Expressed-emotion development and course of schizophrenic illness: considerations based on results of a CFI replication

This study examines the correlation between development of expressed emotion (EE) in relatives and course of illness of 99 DSM-III schizophrenic patients. Patients whose relatives were high EE at baseline and at the 2nd CFI approximately 20 months later had a poor prognosis at the very outset of the study and an unfavourable course of illness. They had a higher rehospitalisation rate, more symptoms, lower psychosocial assessment, and a poorer 2-year and even 8-year outcome. Patients from families with a fluctuating EE or a consistently low EE had better courses. Expessed emotion is therefore a valid predictor not only of symptomatic relapses, but also of other important aspects of schizophrenia. The connection between EE index and course of illness seerns not to be simply reactive or causal, but complex and non-uniform.     

Molekulare Ansätze zur Gentherapie

Zum Thema Zell- und molekularbiologische Methoden haben es in den letzten 25 Jahren erm?glicht, Erkenntnisse in intra- und interzellul?re Funktionsabl?ufe und deren St?rungen zu gewinnen. Besonders in der Onkologie kam es zu einem zunehmenden Wissen über dysregulierte Gene, sog. Onkogene, welche ein dysfunktionelles (Onko)Protein produzieren und damit Zellwachstum und Proliferation in Richtung Malignit?t beeinflussen k?nnen. Tumorsuppressorgene (TSG) wirken regulierend auf den Zellzyklus ein, und im Falle einer vererbten Mutation des einen Allels und einer Deletion des intakten Allels durch Funktionsverlust k?nnen Malignome induziert bzw. Malignomentstehung begünstigt werden. Ein Beispiel hierfür ist das Li-Fraumeni-Syndrom, bei welchem es aufgrund einer Mutation des Tumorsuppressorgens p53 zu einer geh?uften Inzidenz von Mamma- und Ovarialkarzinomen kommt. ?nderungen von Proteasen- oder Adh?sionsmolekülfunktionen von Zellen spielen eine wichtige Rolle bei der Tumorzellinvasion und Metastasierung. Blockierung von Proteasesystemen, z. B. Urokinase/Plasmin-System oder Matrixmetalloproteasen, führen zu einer Inhibierung von Tumorzellinvasion und Metastasierung in vitro und in vivo. Bei einigen Malignomen kommt es zu einer Vermehrung von Genkopien, einer sog. Genamplifikation, wie sie z. B. für Rezeptoren der epidermal „Growth-factor-Familie“ (EGF-R, erbB2, erbB3, erbB4) beschrieben sind. Die betroffenen Zellen reagieren dadurch vermehrt auf autokrine und parakrine Signale und hyperproliferieren. Die Gentherapie stellt durch Wiederherstellung physiologischer Funktionsabl?ufe einen vielversprechenden Ansatz zur Behandlung maligner Erkrankungen dar. Der vorliegende übersichtsartikel wird ohne Anspruch auf Vollst?ndigkeit nach einer kurzen Einführung in die Grundlagenaspekte der Gentherapie und deren derzeitigen Probleme pr?klinische und erste klinische Ergebnisse darstellen.     

The topographic organization of the retinal ganglion cell layer of the lizard Ctenophorus nuchalis.

The numbers of neurons of the ganglion cell layer (GCL) and their distribution in the retina of an Australian lizard Ctenophorus nuchalis were investigated. Retinal wholemounts and sections were prepared for light microscopic and optic nerves for electron microscopic study. Counts of cell numbers in the GCL from wholemounts varied from 200,000 to 380,000. Neurons in the GCL were non-uniformly distributed, forming a high cell density streak along the naso-temporal axis of the retina. Neurons of the GCL formed 2 to 9 layers in the visual streak and a single layer in the rest of the retina. The number of neurons of the GCL in this area was estimated at about 2,100,000. Although the visual streak represented only 16% of the total retinal surface area, it contained about 90% of all neurons of the GCL. Optic axon counts yielded 147,000 myelinated and 2,643,000 unmyelinated fibres. The estimated optic fibre number of 2,790,000 was 18.2% less than the total number of neurons counted from sections in the GCL of the same eye. The unexpected high number of neurons in the area of the visual streak indicates that cell numbers obtained only from wholemount preparations may vastly underestimate the total neuron numbers in the GCL of the lizard retina.     

Safety of virus inactivated antithrombin III concentrate ANTITHROMBIN III IMMUNO (AT III)

In a prospective clinical trial the risk of infection after application of virus inactivated antithrombin III concentrate ANTITHROMBIN III IMMUNO (AT III) was investigated in patients undergoing cardiovascular surgery. The study was conducted according to the recommendations of the International Committee on Thrombosis and Hemostasis (ICTH), with the exception that most patients required additional blood products as well as AT III.

Twenty-seven patients were eligible to test for the risk of acquiring hepatitis B. Twenty-six patients could be evaluated in terms of hepatitis NANB transmission considering ALT-levels whereas 20 patients could be tested for anti-HCV one year after surgery. Samples from 78 patients could be monitored for anti-HIV-1. None of these patients showed any signs of infection. AT III IMMUNO seems to be an antithrombin III concentrate with low or absent infectivity.     

Ultrasound diagnosis of hip dysplasia--current status and future perspectives]

Hip sonography provides a safe pathoanatomical assessment of a newborn hip joint at the earliest possible moment. Based on this safe diagnosis an adequate biomechanical treatment can be started instantly. The mean age of healing even of originally decentered hip joints is 7.5 months, if earliest sonographic diagnosis and adequate biomechanical treatment are performed correctly. Secondary hip surgery can be reduced to a minimum. Cost-benefit-analysis, too, supports the institution of a general sonographic screening of all newborn hip joints.     

Three-dimensional force measurements on mandibular implants supporting overdentures.

The purpose of this study was to determine masticatory and functional forces in three axes on mandibular implants supporting overdentures. Five edentulous test subjects were selected, each having two mandibular implants. Three-dimensional piezoelectric force transducers were mounted on the two-part ITI Bonefit implants and rigidly connected to the denture. Forces in vertical, lateromedial, and anteroposterior directions were measured by means of electrostatic plotter records. The test modalities were light tapping, grinding, maximal occlusal force, and chewing test food. Results showed that the five subjects developed similar stress patterns but quantitatively different occlusal and chewing forces. In all but one subject, reduced maximal occlusal force was found compared to dentate subjects and edentulous subjects with fixed partial prostheses supported by implants. The recordings of chewing cycles when eating test food resulted in very regular rhythmic strokes, similar to those of dentate subjects but with slightly reduced speed. All stress patterns showed that occlusal and chewing forces were mainly directed in vertical, medial, and anterior dimensions. The dominating component was vertical.     

Potential role of flavonoids in the prevention of intestinal neoplasia

Intestinal neoplasia (adenomas and carcinomas) can possibly be prevented by a diet rich in vegetables and fruits, treatment with aspirin and other nonsteroidal antiinflammatory drugs, and early colonoscopic removal of adenomas. Ballast, fiber, and secondary plant products could play a major role in colon cancer prevention. Recently there has been much experimental work in vitro and in vivo about flavonoids as inducers of bioprevention. Flavonoids are secondary plant products with a wide variety of beneficial biological properties, and they possess anticarcinogenic, antimutagenic, and antioxidative modes of actions. Flavonoids are the main components of a healthy diet containing fruits and vegetables and are concentrated especially in tea, apples, and onions. We will focus this review on flavonoids which are derived from tea products such as proanthocyanidins (green tea) and flavons (camomille tea). Oral supplementation with bioflavonoids derived from tea could be used in humans to prevent growth of intestinal neoplasia such as adenomatous polyps of the colon. Flavonoids are a large group of natural compounds of which only a few have been used in animal models, cell cultures, and enzyme studies to inhibit mutagenic and carcinogenic events. Their clinical mode of action was evaluated by epidemiological studies, but no intervention studies in humans have been performed so far. In vitro flavonoids can bind electrophils, inactivate oxygen radicals, prevent lipid peroxidation, and inhibit DNA oxidation. In cell cultures they increase the rate of apoptosis, inhibit cell proliferation, and angiogenesis. In vivo they can induce the activities of protective enzymes (conjugating enzymes such as glutathione transferases and glucuronosyl transferases) of the intestine and the liver. In models of intestinal polyposis, flavonoids suppress polyp formation. Some epidemiological studies show a protective effect of flavonoids contained in fruits, vegetables, and tea.Flavonoid mixtures of tea origin supplied as nutritional supplements could be studied as a new way of bioprevention of intestinal neoplasia (colon adenomas and cancer). Therefore, a controlled, randomized clinical study should be performed to evaluate the efficacy of flavonoids.     

Antiserotonergic inhibition of calcitonin-induced increase of β-endorphin,ACTH, and cortisol secretion

Summary In a previous study we observed that calcitonin increases -endorphin, ACTH, and cortisol secretion. We assumed that calcitonin might have a modulatory role on the pituitary function. The present study was initiated to clarify whether this effect is due to a direct pituitary stimulation or to an indirect stimulation through CRF (corticotropin releasing factor).Fourteen healthy subjects, aged 30–60 years were investigated. All the subjects received 100IU Salmon calcitonin Sandoz i.v. at 8a.m. (time 0). Plasma -endorphin, ACTH and cortisol were estimated every 30min from – 30 to 120 min by specific radioimmunoassay. The same parameters were estimated a second time, at the same intervals, when cyproheptadine 8 mg (7 subjects) and 40 mg propranolol (7 subjects) were given per os at – 30 min and calcitonin i.v. at time 0. -endorphin, ACTH and cortisol levels (Mean ±SEM) rose significantly after calcitonin (peak value at 30–90 min) from 5.2 ±0.7 to 15.1±2.6 pmol/l; from 43.0±2.7 to 70.7±4.1 pg/ml and from 10.6±1.5 to 19.6 ±2.1 g/100 ml respectively (p< 0.0001 by analysis of variance and covariance and repeated measures). Propranolol 40 mg (per os) administered at time – 30 did not alter the response of -endorphin, ACTH and cortisol to calcitonin (infused at time 0).Cyproheptadine, the antiserotonergic substance that inhibits the synthesis and release of CRF completely inhibited the stimulatory effect of calcitonin.We conclude that probably calcitonin has a modulatory role on the hypothalamo-pituitary adrenal axis and that it acts at the hypothalamic level probably by stimulating CRF secretion.     

Localization of SNARE proteins and secretory organelle proteins in astrocytes in vitro and in situ

Astrocytes are capable of regulated release of messenger molecules. Astrocytes cultured from new born rodent brain express a variety of classical presynaptic proteins. We investigated the question whether the capability to express synaptic proteins in culture was a feature only of immature astrocytes, and whether these proteins were also expressed by astrocytes in situ. Experiments were performed with transgenic mice expressing the enhanced green fluorescent protein under the control of the human glial fibrillary acidic protein promoter. Using double fluorescence and astrocytes cultured from 1 to 16 day-old animals we show that the astrocytic expression of synaptic proteins in culture is invariant of the age of donor animals. Culturing can induce the astrocytic expression of specific synaptic proteins such as SV2, synaptophysin and SNAP-25. Astrocytes in brain sections of 1-16 day-old animals revealed a punctuate immunofluorescence for secretory carrier membrane protein (SCAMP), SNAP-23, synaptobrevin II, and cellubrevin, to a minor extent for SNAP-25 and synaptophysin, and none for SV2. Our results demonstrate that cultured astrocytes express synaptic proteins not present in situ. Nevertheless, astrocytic organelles in situ are equipped with molecules that could be involved in regulated exocytosis of messenger substances.