Sheep farming business in Uşak city of Turkey: Economic structure,problems and solutions

The current study was conducted to reveal the current states, structural features and primary problems of the sheep raising businesses in the city of U?ak. The study group of the current study is comprised of 429 sheep raising businesses selected through stratified sampling (provinces) and a questionnaire consisted of 112 items was administered to these businesses. Through the items in the questionnaire, data were collected about the general features of the businesses and their owners, the state of grazing lands, mating of sheep, birth, milking, clipping, health protection, marketing of animals and the states of tools and equipments in the businesses.The findings of the study have revealed that 82.2% of the owners of the sheep raising businesses are elementary school graduates, their average time of being involved in the activity of sheep raising is 9.8?years, 90% of their shepherds are from the family members, 23.5% of them practice additional feeding before mating and the most preferred method for mating is free insemination with 89%.Of the owners of the businesses, 81.1% learned sheep raising from their elders; for 54% of them sheep raising is the sole source of income and 25.6% of them are engaged in sheep raising to support their families. The main problems of the sheep raisers were found to be the high cost of feed, the low prices paid for their products, inadequate and poor quality grazing lands and animal diseases. In order to make sheep raising more attractive, the prices of the products should be increased, grazing lands should be improved, the genetic structure of the herd should be enhanced, the amount of land area where feed crops are cultivated should be extended and suitable credit conditions should be provided. On the other hand, they need to be informed about sheep mating, lamb growing, stock, milking hygiene, general sheep feeding practices and marketing.     

Introduction of d-Phenylalanine enhanced the receptor binding affinities of gonadotropin-releasing hormone peptides

The purpose of this study was to examine whether the introduction of d-Phe could improve the GnRH receptor binding affinities of DOTA-conjugated d-Lys⁶-GnRH peptides. Building upon the construct of DOTA-Ahx-(d-Lys⁶-GnRH1) we previously reported, an aromatic amino acid of d-Phe was inserted either between the DOTA and Ahx or between the Ahx and d-Lys⁶ to generate new DOTA-d-Phe-Ahx-(d-Lys⁶-GnRH) or DOTA-Ahx-d-Phe-(d-Lys⁶-GnRH) peptides. Compared to DOTA-Ahx-(d-Lys⁶-GnRH1) (36.1 nM), the introduction of d-Phe improved the GnRH receptor binding affinities of DOTA-d-Phe-Ahx-(d-Lys⁶-GnRH) (16.3 nM) and DOTA-Ahx-d-Phe-(d-Lys⁶-GnRH) (7.6 nM). The tumor targeting and pharmacokinetic properties of ¹¹¹In-DOTA-Ahx-d-Phe-(d-Lys⁶-GnRH) was determined in MDA-MB-231 human breast cancer-xenografted nude mice. Compared to ¹¹¹In-DOTA-Ahx-(d-Lys⁶-GnRH1), ¹¹¹In-DOTA-Ahx-d-Phe-(d-Lys⁶-GnRH) exhibited comparable tumor uptake with faster renal and liver clearance. The MDA-MB-231 human breast cancer-xenografted tumors were clearly visualized by single photon emission computed tomography (SPECT) using ¹¹¹In-DOTA-Ahx-d-Phe-(d-Lys⁶-GnRH) as an imaging probe, providing a new insight into the design of new GnRH peptides in the future.     

In-vivo dosimetry comparison of supraclavicular junction dose for breast and chest-wall patients with and without deep inspiration breath hold (DIBH)

PurposeThe use of deep inspiration breath-hold (DIBH) for patients with left-sided breast cancer reduces cardiac dose, with the aim of reducing the risk of major coronary events. However, this technique has not been universally adopted for patients requiring regional nodal irradiation (RNI) with one concern related to the junction dose. This study evaluates the dose received at the junction for both DIBH and free-breathing patients having tangential breast/chest wall radiation and regional nodal radiation treated with 3D-conformal or hybrid IMRT radiotherapy.MethodsIn-vivo dosimetry measurements utilizing EBT3 GafChromic™ film were performed for 19 patients during three fractions over their course of treatment. The mean junction dose and variability in junction dose were compared between the DIBH and free breathing patients.ResultsOur results show that for voluntary DIBH (v-DIBH) patients the junction dose is more variable between fractions. However, when comparing the average junction dose for DIBH and free breathing patients over the three measurements, the difference was small and not statistically significant. A larger difference was seen when patient measurements were analysed based on treatment linac.ConclusionsThese results show that the mean junction dose is not significantly compromised by the use of v-DIBH. The small possibility of a change in junction dose due to breathing technique should be weighed against the proven increased risks associated with excess cardiac dose received by free-breathing patients. If junction dose is of concern, an in-vivo study, such as this one, could allow cautious introduction of DIBH for patients requiring supraclavicular irradiation.     

Bioanalysis of drugs by liquid-phase microextraction coupled to separation techniques

The demand for automation of liquid-liquid extraction (LLE) in drug analysis combined with the demand for reduced sample preparation time has led to the recent development of liquid-phase microextraction (LPME) based on disposable hollow fibres. In LPME, target drugs are extracted from aqueous biological samples, through a thin layer of organic solvent immobilised within the pores of the wall of a porous hollow fibre, and into an microl volume of acceptor solution inside the lumen of the hollow fibre. After extraction, the acceptor solution is subjected directly to a final analysis either by high performance liquid chromatography (HPLC), capillary electrophoresis (CE), mass spectrometry (MS), or capillary gas chromatography (GC) without any further treatments. Hollow fibre-based LPME may provide high enrichment of drugs and excellent sample clean-up, and probably has a broad application potential within the area of drug analysis. This review focuses on the principle of LPME, and recent applications of three-phase, two-phase, and carrier mediated LPME of drugs from plasma, whole blood, urine, and breast milk.     

Protein expression pattern distinguishes different lymphoid neoplasms

To identify proteins associated with the histological subtypes of lymphoid neoplasms, we studied the proteomes of 42 cell lines from human lymphoid neoplasms including Hodgkin's lymphoma (HL; four cell lines), B cell malignancies (19 cell lines), T cell malignancies (16 cell lines), and natural killer (NK) cell lymphoma (three cell lines). The protein spots were sequentially selected by (i) Wilcoxon or Kruskal-Wallis tests to find the spots whose intensity was significantly (p <0.05) different among the cell line groups, (ii) by statistical-learning methods to prioritize the spots according to their contribution to the classification, and (iii) by unsupervised classification methods to validate the classification robustness by the selected spots. The selected spots discriminated (i) between HL cells and other cells, (ii) between the cells from B cell malignancies, T cell malignancies, and NK cell lymphoma cells, and (iii) between HL cells and anaplastic large cell lymphoma cells. Among the 31 informative protein spots, MS identified 24 proteins corresponding to 23 spots. Previous reports did not correlate these proteins to lymphocyte differentiation, suggesting that a proteomic study would identify the novel mechanisms responsible for the histogenesis of lymphoid neoplasms. These proteins may have potential as differential diagnostic markers for lymphoid neoplasms.     

Candidate epitope identification using peptide property models: application to cancer immunotherapy

Peptides derived from pathogens or tumors are selectively presented by the major histocompatibility complex proteins (MHC) to the T lymphocytes. Antigenic peptide-MHC complexes on the cell surface are specifically recognized by T cells and, in conjunction with co-factor interactions, can activate the T cells to initiate the necessary immune response against the target cells. Peptides that are capable of binding to multiple MHC molecules are potential T cell epitopes for diverse human populations that may be useful in vaccine design. Bioinformatical approaches to predict MHC binding peptides can facilitate the resource-consuming effort of T cell epitope identification. We describe a new method for predicting MHC binding based on peptide property models constructed using biophysical parameters of the constituent amino acids and a training set of known binders. The models can be applied to development of anti-tumor vaccines by scanning proteins over-expressed in cancer cells for peptides that bind to a variety of MHC molecules. The complete algorithm is described and illustrated in the context of identifying candidate T cell epitopes for melanomas and breast cancers. We analyzed MART-1, S-100, MBP, and CD63 for melanoma and p53, MUC1, cyclin B1, HER-2/neu, and CEA for breast cancer. In general, proteins over-expressed in cancer cells may be identified using DNA microarray expression profiling. Comparisons of model predictions with available experimental data were assessed. The candidate epitopes identified by such a computational approach must be evaluated experimentally but the approach can provide an efficient and focused strategy for anti-cancer immunotherapy development.     

Dendritic cells are dysfunctional in patients with operable breast cancer

Background: Dendritic cells (DCs) play a crucial role in presenting antigens to T lymphocytes and inducing cytotoxic T cells. DCs have been studied in patients with breast cancer to define the factors leading to failure of an effective systemic and locoregional anticancer host response. Methods: Purified DCs were obtained from peripheral blood (PB) and lymph nodes (LNs) of women with operable breast cancer, using immunomagnetic bead selection. The stimulatory capacity of DCs in the allogeneic mixed leukocyte reaction (MLR) and autologous T cell proliferation test (purified protein derivative (PPD) as stimulator), the expression of surface markers on DCs and the production of cytokines in vitro by DCs from patients with operable breast cancer and from healthy donors (controls) were studied. Results: 70–75% purified DCs were isolated from PB and LNs. PBDCs and LNDCs from patients with operable breast cancer demonstrated a reduced capacity to stimulate in an MLR, compared with PBDCs from normal donors (p<0.01). Autologous T cell proliferation in patients had a decreased ability to respond to PPD, when compared with controls (p<0.01). However, T cells from patients responded as well as control T lymphocytes in the presence of control DCs. PBDCs and LNDCs from patients expressed low levels of HLA-DR and CD86, and induced decreased interleukin-12 (IL-12) secretion in vitro, compared with DCs from normal donors (p<0.01). Conclusion: These data suggest a defective DC function in patients with operable breast cancer. Switched-off DCs in patients with early breast cancer and decreased IL-12 production may be important factors for progressive tumour growth.     

Up-regulated expression of low molecular weight protein tyrosine phosphatases in different human cancers

Protein tyrosine phosphorylation, mediated by the balanced action of tyrosine kinases and phosphatases, contributes to the regulation of the growth, migration, and invasion of normal and malignant cells. Among tyrosine phosphatases, low molecular weight protein tyrosine phosphatases (LMW-PTP) have been recognized as a possible "positive factor" in tumour onset and progression. The aim of this work was to assess whether LMW-PTP are differentially expressed in normal and malignant tissues. Using real-time PCR analysis we evaluated the expression levels of total LMW-PTP mRNA in surgical samples of breast, colon and lung cancers (63, 60, and 58, respectively), and in their paired adjacent not affected tissues. Moreover, the same analysis was carried out on a group of neuroblastomas (25 cases). Significant correlations between LMW-PTP overexpression and the most common clinical-pathological features of cancers exist. In colon cancer and neuroblastoma increased total LMW-PTP mRNA expression correlates with unfavourable outcome. While LMW-PTP mRNA expression increases in tumour samples, the relative contribution of the different isoforms does not change. Our findings indicate that LMW-PTP can be considered an oncogene as it is overexpressed in different tumour types and suggests that LMW-PTP enhanced expression is generally prognostic for a more aggressive cancer.     

Saururus cernuus lignans--potent small molecule inhibitors of hypoxia-inducible factor-1

Hypoxia-inducible factor-1 (HIF-1) represents an important tumor-selective therapeutic target for solid tumors. In search of novel small molecule HIF-1 inhibitors, 5400 natural product-rich extracts from plants, marine organisms, and microbes were examined for HIF-1 inhibitory activities using a cell-based reporter assay. Bioassay-guided fractionation and isolation, followed by structure elucidation, yielded three potent natural product-derived HIF-1 inhibitors and two structurally related inactive compounds. In a T47D cell-based reporter assay, manassantin B1, manassantin A, and 4-O-methylsaucerneol inhibited hypoxia-induced HIF-1 activation with IC50 values of 3, 3, and 20 nM, respectively. All three compounds are relatively hypoxia-specific inhibitors of HIF-1 activation, in comparison to other stimuli. The hypoxic induction of HIF-1 target genes CDKN1A, VEGF, and GLUT-1 were also inhibited. These compounds inhibit HIF-1 by blocking hypoxia-induced nuclear HIF-1alpha protein accumulation without affecting HIF-1alpha mRNA levels. In addition, preliminary structure-activity studies suggest specific structural requirements for this class of HIF-1 inhibitors.