Beta-lactamases: a survey of protein diversity

Bacterial resistance to beta-lactam antibiotics and beta-lactamase inhibitors is an ever increasing problem that threatens the clinical utility of drugs that form the cornerstone of the antibiotic armamentarium. Especially among Gram-negative pathogens, elaboration of structurally and mechanistically novel beta-lactamase enzymes is the most important means by which resistance occurs. An appreciation of the tremendous diversity of these drug-modifying enzymes will assist in understanding why so few generally effective inhibitory agents exist for these unique drug targets. This review will give a general background on the reaction mechanisms and classification schemes of the more than 340 beta-lactamase enzymes described to date. A discussion will follow highlighting the emerging Class A SHV and TEM-derived extended-spectrum (ESBLs), and inhibitor-resistant enzymes, non-TEM, non-SHV Class A ESBLs, and carbapenemases, Class B metallo-beta-lactamases and some of their novel inhibitors, plasmid and chromosomally encoded Class C enzymes, and finally, the OXA-type oxacillinases, ESBLs, and carbapenemases of Class D. The clinical importance of multiple resistance mechanisms in conjunction with the production of beta-lactamase enzymes is emphasized.     

Spontaneous canine mast cell tumors express tandem duplications in the proto-oncogene c-kit

Spontaneous mast cell tumors (MCT) are the most common malignant neoplasm in the dog, representing between 7% and 21% of all canine tumors, an incidence much higher than that found in humans. These tumors often behave in an aggressive manner, metastasizing to local lymph nodes, liver, spleen, and bone marrow. The proto-oncogene c-kit is known to play a critical role in the development and function of mast cells. Point mutations in the kinase domain of c-kit leading to tyrosine phosphorylation in the absence of ligand binding have been identified in three mastocytoma lines, (P815, RBL, and HMC-1), and some human patients with various forms of mastocytosis. We now demonstrate that although c-kit derived from canine MCT did not contain the previously described activating point mutations, 5 of the 11 tumors analyzed possessed novel mutations consisting of tandem duplications involving exons 11 and 12. We also show that one such duplication, detected in a canine mastocytoma cell line, was associated with constitutive phosphorylation of c-kit protein (KIT), suggesting that these mutations may contribute to the development or progression of canine MCT.     

Experimental intrahepatic portacaval anastomosis: use of expandable Gianturco stents

Original Gianturco expandable stents and their modifications were used to create an experimental intrahepatic portacaval anastomosis (EIPCA) in 30 young domestic swine without portal hypertension. The study focused on the design of a suitable stent, the technique of its application, and the evaluation of short-term patency of the EIPCA. A stent with a 2.5-cm-long body and wire skirts on both ends was most suitable for EIPCA creation. Well-positioned stents shunted most of the portal blood in the inferior vena cava circulation and remained patent for 4-6 weeks. Ingrowth of liver parenchyma and abundant proliferation of the intima and connective tissue inside the stent lumen in these rapidly growing animals gradually decreased EIPCA patency, and thrombus formation with diminished blood flow closed them completely.     

小鼠脑缺血后的能量代谢改变和药物的作用

应用部分结扎小鼠颈总动脉(包括迷走神经)及小鼠断头法引起脑缺血后,脑组织的ATP和磷酸肌酸明显降低,乳酸明显升高。部分结扎颈动脉出现四肢无力、转圈及昏睡等症状,其严重程度与脑能量代谢改变相平行。皮下注射尼莫地平、硝苯吡啶、尼卡地平和三七皂甙对脑缺血有一定保护作用。苯巴比妥钠能改善正常和脑缺血小鼠的脑能量代谢,人参皂甙Rb₁可降低正常小鼠脑乳酸含量。     

Iron-deficient medium for selective isolation and presumptive identification of enterococci

An Enterococcus Selective Agar (ESA; basal medium plus 0.01% NaN3, pH 9.6, Fe ion-restricted) was applied to a direct, single-step, isolation and presumptive identification of enterococci from clinical urine. The ESA was examined as to rate of colony formation and selectivity together with two conventional culture media, Pfizer Selective Enterococcus Agar (PSE) and Phenyl Ethyl Alcohol Agar (PEA). Significant differences were observed in the rate of colony formation after 14, 17, and 20 hr of incubation at 35 degrees. The size of colonies on ESA was consistently larger than on the other two media. Biochemical testing showed that isolates from ESA conformed more closely to the definition of enterococci than isolates from either PSE or PEA. The improved selectivity of ESA was in large part due to the reduced presence of Fe ions. The medium offers advantages for an expeditious and accurate isolation of enterococcal pathogens.