Altered expression of cell–cell adhesion molecules β-catenin/E-cadherin and related Wnt-signaling pathway in sporadic and syndromal keratocystic odontogenic tumors

Differential diagnosis of the keratocystic odontogenic tumor (KCOT) still represents a challenging problem especially if compared with the dentigerous cyst, which is similar in clinical and radiological course. Histological assessment of this entity may therefore draw crucial attention since various radical procedures are recommended for such lesions in contrast to dentigerous cysts. Since recent reports could prove the involvement of wingless(Wnt)-signaling pathway and β-catenin in the pathogenesis of many odontogenic and neoplastic lesions indicating impairment of cell–cell adhesion, we investigated the expression of two Wnt-signaling pathways, Wnt-1 and Wnt-10A as well as β-catenin and E-cadherin along with other related proteins in both lesions. We found a significant down-regulation in the expression of cell adhesion proteins β-catenin and E-cadherin along with alteration of Wnt-1 and Wnt-10A expression in the epithelium of KCOT. We assessed a specific focal distribution pattern of p63 in the suprabasal cell layer and a significant up-regulation of cyclin D1. Furthermore, laminin α-2 was a characteristic marker labelling only the basement membrane of dentigerous cysts. These results provide a new hypothesis explaining a molecular mechanism to understand initiating and development of KCOTs and an alternative therapeutic approach, especially for syndromal patients, where these multilocal lesions may involve and destroy wide orofacial bony structures.     

VEP and PERG in patients with multiple sclerosis,with and without a history of optic neuritis

Purpose

Visual electrophysiology is routinely used to detect the visual complications of multiple sclerosis, but the analysis mostly focuses on visual evoked potential (VEP) and especially the P100 component. Our goal was to analyze the components and waveform alterations of VEPs and pattern electroretinograms (PERGs) in patients with multiple sclerosis (MS) with good vision.

Methods

The main VEP and PERG components of 85 patients with MS were analyzed in two groups: 38 patients who had optic neuritis in their history (ON group) and 47 patients who had never had optic neuritis (MS group). The results were compared against a control group of 47 healthy subjects.

Results

Both VEP and PERG alterations occurred in a greater number of patients than expected, and these alterations were not necessarily linked to ON in the history or a deterioration of visual acuity.

Conclusions

Both VEP and PERG can detect dysfunction in the visual system in MS, even if the patient has no subjective symptoms. Even if PERG is not routinely used in neuro-ophthalmology, the results suggest that PERG assessment may provide useful information describing the retinal defect in MS.

     

Psychosocial factors in children with idiopathic musculoskeletal pain: a prospective, longitudinal study

Abstract To explore the role of psychosocial factors in the development and persistence of idiopathic musculoskeletal pain (IMP) in children, 23 children with IMP and 52 children with juvenile chronic arthritis (JCA) were compared at first admission to hospital and at 9 y follow-up. Semistructured interviews were performed at both assessments. At first admission, the prevalence of psychiatric diagnoses was high both in patients with IMP and patients with JCA, but patients with IMP more often had pain models, reported more school stress and more often lived with one biological parent. At follow-up, overall psychosocial functioning and level of chronic family difficulties were improved in both groups, but patients with IMP had a higher prevalence of psychiatric diagnoses and more chronic family difficulties and life events than patients with JCA. The persistence of IMP at follow-up was related to pain models, school stress, less parental education and more chronic family difficulties at first admission. Findings support the association between psychosocial factors and childhood IMP.     

Calcium channels are involved in the hypnotic-anesthetic action of dexmedetomidine in rats.

Our study examined whether calcium channels are involved in the anesthetic action of dexmedetomidine (100-300 micrograms/kg), a highly selective alpha 2-adrenoceptor agonist. To investigate this, we studied the effects of verapamil (1.25 or 2.5 mg/kg), a calcium channel blocker, and BAY K8644 (0.5 or 1 mg/kg), a calcium channel agonist, on the hypnotic-anesthetic effect of dexmedetomidine in rats. Loss of the righting reflex was used to determine the presence of anesthesia, and its length in minutes was referred to as the duration of hypnosis. Verapamil significantly enhanced the duration of the hypnotic-anesthetic action of dexmedetomidine (P less than 0.05). In contrast, BAY K8644 caused a significantly increased onset of hypnosis (P less than 0.001) and attenuated the anesthetic property of dexmedetomidine. These results suggest that the hypnotic-anesthetic action of dexmedetomidine is influenced by the activation/gating of calcium channels.     

Kinetics of lymphocytes in Hodgkin's disease

Summary Lymphocyte kinetics was studied in 4 patients withHodgkin's disease (Stage III A and IV B) by means of a single i. v. injection of³H-thymidine (0.15 Ci/g body weight) and autoradiographic analysis of the labelling pattern of blood and tissue lymphocytes over a period of 7–25 days.The cause of the blood lymphocytopenia in the three lymphopenic patients was the accelerated turnover of the majority of the blood lymphocytes. The average turn-over time of the blood lymphocytes in these patients was about 5 days as compared to 27 days in aHodgkin patient without lymphopenia and to 50 days in non-lymphopenic tumour patients. The turnover times of the small blood lymphocytes were about 14 days in the lymphopenic Hodgkin patients and 70–115 days in hematologically normal patients. Lymphocytopoiesis seemed to be increased in the lymph nodes and in the blood inHodgkin's disease. The blood lymphocyte production index was was 61–259 lymphocytes/mm³/day as compared to 40–50 lymphocytes/mm³/day in hematologically normal patients. The generation time of the lymphopoietic cells was estimated to be approximately 24 hours.Our data suggest that the activity of the disease was correlated with accelerated turnover of lymphocytes and increased lymphocytopoiesis.

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Zusammenfassung Bei 4 Patienten mit Lymphogranulomatose (Stadium III A und IV B) wurde die Kinetik von Blut- und Gewebslymphozyten nach einer Einzelinjektion von³H-Thymidin autoradiographisch untersucht.Bei den 3 lymphopenischen Patienten war die Lymphopenie des Blutes durch einen gesteigerten Umsatz der Blutlymphozyten bedingt. Die mittlere Umsatzzeit der Blutlymphozyten betrug bei diesen Patienten 5 Tage, verglichen mit einer mittleren Umsatzzeit von 27 Tagen bei einem Lymphogranulom-Patienten ohne Lymphopenie und von etwa 50 Tagen bei nicht-lymphopenischen Tumorpatienten. Die mittlere Umsatzzeit der kleinen Blutlymphozyten wurde bei den lymphopenischen Lymphogranulomatose-Patienten mit 14 Tagen und bei nicht-lymphopenischen Tumorpatienten mit 70–115 Tagen berechnet. Die Lymphozytopoese bei den Lymphogranulomatose-Patienten war erhöht. Das galt gleichermaßen für die vergrößerten Lymphknoten und das Blut. Der Blutlymphozyten-Produktionsindex betrug 61-259 Lymphozyten/mm³/Tag im Vergleich zu 40–50 Lymphozyten/mm³/Tag bei hämatologisch normalen Patienten. Die Generationszeit der lymphopoetischen Zellen ließ sich auf 24 Stunden schätzen.Die Befunde weisen darauf hin, daß bei der Lymphogranulomatose die Aktivität des Krankheitsprozesses mit gesteigertem Lymphozytenumsatz und stimulierter Lymphozytopoese korreliert ist.

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Research carried out in the Forschergruppe für Experimentelle und Klinische Leukämieforschung, supported by the Deutsche Forschungsgemeinschaft.     

Effect of age on angiotensin II-mediated downregulation of adrenomedullary catecholamine biosynthetic enzymes

Expression of catecholamine biosynthesizing enzymes, tyrosine hydroxylase (TH) and dopamine beta hydroxylase (DbetaH) increase with age in the adrenal medulla, however, the underlying mechanisms are unclear. In the present study, we examined the effect of peripheral angiotensin II (AngII) on the expression of TH and DbetaH, in the adrenal medulla of young (6 mo) and old (23 mo) Fischer-344 rats. Saline or AngII (230 ng/kg/min sc) was infused for 3 days using osmotic minipumps. Adrenomedullary TH and DbetaH mRNA levels increased significantly with age, and while AngII reduced the expression of these enzymes in young animals, it had no such effect in the old animals. Neuropeptide Y (NPY), which is co-released with catecholamines in the adrenal medulla and stimulates the synthesis of TH and DbetaH, was also upregulated with age and downregulated in response to AngII in young rats. However, in the old animals, the already elevated NPY expression remained unchanged following AngII treatment. This data indicate that the hypertensive effect of peripheral AngII is compensated by an inhibition of adrenomedullary catecholamine biosynthesis in young animals, but this mechanism is impaired in senescence, potentially contributing to the age-related increase in catecholamine biosynthesis.     

Reciprocal Lateral Hypothalamic and Raphe GABAergic Projections Promote Wakefulness

The lateral hypothalamus (LH), together with multiple neuromodulatory systems of the brain, such as the dorsal raphe nucleus (DR), is implicated in arousal, yet interactions between these systems are just beginning to be explored. Using a combination of viral tracing, circuit mapping, electrophysiological recordings from identified neurons, and combinatorial optogenetics in mice, we show that GABAergic neurons in the LH selectively inhibit GABAergic neurons in the DR, resulting in increased firing of a substantial fraction of its neurons that ultimately promotes arousal. These DR_GABA neurons are wake active and project to multiple brain areas involved in the control of arousal, including the LH, where their specific activation potently influences local network activity leading to arousal from sleep. Our results show how mutual inhibitory projections between the LH and the DR promote wakefulness and suggest a complex arousal control by intimate interactions between long-range connections and local circuit dynamics.SIGNIFICANCE STATEMENT: Multiple brain systems including the lateral hypothalamus and raphe serotonergic system are involved in the regulation of the sleep/wake cycle, yet the interaction between these systems have remained elusive. Here we show that mutual disinhibition mediated by long range inhibitory projections between these brain areas can promote wakefulness. The main importance of this work relies in revealing the interaction between a brain area involved in autonomic regulation and another in controlling higher brain functions including reward, patience, mood and sensory coding.     

Die Gewebsstruktur der Gliome

Ohne ZusammenfassungAusgeführt zum Teil mit der Unterstützung der FürstPaul Esterh'azyschen Stiftung für wissenschaftliche Forschung.