A novel recessive 15-hydroxyprostaglandin dehydrogenase mutation in a family with primary hypertrophic osteoarthropathy

Abstract

We present two PHO siblings having a novel homozygous truncating mutation in HPGD. The purpose of the study was to attempt medical treatment, and to find the HPGD mutation causing the disease, in a 22-year old Turkish male and his 23-year old sister afflicted with primary hypertrophic osteoarthropathy (PHO). In combination with NSAIDs and colchicine, treatment with sulfasalazine was started in both cases, and methotrexate was added to the treatment regimen of the female patient at the end of the first year. The patients were found to be typical PHO. Ultrasonographic examination of the joints revealed synovitis and inflammation by B mode and power Doppler ultrasonography. Joint symptoms responded to sulfasalazine treatment in both patients. However, after the addition of methotrexate, the female patient had better remission. All exons of HPGD, the known disease gene, were analyzed by Sanger sequencing. A homozygous 2-bp deletion (c.310_311delCT or p.L104AfsX3) was identified. Seven relatives carrying the mutation in the heterozygous state were examined and none was found affected. Although not specific for this disease, skin, soft tissue and joint ultrasonography can be helpful for evaluation of the musculoskeletal findings in the patients.     

Ordered mesoporous silica modified with lanthanum for ibuprofen loading and release behaviour

The ordered mesoporous silicas SBA-15 and KIT-6, modified with lanthanum, have been for the first time applied in investigation of ibuprofen adsorption and release. The materials of hexagonal and regular structure were obtained by the hydrothermal method using a triblock copolymer Pluronic P123 as a template. The mesoporous silicas were impregnated with an aqueous solution of lanthanum(III) chloride in the amount necessary to obtain 1, 3 and 5 wt.% La loading. The physicochemical properties of the modified silicas were characterised by X-ray diffraction, transmission electron microscopy, UV–Vis spectrophotometry and low-temperature nitrogen sorption. The results showed that lanthanum strongly determined structural as well as textural properties of the silicas. The samples of modified silica were checked for the ability to adsorb and release of ibuprofen. The storage capacity of the modified silicas obtained increased with increasing their average pore diameter and percentage content of lanthanum. The amount of ibuprofen adsorbed onto KIT-6 silica modified with La was higher than that adsorbed onto SBA-15 materials. The high coverage of lanthanum on the surface of KIT-6 and SBA-15 solids was found to increase the amount of ibuprofen and the rate of its release.     

Essential Oils of Annual Sideritis Species Growing in Turkey

Water distilled essential oils of five annual Sideritis species collected from different regions of Turkey were analysed by GC/MS. Results are tabulated and compared with main components of the essential oils of perennial Sideritis species from Turkey.     

Overexpression of MAPK15 in gastric cancer is associated with copy number gain and contributes to the stability of c-Jun

This study was aimed at understanding the functional and clinicopathological significance of MAPK15 alteration in gastric cancer. Genome-wide copy number alterations (CNAs) were first investigated in 40 gastric cancers using Agilent aCGH-244K or aCGH-400K, and copy number gains of MAPK15 found in aCGH were validated in another set of 48 gastric cancer tissues. The expression of MAPK15 was analyzed using immunohistochemistry in concurrent lesions of normal, adenoma, and carcinoma from additional 45 gastric cancer patients. The effects of MAPK15 on cell cycle, c-Jun phosphorylation, and mRNA stability were analyzed in gastric cancer cells. Copy number gains of MAPK15 were found in 15 (17%) of 88 tumor tissues. The mRNA levels of MAPK15 were relatively high in the gastric cancer tissues and gastric cancer cells with higher copy number gains than those without. Knockdown of MAPK15 using siRNA in gastric cancer cells significantly suppressed cell proliferation and resulted in cell cycle arrest at G₁-S phase. Reduced c-Jun phosphorylation and c-Jun half-life were observed in MAPK15-knockdowned cells. In addition, transient transfection of MAPK15 into AGS gastric cancer cells with low copy number resulted in an increase of c-Jun phosphorylation and stability. The overexpression of MAPK15 occurred at a high frequency in carcinomas (37%) compared to concurrent normal tissues (2%) and adenomas (21%). In conclusion, the present study suggests that MAPK15 overexpression may contribute to the malignant transformation of gastric mucosa by prolonging the stability of c-Jun. And, patients with copy number gain of MAPK15 in normal or premalignant tissues of stomach may have a chance to progress to invasive cancer.     

Competition for nitrogen between trees in a mixed-species plantation in the Solomon Islands

ABSTRACT

As part of an ACIAR project aiming at improving community forestry in Solomon Islands, mixed-species plantations were established to assess the feasibility of inter-planting teak (Tectona grandis L. f.) and flueggea (Flueggea flexuosa Muell. Arg). Flueggea is a native hardwood used for timber and fence construction, and early removal of flueggea from a mixed-species stand could have a similar silvicultural outcome to thinning a single-species stand of teak. Using ¹⁵N-labelled ammonium sulphate, we investigated the competition for nitrogen (N) between the two species. The ¹⁵N-labelled tracer was applied to the soil surface of plots containing pairs of trees, one of each species, in 2-year-old and 4-year-old mixed-species stands, after the pairs of trees were isolated from the rest of the stand by an impermeable membrane. After 12–18 months, the isolated trees were measured and harvested, and each tree component (roots, stem, branch and foliage) was weighed and analysed for total N and ¹⁵N enrichment. There was no significant difference in the amounts of ¹⁵N between teak and flueggea components at either age, suggesting equal uptake of added ¹⁵N-labelled tracer by both species. The ¹⁵N amount was greater in stem followed by root, foliage and branch for teak and branch followed by stem, root and foliage for flueggea. About 42% and 55% of the applied ¹⁵N tracer were recovered in the 2-year and 4-year plots respectively, suggesting that higher uptake occurs with well-established root structure and that N losses decreased following canopy closure. The amount of total nitrogen was not significantly different between teak and flueggea components at age 2 and 4 years, and may indicate equal access to growth resources, and similar allocation. Although teak had significantly greater stem growth (height, basal area and volume) than flueggea in the 4-year plots, ¹⁵N uptake were similar to flueggea, which may mean that competition for growth resources was still minimal or that access to the resources was equal and growth rates differed between species.     

Cytotoxicity of 15-Deoxy-��12,14-prostaglandin J2 through PPAR��-independent Pathway and the Involvement of the JNK and Akt Pathway in Renal Cell Carcinoma

Introduction: Agonists of peroxisome proliferator-activated receptor gamma (PPARγ) have been examined as chemopreventive and chemotherapeutic agents. The aim was to investigate the cytotoxicity and action mechanisms of 15-deoxy-Δ^12,14-prostaglandin J₂ (15d-PGJ₂), one of endogenous ligands for PPARγ, in terms of PPARγ-dependency and the mitogen-activated protein kinase (MAPK) and Akt pathway in three human renal cell carcinoma (RCC)-derived cell lines.Methods: 786-O, Caki-2 and ACHN cells were used as human RCC-derived cell lines. Cell viability and caspase-3 activity was detected by fluorescent reagents, and chromatin-condensation was observed with a brightfield fluorescent microscope after staining cells with Hoechst33342. The expression levels of proteins were detected by Western blot analysis.Results: 15d-PGJ₂ showed cytotoxicity in dose-dependent manner. 15d-PGJ₂ induced chromatin-condensation and elevated caspase-3 activity, and the cell viability was restored by co-treatment with a pan-caspase inhibitor, Z-VAD-FMK, indicating the involvement of caspase-dependent apoptosis. The cytotoxicity was not impaired by a PPARγ inhibitor, GW9662, suggesting that 15d-PGJ₂ exerted the cytotoxicity in a PPARγ-independent manner. Some antioxidants rescued cells from cell death induced by 15d-PGJ₂, but some did not, suggesting that reactive oxygen species (ROS) did not contribute to the apoptosis. 15d-PGJ₂ also increased the expression levels of phospho-c-Jun N terminal kinase (JNK) in Caki-2 cells, and decreased those of phospho-Akt in 786-O cells, indicating that the JNK MAPK and the Akt pathways participated in the anticancer effects of 15d-PGJ₂ in some cell lines.Conclusion: 15d-PGJ₂ exerted cytotoxic effects accompanying caspase-dependent apoptosis, and this effect was elicited in a PPARγ-independent manner in three cell lines. In addition, the JNK MAPK and Akt pathway was involved in the cytotoxicity of 15d-PGJ₂ to some extent in some cell line. Therefore, our study showed the 15d-PGJ₂ to potentially be an interesting approach for RCC treatment.