Anti-Sa antibody is an accurate diagnostic and prognostic marker in adult rheumatoid arthritis

The aporphine alkaloids boldine and glaucine have been reported to show "neuroleptic-like" actions in mice, suggesting that they may act as dopamine antagonists. We have found that in vitro boldine displaces specific striatal [3H]-SCH 23390 binding with IC50 = 0.4 microM and [3H]-raclopride binding with IC50 = 0.5 microM, while the affinities of glaucine at the same sites are an order of magnitude lower. In vivo, however, 40 mg/kg boldine (i.p.) did not modify specific striatal [3H]-raclopride binding and only decreased [3H]-SCH 23390 binding by 25%. On the other hand, 40 mg/kg glaucine (i.p.) displaced both radioligands by about 50%. Behaviors (climbing, sniffing, grooming) elicited in mice by apomorphine (0.75 mg/kg s.c.) were not modified by boldine at doses up to 40 mg/kg (i.p.) but were almost completely abolished by 40 mg/kg glaucine (i.p.). In the apomorphine-induced (0.1 mg/kg s.c.) rat yawning and penile erection model, boldine and glaucine appeared to be similarly effective, inhibiting both behaviors by more than 50% at 40 mg/kg (i.p.). Boldine and glaucine, injected i.p. at doses up to 40 mg/kg, were poor modifiers of dopamine metabolism in mouse and rat striatum. These data suggest that boldine does not display effective central dopaminergic antagonist activities in vivo in spite of its good binding affinity at D1- and D2-like receptors, and that glaucine, although less effective in vitro, does appear to exhibit some antidopaminergic properties in vivo.     

Signals from Ras and Rho GTPases interact to regulate expression of p21Waf1/Cip1

Small GTPases act as molecular switches in intracellular signal-transduction pathways. In the case of the Ras family of GTPases, one of their most important roles is as regulators of cell proliferation, and the mitogenic response to a variety of growth factors and oncogenes can be blocked by inhibiting Ras function. But in certain situations, activation of Ras signalling pathways arrests the cell cycle rather than causing cell proliferation. Extracellular signals may trigger different cellular responses by activating Ras-dependent signalling pathways to varying degrees. Other signalling pathways could also influence the consequences of Ras signalling. Here we show that when signalling through the Ras-related GTPase Rho is inhibited, constitutively active Ras induces the cyclin-dependent-kinase inhibitor p21Waf1/Cip1 and entry into the DNA-synthesis phase of the cell cycle is blocked. When Rho is active, induction of p21Waf1/Cip1 by Ras is suppressed and Ras induces DNA synthesis. Cells that lack p21Waf1/Cip1 do not require Rho signalling for the induction of DNA synthesis by activated Ras, indicating that, once Ras has become activated, the primary requirement for Rho signalling is the suppression of p21Waf1/Cip1 induction.     

An essential role for ectodomain shedding in mammalian development

The ectodomains of numerous proteins are released from cells by proteolysis to yield soluble intercellular regulators. The responsible protease, tumor necrosis factor-alpha converting enzyme (TACE), has been identified only in the case when tumor necrosis factor-alpha (TNFalpha) is released. Analyses of cells lacking this metalloproteinase-disintegrin revealed an expanded role for TACE in the processing of other cell surface proteins, including a TNF receptor, the L-selectin adhesion molecule, and transforming growth factor-alpha (TGFalpha). The phenotype of mice lacking TACE suggests an essential role for soluble TGFalpha in normal development and emphasizes the importance of protein ectodomain shedding in vivo.     

Correlations among Epworth Sleepiness Scale scores, multiple sleep latency tests and psychological symptoms

Mouse leukemic cell subline L1210/VCR exerts expressive multidrug resistance (MDR) that is mediated by P-glycoprotein. Cells originally adapted to vincristine are also extremely resistant to doxorubicin. Resistance to both vincristine and doxorubicin is connected with depression of drug uptake. While resistance of L1210 cells to vincristine could be reversed by verapamil as chemosensitizer, resistance of cells to doxorubicin was insensitive to verapamil. Action of verapamil (well-known inhibitor of PGP activity) on multidrug resistance was often used as evidence that MDR is mediated by PGP. From this point it may be possible that the resistance of L1210/VCR cells to vincristine is mediated by PGP and the resistance to doxorubicin is mediated by other PGP-independent system. Another and more probable explanation of different effect of verapamil on resistance of L1210/VCR cells to vincristine and doxorubicin may be deduced from the following fact: Using UV spectroscopy we found that doxorubicin dissolved in water buffered medium interacts effectively with verapamil. This interaction may be responsible for the decrease of concentration of both drugs in free effective form and consequently for higher survival of cells. In contrast to doxorubicin vincristine does not give any interaction with verapamil that is measurable by UV spectroscopy and resistance of L1210/VCR cells to vincristine may be fully reversed by verapamil.     

Pb(core)/ZnO(shell) nanowires obtained by microwave-assisted method

In this study, Pb-filled ZnO nanowires [Pb(core)/ZnO(shell)] were synthesized by a simple and novel one-step vapor transport and condensation method by microwave-assisted decomposition of zinc ferrite. The synthesis was performed using a conventional oven at 1000 W and 5 min of treatment. After synthesis, a spongy white cotton-like material was obtained in the condensation zone of the reaction system. HRTEM analysis revealed that product consists of a Pb-(core) with (fcc) cubic structure that preferentially grows in the [111] direction and a hexagonal wurtzite ZnO-(Shell) that grows in the [001] direction. Nanowire length was more than 5 μm and a statistical analysis determined that the shell and core diameters were 21.00 ± 3.00 and 4.00 ± 1.00 nm, respectively. Experimental, structural details, and synthesis mechanism are discussed in this study.     

Two mechanisms of quantized calcium release in skeletal muscle

Skeletal muscle uses voltage sensors in the transverse tubular membrane that are linked by protein-protein interactions to intracellular ryanodine receptors, which gate the release of calcium from the sarcoplasmic reticulum. Here we show, by using voltage-clamped single fibres and confocal imaging, that stochastic calcium-release events, visualized as Ca2+ sparks, occur in skeletal muscle and originate at the triad. Unitary triadic Ca(2+)-release events are initiated by the voltage sensor in a steeply voltage-dependent manner, or occur spontaneously by a mechanism independent of the voltage sensor. Large-amplitude events also occur during depolarization and consist of two or more unitary events. We propose a 'dual-control' model for discrete Ca2+ release events from the sacroplasmic reticulum that unifies diverse observations about Ca(2+)-signalling in frog skeletal muscle, and that may be applicable to other excitable cells.     

Comparison of autologous bone marrow transplantation with sequential chemotherapy for intermediate-grade and high-grade non-Hodgkin's lymphoma in first complete remission: a study of 464 patients. Groupe d'Etude des Lymphomes de l'Adulte

PURPOSE: Intensive chemotherapy followed by autotransplantation has given promising results in partially responding or sensitive relapsed patients with aggressive non-Hodgkin's lymphoma. In 1987, we designed a randomized study to evaluate the potential benefit of a high-dose regimen containing cyclophosphamide, carmustine, and etoposide (CBV) followed by autotransplantation over a consolidative sequential chemotherapy (ifosfamide, etoposide, asparaginase, and cytarabine) in patients in first complete remission with intermediate- and high-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients were younger than 55 years and had at least one adverse prognostic factor. Induction treatment was that of the LNH84 protocol with an open randomization on the anthracycline. Patients in complete remission were further randomly assigned to receive either consolidation procedure. RESULTS: After induction treatment, 464 patients were assessable for the consolidation phase. With a median follow-up duration of 28 months, the 3-year disease-free survival rate was 52% (95% confidence interval, 45% to 59%) in the sequential chemotherapy arm and 59% (95% confidence interval, 52% to 66%) in the autologous transplant arm (P = .46, relative risk = 0.90). The 3-year survival rate did not differ between sequential chemotherapy and autotransplantation, at 71% (95% confidence interval, 64% to 78%) and 69% (95% confidence interval, 62% to 76%), respectively (P = .60, relative risk = 1.11). CONCLUSION: For such a subset of patients, consolidation with the CBV regimen followed by autologous bone marrow transplantation is not superior to sequential chemotherapy.     

Influence of tempering on the feeding value of rolled corn in finishing diets for feedlot cattle

Crossbred yearling steers (n = 125; 372 kg) were used in a 109-d finishing trial. Steers were fed an 88% concentrate diet containing 65% corn (DM basis) as 1) dry rolled corn (DRC); 2) tempered rolled corn (TRC), 43 mg surfactant (SarTemp)/kg corn; 3) TRC, 172 mg surfactant/kg corn; 4) TRC, 430 mg surfactant/kg corn; and 5) steam-flaked corn (SFC). Corn moisture was greater (3.5%, P < .01) for TRC than for DRC but less (10%, P < .05) than for SFC. Starch enzymatic reactivity was less for TRC than for either DRC (18%, P < .05) or SFC (42%, P < .01). Tempering increased the integrity of rolled corn and reduced the amount of particles less than 2 mm in diameter by 54% (P < .01). Steam flaking corn increased (P < .01) proportion (78%) of the grain having a particle size distribution of greater than 8 mm, as compared with TRC (25%) and DRC (3%). Compared with DRC, tempering enhanced (P < .10) ADG (9%), feed efficiency (5%), and dietary NE (3%). Daily weight gain was similar (P > .10) for TRC and SFC. Feed efficiency (P < .10) and dietary NE (P < .01) were greater (6%) for SFC than for TRC. There were no differences (P > .10) between DRC and TRC in ruminal and total tract digestion of OM, N, and starch, and in ruminal microbial efficiency. Ruminal digestion of OM decreased (linear effect, P < .05) and ruminal microbial efficiency increased (linear effect, P < .05) with increasing surfactant concentration. Ruminal digestion of OM and starch, and flow of nonammonia N to the small intestine were greater (31, 56, and 14%, respectively, P < .01) for SFC than for TRC. Postruminal and total tract digestion of OM, N, and starch, and dietary DE were greater (P < .01) for SFC than for TRC. We concluded that tempering corn will enhance animal performance. Increasing the concentration of surfactant used in tempering may enhance ruminal microbial efficiency and lean tissue growth.