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ATP-independent molecular chaperones are important for maintaining cellular fitness but the molecular determinants for preventing aggregation of partly unfolded protein substrates remain unclear, particularly regarding assembly state and basis for substrate recognition. The BRICHOS domain can perform small heat shock (sHSP)-like chaperone functions to widely different degrees depending on its assembly state and sequence. Here, we observed three hydrophobic sequence motifs in chaperone-active domains, and found that they get surface-exposed when the BRICHOS domain assembles into larger oligomers. Studies of loop-swap variants and site-specific mutants further revealed that the biological hydrophobicities of the three short motifs linearly correlate with the efficiency to prevent amorphous protein aggregation. At the same time, they do not at all correlate with the ability to prevent ordered amyloid fibril formation. The linear correlations also accurately predict activities of chimeras containing short hydrophobic sequence motifs from a sHSP that is unrelated to BRICHOS. Our data indicate that short, exposed hydrophobic motifs brought together by oligomerisation are sufficient and necessary for efficient chaperone activity against amorphous protein aggregation.

Recombinant spider silks are of interest but the multimodal and aggregation-prone nature of them is a limitation. Here, the authors report on a miniature spidroin based on the N-terminal domain which forms a hydrogel at 37 degrees C which allows for ease of production and fusion protein modification to generate functional biomaterials.Recombinant spider silk proteins (spidroins) have multiple potential applications in development of novel biomaterials, but their multimodal and aggregation-prone nature have complicated production and straightforward applications. Here, we report that recombinant miniature spidroins, and importantly also the N-terminal domain (NT) on its own, rapidly form self-supporting and transparent hydrogels at 37 degrees C. The gelation is caused by NT alpha-helix to beta-sheet conversion and formation of amyloid-like fibrils, and fusion proteins composed of NT and green fluorescent protein or purine nucleoside phosphorylase form hydrogels with intact functions of the fusion moieties. Our findings demonstrate that recombinant NT and fusion proteins give high expression yields and bestow attractive properties to hydrogels, e.g., transparency, cross-linker free gelation and straightforward immobilization of active proteins at high density.

Unternehmen auf der ganzen Welt stehen vor steigenden Herausforderungen bei der Rekrutierung von qualifizierten Arbeitskraften. Obwohl die verstarkten Sicherheitsbemuhungen in der Rohstoffindustrie in den letzten Jahrzehnten erfolgreich waren, bleibt das Arbeitsumfeld durch seine spezifischen Anforderungen anspruchsvoll und einzigartig. Die Arbeit in der Rohstoffindustrie ist nach wie vor mit dem Vorurteil belastet, dunkel, staubig und gefahrlich zu sein. Daher soll die Schaffung attraktiver und noch sichererer Arbeitsplatze dazu beitragen, die Lucken einer alternden Belegschaft zu schliesen. Das vom EIT Raw Materials geforderte SafeMine-Projekt zielt darauf ab, ein ganzheitliches und belastbares Graduiertenprogramm fur Arbeitssicherheit und Gesundheitsschutz in der Rohstoffindustrie zeitnah zu entwickeln. Die besonderen Ziele des SafeMine-Projekts sind die Ausbildung einer neuen Generation von qualifizierten Fachkraften und die Generierung fortschrittlicher wissenschaftlicher Erkenntnisse. Auf Grundlage einer Gap-Analyse, welche aktuelle Ausbildungsangebote zu Arbeitssicherheit und Gesundheitsschutz in der Rohstoffindustrie (MHS – Mine, Health and Safety) thematisierte, wurden die Bedurfnisse der Industrie identifiziert. Bei dieser Suche wurde kein spezifisches postgraduales Ausbildungsprogramm gefunden, welches sich umfassend und detailliert mit MHS-Themen befasst. Um die Ergebnisse zu erganzen, wurde eine Branchenumfrage durchgefuhrt. Insgesamt reichten 43 Teilnehmer rund 1250 Antworten ein. Die Teilnehmenden kamen uberwiegend aus Europa (76 %) mit einem beruflichen Hintergrund aus der Bergbauindustrie (47 %). Die Ergebnisse zeigen eine deutliche Lucke zwischen den aktuellen Bildungsaktivitaten im MHS-Sektor und den Erwartungen der Industrie. Auf der Grundlage der Ergebnisse wird ein angepasstes Graduiertenprogramm entwickelt. Die verbesserte Ausbildung von Fuhrungskraften in der Rohstoffindustrie ist die Grundlage fur fundierte strategische Entscheidungen in technischen und personellen Fragen und starkt die Wettbewerbsfahigkeit der Unternehmen – so wie es auch von der Europaischen Union unterstutzt und gefordert wird.

Psychosocial factors influence the risk of developing hypertension. Personality traits have a modulating effect against the harmful influences of psychosocial factors. Through a longitudinal clinical study consisting of men and women aged 35 and 55 at the baseline in Estonia and Sweden, to assess the influence of psychosocial factors and personality traits resulting in arterial hypertension. Data analysis based on the cross-sectional study with 2 assessments over 13 years of a sample comprising 158 individuals from Estonia and 213 individuals from Sweden. The Pearlin Mastery Scale, Rosenberg Self-esteem Scale, Depression Model and Gothenburg Quality of Life Instrument were used. Throughout the follow-up period, a higher depressive mood and lower self-assessed quality of life score prevailed among the 35-year-old and 55-year-old Estonians compared with the Swedish study participants (p

Background Effort rupture of the esophagus or Boerhaave’s syndrome is a rare entity, and prognosis is largely dependent on early diagnosis and treatment. Recurrent effort ruptures are very rare, only reported in a few case reports in English literature. We present a case with a third time effort rupture, and to the best of our knowledge there are no such previous publications. Furthermore, the presented case is also distinct because each episode was treated by different methods, reflecting the pathophysiology of recurrent disease as well as the last decade’s advancements in the management of esophageal perforations in our clinic and globally. Case presentation The patient is a 60-year-old White male, suffering from alcohol abuse, mild reflux esophagitis, and a history of effort esophageal ruptures on two previous occasions. He was now admitted to our ward once again because of a third bout of Boerhaave’s syndrome. The first time, 10 years ago, he was managed by thoracotomy and laparotomy with primary repair, and the second time, 5 years ago, by transhiatal mediastinal drainage through a laparotomy and endoscopic stent placement. Now he was successfully managed by endovascular vacuum-assisted closure therapy alone. Conclusions Recurrent cases of Boerhaave’s syndrome are very rare, and treatment must be tailored individually. The basic rationale is, however, no different from primary disease: (1) early diagnosis, (2) adequate drainage of extraesophageal contamination, and (3) restoration of esophageal integrity. Recurrent disease is usually contained and exceptionally suitable for primary endoscopic treatment. To cover the full panorama and difficult nature of complex esophageal disease, endoscopic modalities such as stent placement and endovascular vacuum-assisted closure, as well as the capacity for prompt extensive surgical interventions such as esophagectomy, should be readily accessible within every modern esophageal center.

Water and humidity severely affect the material properties of spider major ampullate silk, causing the fiber to become plasticized, contract, swell and undergo torsion. Several amino acid residue types have been proposed to be involved in this process, but the complex composition of the native fiber complicates detailed investigations. Here, we observe supercontraction in biomimetically produced artificial spider silk fibers composed of defined proteins. We found experimental evidence that proline is not the sole residue responsible for supercontraction and that tyrosine residues in the amorphous regions of the silk fiber play an important role. Furthermore, we show that the response of artificial silk fibers to humidity can be tuned, which is important for the development of materials for applications in wet environments, eg producing water resistant fibers with maximal strain at break and toughness modulus. Exposing spider silk to wet conditions can cause supercontraction. Here, tyrosine amino acid residues within the amorphous regions are found to contribute to supercontraction, which can be controlled by protein engineering.

For a modern mining company with attractive and safe workplaces a new type of leader for tomorrow’s Health and Safety at work is needed. This was the reason for four leading European mining universities to working closely together with industrial partners in order to develop a PhD-Programme with a focus on increasing mine safety, using the most up to date research data and basing their studies on industry-driven, real scenarios and projects. This programme, SafeMine, aims to develop a holistic, timely and resilient PhD-Programme in Health and Safety in mining and to train a cadre of qualified professionals who can lead the future of health and safety work in the European mining industry based on a modern view of how an attractive and safe mine should be designed and organized.

Moderne Bergbauunternehmen, welche attraktive und sichere Arbeitsbedingungen bieten mochten, brauchen zukunftig entsprechend ausgebildetes Fuhrungspersonal. Aus diesem Grund arbeiten vier der fuhrenden europaischen Bergbauuniversitaten mit Industriepartnern zusammen, um ein gemeinsames, koordiniertes Programm zur Doktorandenausbildung mit Fokus auf Arbeitssicherheit und Gesundheitsschutz im Bergbau ins Leben zu rufen. Die Forschungsthemen basieren dabei auf aktuellen, industrierelevanten Forschungsfragen und Herausforderungen. Dieses Programm, SafeMine, bietet einen ganzheitlichen und strukturierten Ansatz, um den zukunftigen Bedarf an hochqualifiziertem Fuhrungspersonal fur den europaischen Bergbausektor im Bereich Arbeitssicherheit und Gesundheitsschutz auszubilden.

Apabetalone is a selective bromodomain and extra-terminal (BET) inhibitor which modulates lipid and inflammatory pathways implicated in atherosclerosis. The impact of apabetalone on attenuated coronary atherosclerotic plaque (AP), a measure of vulnerability, is unknown. The ApoA-1 Synthesis Stimulation and intravascular Ultrasound for coronary atheroma Regression Evaluation (ASSURE; NCT01067820) study employed serial intravascular ultrasound (IVUS) measures of coronary atheroma in 281 patients treated with apabetalone or placebo for 26 weeks. AP was measured at baseline and follow-up. Factors associated with changes in AP were investigated. AP was observed in 31 patients (11%) [27 (13.0%) in the apabetalone group and four (5.5%) in the placebo group]. The apabetalone group demonstrated reductions in AP length by − 1 mm [interquartile range (IQR) − 4, 1] (p = 0.03), AP arc by − 37.0° (IQR − 59.2, 8.2) (p = 0.003) and the AP index by − 34.6 mm° (IQR − 52.6, 10.1) (p = 0.003) from baseline. The change in AP index correlated with on-treatment concentration of high-density lipoprotein (HDL) particles (r = − 0.52, p = 0.006), but not HDL cholesterol (r = − 0.11, p = 0.60) or apolipoprotein A-1 (r = − 0.16, p = 0.43). Multivariable analysis revealed that on-treatment concentrations of HDL particles (p = 0.03) and very low-density lipoprotein particles (p = 0.01) were independently associated with changes in AP index. Apabetalone favorably modulated ultrasonic measures of plaque vulnerability in the population studied, which may relate to an increase in HDL particle concentrations. The clinical implications are currently being investigated in the phase 3 major adverse cardiac event outcomes trial BETonMACE.

The aim of this study was to investigate how patients perceive information and their health-related quality of life 1 month after discharge for colorectal cancer surgery. The aim was also to compare these results with the first 2 weeks at home and to identify factors related to the perception of information. One hundred patients from three surgical clinics in the south of Sweden were included in this study. Perception of information was assessed with EORTC QLQ-INFO25, health-related quality of life with QLQ-C30 and QLQ-CR38, classification of physical status with American Society of Anaesthesiologists (ASA) and sense of coherence with SOC-13. Patients in this study did not receive enough information, and this had not changed significantly since the first 2 weeks at home. Only one subscale about disease information (p = 0.01) had improved since the first 2 weeks at home, while health-related quality of life had improved significantly during the same period. Poorer physical status and living alone were related to a perception of having received less information after discharge. Patients did not receive sufficient information to prepare them for the period at home after discharge, and their perception of information remained during the first month at home. Patients with a poorer preoperative physical status and who live alone constitute a vulnerable group in need of more information at discharge. This enhances the need to individualize the information and to offer multiple ways of accessing information after discharge.

Spider dragline silk is an outstanding material made up of unique proteins-spidroins. Analysis of the amino acid sequences of full-length spidroins reveals a tripartite composition: an N-terminal non-repetitive domain, a highly repetitive central part composed of approximately 100 polyalanine/glycine rich co-segments and a C-terminal non-repetitive domain. Recent molecular data on the terminal domains suggest that these have different functions. The composite nature of spidroins allows for recombinant production of individual and combined regions. Miniaturized spidroins designed by linking the terminal domains with a limited number of repetitive segments recapitulate the properties of native spidroins to a surprisingly large extent, provided that they are produced and isolated in a manner that retains water solubility until fibre formation is triggered. Biocompatibility studies in cell culture or in vivo of native and recombinant spider silk indicate that they are surprisingly well tolerated, suggesting that recombinant spider silk has potential for biomedical applications.

Measurement uncertainty is an important part of a measurement result that still often is neglected. A complete combined uncertainty budget can be calculated for non-routine measurements. However, for routine measurements, this work becomes time-consuming since every measurement result requires an uncertainty analysis. By analysing the uncertainty on a measurement system level in e.g. high resolution gamma spectrometry, the uncertainty analysis will be universal for a particular measurement geometry. The problem is then reduced to implementing the combined uncertainty into measurement software. This work shows how this analysis can be done and implemented into a commercial software for gamma spectrometric measurements.

Background Oesophagectomy is a major procedure with known side effects and reduced postoperative quality of life (QOL). It has been shown that support of patients in their new life situation is often lacking. Knowledge about how QOL changes over time is fundamental for addressing patient needs and for determining the optimal timing of supportive care. The aim of this study was to identify QOL changes over time as well as factors that may impact patient QOL during the first year after oesophagectomy for cancer. Methods Patients operated on for adenocarcinoma or squamous cell cancer of the oesophagus were included in this study. Seventy-nine patients completed the European Organisation for Research and Treatment of Cancer QOL questionnaires (QLQ-C30 and QLQ-OES18) before and 2, 4, 6, 9, and 12 months after surgery. A general linear model with repeated measurement analysis of variance was used for statistical testing. Results There was a significant QOL nadir at 2 months compared to 12 months after surgery (QLQ-C30 function scales p < 0.001, symptom scales p < 0.001, QLQ-OES18 scales p < 0.001). Treatment with proton-pump inhibitors was associated with enhanced QOL according to QLQ-C30 symptom scales (p = 0.003) and OES-18 scales (p = 0.015), but age, gender and American Society of Anaesthesiologists classification did not significantly impact QOL. Conclusions Patient QOL is severely hampered the first year after oesophagectomy for cancer, with a nadir at 2 months after surgery. Treatment with proton-pump inhibitors improved patient responses to symptom scales. Evidence of severely affected QOL after surgery indicates that these patients need support at an early stage after surgery. These results can be used by healthcare professionals to develop a postoperative supportive-care programme that is timed and better optimised to meet patient needs. Trial registration: EudraCT database 2009-009997-28.

The recently reported influence of proinsulin C-peptide on insulin prompted us to examine structural features of the C-peptide. Four sets of limited pattern similarities towards inter-chain end regions of insulin were noticed, involving secondary structure elements, binding residues and intra- as well as inter-peptide residue similarities. Using surface plasmon resonance, we examined insulin binding to truncated, soluble insulin receptor A and IGF-1 receptor, but C-peptide effects on these bindings were not detectable. Two forms of the insulin receptor, differing in activation of gene transcription with regards to (pre)proinsulin and glucokinase, respectively, were also uninfluenced by C-peptide. We conclude that the pattern similarities, if functional, reflect C-peptide interactions with molecules other than both insulin A and B receptors and IGF-1 receptors. Any such effects are of interest in relation to reported binding interactions between insulin and C-peptide.

This article reports on a qualitative study of adolescents living in residential care in Sweden. Six adolescents, three girls and three boys, who were the first to live in a newly opened treatment home, were interviewed about their experiences 2–3 years after they had left the home. Their experiences were in retrospect very different from each other. The results are discussed from the perspectives of individual differences, the special situation in an institution, relationships and gender. It is concluded that in spite of the fact that youth who live in a residential care institution live in the same environment, the individuals perceive it in their own unique ways.

The purpose of this study was to use images from a microwave sensor on a pixel level for simultaneous prediction of moisture content and density of wood. The microwave sensor functions as a line-scan camera with a pixel size of 8mm. Boards of Scots pine (Pinus sylvestris), 25 and 50mm thick, were scanned at three different moisture contents. Dry density and moisture content for each pixel were calculated from measurements with a computed tomography scanner. It was possible to create models for prediction of density on a pixel level. Models for prediction of moisture content had to be based on average values over homogeneous regions. Accuracy will be improved if it is possible to make a classification of knots, heartwood, sapwood, etc., and calibrate different models for different types of wood. The limitations of the sensor used are high noise in amplitude measurements and the restriction to one period for phase measurements.

Proinsulin C-peptide influences a number of physiological parameters in addition to its well-established role in the parent proinsulin molecule. It is of interest as a candidate for future co-replacement therapy with insulin for patients with diabetes mellitus type 1, but specific receptors have not been identified and additional correlation with functional effects is desirable. Based on comparisons of 22 mammalian proinsulin variants, we have constructed analogues for activity studies, choosing phosphorylation of mitogen-activated protein kinases (MAPKs) in Swiss 3T3 fibroblasts for functional measurements. In this manner, we find that effective phosphorylation of MAPKs is promoted by the presence of conserved glutamic acid residues at positions 3, 11 and 27 of C-peptide and by the presence of helix-promoting residues in the N-terminal segment. Previous findings have ascribed functional roles to the C-terminal pentapeptide segment, and all results combined therefore now show the importance of different segments, suggesting that C-peptide interactions are complex or multiple.

The formation of amyloid fibrils is associated with several devastating diseases in humans and animals, including e.g. Alzheimer's disease (AD) and the spongiform encephalopathies. Here, we review and discuss the current knowledge on two amyloid peptides: lung surfactant protein C (SP-C) and the amyloid beta-peptide (Abeta), implicated in human lung disease and in AD, respectively. Both these hydrophobic peptides are derived from the transmembrane region of their precursor protein, and can transit from a monomeric alpha-helical state to a beta-sheet fibril. The alpha helices of SP-C and Abeta are composed of amino acid residues with inherently higher propensities for beta strand than helix conformation. Their helical states are stabilized by a membrane environment, and loss of membrane association thus promotes structural conversion and fibril formation. We speculate that the loss of structural context for sequences with a high propensity for formation of beta sheets may be a common feature of amyloid formation in general.

This study was carried out to investigate the possibility of calibrating a prediction model for the moisture content and density distribution of Scots pine (Pinus sylvestris) using microwave sensors. The material was initially of green moisture content and was thereafter dried in several steps to zero moisture content. At each step, all the pieces were weighed, scanned with a microwave sensor (Satimo 9,4 GHz), and computed tomography (CT)-scanned with a medical CT scanner (Siemens Somatom AR.T.). The output variables from the microwave sensor were used as predictors, and CT images that correlated with known moisture content were used as response variables. Multivariate models to predict average moisture content and density were calibrated using the partial least squares (PLS) regression. The models for average moisture content and density were applied at the pixel level, and the distribution was visualized. The results show that it is possible to predict both moisture content distribution and density distribution with high accuracy using microwave sensors.

Based on the findings that proinsulin C-peptide binds specifically to cell membranes, we investigated the effects of C-peptide and related molecules on the intracellular Ca2+ concentration ([Ca2+]i) in human renal tubular cells using the indicator fura-2/AM. The results show that human C-peptide and its C-terminal pentapeptide (positions 27-31, EGSLQ), but not the des (27-31) C-peptide or randomly scrambled C-peptide, elicit a transient increase in [Ca2+]i. Rat C-peptide and rat C-terminal pentapeptide also induce a [Ca2+]i response in human tubular cells, while a human pentapeptide analogue with Ala at position 1 gives no [Ca2+]i response, and those with Ala at positions 2-5 induce responses with different amplitudes. These results define a species cross-reactivity for C-peptide and demonstrate the importance of Glu at position 1 of the pentapeptide. Preincubation of cells with pertussis toxin abolishes the effect on [Ca2+]i by both C-peptide and the pentapeptide. These results are compatible with previous data on C-peptide binding to cells and activation of Na-,K+ATPase. Combined, all data show that C-peptide is a bioactive peptide and suggest that it elicits changes in [Ca2+]i via G-protein-coupled pathways, giving downstream enzyme effects.

The progress of the joint Pilot Project for time transfer, formed by the International GPS Service (IGS) and the Bureal International des Poids et Mesures (BIPM), was recently reviewed. Three notable milestones were set. (1) The IGS will implement, at least in a test mode, an internally realized time scale based on an integration of combined frequency standards within the IGS network. This will eventually become the reference time scale for all IGS clock products (instead of the current GPS broadcast time). (2) A new procedure for combined receiver and satellite clock products will be implemented officially in November 2000. Receiver clocks are an entirely new product of the IGS. (3) The BIPM will coordinate an effort to calibrate all Ashtech Z12-T (and possibly other) receivers suitable for time transfer applications, either differentially or absolutely. Progress reports will be presented publicly in the spring 2001. © 2001 John Wiley & Sons, Inc.

Nature's high-performance polymer, spider silk, consists of specific proteins, spidroins, with repetitive segments flanked by conserved non-repetitive domains. Spidroins are stored as a highly concentrated fluid dope. On silk formation, intermolecular interactions between repeat regions are established that provide strength and elasticity. How spiders manage to avoid premature spidroin aggregation before self-assembly is not yet established. A pH drop to 6.3 along the spider's spinning apparatus, altered salt composition and shear forces are believed to trigger the conversion to solid silk, but no molecular details are known. Miniature spidroins consisting of a few repetitive spidroin segments capped by the carboxy-terminal domain form metre-long silk-like fibres irrespective of pH. We discovered that incorporation of the amino-terminal domain of major ampullate spidroin 1 from the dragline of the nursery web spider Euprosthenops australis (NT) into mini-spidroins enables immediate, charge-dependent self-assembly at pH values around 6.3, but delays aggregation above pH 7. The X-ray structure of NT, determined to 1.7 A resolution, shows a homodimer of dipolar, antiparallel five-helix bundle subunits that lack homologues. The overall dimeric structure and observed charge distribution of NT is expected to be conserved through spider evolution and in all types of spidroins. Our results indicate a relay-like mechanism through which the N-terminal domain regulates spidroin assembly by inhibiting precocious aggregation during storage, and accelerating and directing self-assembly as the pH is lowered along the spider's silk extrusion duct.

The prevalence of anastomotic strictures in esophageal anastomoses provides us with limited information about the anastomotic healing process. This prospective study evaluates the exact esophageal anastomotic diameters in 256 patients who underwent esophagectomy and esophagogastrostomy without pyloroplasty (n = 107) or total gastrectomy and Roux reconstruction (n = 149). No perioperative chemoradiotherapy was given. Anastomotic strictures and diameters were assessed during endoscopy by a separately inserted (inflated to the anastomotic width) balloon catheter. The anastomotic diameters increased significantly during the first postoperative year in the esophagectomy (p = 0.001) and gastrectomy (p < 0.001) groups. The anastomoses in the gastrectomy group were significantly wider than those in the esophagectomy group 3 (25.7 versus 19.9 mm), 6 (28.5 versus 22.0 mm), and 12 (30.5 versus 23.3 mm) months after surgery (p < 0.001). Neither the anastomotic site (neck or chest) in the esophagectomy group (p = 0.176) nor that in the gastrectomy group (abdomen or chest) (p = 0.577) influenced the anastomotic diameter. Benign anastomotic strictures were most frequently found after 3 months and after esophagectomy. Esophagojejunostomies performed with 2 linear stapling devices or cartridge size 28 mm showed the widest anastomoses with only 1 stricture. Esophagogastric anastomoses following esophagectomy are narrower and develop more strictures than esophagojejunal anastomoses after total gastrectomy, but both dilate during the first year.

The innervation of the knee joint synovial membrane of the guinea pig, i.e., the synoviocyte layer, the subjacent connective tissue and the connective tissue region beneath, was analyzed with immunohistofluorescence and electron microscopy. A screening of the innervation with antibodies against the general axon marker -- protein gene product (PGP) 9,5 -- revealed the presence of nerve fibers distributed in various regions of the knee joint synovial membrane. Confirming previous studies, some of these nerve fibers stained with antibodies to tyrosine hydroxylase (TH), neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP), and vasoactive intestinal polypeptide (VIP). In addition, dynorphin (DYN)-containing fibers were detected, which have not been reported previously in normal joints. In general, the immunoreactive fibers were observed close to the synoviocytes and at blood vessels. Fibers with colocalization of NPY- and TH-like immunoreactivities (LIs), as well as of DYN- and TH-LIs were demonstrated. In the electron microscope, bundles of unmyelinated fibers as well as single fibers were found in the connective tissue region below the synoviocytes. Varicose parts of the nerve fibers contained mainly small, clear vesicles. Small and large dense-cored vesicles were also seen, but less frequently. Denser portions of the plasma membranes of some axons were observed in these regions, facing the extracellular space. Myelinated fibers were also observed in some nerve bundles. These findings emphasize the complex innervation of the synovial membrane, with nerve fibers containing a host of neuroactive substances. Altogether, these fibers are probably involved in many functions such as vasoregulation and control of synovial secretion in addition to being a source of mediators in joint inflammation.

The relationship between perceived physiological arousal and actual heart-rate reactions was studied in two behavioral test situations. The subjects were 70 phobic patients (34 social phobics and 36 claustrophobics) who were given the general form of the Autonomic Perception Questionnaire about 1 month before the respective behavioral test and the specific form immediately after the test. The results showed significant correlations between APQ and actual heart rate for the social phobics, while the picture was more complicated for the claustrophobics. The implications of these results are discussed.