Antibiotic sensitization using biphenyl tetrazoles as potent inhibitors of Bacteroides fragilis metallo-beta-lactamase

BACKGROUND: High level resistance to carbapenem antibiotics in gram negative bacteria such as Bacteroides fragilis is caused, in part, by expression of a wide-spectrum metallo-beta-lactamase that hydrolyzes the drug to an inactive form. Co-administration of metallo-beta-lactamase inhibitors to resistant bacteria is expected to restore the antibacterial activity of carbapenems. RESULTS: Biphenyl tetrazoles (BPTs) are a structural class of potent competitive inhibitors of metallo-beta-lactamase identified through screening and predicted using molecular modeling of the enzyme structure. The X-ray crystal structure of the enzyme bound to the BPT L-159,061 shows that the tetrazole moiety of the inhibitor interacts directly with one of the two zinc atoms in the active site, replacing a metal-bound water molecule. Inhibition of metallo-beta-lactamase by BPTs in vitro correlates well with antibiotic sensitization of resistant B. fragilis. CONCLUSIONS: BPT inhibitors can sensitize a resistant B. fragilis clinical isolate expressing metallo-beta-lactamase to the antibiotics imipenem or penicillin G but not to rifampicin.     

Regional myocyte hypertrophy parallels regional myocardial dysfunction during post-infarct remodeling

The molecular genetic events involved in the etiology of human granulosa cell (GC) tumors, which represent approximately 7% of all malignant ovarian neoplasms, are unknown. Amplification and/or overexpression of the ERBB genes are a feature of many cancer types, and overexpression of erbB2 correlates with poor prognosis in epithelial ovarian cancer. In the present study, we used immunohistochemistry to determine the level and frequency of expression of different erbB receptors in GC tumors. Ten of 12 tumors expressed erbB4 at moderate to high levels in >50% of cancer cells, whereas erbB2 (6 of 12) and erbB3 (2 of 12) were expressed less frequently. Western blot experiments showed that the only available GC tumor cell line, COV434, also expressed erbB receptors. Heregulin (HRG)-beta2, a ligand for erbB3 and erbB4 receptors, stimulated tyrosine phosphorylation of the erbB receptors, which was accompanied by activation of Erk1 and Erk2, two mitogen-activated protein kinases with a functional role in mitogenesis. Importantly, HRG increased cell proliferation in COV434 cells, and treatment with HRG/PE40, a ligand toxin shown previously to be cytotoxic against human breast cancer cells overexpressing erbB receptors, led to a dramatic and irreversible decrease in cell number. These results indicate that erbB receptor signaling pathways may be critical in the control of GC tumor cell proliferation and that HRG/PE40 is a potential therapeutic agent for the treatment of GC tumors.     

The effects of highly selective vagotomy on secretion and emptying of the stomach

The results of a prospective study of 60 patients with nonobstructive duodenal ulcer treated by highly selective vagotomy show that the gastric acid secretion postoperatively is effectively reduced. Judgment of completeness of highly selective vagotomy is only possible by means of an intragastric pH-metry during operation. The Hollander test answers it insufficiently. In a number of patients, highly selective vagotomy caused a fast initial phase of gastric emptying of porradge. The impression is that the contractional activity of the antrum has the same pattern before and after highly selective vagotomy.     

Large-capacity separation of malignant cells and lymphocytes from the Furth mast cell tumor in a reorienting zonal rotor

The Furth murine mastocytoma was adapted to the ascitic form and separated into fractions enriched with respect to lymphocytes and malignant cells by velocity sedimentation in the SZ-14 reorienting zonal rotor or in the isokinetic gradient. Lymphocytes were more highly purified (p less than 0.01) in the isokinetic gradient than in the zonal rotor, i.e., lymphocytes comprised 99.1% of the nucleated cells in the purest fraction from the isokinetic gradient and 80.1% of the nucleated cells in the purest fraction from the zonal rotor. Neoplastic mast cells were similarly purified by the two methods; they comprised 67.7 and 78.5% of the nucleated cells in the purest fractions from the isokinetic gradient and zonal rotor, respectively. Up to 160 million tumor cells can be purified in a single step with the reorienting zonal rotor, whereas 30 to 40 million cells per gradient approach the limit of the isokinetic gradient. After centrifugation in the zonal rotor, recovery was 85.6 +/- 12% (S.D.) of the cells layered over the gradient; and the separated tumor cells retained their ability to form tumors when transplanted into mice. The separation of large numbers of lymphocytes and malignant cells from the same tumor in the SZ-14 rotor should aid in the biochemical and immunological characterization of cancer.     

Comparison between the effects of D-mannoheptulose and its hexaacetate ester upon D-glucose metabolism in rat erythrocytes

At a 2.0 mM concentration, D-mannoheptulose hexaacetate, but not unesterified D-mannoheptulose, inhibited the generation of radioactive acidic metabolites by rat erythrocytes exposed to D-[U-14C]glucose (8.3 mM). It is proposed that D-mannoheptulose hexaacetate represents a valuable tool to interfere with the phosphorylation of D-glucose in cell types otherwise resistant to the heptose.     

塑料性能测试中一些问题的探讨

以熔体流动速率为例，阐述塑料性能测试条件应尽量接近生产和使用奈件。对一些易被曲解和误用的性能进行了讨论。还简要地探讨了CAD和CAE所需的性能数据、性能测试的价格，并对ISO与ASlM测试方法进行了比较。     

Nucleic acid polymerizing enzymes in developing Strongylocentrotus franciscanus embryos

DNA-dependent RNA polymerase, DNA-Dependent DNA polymerase, and terminal riboadenylate transferase (TRT) activities have been measured after DEAE-Sephadex chromatography of whole cell extracts prepared from eggs and staged embryos of the urchin, Stronglyocentrotus franciscanus. Activity of each of these three polymerase classes is present in the egg, and the total activity per embryo is constant throughout embryogenesis to the pluteus stage (approximately 1000 cells). Thus the egg appears to contain sufficient DNA polymerase, RNA polymerase, and TRT TRT for embryogenesis. The increases in the synthesis of DNA, RNA and polyadenylated RNA tracts observed after fertilization must be due to the activation of the preexisting egg enzymes. Separation of the egg into nucleate and anucleate halves demonstrates that the RNA polymerases are not restricted to the egg nucleus. During development, the enzymes become progressively more associated with the cell nucleus. The egg extracts contain low activities (approximately 6% total) of RNA polymerase II as measured by sensitivity to alpha-amanitin. This is confirmed by resolution of the RNA polymerase forms I, II, and III by gradient sievorptive elution on DEAE-Sephadex. Later stage embryos contain more nearly equal activities of RNA polymerase, I, II, and III, although the total RNA polymerase activity per embryo is not changed. Additionally, two chromatographicallly distinct species of RNA polymerase III are detected, one of which is observed only in later stages. Thus interconversion of enzymes via addition of new subunits or coordinate synthesis and loss of enzyme species must occur.     

Microwave leakage during patient treatment

In light of the BRH proposed draft standard for microwave leakage of 10 mW/cm2, microwave leakage measurements were taken under two conditions. The first used a microwave tissue equivalent phantom in which leakage cata was accumulated as a function of net forward power and aperture-to-skin distance (SSD). This is similar to the BRH setup. In the second condition, during actual microwave hyperthermia treatments data was accumulated on several patients at different anatomical sites. The results of these experiments show a marked increase of microwave leakage occurring during patient treatment than that which can be predicted from static phantom results.     

Multiple joint infections with Enterobacter cloacae

An infant with multiple joint infections from Enterobacter cloacae seems not to have been reported previously. The infant survived, incurred a pathologic dislocation of the left hip, but at 18 months of age was well with all other joints functioning normally.