PULMONARY FUNCTION IN RHEUMATOID ARTHRITIS TREATED WITH LOW-DOSE METHOTREXATE: A LONGITUDINAL STUDY

Lung volumes and gas exchange were investigated prospectively in 96 patients with rheumatoid arthritis selected without regard to pulmonary disorders and treated with i.m. methotrexate (MTX) injections [mean weekly dose 13.0 mg (5th-95th percentile (5-95 PC) 7.6-20.8)]. Individual changes over time during MTX treatment [mean duration 2.9 yr (5-95 PC 0.4-5.3)] were assessed by regression analyses in each individual. Forced vital capacity (FVQ remained stable in the majority of patients [mean annual change +0.8% (5-95 PC −8.1 to +14.0) of calculated normal value]. In addition, transfer factor using the indicator gas CO (TLCO) was unaltered in most patients [mean annual change − 2.1% (5-95 PC −16.2 to +11.8) of predicted value]. However, there were significant decreases in the forced expiratory volume in 1 s (FEV1) before and after inhalation of 0.2 mg salbutamol [mean annual change - 0.8% (5-;95 PC −8.4 to +3.2) and −1.3% (5-95 PC −7.8 to +3.9) of the FVC measured, respectively]. In addition, there were significant increases in alveolar-arterial Po2, gradients (P(A-a), O2) at rest and after exercise [mean annual change +1.7 mmHg (5-;95 PC −5.2 to +12.2) and +1.8 mmHg (5-95 PC −3.5 to 9.0), respectively]. Nevertheless, the amounts were small in view of the reliability of the methods applied and reflect, at least in part, the normal process of ageing. The annual change in FEV1 /FVC was negatively correlated with FEV1 /FVC at baseline (Rs = − 0.46, P < 0.001). The annual change in TL, co was also negatively correlated with TL, co at baseline (Rs = − 0.31, P = 0.028). No other risk factors for deterioration of lung volumes or gas exchange were found, including mean weekly MTX dose, age, gender, smoking, presence of rheumatoid factor and pulmonary function at baseline. We conclude that MTX has no major effect on pulmonary function in the majority of patients and that there is no evidence that patients with pre-existing pulmonary disease are at increased risk for further deterioration of lung functio

Oligomeric states in sodium ion-dependent regulation of cyanobacterial histidine kinase-2

Two-component signal transduction systems (TCSs) consist of sensor histidine kinases and response regulators. TCSs mediate adaptation to environmental changes in bacteria, plants, fungi and protists. Histidine kinase 2 (Hik2) is a sensor histidine kinase found in all known cyanobacteria and as chloroplast sensor kinase in eukaryotic algae and plants. Sodium ions have been shown to inhibit the autophosphorylation activity of Hik2 with precedes phosphoryl transfer to response regulators, but the mechanism of inhibition has not been determined. We report on the mechanism of Hik2 activation and inactivation probed by chemical cross-linking and size exclusion chromatography together with direct visualisation of the kinase using negative-stain transmission electron microscopy of single particles. We show that the functional form of Hik2 is a higher-order oligomer such as a hexamer or octamer. Increased NaCl concentration converts the active hexamer into an inactive tetramer. The action of NaCl appears to be confined to the Hik2 kinase domain

Particles in classically forbidden area, neutron skin and halo, and pure neutron matter in Ca isotopes

The nucleon density distributions and the thickness of pure neutron matter in Ca isotopes were systematically studied using the Skyrme-Hartree-Fock model (SHF) from the $\beta$-stability line to the neutron drip-line. The pure neutron matter, related with the neutron skin or halo, was shown to depend not only on the Fermi levels of the neutrons but also on the orbital angular momentum of the valence neutrons. New definitions for the thickness of pure neutron matter are proposed.Comment: 6 pages, 5 figure

Luminosity Functions of Elliptical Galaxies at z < 1.2

The luminosity functions of E/S0 galaxies are constructed in 3 different redshift bins (0.2 < z < 0.55, 0.55 < z < 0.8, 0.8 < z < 1.2), using the data from the Hubble Space Telescope Medium Deep Survey (HST MDS) and other HST surveys. These independent luminosity functions show the brightening in the luminosity of E/S0s by about 0.5~1.0 magnitude at z~1, and no sign of significant number evolution. This is the first direct measurement of the luminosity evolution of E/S0 galaxies, and our results support the hypothesis of a high redshift of formation (z > 1) for elliptical galaxies, together with weak evolution of the major merger rate at z < 1.Comment: To be published in ApJ Letters, 4 pages, AAS Latex, 4 figures, and 2 table

Not going with the flow : locomotor activity does not constrain immunity in a wild fish

Immunity is a central component of fitness in wild animals, but its determinants are poorly understood. In particular, the importance of locomotory activity as a constraint on immunity is unresolved. Using a piscine model (Gasterosteus aculeatus) we combined a 25-month observational time series for a wild lotic habitat with an open flume experiment to determine the influence of locomotor activity (counter-current swimming) on natural variation in immune function. To maximize the detectability of effects in our flume experiment we set flow velocity and duration (10 cm s-1 for 48 h) just below the point at which exhaustion would ensue. Following this treatment, we measured expression in a set of immune-associated genes and infectious disease resistance through a standard challenge with an ecologically-relevant monogenean infection (Gyrodactylus gasterostei). In the wild, there was a strong association of water flow with the expression of immune-associated genes, but this association became modest and more complex when adjusted for thermal effects. Our flume experiment, although statistically well-powered and based on a scenario near the limits of swimming performance in stickleback, detected no counter-current swimming effect on immune-associated gene expression or infection resistance. The field association between flow rate and immune expression could thus be due to an indirect effect and we tentatively advance hypotheses to explain this. This study clarifies the drivers of immune investment in wild vertebrates; although locomotor activity, within the normal natural range, may not directly influence immunocompetence, it may still correlate with other variables that do

Microbiological studies of cockroaches from three localities in Gaborone, Botswana

Cockroaches have become the most common pests in a majority of households in Gaborone, the capital city of Botswana Their presence has always raised safety concerns, especially as carriers of food-borne pathogens and food-spoilage organisms. To address the safety issues, bacteriological investigations were carried out on cockroaches trapped from the kitchens and toilets of three localities in Gaborone, households in Botswana. The bacterial, total spore forming, Bacillus cereus, coliforms and E. coli counts from the surfaces of cockroaches were estimated using bacteriological media. Aerobic and facultatively anaerobic bacteria from the fecal pellets were isolated and characterized. Specialized mediawere used for culturing pathogens. 67 %, 22.2 % and 28.6 % of the cockroaches trapped in the kitchen from Central/Broadhurst, Old Naledi and Tlokweng, respectively, had aerobic plate counts of &gt; 106 CFU/cockroach. The cockroaches trapped from the toilets had higher counts than kitchens. Sporeformers were present in most samples though in lower numbers. However, Bacillus cereus was only found in some of the cockroaches at much lower numbers. As much as 70&ndash; 98.3% of the cockroaches had coliforms; but, E. coli was only found in 5&ndash;6.5% of the cockroaches at &gt; 103 CFU/cockroach. 70 species of bacteria representing 37 genera were isolated from the surface and fecal pellets. Even though the majority of the bacteria that were isolated from the surfaces were Gram negative thosefrom the pellets were mostly Gram positive. The most common and abundant species belonged to Pseudomonas and Serratia, with members of the Enterobacteriaceae following. In the pellets, species of Bacillus were predominant, but, there were some members of Enterobacteriaceae. Pathogens like Salmonella, Shigella and B. cereus were isolated. Opportunistic pathogens like species of Pseudomonas, Klebsiella and Vibrio and food spoilage bacteria such as species of Enterobacter, Citrobacter, Escherichia, Erwinia, and Pseudomonas were also found. Proper care in disposal of food remnants and overall cleanliness at the householdsprevents cockroaches from foraging in the kitchen and toilet

The Morphologically Divided Redshift Distribution of Faint Galaxies

We have constructed a morphologically divided redshift distribution of faint field galaxies using a statistically unbiased sample of 196 galaxies brighter than I = 21.5 for which detailed morphological information (from the Hubble Space Telescope) as well as ground-based spectroscopic redshifts are available. Galaxies are classified into 3 rough morphological types according to their visual appearance (E/S0s, Spirals, Sdm/dE/Irr/Pec's), and redshift distributions are constructed for each type. The most striking feature is the abundance of low to moderate redshift Sdm/dE/Irr/Pec's at I < 19.5. This confirms that the faint end slope of the luminosity function (LF) is steep (alpha < -1.4) for these objects. We also find that Sdm/dE/Irr/Pec's are fairly abundant at moderate redshifts, and this can be explained by strong luminosity evolution. However, the normalization factor (or the number density) of the LF of Sdm/dE/Irr/Pec's is not much higher than that of the local LF of Sdm/dE/Irr/Pec's. Furthermore, as we go to fainter magnitudes, the abundance of moderate to high redshift Irr/Pec's increases considerably. This cannot be explained by strong luminosity evolution of the dwarf galaxy populations alone: these Irr/Pec's are probably the progenitors of present day ellipticals and spiral galaxies which are undergoing rapid star formation or merging with their neighbors. On the other hand, the redshift distributions of E/S0s and spirals are fairly consistent those expected from passive luminosity evolution, and are only in slight disagreement with the non-evolving model.Comment: 11 pages, 4 figures (published in ApJ

Drosophila Insulin receptor regulates the persistence of injury-induced nociceptive sensitization

Diabetes-associated nociceptive hypersensitivity affects diabetic patients with hard-to-treat chronic pain. Because multiple tissues are affected by systemic alterations in insulin signaling, the functional locus of insulin signaling in diabetes-associated hypersensitivity remains obscure. Here, we used Drosophila nociception/nociceptive sensitization assays to investigate the role of Insulin receptor (Insulin-like receptor, InR) in nociceptive hypersensitivity. InR mutant larvae exhibited mostly normal baseline thermal nociception (absence of injury) and normal acute thermal hypersensitivity following UV-induced injury. However, their acute thermal hypersensitivity persists and fails to return to baseline, unlike in controls. Remarkably, injury-induced persistent hypersensitivity is also observed in larvae that exhibit either type 1 or type 2 diabetes. Cell type-specific genetic analysis indicates that InR function is required in multidendritic sensory neurons including nociceptive class IV neurons. In these same nociceptive sensory neurons, only modest changes in dendritic morphology were observed in the InRRNAi-expressing and diabetic larvae. At the cellular level, InR-deficient nociceptive sensory neurons show elevated calcium responses after injury. Sensory neuron-specific expression of InR rescues the persistent thermal hypersensitivity of InR mutants and constitutive activation of InR in sensory neurons ameliorates the hypersensitivity observed with a type 2-like diabetic state. Our results suggest that a sensory neuron-specific function of InR regulates the persistence of injury-associated hypersensitivity. It is likely that this new system will be an informative genetically tractable model of diabetes-associated hypersensitivity

Spin splitting of X-related donor impurity states in an AlAs barrier

We use magnetotunneling spectroscopy to observe the spin splitting of the ground state of an X-valley-related Si-donor impurity in an AlAs barrier. We determine the absolute magnitude of the effective Zeeman spin splitting factors of the impurity ground state to be g$_{I}$= 2.2 $\pm$ 0.1. We also investigate the spatial form of the electron wave function of the donor ground state, which is anisotropic in the growth plane