Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes.

The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding therapeutic decisions and monitoring interventions. We previously demonstrated that plasma samples from recent-onset type 1 diabetes (RO T1D) patients induce a proinflammatory transcriptional signature in freshly drawn peripheral blood mononuclear cells (PBMCs) relative to that of unrelated healthy controls (HC). Here, using cryopreserved PBMC, we analyzed larger RO T1D and HC cohorts, examined T1D progression in pre-onset samples, and compared the RO T1D signature to those associated with three disorders characterized by airway infection and inflammation. The RO T1D signature, consisting of interleukin-1 cytokine family members, chemokines involved in immunocyte chemotaxis, immune receptors and signaling molecules, was detected during early pre-diabetes and found to resolve post-onset. The signatures associated with cystic fibrosis patients chronically infected with Pseudomonas aeruginosa, patients with confirmed bacterial pneumonia, and subjects with H1N1 influenza all reflected immunological activation, yet each were distinct from one another and negatively correlated with that of T1D. This study highlights the remarkable capacity of cells to serve as biosensors capable of sensitively and comprehensively differentiating immunological states.

Negative bias in fast emotion discrimination in borderline personality disorder.

BACKGROUND: The ability to decode emotional information from facial expressions is crucial for successful social interaction. Borderline personality disorder (BPD) is characterized by serious problems in interpersonal relationships and emotional functioning. Empirical research on facial emotion recognition in BPD has been sparsely published and results are inconsistent. To specify emotion recognition deficits in BPD more closely, the present study implemented two emotion recognition tasks differing in response format. METHOD: Nineteen patients with BPD and 19 healthy subjects were asked to evaluate the emotional content of visually presented stimuli (emotional and neutral faces). The first task, the Fear Anger Neutral (FAN) Test, required a rapid discrimination between negative or neutral facial expressions whereas in the second task, the Emotion Recognition (ER) Test, a precise decision regarding default emotions (sadness, happiness, anger, fear and neutral) had to be achieved without a time limit. RESULTS: In comparison to healthy subjects, BPD patients showed a deficit in emotion recognition only in the fast discrimination of negative and neutral facial expressions (FAN Test). Consistent with earlier findings, patients demonstrated a negative bias in the evaluation of neutral facial expressions. When processing time was unlimited (ER Test), BPD patients performed as well as healthy subjects in the recognition of specific emotions. In addition, an association between performance in the fast discrimination task (FAN Test) and post-traumatic stress disorder (PTSD) co-morbidity was indicated. CONCLUSIONS: Our data suggest a selective deficit of BPD patients in rapid and direct discrimination of negative and neutral emotional expressions that may underlie difficulties in social interactions.

[Functional imaging of emotions and emotional dysfunctions in schizophrenia patients]. / Funktionelle Bildgebung von Emotionen und emotionalen Dysfunktionen bei schizophrenen Patienten.

Emotions have been discussed in earliest psychiatric literature as core characteristics of psychiatric patients. More recently emotions got back into the focus of modern neuropsychiatric imaging research. This is due to the outstanding importance of emotions for psychiatric symptomatology and also to recent technical developments in neuroimaging, which lay the ground for more complex paradigms. Especially schizophrenic patients show deficits in emotional functioning, such as in mood induction or emotion discrimination. It is subject to discussion how stable these dysfunctions are over the course of schizophrenia, e.g. in prodromal stage. Therefore research also deals with juvenile patients with schizophrenia-like symptoms. In the future it will be essential to characterize the effect of emotions on cognitive functions in healthy subjects and psychiatric patients.

Respiratory infection in lipid-fed rabbits enhances sudanophilia and the expression of VCAM-1.

The pathogenesis of atherosclerosis has been related to infection of the arterial wall, but it is not clear whether this occurs before or after the development of lipid-containing lesions. Respiratory bacterial infection increases the expression of vascular cell adhesion molecule-1 (VCAM-1). We therefore examined whether a similar infection would enhance atherosclerosis in New Zealand White rabbits fed chow supplemented by 15% (w/w) egg yolk for 50 days. Rabbits with naturally acquired respiratory infection by Pasteurella multocida, pathogen-free (SPF) animals infected by P. multocida in the laboratory, and age-matched SPF rabbits maintained in a disease-free environment were used. Endothelial cells expressing VCAM-1 in the aorta between intercostal arteries 3 and 5 were identified using anti-VCAM-1 (Rb1/9) and an alkaline-phosphatase-linked secondary antibody and quantified in Häutchen preparations. The remainder of the aorta was stained with Sudan IV to show lipid deposition. The expression of VCAM-1 (mean +/- SEM per 10,000 cells) was 22 +/- 8 (n = 5) in the lipid-fed SPF rabbits, significantly different from that in the lipid-fed rabbits with naturally occurring infection (190 +/- 51 (n = 5)) or from rabbits infected in the laboratory (106 +/- 25 (n = 5)). The extent of Sudanophilia was significantly greater in the naturally infected rabbits (8.3 +/- 1.2%) or infected SPF rabbits (10.3 +/- 1.8%) than in the SPF rabbits (2.7 +/- 0.8%; P < 0.05). Antibiotic treatment in naturally infected rabbits reduced the number of cells expressing VCAM-1 and the extent of the Sudanophilia to baseline levels. Thus, Sudanophilia is enhanced by bacterial infection in rabbits fed egg yolk and is associated with a significant increase in VCAM-1.

Morphological alterations in endothelial cells associated with the release of von Willebrand factor after thrombin generation in vivo.

von Willebrand factor (vWF) is synthesized by endothelial cells and stored in endothelium-specific granules, the Weibel-Palade (WP) bodies. The release of vWF from endothelial cells in vitro in response to secretagogues such as thrombin is considered to result in the loss of WP bodies through the fusion of the WP bodies with the plasma membrane. Biochemical and morphological techniques, including transmission (TEM) and scanning (SEM) electron microscopy, were used to examine the plasma profile of vWF in parallel with morphological alterations in endothelial cells associated with the generation of thrombin in vivo. There was a rapid loss of high-molecular-weight multimers of the circulating vWF, with full recovery within 1 hour. Simultaneously, TEM demonstrated that the endothelial cells lost WP bodies and became severely vacuolated; this was associated with the appearance of craters in the endothelial surface on SEM. Release of stored vWF in WP bodies seemed to follow the fusion of multiple rather than individual WP bodies, with the resulting vacuole fusing and rupturing through the plasmatic membrane. Within 1 hour there was increased morphological evidence of metabolic organelle activity associated with replacement of WP bodies, presumably due to de novo synthesis of the basic protomer and its packaging in high-molecular-weight multimeric form in the storage organelles.

Sclerosing mesenteritis. Report of two cases.

Two cases of benign tumor-like mesenteric lesions are presented. The limited literature on comparable and similar lesions is reviewed, and the histologic findings are correlated. The lesions are composed of chronically inflamed adipose and fibrous tissue in various proportions. They probably represent different stages of a reparative process initiated by damage of the mesenteric adipose tissue of various etiologies. Whereas lesions in the younger age groups (mean 39.9 years) are predominatly characterized the fibrosis, those in the older age groups (mean 55.8 years) usually show a chronic inflammatory cell infiltrate rather than fibrosis. More than a dozen terms have been used for these lesions. The summarizing term "sclerosing mesenteritis" is proposed.