The Clinical Significance of Interleukin–1 Receptor Antagonist +2018 Polymorphism in Rheumatoid Arthritis

ObjectiveInterleukin-1 receptor antagonist (IL-1Ra) acts as an inhibitor of IL-1; which is one of the culprit cytokines in rheumatoid arthritis (RA). Although +2018 polymorphism of IL-1Ra has been implicated in the pathogenesis of RA, its importance remains poorly understood. Hence, the purpose of this study was to determine the clinical significance of interleukin-1 receptor antagonist (IL-1Ra) +2018 polymorphism in RA.MethodsPolymerase chain reaction (PCR) and sequencing were used to determine the genotypes of the IL-1Ra +2018 for 77 RA patients and 18 healthy controls. All RA patients were assessed for the disease activity score that includes 28 joints (DAS28) and radiographic disease damage based on Modified Sharp Score (MSS).ResultsThe frequency of the T/T and C/T genotypes did not differ significantly (p = 0.893) between the RA patients and the controls. The C/T genotype had significantly higher mean disease activity (DAS 28) and disease damage (MSS) scores with p values of 0.017 and 0.004, respectively. Additionally, the ESR (erythrocyte sedimentation rate), CRP (C-reactive protein), the number of swollen and tender joints were higher for the C/T individuals. On multivariate analysis the CRP, swollen joint count and MSS remained significant with the following p values i.e. 0.045, 0.046 and less than 0.05.ConclusionsC/T genotype of IL-1Ra +2018 prognosticates more aggressive disease in RA.     

Measurement of pharyngeal cross-sectional area by finite element analysis.

A noninvasive measurement of pharyngeal cross-sectional area (CSA) during sleep would be advantageous for research studies. We hypothesized that CSA could be calculated from the measured pharyngeal pressure and flow by finite element analysis (FEA). The retropalatal airway was visualized by using a fiber-optic scope to obtain the measured CSA (mCSA). Flow was measured with a pneumotachometer, and pharyngeal pressure was measured with a pressure catheter at the palatal rim. FEA was performed as follows: by using a three-dimensional image of the upper airway, a mesh of finite elements was created. Specialized software was used to allow the simultaneous calculation of velocity and area for each element by using the measured pressure and flow. In the development phase, 677 simultaneous measurements of CSA, pressure, and flow from one subject during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep were entered into the software to determine a series of equations, based on the continuity and momentum equations, that could calculate the CSA (cCSA). In the validation phase, the final equations were used to calculate the CSA from 1,767 simultaneous measurements of pressure and flow obtained during wakefulness, NREM, and REM sleep from 14 subjects. In both phases, mCSA and cCSA were compared by Bland-Altman analysis. For development breaths, the mean difference between mCSA and cCSA was 0.0 mm2 (95% CI, -0.1, 0.1 mm2). For NREM validation breaths, the mean difference between mCSA and cCSA was 1.1 mm2 (95% CI 1.3, 1.5 mm2). Pharyngeal CSA can be accurately calculated from measured pharyngeal pressure and flow by FEA.     

Association of folate molecules as determined by proton NMR: implications on enzyme binding

The self-association in aqueous solution of folic acid (FA), 7,8-dihydrofolic acid (DHFA) and 5,6,7,8-tetrahydrofolic acid (THFA) has been studied by the use of proton magnetic resonance (1H NMR) spectroscopy. At concentrations below 10 mM, all three folates exist in (monomer)2 in equilibrium dimer equilibria with association constants (Ka) equal to 400, 66 and 14 M-1 for FA, DHFA and THFA respectively. These values decreased markedly to 157, 18 and 3 M-1, for FA, DHFA and THFA respectively, in the presence of 0.8 M KCl. The high extent of dimerization of FA is believed to impede the interaction with the active site of dihydrofolate reductase (DHFR) rendering it a poor substrate. In contrast, the DHFA with a much lower Ka is a better substrate. Conditions that lower the Ka of both FA and DHFA, (i.e., 0.8M KCl) turn them into better substrates. Based on the findings of the present study, it is also predicted that dihydro MTX may be a better inhibitor of DHFR than MTX.     

Motile aeromonas infection of striped (grey) mullet Mugil cephalus

Infection of striped mullet (Mugil cephalus) with Aeromonas hydrophila results in an acute septicemic disease. The disease can be experimentally induced by intramuscular injection, skin or gill scarification or by the oral route using pellets purposely seeded with bacteria. The organism was isolated from the blood 1–2 days after infection and from all organs 24 hr or longer after infection. The disease is characterized by early inflammatory and proliferative changes and later necrotic changes. Enteritis and hepatic necrosis are constant findings in aeromonad disease of M. cephalus but surface lesions are not pathognomic for these infections in mullet. Death of infected fish may be attributed to bacterial toxins which cause necrosis of parenchymal organs and soft tissue structure.     

Amphiphilic and Nonamphiphilic Forms of Torpedo Cholinesterases: I. Solubility and Aggregation Properties

We report an analysis of the solubility and hydrophobic properties of the globular forms of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) from various Torpedo tissues. We distinguish globular nonamphiphilic forms (Gna) from globular amphiphilic forms (Ga). The Ga forms bind micelles of detergent, as indicated by the following properties. They are converted by mild proteolysis into nonamphiphilic derivatives. Their Stokes radius in the presence of Triton X-100 is approximately 2 nm greater than that of their lytic derivatives. The G2a forms fall in two classes. Class I contains molecules that aggregate in the absence of detergent, when mixed with an AChE-depleted Triton X-100 extract from electric organ. AChE G2a forms from electric organs, nerves, skeletal muscle, and erythrocyte membranes correspond to this type, which is also detectable in detergent-soluble (DS) extracts of electric lobes and spinal cord. Class II forms never aggregate but only present a slight shift in sedimentation coefficient, in the presence or absence of detergent. This class contains the AChE G2a forms of plasma and of the low-salt-soluble (LSS) fractions from spinal cord and electric lobes. The heart possesses a BuChE G2a form of class II in LSS extracts, as well as a similar G1a form. G4a forms of AChE, which are solubilized only in the presence of detergent and aggregate in the absence of detergent, represent a large proportion of cholinesterase in DS extracts of nerves and spinal cord, together with a smaller component of G4a BuChE. These forms may be converted to nonamphiphilic derivatives by Pronase. Nonaggregating G4a forms exist at low levels in the plasma (BuChE) and in LSS extracts of nerves (BuChE) and spinal cord (AChE).     

Studies on the effect of NAD(H) on nitrogenase activity in Rhodospirillum rubrum

The effect of NAD(P) and analogs of this nucleotide on nitrogenase activity in Rhodospirillum rubrum has been studied. Addition of NAD⁺ to nitrogen fixing Rsp. rubrum leads to inhibition of nitrogenase. NADP⁺ has the same effect but NADH or analogs modified in the nicotinamide portion do not cause inhibition. In contrast to ammonium ions, addition of NAD⁺ leads to inhibition of nitrogenase in cells that have been N-starved under argon. The inhibitory effect of NAD⁺ is more pronounced at lower light intensities. Addition of NAD⁺ also leads to inhibition of glutamine synthetase, a phenomenon also occurring when “switchoff” is produced by the addition of effectors such as ammonium ions or glutamine. It is also shown that NAD⁺ is taken up by Rsp. rubrum cells.     

Chromosome association and pollen fertility of parental and interspecific hybrids of Lycopersicon esculentum X L. hirsutum and L. pennellii

Cytological studies were carried out on two wild species (L. hirsutum and L. pennellii) and the cultivated species (L. esculentum) of tomato and their F1 hybrids. Both parents and hybrids show a diploid chromosome number of 2n=24. The meiotic behaviour of the cultivated species showed a high degree of chromosome homology resulting in a high level of chiasmata frequency per bivalent. In contrast, the two wild species showed a slight increase in uniyalent frequency and a decrease in bivalent formation and chiasmata frequency. The meiotic behaviour of the hybrids showed a high level of univalents and low levels of bivalents as well as trivalents. Highly significant decreases in chiasmata frequency and increases in meiotic abnormalities, especially in the L. esculentum X L. pennellii hybrid, also were detected. The high meiotic irregularity and low chiasmata frequency recorded in the second hybrid indicated the disharmony and difference between its parental genomes and also served to predict its sterility. With regard to degree of pairing recorded in the hybrids, there is a possibility that sterility in such cases may refer to genetic factors in addition to the previously mentioned reasons. Pollen fertility showed no great difference between L. esculentum and L. hirsutum and their F1 hybrid, but a significant decrease was recorded in the L. esculentum X L. pennellii hybrid, which was clearly associated with high meiotic irregularity, low chiasmata frequency and chromosome association.     

Inhibition of the rat adrenal ornithine decarboxylase activity by immobilization stress and/or dexamethasone

The effects of immobilization stress and/or dexamethasone (DEX) on the adrenal ornithine decarboxylase (ODC) activities of sham-operated and adrenal-medulloectomized (enucleated) male Sprague-Dawley rats were investigated. On day 11 after surgery, rats were injected with saline or DEX (1 mg/kg), 3 h before the time of sacrifice (0600 h or 1800 h). Four groups, from sham-operated and enucleated rats (ENU) treated with saline or DEX were subjected to immobilization stress for 1 h prior to sacrifice. Groups of rats from stress-sham-DEX, non stress-sham-DEX, stress-sham, non stress-sham, stress-ENU-DEX, non stress-ENU-DEX, stress-ENU, and non stress-ENU were sacrificed at 0600 h or 1800 h on day 11 after surgery. Adrenal glands were excised and later analyzed for ODC activities. Results indicated that DEX and/or immobilization stress inhibited ODC activities (p < 0.05) in normal and regenerating adrenal glands at 1800 h and ODC activity varies diurnally, the activity being greater at 1800 h than at 0600 hours (p < 0.001).