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51.
52.
Jones JB Stanley EH Mulholland PJ 《Science (New York, N.Y.)》2003,302(5647):985-7; author reply 985-7
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Walensky LD Kung AL Escher I Malia TJ Barbuto S Wright RD Wagner G Verdine GL Korsmeyer SJ 《Science (New York, N.Y.)》2004,305(5689):1466-1470
BCL-2 family proteins constitute a critical control point for the regulation of apoptosis. Protein interaction between BCL-2 members is a prominent mechanism of control and is mediated through the amphipathic alpha-helical BH3 segment, an essential death domain. We used a chemical strategy, termed hydrocarbon stapling, to generate BH3 peptides with improved pharmacologic properties. The stapled peptides, called "stabilized alpha-helix of BCL-2 domains" (SAHBs), proved to be helical, protease-resistant, and cell-permeable molecules that bound with increased affinity to multidomain BCL-2 member pockets. A SAHB of the BH3 domain from the BID protein specifically activated the apoptotic pathway to kill leukemia cells. In addition, SAHB effectively inhibited the growth of human leukemia xenografts in vivo. Hydrocarbon stapling of native peptides may provide a useful strategy for experimental and therapeutic modulation of protein-protein interactions in many signaling pathways. 相似文献
56.
Kuehner KA Marks SL Kass PH Sauter-Louis C Grahn RA Barutzki D Hartmann K 《Journal of Feline Medicine and Surgery》2011,13(4):251-258
The aim of this study was to determine the prevalence of Tritrichomonas foetus infection and associated clinical signs in purebred cats in Germany, to investigate the role of co-infection, and identify determinants of infection. Faecal specimens accompanied by epidemiological questionnaires were scored and collected from 230 purebred cats. Faeces were examined for trichomonads and other enteroparasites. The prevalence of T foetus was 15.7% among cats and 18.5% among catteries. An abnormal faecal score and history of diarrhoea were observed in 64% and 61% of T foetus-positive cats, respectively, and correlated significantly with infection. Co-infection, observed in 36% of T foetus-infected cats, was not associated with diarrhoea. Norwegian Forest cats were infected significantly more often than other breeds. No association was found with any environmental factors. This study demonstrated a high prevalence of symptomatic T foetus infections in purebred cats in Germany. Co-infection with other enteroparasites did not worsen clinical signs of trichomonosis. 相似文献
57.
Grundon RA Anderson GA Lynch M Hardman C O'Reilly A Stanley RG 《Veterinary ophthalmology》2011,14(5):292-295
Objective To estimate mean Schirmer tear test (STT) and intraocular pressure (IOP) values in healthy koalas both conscious and anesthetized. Methods Data were gathered from koalas in Victoria, Australia. Conscious examinations were performed on captive koalas. Free‐ranging (wild) koalas were examined under anesthesia. Anesthesia was induced using alfaxalone, and animals were maintained on oxygen and isoflurane if required. All animals were healthy and had no surface ocular pathology detectable during slit lamp biomicroscopy. STT I tests were performed using commercial STT test strips placed in the lower fornix for 1 min. IOP was measured using an applanation tonometer after topical anesthesia. The higher value of the two eyes for both STT and IOP was analyzed. STT was measured in 53 koalas (34 conscious, 19 anesthetized) and IOP was measured in 43 koalas (30 conscious, 13 anesthetized). A two‐sample t‐test was used to compare means. A P‐value <0.05 was regarded as significant. Mean ± SD is presented. Results The mean higher STT in conscious koalas was 10.3 ± 3.6 mm wetting/min and in anesthetized koalas it decreased to 3.8 ± 4.0 mm wetting/min (P < 0.0001). The mean higher IOP in conscious koalas was 15.3 ± 5.1 mmHg, and in anesthetized koalas it was 13.8 ± 3.4 mmHg (P = 0.32). There was no effect of sex on either STT or IOP. Conclusions The mean and SD of STT and IOP values for koalas both conscious and anesthetized were reported. The mean STT was significantly reduced by alfaxalone anesthesia. 相似文献
58.
Harrison TM Stanley BJ Sikarskie JG Bohart G Ames NK Tomlian J Marquardt M Marcum A Kiupel M Sledge D Agnew D 《Journal of zoo and wildlife medicine》2011,42(2):317-321
A 14-yr-old female eastern black rhinoceros (Diceros bicornis michaeli) presented with progressive suppurative osteomyelitis in her left hind lateral toe. beta-Hemolytic Streptococcus sp. was isolated. The animal was treated with multiple systemic antibiotics, and topical wound cleansing. Repeated debridements and nail trimmings were performed for 5 mo prior to electing amputation. The toe was surgically amputated under general anesthesia between the first and second phalanges. Analgesia was diffused into the wound topically via a catheter and elastomeric pump. The open amputation site was covered with adherent drapes and a negative-pressure wound therapy device provided vacuum-assisted closure (V.A.C.) for 72 hr. Three months later this animal developed a deep dermal ulcer on the lateral aspect of the right hind limb, at the level of the stifle. Methicillin-resistant Staphylococcus aureus was isolated. The wound was managed by initial daily lavage, followed by 1 mo of V.A.C. therapy, with 72 hr between dressing changes. Clinically, this therapy expedited the formation of healthy granulation tissue and overall healing was accelerated. The animal tolerated the machine and bandage changes well via operant conditioning. The use of negative-pressure wound therapy appeared to shorten time to resolution of slow-healing wounds in black rhinoceros. 相似文献
59.
A rapid and sensitive method is described for the quantitation of erythromycin A (EA) in edible salmon tissue by liquid chromatography (LC) analysis using either electrochemical detection (ED) or electrospray ionization mass spectrometric (ESI/MS) detection. The salmon tissue is extracted with 10 mM ammonium formate. The extract is then purified by solid phase extraction using a hydrophilic-lipophilic balanced (HLB) polymeric-based C18 packing, followed by partitioning of EA into methylene chloride at alkaline pH, evaporation, and final dilution. The mean recoveries of EA at 50, 100, 200, and 400 ppb levels in fortified salmon tissue were 63.8 +/- 6.0 and 75.5 +/- 5.4% by LC-ED and LC-ESI/MS, respectively. There was no evidence of formation of the anhydro-EA (m/z 716) decomposition product of EA (m/z 734) that was reported to occur by other published methods. 相似文献
60.
Jun M Shao Y Ho CT Koetter U Lech S 《Journal of agricultural and food chemistry》2003,51(21):6340-6346
The degradation profile of glucosamine bulk form stressed at 100 degrees C for 2 h in an aqueous solution was studied. Column chromatography of acetylated product mixture led to isolation of two pure compounds (1b and 2b) and a mixture of at least three isomers (3b). 1a and 2a were identified as 5-(hydroxymethyl)-2-furaldehyde (5-HMF) and 2-(tetrahydroxybutyl)-5-(3',4'-dihydroxy-1'-trans-butenyl)pyrazine, respectively, by utilizing a variety of analytical techniques, such as GC-MS, LC-MS, on-line UV spectrum, (1)H and (13)C NMR, and DEPT, as well as (1)H-(1)H COSY. 3a was identified as 2-(tetrahydroxybutyl)-5-(2',3',4'-trihydroxybutyl)pyrazine, commonly known as deoxyfructosazine. In addition, glucosamine solid dosage form was exposed to 40 degrees C/75% relative humility for 10 weeks. Methanol extract of glucosamine solid dosage form was analyzed after acetylation by LC-MS, resulting in degradants 3b and 4b. 3a and 4a were, therefore, determined as deoxyfructosazine and 2,5-bis(tetrahydroxybutyl)pyrazine (fructosazine), respectively. Furthermore, the mechanisms of formation of identified degradation products are proposed and briefly discussed. 相似文献