray conversion. As a result, these devices face a severe trade-off between x-ray quantum efficiency (QE) and spatial resolution, thus, significantly limiting their imaging performance. In this work, we present a novel detector design for indirect detection-based AMFPI EPIDs that aims to circumvent this trade-off. The detectors were developed using micro-electro-mechanical system (MEMS)-based fabrication techniques and consist of a grid of up to approximately 2 mm tall, optically isolated cells of a photoresist material, SU-8. The cells are dimensionally matched to the pixels of the AMFPI array, and packed with a scintillating phosphor. In this paper, various design considerations for such detectors are examined. An empirical evaluation of three small-area (approximately 7 x 7 cm2) prototype detectors is performed in order to study the effects of two design parameters--cell height and phosphor packing density, both of which are important determinants of the imaging performance. Measurements of the x-ray sensitivity, modulation transfer function (MTF) and noise power spectrum (NPS) were performed under radiotherapy conditions (6 MV), and the detective quantum efficiency (DQE) was determined for each prototype SU-8 detector. In addition, theoretical calculations using Monte Carlo simulations were performed to determine the QE of each detector, as well as the inherent spatial resolution due to the spread of absorbed energy. The results of the present studies were compared with corresponding measurements published in an earlier study using a Lanex Fast-B phosphor screen coupled to an indirect detection array of the same design. The SU-8 detectors exhibit up to 3 times higher QE, while achieving spatial resolution comparable or superior to Lanex Fast-B. However, the DQE performance of these early prototypes is significantly lower than expected due to high levels of optical Swank noise. Consequently, the SU-8 detectors presently exhibit DQE values comparable to Lanex Fast-B at zero spatial frequency and significantly lower than Fast-B at higher frequencies. Finally, strategies for reducing Swank noise are discussed and theoretical calculations, based on the cascaded systems model, are presented in order to estimate the performance improvement that can be achieved through such noise reduction.
Neutron dose equivalent measurements were performed in and around an 18 MV x-ray beam using superheated drop detectors (SDD) and phosphorous pentoxide (P2O5) powder. The neutron dose equivalent profiles for various field sizes of 10 X 10 cm2, 20 X 20 cm2, and 30 X 30 cm2 were measured. The results measured with the P2O5 were checked for any gross systematic errors by comparing with the published results computed by using Monte Carlo calculations. A comparison was then made between the neutron dose equivalent profiles measured with the P2O5 and the SDD. The results of this comparison show that the neutron dose equivalents measured with the two types of detectors agree with each other for measurements about 20 cm away from the beam edges. However, in and near the beam edges the SDD measurements are upto 50% less than the neutron dose equivalents measured using P2O5 for the 18 MV x-ray beam.
Antisense phosphorodiamidate morpholino oligomers (PMO) inhibit targeted gene expression by preventing ribosomal assembly, thus preventing translation. Inhibition of cytochrome P450 (P450) 3A4 expression was examined in primary human hepatocytes from 11 donors and in Caco-2 cells (stably transfected with CYP3A4 cDNA on an extrachromosomal vector) by evaluating the metabolism of substrate 7-benzyloxy-4-[trifluoromethyl]-coumarin and Western immunoblot analysis. Cellular uptake of PMO was confirmed in both cell systems using fluorescein-labeled PMOs. Three antisense PMO sequences and two control PMO sequences were tested. AVI-4557, a 20-mer PMO with the sequence 5'-CTGGGATGAGAGCCATCACT-3' was selected as the optimal agent. AVI-4557 inhibited expression of CYP3A4 in Caco-2/h3A4 cells by 64% at 24 h following administration of 2.8 microM by an assisted delivery protocol. Inhibition of CYP3A activity was observed in primary human hepatocytes after 24 h exposure to AVI-4557 by an average of 32 +/- 11%. Furthermore, AVI-4557 exposure resulted in a sequence-dependent inhibition of cyclophosphamide-related cytocidal activity and a sequence-dependent induction of paclitaxel-related cytocidal activity in both cell types. Finally, the cytocidal activity of cisplatin was not affected with AVI-4557 treatment in either cell type. These studies indicate AVI-4557 is an effective and specific inhibitor of CYP3A4 expression.
"Nitrosoguanidine" (N-methyl-N'-nitro-N-nitrosoguanidine) acts on polynucleotides in neutral aqueous solution, methylating guanine in the 7-position, and, to a much lesser extent, adenine. In 67 percent dimethylformamide the effect on the purines decreased, and what seems to be 3-methyl-cytosine appeared. In formamide solution no base changes were detected. Nitrosoguanidine had little mutagenic effect on tobacco mosaic virus RNA in water; it had greater effect in dimethylformamide, and even greater in formamide; it was a strong mutagen only when it acted on intact tobacco mosaic virus particles. Thus, neither the methylation of guanine nor the cytosine modification represents the main mutagenic event.
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The reverse transcriptase inhibitor 9-[2-(phosphonomethoxy)propyl]adenine (PMPA; tenofovir) was previously found to offer strong prophylactic and therapeutic benefits in an infant macaque model of pediatric human immunodeficiency virus (HIV) infection. We now summarize the toxicity and safety of PMPA in these studies. When a range of PMPA doses (4 to 30 mg/kg of body weight administered subcutaneously once daily) was administered to 39 infant macaques for a short period of time (range, 1 day to 12 weeks), no adverse effects on their health or growth were observed; this included a subset of 12 animals which were monitored for more than 2 years. In contrast, daily administration of a high dose of PMPA (30 mg/kg subcutaneously) for prolonged periods of time (>8 to 21 months) to 13 animals resulted in a Fanconi-like syndrome (proximal renal tubular disorder) with glucosuria, aminoaciduria, hypophosphatemia, growth restriction, bone pathology (osteomalacia), and reduced clearance of PMPA. The adverse effects were reversible or were alleviated following either complete withdrawal of PMPA treatment or reduction of the daily regimen from 30 mg/kg to 2.5 to 10 mg/kg subcutaneously. Finally, to evaluate the safety of a prolonged low-dose treatment regimen, two newborn macaques were started on a 10-mg/kg/day subcutaneous regimen; these animals are healthy and have normal bone density and growth after 5 years of daily treatment. In conclusion, our findings suggest that chronic daily administration of a high dose of PMPA results in adverse effects on kidney and bone, while short-term administration of relatively high doses and prolonged low-dose administration are safe.
Recombinant sucrose-6-phosphate synthase (SpsA) was synthesized in Escherichia coli BL21DE3 by using the spsA gene of the cyanobacterium Synechocystis sp. strain PCC 6803. Transformants exhibited a 10,000-fold increase in survival compared to wild-type cells following either freeze-drying, air drying, or desiccation over phosphorus pentoxide. The phase transition temperatures and vibration frequencies (P==O stretch) in phospholipids suggested that sucrose maintained membrane fluidity during cell dehydration.
Marine bacterioplankton were isolated and grown in batch cultures until their growth became limited by organic carbon (C), nitrogen (N), or phosphorus (P). Samples were taken from the cultures at both the exponential and stationary phases. The elemental composition of individual bacterial cells was analyzed by X-ray microanalysis with an electron microscope. The cell size was also measured. The elemental content was highest in exponentially growing cells (149 +/- 8 fg of C cell(-1), 35 +/- 2 fg of N cell(-1), and 12 +/- 1 fg of P cell(-1); average of all isolates +/- standard error). The lowest C content was found in C-limited cells (39 +/- 3 fg of C cell(-1)), the lowest N content in C- and P-limited cells (12 +/- 1 and 12 +/- 2 fg of N cell(-1), respectively), and the lowest P content in P-limited cells (2.3 +/- 0.6 fg of P cell(-1)). The atomic C:N ratios varied among treatments between 3.8 +/- 0.1 and 9.5 +/- 1.0 (average +/- standard error), the C:P ratios between 35 +/- 2 and 178 +/- 28, and the N:P ratios between 6.7 +/- 0.3 and 18 +/- 3. The carbon-volume ratios showed large variation among isolates due to different types of nutrient limitation (from 51+/- 4 to 241 +/- 38 fg of C microm(-1); average of individual isolates and treatments +/- standard error). The results show that different growth conditions and differences in the bacterial community may explain some of the variability of previously reported elemental and carbon-volume ratios.
Eighty-four transfer-deficient mutants of Flac have been isolated; 27 of these bear amber mutations and 1 mutant is temperature-sensitive. All the mutants transfer between 10(-2) and <10(-5)% as well as wild-type Flac, all are curable by acridine orange treatment, and all are resistant to the female-specific phage phi(II). Some of the mutants are partially sensitive to female-specific phage tau. Sixty-three of the mutants are resistant to the male-specific phages f1, f2, and Qbeta; 15 are resistant only to f2; and 6 are sensitive to all three male-specific phages. Most of the mutants are still poor recipients in conjugation, but four of the mutants resistant to f1, f2, and Qbeta have become good recipients. Those mutants resistant to all three male-specific phages do not seem to make F-pili.
The kinetics of phosphate uptake by exponentially growing Neurospora crassa were studied to determine the nature of the differences in uptake activity associated with growth at different external phosphate concentrations. Conidia, grown in liquid medium containing either 10 mM or 50 micronM phosphate, were harvested, and their phosphate uptake ability was measured. Initial experiments, where uptake was examined over a narrow concentration range near that of the growth medium, indicated the presence of a low-affintiy (high Km) system in germlings from 50 micronM phosphate. Uptake by each system was energy dependent and sensitive to inhibitors of membrane function. No efflux of phosphate or phosphorus-containing compounds could be detected. When examined over a wide concentration range, uptake was consistent with the simultaneous operation of low- and high-affinity systems in both types of germlings. The Vmax estimates for the two systems were higher in germlings from 50 micronM phosphate than for the corresponding systems in germlings from 10 mM phosphate. The Km of the high-affinity system was the same in both types of germlings, whereas the Km of the low-affinity system in germlings from 10 mM phosphate was about three three times that of the system in germlings from 50 micronM phosphate.
In this paper we show that partial deprivation of a carbon source, a nitrogen source, or phosphate in the presence of all other nutrients needed for growth initiates meiosis and sporulation of Saccharomyces cerevisiae homothallic strain Y55. For carbon deprivation experiments, cells were grown in synthetic medium (pH 5.5) containing an excess of one carbon source and then transferred to the same medium containing different concentrations of the same carbon source. In the case of transfer to different acetate concentrations, the log optical density at 600 nm increased at the previous rate until the cells had used up all of the acetate, whereupon the cells entered a stationary phase and did not sporulate. The same was observed with ethanol. In contrast, at different concentrations of dihydroxy-acetone or pyruvate, cells grew at different rates and sporulated optimally at intermediate concentrations (50 to 75 mM). The response to galactose was similar but reflected the presence of a low-affinity galactose transport system and the induction of a high-affinity galactose transport system. Cells could also sporulate when a glucose medium ran out of glucose, apparently because they initiated sporulation during the subsequent lag period and then used the produced ethanol as a carbon source. For phosphate deprivation experiments, cells growing with excess ethanol or pyruvate and phosphate were transferred to the same medium containing limiting amounts of phosphate. First, they used up the intracellular phosphate reserves for rapid growth, and then they sporulated optimally when an intermediate concentration (30 muM) of phosphate had been added to the medium. For nitrogen deprivation experiments, cells grown with excess acetate, ethanol, or pyruvate and NH(4) (+) were transferred to the same medium from which all nitrogen had been removed. These cells sporulated well in acetate medium but poorly in ethanol and pyruvate media. However, the sporulation frequency in the latter media could be increased greatly by adding intermediate concentrations (1 mM) of the slowly metabolizable amino acids glycine, histidine, or phenylalanine. If one assumes that the sporulation response to partial deprivation of carbon-, nitrogen-, or phosphorus-containing compounds reflects control by a single metabolite, the intracellular concentration of this metabolite may decide at the START position (G1 phase) of the cell cycle whether a/alpha cells enter mitosis or meiosis.
The first molecular and genetic characterization of a biochemical pathway for oxidation of the reduced phosphorus (P) compounds phosphite and hypophosphite is reported. The pathway was identified in Pseudomonas stutzeri WM88, which was chosen for detailed studies from a group of organisms isolated based on their ability to oxidize hypophosphite (+1 valence) and phosphite (+3 valence) to phosphate (+5 valence). The genes required for oxidation of both compounds by P. stutzeri WM88 were cloned on a single ca. 30-kbp DNA fragment by screening for expression in Escherichia coli and Pseudomonas aeruginosa. Two lines of evidence suggest that hypophosphite is oxidized to phosphate via a phosphite intermediate. First, plasmid subclones that conferred oxidation of phosphite, but not hypophosphite, upon heterologous hosts were readily obtained. All plasmid subclones that failed to confer phosphite oxidation also failed to confer hypophosphite oxidation. No subclones that conferred only hypophosphite expression were obtained. Second, various deletion derivatives of the cloned genes were made in vitro and recombined onto the chromosome of P. stutzeri WM88. Two phenotypes were displayed by individual mutants. Mutants with the region encoding phosphite oxidation deleted (based upon the subcloning results) lost the ability to oxidize either phosphite or hypophosphite. Mutants with the region encoding hypophosphite oxidation deleted lost only the ability to oxidize hypophosphite. The phenotypes displayed by these mutants also demonstrate that the cloned genes are responsible for the P oxidation phenotypes displayed by the original P. stutzeri WM88 isolate. The DNA sequences of the minimal regions implicated in oxidation of each compound were determined. The region required for oxidation of phosphite to phosphate putatively encodes a binding-protein-dependent phosphite transporter, an NAD+-dependent phosphite dehydrogenase, and a transcriptional activator of the lysR family. The region required for oxidation of hypophosphite to phosphite putatively encodes a binding-protein-dependent hypophosphite transporter and an alpha-ketoglutarate-dependent hypophosphite dioxygenase. The finding of genes dedicated to oxidation of reduced P compounds provides further evidence that a redox cycle for P may be important in the metabolism of this essential, and often growth-limiting, nutrient.
The htx and ptx operons of Pseudomonas stutzeri WM88 allow for the use of the inorganic reduced phosphorus (P) compounds hypophosphite (P valence, +1) and phosphite (P valence, +3) as sole P sources. To support the proposed in vivo role for the htx and ptx operons, namely the use of phosphite and hypophosphite as alternative P sources, we used reporter gene fusions to examine their expression levels with respect to various P conditions. Expression of the htx and ptx operons was induced up to 17- and 22-fold, respectively, in cultures grown under phosphate starvation conditions relative to expression in medium with excess phosphate (Pi). However, the presence of the reduced P substrate hypophosphite, phosphite, or methylphosphonate, in addition to excess Pi, did not result in an increase in the expression of either operon. To provide further support for a role of the htx and ptx operons in Pi acquisition, we identified P. stutzeri phoBR homologs and constructed deletion mutants. Induction of the htx and ptx reporter gene fusions in response to growth on limiting Pi was abolished in DeltaphoB, DeltaphoR, and DeltaphoBR mutants, demonstrating that htx and ptx expression is phoBR dependent. The putative LysR-type regulator encoded by ptxE has no apparent role in the expression of the htx and ptx operons, as no effect was observed on the level of induction of either operon in a DeltaptxE mutant.