Spiroidesin (1), a novel d-amino acid-containing linear lipopeptide, was isolated from waterblooms of the cyanobacterium Anabaena spiroides. The structure was identified by 2D NMR and chemical ...degradation analyses. Spiroidesin inhibited cell growth of the toxic cyanobacterium Microcystis aeruginosa (IC50, 1.6 × 10-6 M).
Quantitative assays to measure the binding of defined synthetic antigenic peptides and purified MHC class I molecules are described for several common human HLA-A alleles (A1, A2.1, A3, A11 and A24). ...Under appropriate conditions, the binding of radiolabeled peptides to purified MHC class I molecules is very effective, highly specific, and appears to be dependent on the specific sequence motif of the peptide as defined by critical anchor residue positions. Establishment and optimization of the assay reveals that a relatively high fraction of the MHC class I molecules isolated from EBV transformed B cell line sources is capable of binding exogenously added peptide. Scatchard analysis for all alleles yields 5-10% occupancy values. There is a stringent peptide size requirement that is reflected by the direct influence of peptide length on the binding affinity. The peptide-MHC class I interactions demonstrate remarkable similarity to peptide-MHC class II interactions, both in overall affinity and kinetic behavior. The immunological relevance of the peptide-MHC class I binding assay is also demonstrated by measuring the affinity of a panel of previously described HLA restricted peptides for their HLA restriction element. In 91% (10/11) of the cases, the peptides bound with affinities of 50 nM or less, and in the remaining 9% (1/11) of the cases, in the 50 to 500 nM range. Thus, these data provide the first quantitative estimate of what level of HLA-A binding affinity is associated with a diverse panel of immunodominant CTL epitopes in man.
Obstructive sleep apnea subjects the failing heart to adverse hemodynamic and adrenergic loads and may thereby contribute to the progression of heart failure. We hypothesized that treatment of ...obstructive sleep apnea by continuous positive airway pressure in patients with heart failure would improve left ventricular systolic function.
Twenty-four patients with a depressed left ventricular ejection fraction (45 percent or less) and obstructive sleep apnea who were receiving optimal medical treatment for heart failure underwent polysomnography. On the following morning, their blood pressure and heart rate were measured by digital photoplethysmography, and left ventricular dimensions and left ventricular ejection fraction were assessed by echocardiography. The subjects were then randomly assigned to receive medical therapy either alone (12 patients) or with the addition of continuous positive airway pressure (12 patients) for one month. The assessment protocol was then repeated.
In the control group of patients who received only medical therapy, there were no significant changes in the severity of obstructive sleep apnea, daytime blood pressure, heart rate, left ventricular end-systolic dimension, or left ventricular ejection fraction during the study. In contrast, continuous positive airway pressure markedly reduced obstructive sleep apnea, reduced the daytime systolic blood pressure from a mean (+/-SE) of 126+/-6 mm Hg to 116+/-5 mm Hg (P=0.02), reduced the heart rate from 68+/-3 to 64+/-3 beats per minute (P=0.007), reduced the left ventricular end-systolic dimension from 54.5+/-1.8 to 51.7+/-1.2 mm (P=0.009), and improved the left ventricular ejection fraction from 25.0+/-2.8 to 33.8+/-2.4 percent (P<0.001).
In medically treated patients with heart failure, treatment of coexisting obstructive sleep apnea by continuous positive airway pressure reduces systolic blood pressure and improves left ventricular systolic function. Obstructive sleep apnea may thus have an adverse effect in heart failure that can be addressed by targeted therapy.
Crotamine is a cationic peptide (4.9 kDa, pI 9.5) of South American rattlesnake,
Crotalus durissus terrificus' venom. Its presence varies according to the subspecies or the geographical locality of a ...given species. At the genomic level, we observed the presence of 1.8 kb gene,
Crt-p1, in crotamine-positive specimens and its absence in crotamine-negative ones. In this work, we described a crotamine-related 2.5 kb gene, crotasin (
Cts-p2), isolated from crotamine-negative specimens. Reverse transcription coupled to polymerase chain reaction indicates that
Cts-p2 is abundantly expressed in several snake tissues, but scarcely expressed in the venom gland. The genome of crotamine-positive specimen contains both
Crt-p1 and
Cts-p2 genes. The present data suggest that both crotamine and crotasin have evolved by duplication of a common ancestor gene, and the conservation of their three disulfide bonds indicates that they might adopt the same fold as β-defensin. The physiological function of the crotasin is not yet known.
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