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991.
Borromeo V Sereikaite J Bumelis VA Secchi C Scirè A Ausili A D'Auria S Tanfani F 《The protein journal》2008,27(3):170-180
Fourier-transform infrared spectroscopy, in vitro bioassay and enzyme-linked immunoassay were used to study the structural-functional
relationships of recombinant mink growth hormone (mGH), refolded and stored under different conditions. Porcine GH (pGH) was
synthesized and used as an example. These two hormones, when refolded and stored the same way, had the same secondary structures,
biological and immunological efficacy, and biological potency. Only the immunological potency differed, mGH being significantly
less potent than pGH. Renaturation pH and storing frozen or at 4 °C in 5% glycerol did not affect either the secondary structure
or the activity. However, freeze-drying raised the content of buried α-helices and lowered that of solvated α-helices and
of unordered structures. These conformational changes were associated with a reduction of immunological and biological potency
of mGH and of immunological potency of pGH. These findings provide original information on the secondary structure of mGH,
and show that conformational changes induced by lyophilization adversely affect its activity. 相似文献
992.
A glial variant of the vesicular monoamine transporter is required to store histamine in the Drosophila visual system
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Romero-Calderón R Uhlenbrock G Borycz J Simon AF Grygoruk A Yee SK Shyer A Ackerson LC Maidment NT Meinertzhagen IA Hovemann BT Krantz DE 《PLoS genetics》2008,4(11):e1000245
Unlike other monoamine neurotransmitters, the mechanism by which the brain's histamine content is regulated remains unclear. In mammals, vesicular monoamine transporters (VMATs) are expressed exclusively in neurons and mediate the storage of histamine and other monoamines. We have studied the visual system of Drosophila melanogaster in which histamine is the primary neurotransmitter released from photoreceptor cells. We report here that a novel mRNA splice variant of Drosophila VMAT (DVMAT-B) is expressed not in neurons but rather in a small subset of glia in the lamina of the fly's optic lobe. Histamine contents are reduced by mutation of dVMAT, but can be partially restored by specifically expressing DVMAT-B in glia. Our results suggest a novel role for a monoamine transporter in glia that may be relevant to histamine homeostasis in other systems. 相似文献
993.
Clinical similarities between Cushing's syndrome and obesity/metabolic syndrome have led to speculation of a role for glucocorticoids (GCs) in the etiopathogenesis of obesity. People with idiopathic obesity have normal circulating cortisol concentrations. However, there may be considerable interindividual variation in GC sensitivity. The objective of this study was to determine whether enhanced GC sensitivity in the absence of GC excess was a characteristic of obese people with cushingoid features. We studied 12 obese subjects with cushingoid features in the absence of Cushing's syndrome and six slim control participants. Data recorded included BMI, waist-to-hip ratio, blood pressure, glucose and insulin response to 75 g oral glucose challenge, and low-dose (0.25 mg) overnight dexamethasone (DEX) suppression test (ODST-0.25 mg). To study GC-sensitivity in vitro, we performed dose-response studies of DEX-induced suppression of interleukin-6 (IL-6) secretion in skin fibroblast cultures. Seven obese subjects were normosensitive and five subjects hypersensitive to GCs in vitro. ODST-0.25 mg resulted in a median suppression of cortisol from baseline of 32% in normosensitive and 60% in hypersensitive obese subjects (P < 0.004). No other clinical or biochemical measures were discriminatory between these two groups. These data from two independent measures of GC sensitivity suggest that enhanced GC sensitivity may characterize a substantial proportion of obese people with cushingoid appearance. 相似文献
994.
Swanson SD Kukowska-Latallo JF Patri AK Chen C Ge S Cao Z Kotlyar A East AT Baker JR 《International journal of nanomedicine》2008,3(2):201-210
A target-specific MRI contrast agent for tumor cells expressing high affinity folate receptor was synthesized using generation five (G5) ofpolyamidoamine (PAMAM) dendrimer. Surface modified dendrimer was functionalized for targeting with folic acid (FA) and the remaining terminal primary amines of the dendrimer were conjugated with the bifunctional NCS-DOTA chelator that forms stable complexes with gadolinium (Gd III). Dendrimer-DOTA conjugates were then complexed with GdCl3 followed by ICP-OES as well as MRI measurement of their longitudinal relaxivity (T1 s(-1) mM(-1)) of water. In xenograft tumors established in immunodeficient (SCID) mice with KB human epithelial cancer cells expressing folate receptor (FAR), the 3D MRI results showed specific and statistically significant signal enhancement in tumors generated with targeted Gd(III)-DOTA-G5-FA compared with signal generated by non-targeted Gd(III)-DOTA-G5 contrast nanoparticle. The targeted dendrimer contrast nanoparticles infiltrated tumor and were retained in tumor cells up to 48 hours post-injection of targeted contrast nanoparticle. The presence of folic acid on the dendrimer resulted in specific delivery of the nanoparticle to tissues and xenograft tumor cells expressing folate receptor in vivo. We present the specificity of the dendrimer nanoparticles for targeted cancer imaging with the prolonged clearance time compared with the current clinically approved gadodiamide (Omniscan) contrast agent. Potential application of this approach may include determination of the folate receptor status of tumors and monitoring of drug therapy. 相似文献
995.
996.
Beata Kułek Jolanta Floryszak-Wieczorek Hanna Jackowiak 《Acta Physiologiae Plantarum》2004,26(1):95-102
The involvement of β-D-glucosidase activity in grey mould was studied in two ornamental plant species attacked by Botrytis cinerea.
β-D-glucosidase activity in the susceptible pelargonium cultivar ‘Shiva’ gradually increased with the disease development
in the leaf spots and their surroundings. The endogenic level of the studied hydrolase in the resistant pelargonium ‘Cascade’
was several times higher than in the susceptible cultivar ‘Shiva’ and in principle underwent no changes after inoculation.
The postinfection increase in the activity of β-D-glucosidase noted in the leaves of the susceptible poinsettia cultivar ‘Malibu
Red’ was evidently weaker in the intensity, but its tendencies were similar to those of the susceptible pelargonium cultivar.
In the leaves of the medium-resistant poinsettia ‘Coco White’ the constitutional level of β-D-glucosidase was 2-3-fold higher
in that cultivar than in the susceptible cv. ‘Malibu Red’. In attacked leaves of ‘Coco White’, the enzyme activity continued
to increase temporarily until the 3rd h after inoculation.
The process of healthy leaf senescence in both species had no significant influence on the change of the studied enzyme activity
which was generally low. A high activity of β-D-glucosidase was also observed in the homogenate prepared from mycelium and
in the fungal spores. 相似文献
997.
Kos-Kudła B Bolanowski M Handkiewicz-Junak D Jarzab B Królicki L Krzakowski M Kunikowska J Nasierowska-Guttmejer A Nowak A Rydzewska G Starzyńska T Szawłowski A;oraz Pozostali Uczestnicy Konferencji Okragłego Stołu 《Endokrynologia Polska》2008,59(1):41-56
We have recently observed an increased interest in gastro-entero-pancreatic neuroendocrine tumors (GEP NET). They are rare cancer types and therefore collaborative effort of specialists in various disciplines of medicine is necessary to work out the diagnostic and therapeutic guidelines. In this publication we present general guidelines of the Polish Network of Neuroendocrine Tumors for the management of patients with GEP NET, developed at the Round Table Conference which took place in Kliczków near Wroc?aw in November 2007. In the subsequent parts of this publication, we present the rules of diagnostic and therapeutic management of: - endocrine tumors of the stomach and duodenum (including gastrinoma); - pancreatic endocrine tumors; - neuroendocrine tumors of the small intestine and the appendix; - neuroendocrine tumors of the colon. We hope that the proposed guidelines by Polish and foreign experts representing various disciplines of medicine, including endocrinology, gastroenterology, surgery, oncology, nuclear medicine and pathomorphology, will become a useful tool in the diagnostics and treatment of these patients. 相似文献
998.
Choi BK Actor JK Rios S d'Anjou M Stadheim TA Warburton S Giaccone E Cukan M Li H Kull A Sharkey N Gollnick P Kocieba M Artym J Zimecki M Kruzel ML Wildt S 《Glycoconjugate journal》2008,25(6):581-593
Traditional production of therapeutic glycoproteins relies on mammalian cell culture technology. Glycoproteins produced by mammalian cells invariably display N-glycan heterogeneity resulting in a mixture of glycoforms the composition of which varies from production batch to production batch. However, extent and type of N-glycosylation has a profound impact on the therapeutic properties of many commercially relevant therapeutic proteins making control of N-glycosylation an emerging field of high importance. We have employed a combinatorial library approach to generate glycoengineered Pichia pastoris strains capable of displaying defined human-like N-linked glycans at high uniformity. The availability of these strains allows us to elucidate the relationship between specific N-linked glycans and the function of glycoproteins. The aim of this study was to utilize this novel technology platform and produce two human-like N-linked glycoforms of recombinant human lactoferrin (rhLF), sialylated and non-sialylated, and to evaluate the effects of terminal N-glycan structures on in vitro secondary humoral immune responses. Lactoferrin is considered an important first line defense protein involved in protection against various microbial infections. Here, it is established that glycoengineered P. pastoris strains are bioprocess compatible. Analytical protein and glycan data are presented to demonstrate the capability of glycoengineered P. pastoris to produce fully humanized, active and immunologically compatible rhLF. In addition, the biological activity of the rhLF glycoforms produced was tested in vitro revealing the importance of N-acetylneuraminic (sialic) acid as a terminal sugar in propagation of proper immune responses. 相似文献
999.
Pietrzak M Halicka HD Wieczorek Z Wieczorek J Darzynkiewicz Z 《Biophysical chemistry》2008,135(1-3):69-75
We have investigated the ability of chlorophyllin (CHL) to interact with acridine mutagen ICR-191 (2-methoxy-6-chloro-9-(3-(2-chloroethyl)aminopropylamino)acridine) and also its ability to decrease binding of ICR-191 to DNA in a simple three-component competition system: CHL-ICR–DNA. Our data indicate a strong association of ICR-191 with CHL, stronger even than the association of ICR-191 with DNA. Calculations based on the measured affinity data show that a two- to three-fold excess of CHL reduces by about two-fold the concentration of the mutagen-DNA complex. We also exposed human leukemic HL-60 cells to ICR-191 in the absence and presence of CHL and measured the mutagen-induced DNA damage. The extent of DNA damage was assessed by analysis of histone H2AX phosphorylation. While ICR-191 induced significant increase in expression of phosphorylated H2AX (γH2AX), particularly in DNA replicating cells, this increase was totally abolished in the cells treated with ICR-191 in the presence of CHL. 相似文献
1000.
Gaudet MM Lacey JV Lissowska J Peplonska B Brinton LA Chanock S Garcia-Closas M 《Human genetics》2008,123(2):155-162
Genetic variation in CYP17 is suspected to be related to endometrial cancer risk based on its role in the regulation of steroid and non-steroid hormone
biosynthesis. Reported associations between CYP17 and higher levels of estradiol in some studies suggest that the C allele of a T-to-C single nucleotide polymorphism (SNP)
in the 5′UTR of CYP17 (rs743572) may be associated with an increased risk of hormone-related cancers. However, five relatively small epidemiologic
studies of endometrial cancer have reported that women with the rs743572 C allele have a decreased risk of endometrial cancer.
To examine this association, we genotyped rs743572 and eight other haplotype-tagging SNPs (htSNPs), which are estimated to
capture >80% of the variation in CYP17 in a population-based study of 497 endometrial cancer cases and 1,024 controls in Poland. Significant associations were not
found for rs743572 (per C allele: OR = 1.12, 95%CI 0.96–1.30; P-trend = 0.15), for individual htSNPs, or for extended haplotypes (global P-value = 0.60). When we pooled data from previously published studies with our own (a total of 1,004 endometrial cases and
1,907 controls), we observed significant study heterogeneity in summary estimates of the association between rs743572 and
endometrial cancer, as well as evidence of publication bias. In conclusion, our data are not consistent with a decreased endometrial
cancer risk associated with rs743572, as previously reported, or with other haplotype-tagging polymorphisms. Further evaluation
in consortia is necessary to confirm potential weak associations between common variation in CYP17 and endometrial cancer risk and to address the concern of publication bias.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献