In vivo release and turnover of secreted platelet antiheparin proteins in rhesus monkey (Macaca mulatta)

Human and rhesus monkey platelets secrete at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4). Neither of these proteins showed species-related antigenic differences. As determined by radioimmunoassay, the levels of PF4 and LA-PF4 antigen per 10(9) monkey platelets amounted to 10.7 and 20.3 microgram, respectively. One milliliter of monkey plasma prepared from blood collected into an anticoagulant composed of EDTA, prostaglandin E1, and theophylline solution contained 22.4 ng LA-PF4 and 8.0 ng PF4. Concentrations of these two platelet-specific proteins in monkeys closely resembled levels found in human platelets and plasma. Infusion of prostacyclin (PGI2) (100 or 300 ng/kg/min) into monkeys for 15 min resulted in a significant decrease of plasma levels of LA-PF4 antigen and of PF4 by 40%--60% (p < 0.0001). This decrease was related to the inhibitory effect of PGI2 on the secretion of platelets stimulated by a catheter or by venipuncture. Longer infusion of PGI2 did not produce further significant change. The supernate obtained after aggregation of human platelets stimulated by thrombin was injected into monkeys receiving PGI2 infusion. The disappearance of LA-PF4 antigen in monkey plasma followed a biphasic exponential curve with half-lives for the fast and slow components of 8.4 and 63 min. PF4 disappeared faster but followed the same pattern (half-lives for the fast and slow component of 2.1 and 70 min). Analysis of the experimental data suggests that the low levels of secreted platelet proteins in monkey plasma are related to their minimal in vivo release and to their rapid clearance.     

Characterization of autoantigenic epitopes on platelet glycoprotein IIb/IIIa using random peptide libraries

Most patients with chronic immune thrombocytopenic purpura (ITP) have autoantibodies directed against the glycoprotein (GP) IIb/IIIa complex. We have used a filamentous phage library that displays random linear hexapeptides to identify peptide sequences recognized by these autoantibodies. Plasma antibody eluates from two patients were used to select for phage displaying autoantibody-reactive peptides. From patient ITP-1 (known to have two distinct autoantibodies), we identified anti-GPIIb/IIIa antibody-specific phage encoding the peptide sequences Arg-Glu-Lys-Ala-Lys-Trp (REKAKW) and Pro-Val-Val-Trp-Lys-Asn (PVVWKN). Patient ITP-2 bound phage encoding the hexapeptide sequence Arg-Glu-Leu-Leu-Lys-Met. Each phage showed saturable dose-dependent binding to immobilized autoantibody, and binding could be blocked with purified GPIIb/IIIa. Patient ITP-1 autoantibody recognition of phage encoding REKAKW could be blocked with a synthetic peptide derived from the GPIIIa cytoplasmic tail; however, the PVVWKN was not. Using sequential overlapping peptides from the GPIIIa cytoplasmic region, an epitope for ITP-1 was localized to the sequence Arg-Ala-Arg-Ala-Lys-Trp (GPIIIa 734-739). Inhibition studies using synthetic peptides showed that phage REKAKW and PVVWKN were recognized by distinct autoantibodies from patient ITP-1. To determine whether individual patients with ITP possessed autoantibodies that recognize similar antigenic determinants on GPIIb/IIIa, the three phage were tested for binding to five other ITP patient autoantibodies. The phage encoding the peptide PVVWKN was found to bind ITP-1 and one other patient autoantibody. This result suggests that ITP patients recognize a limited number of shared epitopes.     

Manuelle Medizin in der begleitenden Behandlung von Kindern mit infantiler Zerebralparese

Manuelle Medizin - Die Bezeichnung „infantile Zerebralparese“ ist ein Oberbegriff, der den Zeitpunkt der Entstehung der Störung (Schwangerschaft bis Ende der Markreifung im...     

Erratum zu: Manuelle Medizin in der begleitenden Behandlung von Kindern mit infantiler Zerebralparese

Manuelle Medizin - Sehr geehrte Leserin, sehr geehrter Leser, leider wurden in der Online-First-Version des Beitrags nicht alle Autoren angezeigt. Bitte beachten Sie die vollständige Nennung...     

儿童癌症幸存者成年后的慢性疾病

由于治疗方法的进步,近80%的儿童和青少年癌症患者能够长期生存。在美国,约有270000例儿童癌症的幸存者,即每640名20至39岁成年人中就有一名幸存者。大量的幸存者有利于儿童癌症治疗后长期健康结果的研究。现在可以明确的是,化疗和放疗所致的儿童各器官系统损害在临床上可能潜伏多年。为了全面了解治疗儿童癌症而继发的健康问题,重要的是衡量三项长期结果:健康状况、死亡率和患病率。这三项中,关于前两项已有相当好的研究报道。在一项对20227例癌症5年生存者的回顾性分析中,Mertens等发现以下原因导致的超额死亡率具有统计学意义:继发癌症(…     

Premature or Just Small? Training Guatemalan Birth Attendants to Weigh and Assess Gestational Age of Newborns: An Analysis of Outcomes

We describe Guatemalan birth attendants’ identification of vulnerable newborns, their evaluation of gestational age and anthropometry, and the validity of the Capurro and New Ballard newborn gestational age assessment methods. We interviewed 49 birth attendants and trained 10 of these women to assess 63 newborns. The Capurro and Ballard methods were correlated (Spearman rho = .75, p < .001) and showed agreement (Bland-Altman plot, difference and bias, ?0.33 ± 1.3 weeks). Prematurity was estimated at 27% (Ballard) and 24% (Capurro); low birth weight (LBW) was 30%. Capurro provided a simplified, equivalent estimate of gestational age compared with New Ballard that could be used by birth attendants.     

Differenzialdiagnostik manualmedizinischer Syndrome der oberen Extremität

Pain in the upper extremities is as frequent as pain in the shoulder-region and these also often occur in combination. Patients are often severely affected. In this article manual medical syndromes are described which partially fit into existing concepts, such as epicondylopathy but also represent independent entities. Typical manual medical findings are presented on the basis of the main symptoms. The differential diagnostic delimitations, particularly of neurological and orthopedic syndromes are outlined in detail. The proposed manual medical osteopathic approach makes differential diagnostic considerations possible beyond compression of peripheral nerves, bone or joint-associated illnesses or circulatory disorders. It offers the possibility of an effective functional treatment planning and in particular cases could possibly replace invasive interventions.     

Repeatability of near visual acuity measurement at high and low contrast

Purpose: The aim of this study was to determine the repeatability of high‐ and low‐contrast visual acuity (VA) measurements at near. Methods: Fifty‐five normal subjects were recruited. Inclusion criteria included visual acuity of at least 0.00 logarithm of minimum angle of resolution (logMAR) on each eye at distance. One eye was selected for this study, either the one with a better acuity or randomly chosen if there was no difference between the two eyes. Near VA was measured in a random order with the PolyU high‐contrast (PolyU‐HC), the PolyU low‐contrast (PolyU‐LC), the Precision high‐contrast (P‐HC) and the Precision low‐contrast (P‐LC) charts at 400 mm. Measurements were repeated after one to two weeks. Repeatability was presented using the 95% limits of agreement between visits. Results: The between‐visit repeatability was ±0.063 logMAR for high‐contrast and ±0.141 for low‐contrast using the PolyU charts. The between‐visit repeatability was ±0.120 logMAR for high‐contrast and ±0.110 for low‐contrast using the Precision charts. Seventeen subjects had high‐contrast VA better than ‐0.10 logMAR using Precision chart, which could not be measured by PolyU chart. The mean difference between high‐ and low‐contrast VA was 0.108 from the Precision charts (median difference of 0.10 or one line). Conclusions: The Precision charts could measure high‐contrast near VA to threshold level. Practitioners should be aware of a VA difference of more than one line in repetitive measurement, at both high and low contrast. A difference in near high‐ and low‐contrast VA of more than one line may warrant further investigation.