The phenotype of Gorlin-Goltz syndrome or basal cell nevus syndrome (BCNS, #109400, OMIM), a Mendelian trait due to PTCH mutations has been reported in a few cases of interstitial deletion of chromosome 9q. We present an 11-year-old girl with clinical features consistent with BCNS including bridging of sella turcica, biparietal bossing, downward slanting palpebral fissures, mandible prognathism, pectus excavatum, thumb abnormalities, occult spina bifida at L5-S4, numerous basal cell nevi, and single basal cell carcinoma. Cytogenetic analysis using high-resolution banding techniques and fluorescence in situ hybridization (FISH) revealed interstitial chromosome deletion 9q22.32-q33.2 involving the PTCH gene as a secondary breakage event to a chromosome translocation t(9;17)(q34.1;p11.2)mat. Further FISH studies showed the translocation breakpoint on 9q34.11 maps proximal to ABL, between the BAC clone RP11-88G17 and the LMX1B gene. The latter gene encodes a transcription factor, in which loss of function mutations are responsible for the nail-patella syndrome (NPS, #161200 OMIM). Interestingly, some features of our proband (e.g., bilateral patellar dysplasia and abnormal clavicular shape), as well as her healthy sister who carries the same translocation, are also found in patients with NPS. The chromosome 17p11.2 breakpoint maps in the Smith-Magenis syndrome common deletion region, within two overlapping BAC clones, CTD-2354J3 and RP11-311F12.

The objective of this work was to identify the nutritional and physiological effects of commercial soy and whey protein preparations. Wistar rats were fed with soy (S), whey (W), or casein (C) preparations as the sole dietary protein source. The nitrogen balance, body composition, changes in caecal microbiota, mucosal and bacterial enzyme activities, and allergenic potential of the preparations were analysed. The whey diet elicited greater skeletal muscle anabolism than the soy diet. Rats from the S group had the lowest values of body weight, fat, and lean mass gain. Compared to casein, soy and whey preparations decreased the protein efficiency ratio, increased N in the urine, and triggered the reduction of ammonia levels in the caecum. Changes in β-glucuronidase and β-galactosidase activities in the small intestine, caecum, and colon between experimental groups were observed. Significant differences were noted in the total counts of anaerobic bacteria and sulphite reducing bacteria during soy and whey treatments. This probably affected the short chain fatty acid level in caecal digesta resulting in the lowest propionic acid and total putrefactive short chain fatty acid levels during S treatment. Generally, whey preparations are a good choice for rapid bodybuilding (skeletal muscles), whereas soy preparations are more helpful during mass reduction.

We investigated the yogurt starter cultures of Lactobacillus bulgaricus 151 and Streptococcus thermophilus MK-10 for their effect on the severity of experimental colitis, lymphocyte profile, and regulatory T-cell response. Colitis was induced in BALB/c mice via the administration of 3.5% dextran sulfate sodium salt (DSS) in drinking water for 6 d. Next, the mice were gavaged intragastrically with an active yogurt cultures (YC) mixture (~5 × 10 9 cfu/mouse per day) or saline (vehicle) for 8 d. Mice receiving DSS or saline alone served as positive and negative controls, respectively. The length of the colon, disease activity index, histological scores, myeloperoxidase activity, epitheliumassociated microbes, short-chain fatty acid profile, total IgA antibody-forming cells, CD3 + CD8 + , CD3 + CD4 + , CD3 + CD4 + CD25 + , CD3 + CD4 + CD25 + Foxp3 + T-cell subsets, and cytokine profiles (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, and tumor necrosis factor) were examined after termination of the mice. Feeding mice with YC mixture reduced disease symptoms and modified intestinal microbiota and host inflammatory responsiveness to DSS. We observed limited weight loss and a decreased disease activity index score, lowered myeloperoxidase activity, and somewhat reduced damage of the intestine. The YC mixture upregulated the colon length, increased the amount and diversity of mucosaassociated microbes (enterobacteria, enterococci, and yeast), and decreased the concentration of putrefactive short-chain fatty acids in the cecal contents. It downregulated the input of cytotoxic CD3 + CD8 + T cells and CD3 + CD4 + CD25 + FoxP3 + regulatory T cells in Peyer's patches and enhanced CD3 + CD4 + CD25 + T cells in spleens and CD3 + CD4 + CD25 + FoxP3 + cells in peripheral blood mononuclear cells. Simultaneously, IgA antibody-forming cells were downregulated in mesenteric lymph nodes (MLN) and enhanced in spleens (SPL). The cultures mostly enhanced the production of cytokines tested in MLN and SPL, except for IL-6, which was downregulated in MLN. Interleukin-2 and IL-4 were the most upregulated in MLN, whereas IL-10, IL-4, IL-2, IFN-γ, and tumor necrosis factor were most upregulated in SPL. In serum, the YC mixture downregulated IFN-γ and clearly increased IL-2. Based on these results, we recognize the high anti-inflammatory and immunomodulatory potential of the L. bulgaricus 151 and S. thermophilus MK-10 set. The strains possess the ability to modulate the intestinal mucosal and systemic immune system toward both IgA production and induction of regulatory T cells, shifting Th1/Th2 balance.

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2-Alkoxy-2-thiono-1,3,2-oxathiaphospholanes are readily transformed into phosphorothioate monoesters of the corresponding alcohols in a one-pot process, involving the reaction with 3-hydroxypropionitrile in the presence of DBU, followed by treatment with aqueous ammonia. In this way a series of nucleoside-3¢-O-and 5¢-O-phosphorothioates were prepared, as well as phosphorothioate derivatives of selected polyols.Nucleoside phosphoromonothioates, originally introduced by Eckstein, 1 became an important tool for studying the mechanisms of action of nucleolytic enzymes 1-3 and are widely employed as intermediates in the synthesis of other phosphorothioate derivatives of nucleosides. 4 The procedure employed by Eckstein 1 involved the treatment of appropriately protected nucleoside with thiophosphoryl tris-imidazolide. The procedure was not very efficient and was limited to the synthesis of nucleoside 5¢-O-phosphorothioates. For the synthesis of this class of compounds much a more convenient methodology was introduced by Murray and Atkinson 2 who treated unprotected adenosine with thiophosphoryl chloride in triethyl phosphate as a solvent. This approach was further extended to other nucleosides in both the ribo-5 and deoxyribonucleoside series. 6 Another example of 5¢-O-thiophosphorylation of unprotected nucleosides was described by Chen and Benkovic 7 who treated nucleoside with phosphorous acid in the presence of DCC, followed by sulfurization of resulting nucleoside 5¢-O-H-phosphonate with elemental sulfur. Other procedures, which were described in the literature for thiophosphorylation of nucleosides required selective protection of reactive groups at the sugar and/or nucleobase moiety. Thus, the synthesis of thymidine 3¢-O-phosphorothioate was accomplished by treatment of 5¢-O-protected thymidine with thiophosphoryl chloride in the presence of pyridine followed by work-up with alkali. 8 An efficient thiophosphorylation of 3¢-O-or 5¢-O-protected nucleosides was also performed by Cook, 9 with S-2-carbamoylethyl phosphorothioate in the presence of DCC as condensing agent. In a similar manner S-2-cyanoethyl phosphorothioate was employed for introducing of phosphorothioate functions into nucleoside moiety. 10 In both cases the S-protecting groups were selectively removed by postsynthetic work-up with alkali. More recently, the phosphoramidite methodology was successfully adopted for both 5¢-O-and 3¢-O-thiophosphorylation of nucleosides. 11,12 The procedure involved phosphitylation of appropriately protected nucleoside with reagents such as bis(2-cyanoethoxy)-N,N-diisopropylaminophosphoramidite, 11 bis[2-(4-nitrophenyl)-ethoxy]-N,N-diisopropylaminophosphoramidite, 11a or 2-cyanoethoxy-2-(dimethoxytrityloxyethylsulfonyl)-ethoxy-N,N-diiso-propylaminophosphoramidite 12 in the presence of tetrazole, followed by sulfurization with elemental sulfur. The phosphorothioate O-protecting groups were removed by b-elimination by treatment with appropriate base. In addition to nucleosides, the phosphoramidite methodology was successf...

Epidemiological studies on myelodysplastic syndromes (MDS) in Middle-Eastern Europe are scarce. No data about the demographic, clinical, and laboratory features of Polish MDS patients have been published. The aim of this study was to assess the epidemiological data and toxic exposure of Polish MDS patients and their association with hematological parameters and clinical outcomes. For 15 months, 966 living MDS patients were enrolled at 24 centers (12 university and 12 community hospitals). Follow-up was conducted for the next 55 months. The percentage of patients older than 80 years (16%) was between the values for Eastern and Western countries. In patients younger than 55 years, a female predominance was observed (male/female ratio 0.70:1 vs. 1.29:1; p < 0.001). Female patients had higher platelet counts (160 × 10⁹/l vs. 111 × 10⁹/l; p < 0.001). Patients exposed to chemicals were younger than patients without such exposure; their median age at MDS diagnosis was 66 vs. 70 years (p = 0.037). Smokers had significantly lower hemoglobin concentrations (8.6 vs. 9.1 g/dl; p = 0.032) and lower platelet counts (99 × 10⁹/l vs. 137 × 10⁹/l; p < 0.001) than nonsmokers. We provide the first description of the characteristics of Polish MDS patients. Females predominated in the group aged <60 years and they had higher platelet counts. The course of the disease is affected by toxic exposure and smoking.