Decreased survivability and a DNA repair defect in the cells of patients with xeroderma pigmentosum and Cockayne syndrome under the action of radiation and chemical mutagens

The action of ionizing radiation and chemical mutagens--epoxides (ethylene oxide, propylene oxide, epichlorohydrin)--upon survival and repair processes in xeroderma pigmentosum (XP2SP) and Cockayne syndrome (CS1SP) patients' cells was studied, compared to healthy donor's cells VH-10 and C5RO. Ionizing radiation was demonstrated to enhance significantly higher survival decrease of XP2SP and CS1SP fibroblasts, compared to healthy donor's cells, according to the cloning efficiency criterion. In contrast to this, no significant difference between XP2SP and healthy donor's cells was found, according to cells' ability to replicative DNA synthesis after gamma irradiation. Differences in survival of mutant cells and healthy donor's cells after treatment by epoxides were found significant only following XP2SP being treated by ethylene oxide. DNA single-string breaks in XP2SP and in CS1SP cells treated by mutagens studied were proved to occur with the same frequency as in the DNA of the control cells; however the DNA repair according to this criterion was significantly suppressed in mutant cells.     

Influence of substituents in fluorobenzene derivatives on the cytochrome P450-catalyzed hydroxylation at the adjacent ortho aromatic carbon center

In the present study, the effects of extracellular magnesium concentration ([Mg2+]ex) on stimulus-secretion coupling processes were investigated in rat gastric parietal cells in vitro. Extracellular magnesium reduction resulted in (1) an increase of basal intracellular free calcium concentration ([Ca2+]in), (2) an enhancement of both carbachol and thapsigargin-induced calcium responses, (3) an improved filling state of intracellular calcium stores, (4) an increase of both basal and carbachol-induced acid secretion, whereas intracellular adenosine 3',5'-cyclic monophosphate (cyclicAMP) levels and histamine stimulated acid secretion were not affected. The effects of high [Mg2+]ex were opposite to the described results, except that high [Mg2+]ex was able to decrease significantly histamine-stimulated cyclicAMP levels and acid secretion. These findings indicate a modulatory role of [Mg2+]ex on the intracellular signalling processes and acid secretory properties in rat parietal cells. These effects seemed to be mediated by regulating (1) calcium loading capacity of intracellular stores, (2) the permeability of the calcium influx pathway, and (3) the formation of cyclicAMP.     

The biological properties of Serratia marcescens bacteriophages]

Sixteen phages active against bacteria of the genus Serratia have been divided into 4 groups on the basis of the study of their biological properties. As a result, 5 typing phages have been selected, which permitted the typing of 77.3% of S. marcescens cultures under study, divided into 13 phage types.     

The isolation and analysis of lymphoblastoid cell lines from patients with xeroderma pigmentosum and progeria

Lymphoblastoid cell lines from patients with xeroderma pigmentosum (2 forms) and progeria (unusual form) were established using transformation of peripheral blood lymphocytes by Epstein--Barr virus. The influence of different UV doses on cell vitality, proliferation and cell cycle progression was studied by means of flow cytometry. The cell vitality was determined after incubation of cells with etidium bromide and FDA. We used cytograms with two logarithmic signals (log green/log red) to discriminate the cell cycle status. Cell cultures were used with density of 500,000 cells per 1 ml, previously synchronized at G-phase by the incubation in a medium with low serum content. The effect of UV irradiation was followed during 72 h. Among four analysed cell lines only line XP2SP demonstrated enhanced UV sensitivity, expressed by decreasing of the amount of living cells after the UV dose of 2.5 J/m2 and higher. The cell cycle studies showed that cells were blocked in S-phase and simultaneously the amount of apoptotic cells with both reduced DNA content and ability to bind FDA was seen increased. Similar events were observed in the control line only after the dose of 20 J/m2 and higher.     

Chemoprevention of prostate cancer: the Prostate Cancer Prevention Trial

The possible relationship between physeal diseases and physeal form prompted investigation of change in steepness of the physis in young foals. The distal and proximal aspects of the longbones were sawn sagittally in the right and frontally in the left bones. The slabs were washed to remove saw debris, arranged in order and inspected. The proximal physes had a flat or gently arched form, without obvious inclination. In the distal physes there were distinct inclinations. Inspection of an identical slab from the medial aspect of the distal radius of two series of foals of different breeds showed that the degree of inclination of the physis with respect to the long axis of the bone increased with age. In a further series of foals, the angle of inclination was measured from radiographs of identical sagittal and frontal slabs of the distal radius. A line drawn through the secondary spongiosa was produced to intersect a line drawn along the physis where it was mostly steeply inclined, and the angle measured. The angle decreased (physeal inclination increased) with increasing age, up to 35-90 days. The steepness in the lateral aspect of the physis was similar to that in the medial aspect, although evident in a different plane.     

Compliance of the lung-thorax system in pregnancy complicated by pre-eclampsia

Compliance of the lungs and thorax was studied in 65 pregnant women during cesarean section. The measurements were carried out in a group of healthy controls and in patients with preeclampsia. The detected changes indicated increased rigidity of the lungs even in normal pregnancy. Comparison of the results indicates an appreciable increase of rigidity of the lungs in patients with preeclampsia, this permitting us to regard it as a status involving interstitial pulmonary hyperhydration.     

The effects of D-23129, a new experimental anticonvulsant drug, on neurotransmitter amino acids in the rat hippocampus in vitro

Recent literature continues to promote the early use of disease-modifying antirheumatic drugs (DMARDs), especially the less toxic agents such as hydroxychloroquine. Reports of combination DMARD treatments have been disappointing, and careful attention must be paid to clinical trial design if the efficacy of combination therapies is to be established. Methotrexate retains its prominent role, and its mechanism of action has been the subject of many reports; its toxicity remains the most common reason for treatment termination. Guidelines for monitoring hepatic toxicity of methotrexate have been published and may help reduce the need for invasive biopsy procedures. Significant risk factors for methotrexate pulmonary toxicity remain difficult to identify. Large placebo-controlled studies of both sulfasalazine and hydroxychloroquine have been reported and have demonstrated the efficacy of these agents in the treatment of early rheumatoid arthritis. Awareness of drug-toxicity profiles is important for physicians who prescribe these agents.     

A stereoselective cobalt-containing nitrile hydratase

Nitrile hydratase from Pseudomonas putida NRRL-18668 has been purified and characterized. The purified enzyme catalyzes the hydration of 2(S)-(4'-chlorophenyl)-3-methylbutyronitrile at least fifty times faster than that of 2(R)-(4'-chlorophenyl)-3-methylbutyronitrile. This enzyme is a member of the class of nitrile hydratase that contains cobalt. Visible absorption and CD spectra suggest the cobalt exists as a non-corrin low-spin Co3+ ion in a tetragonally-distorted octahedral ligand field. Chemical reduction of the native enzyme results in a species with the EPR signature of a low-spin Co2+ complex. Like the other cobalt-containing nitrile hydratases, this enzyme is relatively stable, maintaining its activity below 35 degrees C, and it shows a broad activity optimum between pH 7.2 and 7.8. The structural genes for this enzyme have been cloned and sequenced. The deduced amino acid sequences for the alpha and beta subunits show 48-63% and 35-41% homology, respectively, to other sequenced nitrile hydratases. In particular, the cysteine residues in the alpha subunit that have been suggested to coordinate the metal ion in the iron-containing nitrile hydratases [Brennan, B. A., Cummings, J. G., Chase, D. B., Turner, I. M., Jr., & Nelson, M. J. (1996) Biochemistry 35, 10068-10077] are conserved in this enzyme, suggesting that this nitrile hydratase, like the enzyme from Rhodococcus rhodochrous J1, is a member of a newly described class of metalloenzymes with Co3+-thiolate ligation [Brennan, B. A., Alms, G., Nelson, M. J., Durney, L. T., & Scarrow, R. C. (1996) J. Am. Chem. Soc. 118, 9194-9195].