竹叶特种氨基酸的存在及其生物学意义

在竹叶及其提取物中检出了相当含量的一种羟化赖氨酸—δ－ＯＨ－Ｌｙｓ，主要以游离单体和小肽的形式存在。从桂竹和金毛竹叶样分别测得其含量占干叶氨基酸总量的１．３３％和１．４０％，约相当于其中Ｌｙｓ含量的１／４．醇－水提取的过程有富集δ－ＯＨ－Ｌｙｓ的作用，其在提取物中的含量远远高于Ｌｙｓ．这一特殊的非蛋白氨基酸以相当含量存在于竹叶中，可能有着特殊的生物学意义。     

Neck masses due to internal jugular vein phlebectasia: Frequency in Menkes disease and literature review of 85 pediatric subjects

Classic Menkes disease is a rare X‐linked recessive disorder of copper metabolism caused by pathogenic variants in the copper transporter gene, ATP7A. Untreated affected individuals suffer failure to thrive and neurodevelopmental delays that begin at 6–8 weeks of age and progress inexorably to death, often within 3 years. Subcutaneous injections of Copper Histidinate (US Food and Drug Administration IND #34,166, Orphan product designation #12‐3663) are associated with improved survival and neurological outcomes, especially when commenced within a month of birth. We previously identified internal jugular vein phlebectasia (IJP) in four Menkes disease subjects. This feature and other connective tissue abnormalities appear to be consequences of deficient activity of lysyl oxidase, a copper‐dependent enzyme. Here, we report results from a prospective study of IJP based on 178 neck ultrasounds in 66 Menkes subjects obtained between November 2007 and March 2018. Nine patients met the criterion for IJP (one or more cross‐sectional area measurements exceeding 2.2 cm²) and five subjects had clinically apparent neck masses that enlarged over time. Our prospective results suggest that IJP occurs in approximately 14% (9/66) of Menkes disease patients and appears to be clinically benign with no specific medical or surgical actionability. We surveyed the medical literature for prior reports of IJP in pediatric subjects and identified 85 individuals and reviewed the distribution of this abnormality by gender, sidedness, and underlying etiology. Taken together, Menkes disease accounts for 16% (15/94) of all reported IJP individuals. Neck masses from IJP represent underappreciated abnormalities in Menkes disease.     

Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes

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Descending pathways to the spinal cord in the himé salmon (landlocked red salmon, Oncorhynchus nerka)

Distribution and morphology of the cells of origin of the descending spinal pathways and their axonal courses were studied in the himé salmon, using retrograde labelling with cobaltic lysine and horseradish peroxidase (HRP). Following application of the tracers to the cut end of the spinal cord or injection of the tracers at the 10th to 15th spinal segment, neurons mainly labelled via the axons of passage were distributed in the mesencephalon and the rhombencephalon. Mesencephalic cell groups consisted of the nucleus pretectalis, the nucleus fasciculi longitudinalis medialis, and the nucleus ruber. The former two cell groups sent their axons to the fasciculus longitudinalis medialis. The axons of the nucleus ruber formed a separate loose bundle, the "tractus rubrospinalis." The rhombencephalic cell groups consisted of the rhombencephalic reticular formation, the Mauthner cells (one cell for each side), and the octavolateral area. The rhombencephalic reticular formation could be further subdivided into the nucleus reticularis superior, nucleus reticularis medius, and nucleus reticularis inferior. The axons of these cell groups joined the fasciculus longitudinalis medialis and the "tractus bulbospinalis." The Mauthner cell had two main gigantic dendrites, and its giant axons formed a conspicuous fiber of Mauthner throughout the rhombencephalon down to the spinal cord. The octavolateral area could be subdivided into the nucleus vestibularis magnocellularis, nucleus tangentialis, nucleus vestibularis descendens and nucleus intermedius. The axons of the nucleus vestibularis magnocellularis and nucleus intermedius entered the fasciculus longitudinalis medialis and/or the tractus bulbospinalis. Those of the nucleus vestibularis descendens and nucleus tangentialis formed the "tractus vestibulospinalis". The descending spinal pathways of the himé salmon were compared with those of other fishes and other vertebrates. The significance of these descending spinal pathways in the control of locomotion and sexual behavior is also discussed.     

Alterations of Collagen Matrix in Weight-Bearing Bones during Skeletal Unloading

Skeletal unloading induces loss of bone mineral density in weight-bearing bones. The objectives of this study were to characterize the post-translational modifications of collagen of weight-bearing bones subjected to hindlimb unloading for 8 weeks. In unloaded bones, tibiae and femurs, while the overall amino acid composition was essentially identical in the unloaded and control tibiae and femurs, the collagen cross-link profile showed significant differences. Two major reducible cross-links (analyzed as dihydroxylysinonorleucine and hydroxylysinonorleucine) were increased in the unloaded bones. In addition, the ratios of the former to the latter as well as pyridinoline to deoxypyridinoline were significantly decreased in the unloaded bones indicating a difference in the extent of lysine hydroxylation at the cross-linking sites between these two groups. These results indicate that upon skeletal unloading the relative pool of newly synthesized collagen is increased and it is post-translationally altered. The alteration could be associated with impaired osteoblastic differentiation induced by skeletal unloading that results in a mineralization defect.     

Optimal airway antimicrobial therapy for cystic fibrosis: the role of inhaled aztreonam lysine

Importance of the field: Chronic endobronchial infection in cystic fibrosis (CF) leads to progressive lung function loss and respiratory failure. Most adult CF patients are infected with Pseudomonas aeruginosa, an important predictor of mortality. Suppressing chronic P. aeruginosa infection with inhaled antibiotics is standard of care for CF patients.

Areas covered in this review: This review describes the development (2003 – 2010) of aztreonam lysine 75 mg powder and solvent for nebulizer solution (AZLI; Cayston^®), an aerosolized formulation of the monobactam antibiotic aztreonam.

What the reader will gain: AZLI was studied in patients with CF and chronic P. aeruginosa airway infection. In placebo-controlled trials, AZLI improved respiratory symptoms, increased forced expiratory volume in 1 sec (FEV₁), decreased sputum P. aeruginosa density, and was well tolerated. An open-label follow-on trial of nine ‘on/off’ courses showed that AZLI was safe and the effect durable with repeated administration. AZLI was recently approved for use in CF patients in Australia and the USA, and conditionally approved in Canada and the European Union. AZLI is given three times daily for 28 days (2 – 3 min/dose), followed by 28 days off-drug. AZLI is used only with the Altera Nebulizer System?, which provides appropriate particle size and small airway deposition, and has excellent portability.

Take home message: AZLI is a new therapy that is safe and effectively improves respiratory symptoms and FEV₁ in patients with CF.     

Effects of lysine aspirin on lung AQP5 expression and lymphocyte apoptosis in paraquat-poisoned rats

Objective: This study explored the effects of lysine aspirin on lung aquaporin 5 (AQP5) expression and lymphocyte apoptosis in paraquat-poisoned rats. Methods: Thirty healthy male Wales rats were randomly divided into three groups (n?=?10): the control group received 0.9% sodium chloride (0.4?mL, intragastric administration; 0.8?mL, intraperitoneal injection); the paraquat group received 40?mg/kg paraquat (intragastric administration) and 0.9% sodium chloride (intraperitoneal injection); and the paraquat + lysine aspirin group received 40?mg/kg paraquat (intragastric administration) and 20?mg/kg lysine aspirin (intraperitoneal injection). Rats were killed at 24 and 48?h. RT-PCR and immunohistochemical staining were performed in lung tissue to determine the AQP5 mRNA and protein expression. Blood from the arterial vein was used to evaluate lymphocyte apoptosis. Results: The lung tissue of paraquat-treated rats displayed pulmonary hemorrhage, interstitial edema and inflammatory cell infiltration. AQP5 mRNA and protein expression in the paraquat-treated group decreased after 24 and 48?h, whereas the peripheral blood lymphocyte apoptosis ratio significantly increased. In contrast, paraquat + lysine aspirin treatment ameliorated these changes. Conclusion: Paraquat decreases AQP5 expression in rat lungs and increases peripheral blood lymphocyte apoptosis. Lysine aspirin can reduce these alterations.     

Differential inhibitory action of cationic amino acids on protein synthesis in pancreatic rat islets

Summary The effect of cationic amino acids, i.e. L-arginine and L-lysine, on protein synthesis in isolated rat islets of Langerhans has been investigated. Except for prosomatostatin, the formation of islet proteins is strongly depressed by these amino acids. This effect can be demonstrated within a few minutes and is rapidly reversible. For proglucagon, efficient concentrations of arginine are in the range of 1 to 10 mmol/l. The sensitivity of proinsulin formation to arginine is glucose-dependent: at 2.5 mmol/l, inhibitory concentrations of arginine are 10-fold lower than in the case of proglucagon. High glucose (20 mmol/l) almost completely protects proinsulin synthesis from this inhibition. The proteolytic conversion steps in hormonal precursor processing are not influenced by cationic amino acids as studied in intact islets and in a cell-free translational system. It is concluded that arginine and lysine inhibit protein synthesis in islet cells at the translational level. The release of these amino acids by prohormone conversion may exert a feed-back control on proinsulin formation that is modulated by glucose.     

Dicarbonyl Electrophiles Mediate Inflammation-Induced Gastrointestinal Carcinogenesis

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Surface-displayed glyceraldehyde 3-phosphate dehydrogenase and galectin from Dirofilaria immitis enhance the activation of the fibrinolytic system of the host

Cardiopulmonary dirofilariosis is a cosmopolitan disease caused by Dirofilaria immitis, a filaroid parasite whose adult worms live for years in the vascular system of its host. Previous studies have shown that D. immitis can use their excretory/secretory (ES) and surface antigens to enhance fibrinolysis, which could limit the formation of clots in its surrounding environment. Moreover, several isoforms of the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and galectin (GAL) were identified in both antigenic extracts as plasminogen-binding proteins. The aim of this work is to study the interaction of the GAPDH and GAL of D. immitis with the fibrinolytic system of the host. This study includes the cloning, sequencing and expression of the recombinant forms of the GAPDH and GAL of D. immitis (rDiGAPDH and rDiGAL) and the analysis of their capacity as plasminogen-binding proteins. The results indicate that rDiGAPDH and rDiGAL are able to bind plasminogen and stimulate plasmin generation by tissue plasminogen activator (tPA). This interaction needs the involvement of lysine residues, many of which are located externally in both proteins as have been shown by the molecular modeling of their secondary structures. In addition, we show that rDiGAPDH and rDiGAL enhance the expression of the urokinase-type plasminogen activator (uPA) on canine endothelial cells in culture and that both proteins are expressed on the surface of D. immitis in close contact with the blood of the host. These data suggest that D. immitis could use the associated surface GAPDH and GAL as physiological plasminogen receptors to shift the fibrinolytic balance towards the generation of plasmin, which might constitute a survival mechanism to avoid the clot formation in its intravascular habitat.