Coexpression of C-myc and transforming growth factor alfa in the liver promotes early replicative senescence and diminishes regenerative capacity after partial hepatectomy in transgenic mice

We have recently shown that overexpression of c-myc and transforming growth factor alpha (TGF-alpha) in the liver of double-transgenic mice results in severe DNA damage, aberrant hepatic growth, and development of tumors at a much younger age than that observed in c-myc single-transgenic mice. We now report that double-transgenic TGF-alpha/c-myc hepatocytes rapidly lose their ability to proliferate upon mitogenic stimulation following partial hepatectomy (PH). At 4 weeks of age, the overall rate of bromodeoxyuridine (BrdU) incorporation following PH was comparable in c-myc and TGF-alpha/c-myc livers and exceeded that seen in wild-type (WT) mice. However, by 10 weeks of age, c-myc single-transgenic hepatocytes showed proliferative advantages over the WT cells, whereas TGF-alpha/c-myc double-transgenic hepatocytes had a decreased capacity to proliferate upon mitogenic stimulation. This decreased proliferative response was accompanied by a reduction in the total fraction of proliferating hepatocytes, as well as by a decline in the induction of cyclin A, cyclin B, and cdc2 gene expression. These data show that constitutive coexpression of c-myc and TGF-alpha accelerates age-related loss in the regenerative potential following PH, and suggest that early replicative senescence of differentiated hepatocytes may have a role in providing a selective growth advantage to initiated cell populations in this model.     

Successful therapy with danazol in refractory autoimmune thrombocytopenia associated with rheumatic diseases

The objective was to assess the efficacy of therapy with danazol in refractory immune thrombocytopenia associated with different rheumatic diseases. Patients with severe immune thrombocytopenia (platelet counts < 40 x 10(9)/l) with a bone marrow biopsy showing megakaryocytes in normal or increased number and normal morphology were included if they fulfilled at least one of the following criteria: (a) thrombocytopenia refractory to prednisone (> or = 1 mg/kg/day during > or = 4 weeks); (b) patients requiring an unacceptably high dose of prednisone for > 2 months (prednisone dose > or = 20 mg/day); (c) no response to at least another drug besides corticosteroids. Other causes of thrombocytopenia were excluded. They were treated with danazol (100-200 mg q.i.d.) and followed for at least 12 months. Four patients diagnosed with systemic lupus erythematosus, two with rheumatoid arthritis and one with primary antiphospholipid syndrome met the inclusion criteria. All of them achieved acceptable platelet counts within the first 4 weeks of danazol therapy that allowed the prednisone dosage to be tapered. No important side-effects related to danazol therapy were observed. Danazol therapy seems to be a useful and well-tolerated treatment for refractory immune thrombocytopenia associated with different rheumatic diseases.     

Effects of hydrogen sulfide containing gas condensate on the hepatic microsomal monooxygenase system]

Chronic action of different xenobiotics which form a part of condensed hydrogen sulphide-containing gas causes substantial changes in the activity of xenobiotic metabolic enzymes, which is suggestive of the damaged hepatic microsomal monooxygenase system. As the rate of biotransformation becomes higher, there are increases in the activity of microsomal monooxygenases and in the generation of active oxygen forms and hydrogen peroxide, by impairing antiradical and antiperoxide mechanisms. The experimentally used concentration of substances as constituents of condensed gas corresponds to the maximum acceptable air concentration of in the working area of gas-refining plants, but the functional features of the body's detoxifying system--the hepatic monooxygenase system should be taken into account while developing preventive measures of occupational diseases.     

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.     

Isolated left superior vena cava to the left atrium with situs solitus and dextrocardia: extracardiac repair facilitated by juxtaposition of the atrial appendages

We describe an extremely unusual case, with isolated left superior vena cava to the left atrium, normal intracardiac anatomy, and left juxtaposition of the atrial appendages. Surgical repair was performed without cardiopulmonary bypass by anastomosing the left superior cava to the superior aspect of the right atrial appendage, and was facilitated by the ectopic location of the appendage.     

The effects of alcohol on the heart: detrimental or beneficial?

Alcohol abuse is a substantial public health problem, resulting in staggering financial costs and other burdens. Prolonged alcohol abuse leads to cardiomyopathy in a minority of alcohol abusers, but because alcoholism is so widespread, alcohol is the major cause of nonischemic cardiomyopathy in Western society. In contrast, substantial evidence now suggests that moderate alcohol consumption has cardioprotective effects. It not only reduces the incidence of fatal ischemic heart disease, but it improves outcome in patients who have other risks for coronary events and go on to have myocardial infarctions. Therefore, physicians' recommendations about alcohol consumption should be as individualized as their patients.     

Temperament as a prerequisite of creative capabilities

Temperamental and creative characteristics were compared in three groups of subjects who manifested a bent for creative activity. The groups differed in their age: 14-year-old schoolchildren of architectural class (n = 20), 18 to 20-year-old students of architectural institute (n = 94), and 25 to 45-year-old professional architects (n = 25). The temperamental properties were measured using the STQ method. The creative characteristics were evaluated by E. P. Torrance's non-verbal tests of creative thinking. In the structure of creative abilities, only two creative characteristics, i.e., fluency and flexibility, correlated at the statistically significant level with temperamental properties in all the age-specific groups under study. The closest correlations were found with plasticity and emotionality of temperament both in object-related and subject-related spheres.     

Epidermal ornithine decarboxylase and polyamines in mice exposed to 50 Hz magnetic fields and UV radiation

We studied the influence of magnetic fields (MFs) and simulated solar radiation (SSR) on ornithine decarboxylase (ODC) and polyamines in mouse epidermis. Chronic exposure to combined MF and SSR did not cause persistent effects on ODC activity or polyamines compared to the animals exposed only to UV, although the same MF treatment was previously found to accelerate skin tumor development. In an acute 24-h experiment, an elevation of putrescine and down-regulation of ODC activity was observed in the animals exposed to a 100-microT MF. No effect was seen 24 h after a single 2-MED (minimal erythemal dose) exposure to SSR. The results indicate that acute exposure to 50 Hz MF does exert distinctive biological effects on epidermal polyamine synthesis.     

Expression of complement receptors 1 and 2 on follicular dendritic cells is necessary for the generation of a strong antigen-specific IgG response

Two mechanisms could account for the impaired humoral immune response found in Cr2-/- mice. The absence of complement receptors 1 and 2 (CR1, CR2) on B cells could affect their activation. Alternatively, impaired Ag trapping by follicular dendritic cells (FDC) could affect B cell maturation into Ig-secreting or memory B cells. To compare the roles of CR1 and CR2 on B cells vs FDC in this abnormal response, bone marrow (BM) chimeric mice were generated and immunized with specific T-dependent Ags. The primary and secondary Ab response was measured. Cr2+/+ animals reconstituted with a Cr2-/- BM generated a diminished but detectable humoral immune response compared with controls. When injected with preformed immune complexes (IC), these mice maintained follicular IC localization. Cr2-/- animals reconstituted with a Cr2+/+ BM had an initial rise in the Ab titer, but were unable to maintain it as shown by a pronounced decrease in the IgG titer. This defect persisted during the secondary immune response. Follicular IC trapping was also impaired. Despite the abnormal Ab response, germinal center formation was retained in all of the chimeric animals. These experiments are the first to demonstrate an absolute requirement for CR1 and CR2 expression on FDC in the generation of a normal humoral immune response.