Concomitant treatment with mild hyperthermia, cisplatin and low dose-rate irradiation in human ovarian cancer cells sensitive and resistant to cisplatin

Hyperthermia has been shown to be an effective radiation sensitizer. Cisplatin has also been shown to cause radiosensitization. In part, the sensitization is through the inhibition of repair of radiation damage. In this study we have set out to combine low dose-rate irradiation (during which extensive repair occurs) with both cisplatin and hyperthermia to maximize the radiation sensitizing effect. Two human ovarian carcinoma cell lines, one parental (A2780S) and the other a cisplatin resistant derivative (A2780CP) cell line were used in these experiments. Long duration hyperthermia at 40 degrees C was combined with low concentrations of cisplatin (0.5-3 microg/ml) and low dose-rate irradiation (LDRI). The responses to the individual treatments showed that there was cross resistance in the two cell lines for cisplatin and radiation, but for hyperthermia the opposite effect was found. When all treatments were given concurrently the response was greater than the calculated response of all three individual treatments, indicating a synergistic interaction. The effect was greater in the cisplatin resistant cell line. The combination of mild hyperthermia, low dose cisplatin and LDRI are a good combination for potential clinical application. In addition, this could be a good approach to deal with cisplatin resistance.     

Fibroblast-like cells from tendons differ from skin fibroblasts in their ability to form three-dimensional structures in vitro

Recent structural information suggests that the HC(X)5R active-site motif defines three distinct evolutionary families of phosphatases that employ a common catalytic mechanism. In two instances, regulation of phosphatase activity employs autoinhibitory mechanisms involving either intermolecular or intramolecular interactions, whereby inhibition is mediated by sterically blocking the active-site cleft.     

Recurrence of haemolytic-uraemic syndrome in renal transplants: a single-centre report

BACKGROUND: The incidence of recurrence of haemolytic-uraemic syndrome (HUS) in renal allografts appears to vary by centre, with the highest rates reported from the University of Minnesota. It is possible that the high rate of HUS recurrence at this institution reflects a transplant population skewed towards patients with a form of HUS that is more likely to recur in the allograft. METHODS: This study examined whether the initial episode of HUS in the native kidneys was preceded by a diarrhoeal prodrome ('classical HUS') or not ('atypical HUS'), and evaluated transplant outcomes in 24 patients who received 36 transplants at the University of Minnesota between 31 May 1972 and 31 December 1994. RESULTS: Eighteen of the 24 patients had atypical HUS, three had classical HUS, and in three patients the presence or absence of a diarrhoeal prodrome could not be determined. Recurrent HUS, defined as microangiopathic haemolytic anaemia, thrombocytopenia, renal insufficiency, and allograft biopsy findings compatible with HUS, occurred 16 times in 14 grafts in 11 patients. Nine of these patients had atypical HUS, one had classical HUS, and in one the nature of the prodrome could not be determined. Eleven of the 14 initial recurrences took place within 2 months of transplant. Recurrence was not more frequent in patients who received cyclosporin or antilymphocyte preparations. Actuarial analysis using matched controls showed poorer graft survival in patients with a primary diagnosis of HUS (P = 0.007), due to the high frequency of graft loss in HUS patients with recurrence. CONCLUSION: Based upon these data and a review of the literature, it can be concluded that the risk of recurrence of HUS in the allograft is confined almost entirely to patients with atypical forms of HUS.     

Lack of volatilization and escape of orally administered trichloroethylene from the gastrointestinal tract of rats

The sugar residues in glycoconjugates present in the parotid and mandibular glands of the adult fallow-deer were detected and characterized by using a battery of eight different lectin-horseradish peroxidase conjugates. In some cases a treatment with sialidase preceded the lectin staining. Parotid secretory cells produced glycoconjugates with N-acetylgalactosamine, N-acetylglucosamine and mannose residues. Mucous acinar cells were the most reactive sites of the mandibular gland and contained conspicuous quantities of oligosaccharides with terminal sialic acid radicals. Galactosil-(beta 1-->3)N-acetylgalactosamine was the most abundant penultimate sugar linked to N-acetylneuraminic acid. Mandibular mucous cells also presented N-acetylglucosamine and sialylated components with the terminal dimer sialic acid-N-acetylgalactosamine. Demilunar cells contained glycoconjugates with fucose and mannose residues. The apical surface of duct cells was stained by all the lectins.     

Mutagenicity of azo dyes used in foods, drugs and cosmetics before and after reduction by Clostridium species from the human intestinal tract

Various azo dyes currently approved by the US FDA for use in foods, drugs and cosmetics are reduced by anaerobic bacteria from the human intestinal tract. These bacteria with azoreductase activities include several Clostridium species. Seven of these azo dyes and their reduction products following incubation with a Clostridium sp. were evaluated for mutagenicity in Salmonella typhimurium strains TA98 and TA100. No mutagenicity was induced in either TA98 or TA100 by any of the seven azo dyes or the reduced metabolites when tested at concentrations as high as 200 microg/plate, with or without exogenous metabolic activation by rat liver fraction S-9.     

Interaction of biotin with streptavidin. Thermostability and conformational changes upon binding

The effect of biotin binding on streptavidin (STV) structure and stability was studied using differential scanning calorimetry, Fourier transform infrared spectroscopy (FT-IR), and fluorescence spectroscopy. Biotin increases the midpoint temperature Tm, of thermally induced denaturation of STV from 75 degrees C in unliganded protein to 112 degrees C at full ligand saturation. The cooperativity of thermally induced unfolding of STV changes substantially in presence of biotin. Unliganded STV monomer has at least one domain that unfolds independently. The dimer bound to biotin undergoes a single coupled denaturation process. Simulations of thermograms of STV denaturation that take into account only the thermodynamic effects of the ligand with a Ka approximately 10(15) reproduce the behavior observed, but the estimated values of Tm are 15-20 degrees C lower than those experimentally determined. This increased stability is attributed to an enhanced cooperativity of the thermal unfolding of STV. The increment in the cooperativity is as consequence of a stronger intersubunit association and an increased structural order upon binding. FT-IR and fluorescence spectroscopy data reveal that unordered structure found in unliganded STV disappears under fully saturating conditions. The data provide a rationale for previous suggestions that biotin binding induces an increase in protein tightness (structural cooperativity) leading, in turn, to a higher thermostability.