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81.
Expression of the gastrin-releasing peptide gene in human small cell lung cancer. Evidence for alternative processing resulting in three distinct mRNAs 总被引:11,自引:0,他引:11
82.
Three patients with elevated blood lactate values are described. The first, despite moderate hyperlactatemia of 5.3 mEq./1. and severe acidosis with an arterial blood pH of 6.98, had no “excess lactate”. In a second patient, moderate acidosis with a pH of 7.27 and blood lactate of 7.5 mEq./1., of which 33% was excess lactate, was found to be secondary to tissue hypoxia on an ischemic basis and preceded the onset of clinical shock by four hours. A third patient, diabetic and under treatment with phenformin hydrochloride, presented with many features suggestive of pulmonary embolism, including marked pulmonary hypertension. A diagnosis of idiopathic lactic acidosis was established when the arterial blood pH was found to be 6.77 and a blood lactate value of 14.2 mEq./1., 60% as excess lactate, was discovered in the absence of a demonstrable cause of tissue hypoxia. Exploration of the pulmonary vascular bed showed no sign of mechanical blockage. The diagnostic, therapeutic and prognostic value of measuring blood lactic acid, and of quantitating the proportion circulating as “excess lactate”, is emphasized. 相似文献
83.
Bombinin-like peptides with antimicrobial activity from skin secretions of the Asian toad, Bombina orientalis. 总被引:5,自引:0,他引:5
B W Gibson D Z Tang R Mandrell M Kelly E R Spindel 《The Journal of biological chemistry》1991,266(34):23103-23111
The structures and hemolytic and bactericidal activities of three bombinin-like peptides, or BLP-1-3, from the skin of Bombina orientalis are described. The peptides were isolated from the skin of B. orientalis and sequenced by tandem mass spectrometry and are amphipathic, cationic peptides of 25-27 amino acids in length. The sequence of the most abundant member (BLP-1) is: Gly-Ile-Gly-Ala-Ser-Ile-Leu-Ser-Ala-Gly-Lys-Ser-Ala-Leu-Lys-Gly-Leu- Ala-Lys-Gly-Leu-Ala-Glu-His-Phe-Ala-Asn-NH2. All three peptides were found to share considerable, but not complete, homology with bombinin, an antimicrobial, hemolytic peptide first isolated by Michl and Csordas (Csordas, A., and Michl, A. (1970) Monatsh. Chem. 101, 182-189) from the skin of Bombina variegata. The BLPs have been assayed for antibiotic and hemolytic activity and found to be more potent than magainin 2 (a related antimicrobial peptide from Xenopus laevis) in their ability to kill bacteria. However, no significant hemolytic activity was found for these peptides which suggests a selectivity for prokaryotic over eukaryotic membranes. The molecular basis for antibacterial activity is presumed to be due to their predicted amphipathic alpha-helical structures which is supported by circular dichroism measurements that found significant helical content (63-69% alpha-helix) in 40% trifluoroethanol. Last, a cDNA library was constructed from the skin of B. orientalis and screened with an oligonucleotide probe complementary to the COOH terminus of BLP-1. Several clones were isolated and sequenced that encode BLP-1 and BLP-3, as well as an additional peptide (BLP-4) that differs by two amino acid substitutions from BLP-3. 相似文献
84.
In vitro mutagenesis was used to supplement the sulfur amino acid codon content of a gene encoding -phaseolin, a Phaseolus vulgaris storage protein. The number of methionine codons in the phaseolin gene was increased from three to nine by insertion of a 45 base pair (bp) synthetic duplex. Either modified or normal phaseolin genes were integrated into the genome of tobacco plants through Agrobacterium tumefaciens-mediated transformation. Although similar levels of phaseolin RNA are detected in seeds of plants transformed with either the normal or modified (himet) gene, the quantity of himet protein is consistently much lower than normal -phaseolin. Himet phaseolin is expressed in a temporal- and organ-specific fashion, and is N-glycosylated and assembled into trimers in the manner of normal phaseolin. After germination, both types of phaseolin are hydrolyzed, but the himet protein is more quickly degraded. Electron microscopic immunocytochemical observations of developing seeds indicate that the himet protein is primarily localized in the endoplasmic reticulum (ER) and in Golgi apparatus secretion vesicles. Himet phaseolin is absent from protein storage vacuoles, termed protein bodies, where normal phaseolin is deposited in transgenic tobacco. We interpret the immunocytochemical data to indicate that himet phasolin is transported through the ER and Golgi apparatus and is then degraded in Golgi secretion vesicles or the protein bodies.Mention of trademark, proprietary product, or vendor does not constitute a guarantee of warranty of the product by the United States Department of Agriculture and does not imply its approval to the exclusion of other products or vendors that may also be suitable. Publication No. 70 from Agrigenetics Advanced Science Company. 相似文献
85.
Galen M. Pieper Wallace J. Murray J.M. Salhany Shao T. Wu Robert S. Eliot 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1984,803(4):241-249
The beneficial effects of l-carnitine perfusion on energy metabolism and coenzyme A acylation were studied in isolated hearts from control and diabetic rats. All hearts were perfused at a constant flow rate with a glucose/albumin buffer which contained 2.0 mM palmitate. 31P-NMR was utilized to assess sequential phosphocreatine and ATP metabolism during 1 h of recirculation perfusion. l-Carnitine (5.0 mM final concentration) was added after 12 min of baseline recirculation perfusion. Frozen samples were taken after 1 h of recirculation perfusion for spectrophotometric analysis of high-energy phosphates and the free and acylated fractions of coenzyme A. l-Carnitine perfusion of diabetic hearts attenuated or prevented the reduction of ATP observed in untreated diabetic hearts. It also attenuated the accumulation of long-chain fatty-acyl coenzyme A. Although l-carnitine improved myocardial function in diabetic hearts, this was independent of any direct effect on physiological indices. Thus, the salutory effect of acute perfusion with l-carnitine on energy metabolism in the isolated perfused diabetic rat heart appears to be a direct effect on lipid metabolism. 相似文献
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Hela Azaiez Amanda R. Decker Kevin T. Booth Allen C. Simpson A. Eliot Shearer Patrick L. M. Huygen Fengxiao Bu Michael S. Hildebrand Paul T. Ranum Seiji B. Shibata Ann Turner Yuzhou Zhang William J. Kimberling Robert A. Cornell Richard J. H. Smith 《PLoS genetics》2015,11(3)
Hereditary hearing loss is a clinically and genetically heterogeneous disorder. More than 80 genes have been implicated to date, and with the advent of targeted genomic enrichment and massively parallel sequencing (TGE+MPS) the rate of novel deafness-gene identification has accelerated. Here we report a family segregating post-lingual progressive autosomal dominant non-syndromic hearing loss (ADNSHL). After first excluding plausible variants in known deafness-causing genes using TGE+MPS, we completed whole exome sequencing in three hearing-impaired family members. Only a single variant, p.Arg185Pro in HOMER2, segregated with the hearing-loss phenotype in the extended family. This amino acid change alters a highly conserved residue in the coiled-coil domain of HOMER2 that is essential for protein multimerization and the HOMER2-CDC42 interaction. As a scaffolding protein, HOMER2 is involved in intracellular calcium homeostasis and cytoskeletal organization. Consistent with this function, we found robust expression in stereocilia of hair cells in the murine inner ear and observed that over-expression of mutant p.Pro185 HOMER2 mRNA causes anatomical changes of the inner ear and neuromasts in zebrafish embryos. Furthermore, mouse mutants homozygous for the targeted deletion of Homer2 present with early-onset rapidly progressive hearing loss. These data provide compelling evidence that HOMER2 is required for normal hearing and that its sequence alteration in humans leads to ADNSHL through a dominant-negative mode of action. 相似文献