Environmental conditions and variation in levels of sun exposure among children in child care

Sun exposure in childhood is 1 of the risk factors for developing skin cancer, yet little is known about levels of exposure at this age. This is particularly important in countries with high levels of ultraviolet radiation (UVR) such as Australia. Among 49 children 3 to 5 years of age attending child care centers, UVR exposure was studied under 4 conditions in a repeated measures design; sunny days, cloudy days, teacher’s instruction to stay in the shade, and a health professionals instruction to apply sunscreen. Three different data collection methods were employed: (a) completion of questionnaire or diary by parents and researcher, (b) polysulphone dosimeter readings, and (c) observational audits (video recording). Results of this study indicated that more than half the children had been sunburnt (pink or red) and more than a third had experienced painful sunburn (sore or tender) in the last summer. Most wore short sleeve shirts, short skirts or shorts and cap, that do not provide optimal levels of skin protection. However, sunscreen was applied to all exposed parts before the children went out to the playground. Over the period of 1 hr (9–10 a.m.) the average amount of time children spent in full sun was 22 min. On sunny days there was more variation across children in the amount of sun exposure received. While the potential amount of UVR exposure for young children during the hour they were outside on a sunny day was 1.45 MED (Minimum Erythemal Dose), they received on average 0.35 MED, which is an insufficient amount to result in an erythemal response on fair skin even without the use of sunscreen.     

Nucleolin Promotes Homologous DNA Pairing in vitro

We purified to near homogeneity a previously identified 100 kDa mammalian homologous DNA pairing protein. The purified 100 kDa protein also catalyzed high levels of cell-free homologous DNA recombination activity. This ATP-dependent activity was capable of forming conservative recombinant products between two circular, double-stranded DNA molecules. We were unable to detect any DNA polymerase, DNA ligase, or 5' or 3' exonuclease activity associated with this purified material. The purified 100 kDa protein bound silver nitrate as well as a monoclonal antibody specific for nucleolin. A recombinant protein comprised of the Escherichia coli maltos-ebinding protein fused to the carboxyl-terminal two-thirds of human nucleolin possessed homologous DNA pairing activity. These data indicate that the 100 kDa homologous DNA pairing protein is nucleolin. The observation that nucleolin can carry out homologous DNA strand pairing in vitro raises the prospect that it may function similarly in vivo.     

The dentino-enamel junction revisited

The dentino-enamel junction is not an simple inert interface between two mineralized structures. A less simplistic view suggests that the dentino-enamel junctional complex should also include the inner aprismatic enamel and the mantle dentin. At early stages of enamel formation, fibroblast growth factor (FGF)-2 is stored in and released from the inner aprismatic enamel, possibly under the control of matrix metalloproteinase (MMP)-3. The concentration peak for MMP-2 and -9 observed in the mantle dentin coincided with a very low labeling for TIMP-1 and -2, favoring the cross-talk between mineralizing epithelial and connective structures, and as a consequence the translocation of enamel proteins toward odontoblasts and pulp cells, and vice versa, the translocation of dentin proteins toward secretory ameloblasts and cells of the enamel organ. Finally, in X-linked hypophosphatemic rickets, large interglobular spaces in the circumpulpal dentin were the major defect induced by the gene alteration, whereas the mantle dentin was constantly unaffected. Altogether, these data plead for the recognition of the dentino-enamel junctional complex as a specific entity bearing its own biological characteristics.     

Glycoconjugate metabolism in a cystic fibrosis knockout mouse model

Cystic fibrosis knockout mice (cftr(-/-)) die prematurely of obstruction of the intestine which may result from accumulation of dehydrated glycoconjugate-containing mucus. We noted an increase in the specific activity of [(14)C]glucosamine-labeled high-molecular weight glycoconjugates, probably mucin, in the lumen of the intestine of cftr(-/-) (homozygous) mice compared to cftr(+/+) (wild-type) and cftr(+/-) (heterozygous) mice and a decrease in the turnover of glycoconjugates of several organs of the cftr(-/-) mice. No difference in the anionic composition of secreted intestinal glycoconjugates was detected and no difference in the amount of mucin 1 (Muc1) was found in the small intestine, colon, pancreas, and lungs of the different genotypes. In addition, the spleen of the cftr(-/-) mice was significantly smaller than that of control mice and the small intestine and colon were, respectively, longer and shorter compared to control mice. These results indicate modified glycoconjugate metabolism in cystic fibrosis knockout mice and morphologic changes to the spleen and intestine where the latter modifications are possibly related to the intestinal malabsorption associated with cystic fibrosis.     

Gene transfer by adenovirus-mimetic peptides in the presence of a cationic lipid and/or adenovirus. Analysis of the contribution of the viral and nonviral components

Summary.  Peptide and cationic lipid-based gene transfer vectors have shown promise for gene therapy but are still less efficient than viral gene transfer vectors. We have examined the mechanism of gene transfer of different adenovirus-mimetic peptides in the presence and absence of a cationic lipid, lipofectamine and/or adenovirus with the aim of improving the design of nonviral vectors for efficient gene transfer. Three polylysine-adenovirus-mimetic peptides were synthesised and examined for their efficacy for gene transfer. Transfection levels in four cell lines: adenovirus permissive human tracheal epithelial (56FHTE8o⁻), human lung carcinoma (A549), human colon carcinoma (Caco-2) cells, and adenovirus low-permissive Chinese hamster ovary (CHO) cells, were examined. The polylysine-adenovirus-mimetic peptides increased the level of transfection of a reporter transgene in all cell lines. Transfection was substantially increased when an adenovirus was added to cells after pre-incubation with the vector complexes. Formulation of the peptide vector complexes with lipofectamine increased their transfection efficacy and the subsequent addition of an adenovirus increased transfection levels even further but only in permissive cells. Pre-incubation of cells with lipofectamine-peptide vector complexes increased cell binding of the adenovirus but uptake was only increased in intermediate- or non-permissive cells. The addition of lipofectamine increased transgene expression of a recombinant adenovirus in non-permissive cells but not in permissive cells. Enhancement with an adenovirus of peptide vector gene transfer is probably due to more efficient endosome escape while enhancement of gene transfer by peptide vectors complexed to lipofectamine is due to an increase in cellular binding and/or internalisation of the adenovirus. Received February 8, 2002; accepted August 23, 2002     

Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers

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Effects of tibolone on lipoprotein(a) and HDL subfractions

Objective: To determine the effects of tibolone, a synthetic steroid used to alleviate climacteric symptoms and prevent osteoporosis, on lipoprotein metabolism, with particular reference to lipoprotein(a) levels and HDL subfraction profiles.Design: Thirty nine postmenopausal women were treated with tibolone (Livial) 2.5 mg/day for 6 months and fasting serum lipoprotein levels were estimated at 0, 2, 4 and 6 months. Results: Lipoprotein(a) levels were reduced significantly over the 6 months from a median level of 245 (range <60–780) mg/I to 152 (range <60–530) mg/l, a reduction of 39% in the median level. A decrease was observed in approximately two thirds of the women. Reductions were noted in all 6 subjects whose pretreatment levels were high, although concentrations remained at a level associated with increased risk in all but one. There were significant decreases in triglycerides and VLDL cholesterol and no significant change in LDL cholesterol. There was a significant reduction of 18% in HDL cholesterol and a 26% reduction in the HDL₂:HDL₃ ratio. Conclusion: The reduction in lipoprotein(a) levels may have a beneficial effect on cardiovascular risk, which could go some way towards balancing the potentially adverse effect on the cardiovascular system caused by the reduction in HDL cholesterol.     

The radioprotector WR1065 reduces radiation-induced mutations at the hypoxanthine-guanine phosphoribosyl transferase locus in V79 cells

N-(2-mercaptoethyl)-lt3-diaminopropane (WR1065) protects againstradiation-induced cell killing and mutagenesis at the hypoxanthine-guaninephosphoribosyl transferase (HGPRT) locus in V79 Chinese hamsterhing fibroblast cells. At a concentration of 4 mM, WR1065 wasfound to be effective in protecting against radiation-inducedcell lethality only if present during irradiation, e.g., a dosemodification factor (DMF) of 1.9. No protective effect was observedif the protector was added within 5 min after irradiation or3 h later, e.g., DMFs of 1.0 and 1.1, respectively. The effectof WR1065 on radiation-induced mutation, expressed as resistanceto the cytotoxic purine analogue 6-thioguanine (HGPRT), wasalso investigated. In contrast to the treatment-schedule dependencefor protection by WR1065 against cell killing, this agent waseffective in reducing radiation-induced mutations regardlessof when it was administered. Following a dose of 10 Gy of ⁶⁰Co-rays, the mutation frequencies observed per 10⁶ survivors were77 ± 8, 27 ± 6, 42 ± 7, and 42 ±7 for radiation only, and WR1065 present during, immediatelyafter, or 3 h after irradiation. These data suggest that althougha segment of radiation-induced damage leading to reproductivedeath cannot be modulated through the postirradiation actionof WR1065, processes leading to the fixation of gross geneticdamage and mutation induction in surviving cells can be effectivelyaltered and interfered with leading to a marked reduction inmutation frequency.     

Catheter obstruction during prolonged parenteral alimentation. Are lipids responsible?

Catheter obstruction is a serious incident during prolonged parenteral nutrition (PN). This retrospective study was carried out in order to compare the frequencies of catheter obstruction with nutritive mixtures in bags according to whether or not lipids were mixed with the entire 24 h nutritional supply (Group I, n=33) or infused separately (Group II, n=30). Our results show that obstructions are significantly more frequent in Group I (11 13 ) than in group 2 (3 10 ), appearing within a mean interval of 29 days after inserting the catheter. The global percentages of patients undergoing cyclic PN were the same in both patient groups. In group I, however, the percentage of patients on cyclic PN was significantly higher for the obstructed catheters (100%) than for the unobstructed catheters (59%). In conclusion, the mixture of lipids with the remainder of the nutrients in the conditions of this study is the prime cause of catheter obstruction, although the exact mechanism is not elucidated. The role of cyclic PN appears to be accessory.