Validation of a model predicting enrollment status in a chemoprevention trial for breast cancer

A simple, rapid, and sensitive method which allows us to simultaneously determine bromvalerylurea (BVU) and its three metabolites (3-methylbutyrylurea [MVU], alpha-(cystein-S-yl)isovalerylurea [CVU], and alpha-(N-acetylcystein-S-yl)isovalerylurea [AcCVU]) was investigated by frit-fast atom bombardment liquid chromatography-mass spectrometry (frit-FAB LC-MS). The LC-MS analysis was performed after the solid-phase extraction from tissue and urine samples with a Sep-Pak C18 cartridge. Tissue homogenates and urine were adjusted to pH 4.0 and applied to the cartridges. The retained BVU and its metabolites were eluted from the cartridge with 2 mL of acetonitrile/10 mM ammonium acetate buffer (pH 3.5, 50:50, v/v). The eluate was analyzed by LC-MS, which employs a semimicro type L-column ODS column. The proposed conditions are as follows: mobile phase A, 0.4% glycerol in acetonitrile/10 mM ammonium acetate buffer (pH 3.5) (5:95, v/v); mobile phase B, 0.4% glycerol in acetonitrile; elution mode, linear gradient, 100% A (5 min) to 100% B in 15 min; flow rate, 0.2 mL/min; split ratio, 1:40. Extraction recoveries of BVU and its metabolites were 91.90-97.79% from the spiked liver homogenate and 89.68-96.13% from the spiked urine. The detection limits ranged from 10 to 25 ng/g in selected ion monitoring mode.     

Association of phosphoinositide-specific phospholipase Cgamma1 with elements of cytoskeleton in A-431 cells

It is shown that phosphoinositide-specific phospholipase C gamma 1 (PLC gamma 1), a substrate of growth factor receptors, is associated with cytoskeleton in A-431 cells. PLC gamma 1 is co-localized only with the cortical actin but not with actin stress fibers. Since EGF receptor is also co-localized with the cortical actin it is concluded that PLC gamma 1 co-localized with actin is mediated by the EGF receptor. After the treatment with cytochalasin B PLC gamma 1 is co-localized with actin aggregates and cytoskeleton elements other than actin. Using double immunofluorescence PLC gamma 1 is shown to be associated with cytokeratin intermediate filaments. The cross-talking of different cytoskeleton elements and their participation in cell signaling is discussed.     

Identification of two Escherichia coli pseudouridine synthases that show multisite specificity for 23S RNA

Several putative Escherichia coli pseudouridine (Psi) synthases have been identified by iterative searching of genomic databases for ORFs homologous to known Psi synthases [Gustafsson et al. (1996) Nucleic Acids Res. 24, 3756-3762]. Of these, yceC and yfiI were proposed to encode Psi synthases which modify 23S rRNA. In the present work, yceC and yfiI were cloned and overexpressed in E. coli, and the encoded enzymes, YceC and YfiI, were purified to homogeneity. Both proteins converted Urd residues of rRNA to Psi, thus confirming their identities as Psi synthases. However, in in vitro experiments both enzymes extensively modified Urd residues of both 23S rRNA and 16S rRNA. Gene-disruption of yceCresulted in the absence of Psi modification at positions U955, 2504, and 2580 of 23S RNA, thus identifying these sites as in vivo targets for YceC. Likewise, yfiI disruption resulted in the absence of Psi modification at positions U1911, 1917, and possibly 1915 of 23S RNA. Disruption of yceC did not affect the growth under the conditions tested, whereas yfiI-disrupted cells showed a dramatic decrease in growth rate. Since YceC and YfiI hypermodify RNA in vitro, factors in addition to ribonucleotide sequence must contribute to the in vivo specificity of these enzymes.     

Stereotactic Radiation Therapy on Intracranial Structures Using an LUÉR-20M Medical Linear Accelerator

A system for stereotactic radiation therapy using narrow bremsstrahlung beams for pathological and normal intracranial structures is examined. The system is based on an LUÉR-20M medical linear accelerator.The method is based on stereotactic centering of a small intracranial target using an x-ray centering guide and rigidly securing the patient's head, with no bleeding, on a treatment table using a rapidly solidifying individual plastic mask, isocentric movement of the treatment table toward the linear accelerator, and subsequent treatment with a narrow static or rotating photon beam. One hundred patients have been treated. The results show that this treatment method is effective.Stereotactic photon beam therapy can be an alternative method to surgery and treatment with a photon beam.     

Pregnancy and lactation in homozygous beta-thalassemia major

Ki-1 anaplastic large cell lymphoma is a well-described subtype of non-Hodgkin's lymphoma with distinctive characteristics from the cytological, immunohistochemical and clinical points of view. One of the clinical behavior characteristic is that it rarely evolves into a leukaemic phase. We report the case of a 72-year-old man in which the appearance of tumor cells in peripheral blood was one of the most revealing information. The patient showed B-symptoms, bicytopenia and bone marrow involvement, together with hepatosplenomegaly and right axilar adenopathy, which after biopsied lead to Ki-1 anaplastic large cell lymphoma's diagnosis (stage IV-B). As far as the treatment and evolution are concerned, we choose a polychemotherapy (ACOP-B) because of the patient's age. Up to now clinical and analitical course is excellent and the patient is now in remission.     

Dynamic changes in the reactivity of the hormonal system regulation with the impact by LBNP sessions in long-term space mission

Experiment INTERSTITIUM was performed on days 3, 170, 287, and 430 of the long-term MIR mission of the Russian cosmonaut-physician in order to evaluate reactivity of the system of hormonal regulation of homeostasis during LBNP sessions. Data of the experiment displayed different types of reaction of the volume controls to LBNP at the onset (F-3), in the course of and soon after recovery (R-4) from the extended mission which are signs of specific phases of adaptive shifts in the organism of cosmonaut. Exaggerated reactivity of the hormonal systems during LBNP in flight suggests more significant consequences of the test for the cardiovascular system of human in microgravity. The most expressed hormonal reaction to LBNP was documented at the very beginning of the postflight period. Plasma cGMP was materially reduced in the process of the mission and remained quite low on R-4; return of nucleotides to the norm was observed no earlier than on R-90. Complete recovery from the space mission took three months when the hormonal reaction to LBNP was same as prior to launch.     

A PIL for every ill? Patient information leaflets (PILs): a review of past, present and future use

PURPOSE: The necessity of effective prevention of DVT is generally accepted. However, attitudes and beliefs concerning prophylaxis vary greatly in terms of the risk groups receiving prophylaxis and the prophylactic methodology. This paper reviews current research on the subject and seeks to provide recommendations. RESULTS: Known clinical risk factors allow the classification of patients according to high, medium and low risk of developing thromboembolism. Basic forms of prophylaxis are physiotherapy and early mobilisation. However, there are no data on the safety and efficacy of these methods. Mechanical devices used include external intermittent pneumatic compression and graduated compression stockings. Used in isolation, these methods reduce the incidence of deep vein thrombosis in low and moderate risk patients by one half or one third. There is no distinction between mechanical and pharmacological methods in terms of safety and efficacy. Furthermore, secondary effects are extremely rare. Moderate and high risk category patients should receive combined modes of mechanical and pharmacological treatment. A direct comparison of safety in moderate risk patients fixed doses of standard heparin vs. low molecular weight heparin revealed no significant differences. In the case of high risk patients, adjusted dose heparin administered subcutaneously or fixed dose low molecular heparin is recommended. A severe secondary effect of heparin-prophylaxis is heparin-induced thrombocytopenie. The optimum duration of pharmacological prophylaxis is not yet clear. CONCLUSION: The methods and duration of prophylaxis remain subject to an individual medical assessment of the clinically significant benefits in relation to the risk secondary effects of the treatment. On major questions there are significant variations in the specialist literature. This means that standards cannot be formulated, although recommendations can be given.     

Characterization of the large (L) RNA of peanut bud necrosis tospovirus

The nucleocapsids purified from peanut plants systemically infected with peanut bud necrosis virus (PBNV), a member of the genus Tospovirus, contained both viral(v) and viral complementary(vc) sense L RNAs. Defective forms of L RNA containing 'core polymerase region' were observed. The full length L RNA of PBNV was sequenced using overlapping cDNA clones. The 8911 nucleotide L RNA contains a single open reading frame (ORF) in the vc strand, and encodes a protein of 330 kDa. At the 5' and 3' termini of the v sense RNA there were 247 and 32 nt untranslated regions, respectively, containing an 18 nt complementary sequence with one mismatch. Comparisons of the predicted amino acid sequence of the L protein of PBNV with other members of Bunyaviridae suggest that the L protein of PBNV is a viral polymerase. The L protein had highest identity in the 'core-polymerase domain' with the corresponding regions of other tospoviruses, tomato spotted wilt virus and impatiens necrotic spot virus.