The effect of hadacidin, ultraviolet irradiation of blood (UVB) and thiamine on the prenatal development of Uje:WIST rats: correlation with the hepatic activity of gamma-glutamyltranspeptidase (GGT)]

The influence of hadacidin, a model substance for induction of cheilognathouranoschisis in rat fetuses (2,550 mg/kg b.m. at gestation day 12), ultraviolet irradiation (UVB) of blood (1 week before gestation) and thiamine (25 mg/kg b.m. from gestation days 12 to 15) on the prenatal development of rats at the 20th day of gestation was investigated. Using the body mass and the hepatic GGT-activity as parameters. Hadacidin caused a distinct retardation of the fetal somatic development. Partially, the embryotoxic effect was compensated by UVB or thiamine. The combination of both procedures was more effective. There is a good correlation between the maturation grade of fetuses at day 20 of gestation and the hepatic GGT activity.     

Radioprotective activity of aminoarylthiazoles and various mechanisms of action

The amino group is shown to be the reaction center that is primarily responsible for the radioprotective effect of the thiazoles under study. A phenyl residue also contributes to the radioprotective effect. The influence of thiazoles on DNA biosynthesis on radiosensitive tissues plays an important role in the biochemical mechanism of their radioprotective action.     

Use of action spectra for identifying molecular targets and mechanisms of action of solar ultraviolet light

The use of action spectra in the elucidation of the mechanisms of biological action of solar ultraviolet radiation that reaches the surface of the earth is reviewed, and precautions in the preparation and interpretation of such action spectra are discussed. Original experiments are also described which show correlations between lethality and DNA breakage caused by monochromatic solar ultraviolet (UV) wavelengths in Escherichia coli and Bacillus subtilis , which may constitute evidence for an important biological role of DNA breaks leading to lethality in these microorganisms.     

Collagen fragments inhibit hyaluronan synthesis in skin fibroblasts in response to ultraviolet B (UVB): new insights into mechanisms of matrix remodeling

UVB irradiation causes characteristic features of skin aging including remodeling of the dermal extracellular matrix. A key feature during this process is the up-regulation of matrix metalloproteinases and cleavage of collagen. Hyaluronic acid (HA), a major component of the dermal matrix, decreases after chronic UVB exposure. However, the factors that govern the decline of HA synthesis during the course of actinic aging are largely unknown. The aim of the present study was to explore whether collagen degradation causes inhibition of HA synthesis in human skin fibroblasts. After treatment of fibroblasts with collagen fragments (CF) in vitro, resolution of the actin cytoskeleton and inhibition of HA secretion occurred because of specific down-regulation of hyaluronan synthase 2 (HAS2) expression. The α(v)β(3)-agonist, RGDS, latrunculin A, and an inhibitor of Rho-activated kinase inhibited HAS2 expression. Conversely, blocking antibodies to α(v)β(3) abolished the down-regulation of HAS2 and the cytoskeletal effects. Furthermore, inhibition of cofilin phosphorylation in response to CF was prevented by α(v)β(3)-blocking antibodies. The key role of ERK signaling was shown by reduced nuclear accumulation of phosphoERK and of ELK-1 phosphorylation in response to CF. In addition, the ERK inhibitor PD98059 reduced HAS2 expression. Also, UVB irradiation of fibroblasts caused down-regulation of HAS2, which was sensitive to matrix metalloproteinase inhibitors and to α(v)β(3)-blocking antibodies. In conclusion, these data suggest that CF activate α(v)β(3)-integrins and in turn inhibit Rho kinase (ROCK) signaling and nuclear translocation of phosphoERK, resulting in reduced HAS2 expression. Therefore, a novel mechanism is presented how proteolytic collagen cleavage may inhibit HA synthesis in dermal fibroblasts during extrinsic skin aging.     

Whirling disease (Myxosoma cerebralis): control with ultraviolet irradiation and effect on fish.

Water contaminated by Myxosoma cerebralis was disinfected with ultraviolet irradiation to control whirling disease. Irradiation at 18,000 microwatt seconds/cm2 (MWS/cm2) reduced infectivity of M. cerebralis by 31-86% and 27,650 MWS/cm2 reduced infectivity by 86-100%, even in the presence of a small amount of silt.     

Effect of ultraviolet ray irradiation of blood on thrombocyte function and cholesterol level

Action of the ultraviolet irradiation of autologous blood on thrombocyte function and serum cholesterol values. By means of a screen pressure measurement in vitro in patients with arterial occlusive disease during the course of treatment with ultraviolet irradiation of autologous blood a normalisation of thrombocyte functions is evident. This effect lasted up to a year after beginning of treatment. In the same time a significant diminuation of serum cholesterol levels appeared. The course of these parameters permits a theoretical confirmation of the observed good clinical long term effects of the ultraviolet irradiation of autologous blood and corroborates the acceptability of this therapy in cardiological and vascular dispensaires.     

Different sensitivity of carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss) to the immunomodulatory effects of UVB irradiation

In order to study the sensitivity of two fish species, carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss), to the immunomodulatory effects of ultraviolet B (UVB) radiation, the fish were exposed to a single UVB dose of 50, 250, 500 or 1,000 mJ cm(-2). These species represent different phylogenetic groups of fish, and they differ also in their behaviour inhabitating often dark and turbid (carp) or clear and transparent waters (salmonids). Immune responses were studied on day 1 post-irradiation. Unexposed fish, and fish exposed to radiation depleted of UV wavelengths served as controls. UVB irradiation markedly enhanced the blood respiratory burst and cytotoxic activity in carp, but in the head kidney these parameters were significantly suppressed. Rainbow trout respiratory burst was affected only after exposure with the highest dose of UVB. Lymphopenia and granulophilia were noted in both fish blood after exposure. This study indicates that UVB irradiation modulates immune functions in both fish species studied, and that rainbow trout is more tolerant than carp against UVB. Fish are clearly adapted to the environmental UVB levels prevailing in their usual living habitats, but are also a target of undesired effects of UVB on immune functions whenever exposed to increased radiation levels.     

Phosphoproteins crosslinked to poly(A) + heterogeneous nuclear RNA after irradiation with ultraviolet light

Isolated liver nuclei or whole lymph node lymphocytes stimulated with concanavalin A in culture were irradiated with ultraviolet light. The crosslinked structures of poly(A)+ heterogeneous nuclear RNA and protein were purified on oligo(dT)-cellulose after labelling irradiated nuclei in the presence of adenosine 5'-[gamma-32P]triphosphate and analysed by SDS-polyacrylamide gel electrophoresis. The liver and lymphocyte nuclear proteins included about 17-19 species of 35-150 kDa and were shown to produce quite similar electrophoretic band patterns. Two proteins of 110-120 and 40-42 kDa were phosphorylated. Using partial proteolytic digestion the large-size crosslinked phosphoprotein has been identified as the 110 kDa component described previously (Schweiger, A. and Kostka, G. (1984) Biochim. Biophys. Acta 782, 262-268). The 40-42 kDa band was presumably related to the group C species of main proteins associated with heterogeneous nuclear RNA. In crosslinked nuclear structures from rats treated with low doses of alpha-amanitin for 1 h the relative amount of the 110-120 kDa phosphoprotein was reduced while the labelling with [32P]ATP was almost abolished.     

Molecular mechanisms of severe acute respiratory syndrome (SARS)

Background

The mechanisms during the initial phase of oxygen toxicity leading to pulmonary tissue damage are incompletely known. Increase of tumour necrosis factor alpha (TNFalpha) represents one of the first pulmonary responses to hyperoxia. We hypothesised that, in the initial phase of hyperoxia, TNFalpha activates the caspase cascade in type II pneumocytes (TIIcells).

Methods

Lung sections or freshly isolated TIIcells of control and hyperoxic treated rats (48 hrs) were used for the determination of TNFalpha (ELISA), TNF-receptor 1 (Western blot) and activity of caspases 8, 3, and 9 (colorimetrically). NF-kappaB activation was determined by EMSA, by increase of the p65 subunit in the nuclear fraction, and by immunocytochemistry using a monoclonal anti-NF-kappaB-antibody which selectively stained the activated, nuclear form of NF-kappa B. Apoptotic markers in lung tissue sections (TUNEL) and in TIIcells (cell death detection ELISA, Bax, Bcl-2, mitochondrial membrane potential, and late and early apoptotic cells) were measured using commercially available kits.

Results

In vivo, hyperoxia activated NF-kappaB and increased the expression of TNFalpha, TNF-receptor 1 and the activity of caspase 8 and 3 in freshly isolated TIIcells. Intratracheal application of anti-TNFalpha antibodies prevented the increase of TNFRI and of caspase 3 activity. Under hyperoxia, there was neither a significant change of cytosolic cytochrome C or of caspase 9 activity, nor an increase in apoptosis of TIIcells. Hyperoxia-induced activation of caspase 3 gradually decreased over two days of normoxia without increasing apoptosis. Therefore, activation of caspase 3 is a temporary effect in sublethal hyperoxia and did not mark the "point of no return" in TIIcells.

Conclusion

In the initiation phase of pulmonary oxygen toxicity, an increase of TNFalpha and its receptor TNFR1 leads to the activation of caspase 8 and 3 in TIIcells. Together with the hyperoxic induced increase of Bax and the decrease of the mitochondrial membrane potential, activation of caspase 3 can be seen as sensitisation for apoptosis. Eliminating the TNFalpha effect in vivo by anti-TNFalpha antibodies prevents the pro-apoptotic sensitisation of TIIcells.     

Different mechanisms of blood thymidine levels caused by irradiation and polyanion administration

The administration of dextran sulfate causes an increase in the thymidine content of rat blood comparable with the postirradiation thymidinemia. In contrast to radiation dextran sulfate does not increase polydeoxynucleotide content of thymus. Isoptin, a calcium antagonist, decreases thymidinemia induced by dextran sulfate to a greater extent than that induced by ionizing radiation. Thymidinemia induced by dextran sulfate is supposed to be due to its effect on cell membranes. In radiation-induced thymidineamia this mechanism is of lesser significance.     

Effects of ultraviolet irradiation on structural and functional condition of T- and B-lymphocytes of human blood

The influence of ultraviolet (UV) radiation on structural and functional condition of membranes T- and B-lymphocytes of human blood is investigated. It is shown, that intergral flow of UV-light (240-390 nm) in doses 151-1359 J/m2 leads to the increase of the expression of some HLA-antigen (DR1, DR2, DR5, DR7) and Fc-receptors on membranes of B-lymphocytes. The level of HLA-antigen was increased by 20-500% from the initial state after exposure to different doses. The growth of the expression of Fc-receprots was registered in 80% of the donors in the range from 20 up to 540%. The minimum dose of UV-light (151 J/m2) caused the maximum effect. The reduction of the level of Fc-receptors by 10-90% relatively to the native condition was registered for T-cells in 80% of the donors. Groups of the donors were revealed, T-lymphocytes of which differed by the sensitivity to UV-radiation. The effect of "strengthening--weakening", resulting to the reduction of the initially high parameters and to increase in the initially low ones was found.     

Transforming growth factors (TGFs): Properties and possible mechanisms of action

Transforming growth factors (TGFs) are growth-promoting polypeptides that cause phenotypic transformation and anchorage-independent growth of normal cells. They have been isolated from several human and animal carcinoma and sarcoma cells. One TGF is sarcoma growth factor (SGF) which is released hy murine sarcoma virus-transformed cells. The TGFs interact with epidermal growth factor (EGF) cell membrane receptors. TGFs are not detectable in culture fluids from cells which contain high numbers of free EGF cell membrane receptors. SGF acts as a tumor promoter in cell culture systems and its effect on the transformed phenotype is blocked by retinoids (vitamin A and synthetic analogs). The production of TGFs by transformed cells and the responses of normal cells to the addition of TGFs to the culture medium raise the possibility that cells “autostimulate” their own growth by releasing factors that rebind at the cell surface. The term “autocrine secretion” has been proposed for this type of situation where a cell secretes a hormone-like substance for which it has external cell membrane receptors. The autocrine concept may provide a partial explanation for some aspects of tumor cell progression.