Psychological aspects of systemic lupus erythematosus: cognitive function, mood, and self-report

Previous studies have shown that Tetrahymena citrate synthase and the Tetrahymena 14-nm filament protein are encoded by a single gene and translated from one species of mRNA, and that they are identical in terms of molecular weight, antigenicity, and some enzymatic properties. In this study, using two-dimensional gel electrophoresis, we demonstrated that the citrate synthase comprised pI 7.7 and 8.0 isoforms, while the 14-nm filament protein comprised three isoforms with isoelectric points of 7.7, 8.0, and 8.4. The amino acid sequences of the NH2-terminal portions of all isoforms were identical and the peptide maps with V8 protease were almost the same. In addition, when the citrate synthase activity of each isoform was measured after separation by non-urea isoelectric focusing without denaturing treatment, the pI 7.7 and/or pI 8.0 isoforms exhibited the citrate synthase activity, but the pI 8.4 isoform only found for the 14-nm filament protein did not possess this activity. These results suggest that the polymorphism of these isoforms is caused by some posttranslational modifications, and that it may have resulted in the different compartmentalization and functions of Tetrahymena citrate synthase and the 14-nm filament protein.     

The aminothiol WR-1065 protects T lymphocytes from ionizing radiation-induced deletions of the HPRT gene

Aminothiols, such as WR-2721 and its active free thiol, WR-1065, reduce mutations from ionizing radiation in exponentially growing cells. In this study, human noncycling G0 T lymphocytes were exposed in vitro to gamma-irradiation in the presence or absence of WR-1065. The five treatment groups were: (a) control; (b) treatment with 4 mM WR-1065; (c) treatment with 3 Gy of gamma-radiation, from a 137Cs source; and (d) and (e) treatment with WR-1065 30 min prior to or 3 h after 3 Gy of gamma-irradiaiton, respectively. A total of 224 cloned HPRT mutants representing 179 independent mutations were analyzed for genetic alterations using multiplex PCR. Ionizing radiation alone significantly increased the percentage of mutations with gross structural alterations compared to controls (P = 0.02). Although the frequency of such large structural mutations was not different from control cells treated with WR-1065 alone, this aminothiol significantly reduced their frequency among irradiated mutants (P = 0.01) when the radioprotector was present during the irradiation. Addition of WR-1065 3 h postirradiation also greatly reduced the percentage of gross structural alterations; however, due to small numbers, this was not statistically significant. This is the first demonstration that the antimutagenicity of WR-1065 in human cells specifically protects against these kinds of large-scale DNA alterations induced by ionizing radiation. WR-1065 and similar aminothiol compounds may afford protection against radiation-induced mutations through polyamine-like processes, e.g., stabilization of chromatin structure, inhibition of cell proliferation, and influences on DNA repair systems.     

Late cytomegalovirus disease in marrow transplantation is predicted by virus load in plasma

Late occurrence of cytomegalovirus (CMV) disease after day 100 after bone marrow transplantation has become an increasing problem; whether a quantitative measurement of CMV DNA in plasma by polymerase chain reaction (P-PCR) could be predictive of such disease was investigated. In a prospective study, 117 subjects undergoing allogeneic marrow transplantation were followed for 120 days with weekly CMV blood cultures, with day 35 bronchoalveolar lavage CMV cultures, with weekly CMV P-PCR, and with clinical follow-up for an additional 1-2 years. Despite preemptive ganciclovir, CMV disease occurred in 9% of subjects, with a median time of onset of 176 days. Quantitative CMV P-PCR was associated with the late development of CMV disease (P = .01). Of 43 subjects with positive P-PCR results, 23% developed CMV disease, but no disease occurred in the 74 subjects with negative P-PCR (P < .001), despite the fact that 22% had CMV isolated from lung lavage fluid and 32% had CMV isolated from blood.     

Aldosterone and dexamethasone stimulate calcineurin activity through a transcription-independent mechanism involving steroid receptor-associated heat shock proteins

1. PD 81,723 has been shown to enhance binding of adenosine to A1 receptors by stabilizing G protein-receptor coupling ('allosteric enhancement'). Evidence has been provided that in the perfused hearts and isolated atria PD 81,723 causes a sensitization to adenosine via this mechanism. 2. We have studied the effect of PD 81,723 in guinea-pig isolated atrial myocytes by use of whole-cell measurement of the muscarinic K+ current (I[K(ACh)]) activated by different Gi-coupled receptors (A1, M2, sphingolipid). PD 81,273 caused inhibition of I[K(ACh)] (IC50 approximately 5 microM) activated by either of the three receptors. Receptor-independent I[K(ACh)] in cells loaded with GTP-gamma-S and background I[K(ACh)], which contributes to the resting conductance of atrial myocytes, were equally sensitive to PD 81,723. At no combination of concentrations of adenosine and PD 81,723 could an enhancing effect be detected. 3. The compound was active from the outside only. Loading of the cells with PD 81,723 (50 microM) via the patch pipette did not affect either I[K(ACh)] or its sensitivity to adenosine. We suggest that PD 81,723 acts as an inhibitor of inward rectifying K+ channels; this is supported by the finding that ventricular I(K1), which shares a large degree of homology with the proteins (GIRK1/GIRK4) forming I[K(ACh)] but is not G protein-gated, was also blocked by this compound. 4. It is concluded that the functional effects of PD 81,723 described in the literature are not mediated by the A1 adenosine receptor-Gi-I[K(ACh)] pathway.     

Chondroma of the mandibular condyle: an example of a rare tumour

Chondromas are benign tumours of cartilage which are rare in the head and neck. We present a case report of a chondroma in the neck of condyle and demonstrate the value of multiplanar spiral CT and the limitations of 3D reconstruction.     

Action of prostanoids on the emetic reflex of Suncus murinus (the house musk shrew)

Several prostanoids were investigated for a potential to induce emesis in Suncus murinus. The TP receptor agonist 11alpha,9alpha-epoxymethano-15S-hydroxyprosta-5Z,13E-dienoic acid (U46619) induced emesis at doses as low as 3 microg/kg, i.p. but the DP receptor agonist 5-(6-Carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl) hydantoin (BW245C) was approximately 1000 times less potent. The emetic action of U46619 (300 microg/kg, i.p.) was antagonized significantly by the TP receptor antagonist, vapiprost (P<0.05). EP (prostaglandin E(2), 17-phenyl-omega-trinor prostaglandin E(2), misoprostol and sulprostone), FP (prostaglandin F(2alpha) and fluprostenol) and IP (iloprost and cicaprost) receptor agonists failed to induce consistent emesis at doses up to 300-1000 microg/kg, i.p. Fluprostenol reduced nicotine (5 mg/kg, s.c.)-but not copper sulphate (120 mg/kg, intragastric)-induced emesis; the other inconsistently emetic prostanoids were inactive to modify drug-induced emesis. The results indicate an involvement of TP and possibly DP and FP receptors in the emetic reflex of S. murinus.