TEMPS-a scale in 'mixed' and 'pure' manic episodes: new data and methodological considerations on the relevance of joint anxious-depressive temperament traits

BACKGROUND: Temperament is an important factor in affective illness. There is some indication that mixed episodes result from an admixture of inverse temperamental factors (e.g. depressive and/or anxious) to a manic syndrome. To test this hypothesis, which has been first formulated by Akiskal [Clin. Neuropharmacol. 15 (Suppl. 1A) (1992) 632-633], we compared the temperament of non-acute bipolar affective patients with and without the history of a previous mixed episode. METHODS: Patients who had been hospitalized for a bipolar disorder were re-assessed at least 6 months after their last in-patient treatment. Those who met the criteria for a partially remitted or full affective or psychotic episode at re-assessment were excluded from the study. Data concerning illness history, current psychopathology (SCID-I interview), depression (BDI), mania (Self-Report Manic Inventory) and temperament (TEMPS-A scale) were obtained. Patients with and without a history of previous mixed episodes were compared. RESULTS: Of 49 eligible former patients, 22 subjects with and 23 subjects without a former mixed episode in bipolar affective disorder fulfilled the inclusion criteria. Subjects suffering from bipolar affective disorder exhibited significantly more depressive and anxious and less hyperthymic temperament, if they had experienced a mixed episode previously. Concerning cyclothymic and irritable temperament, bipolar affective patients with a former mixed episode presented non-significantly higher scores. Patients with a former mixed episode presented with higher depression scores than patients without such a history. No group differences were found concerning current mania scores. LIMITATIONS: (1). This is a preliminary report from an ongoing study. (2). Temperament had not been assessed premorbidly. (3). Although group comparisons revealed significant differences, these did not seem great enough to fully explain the emergence of a mixed episode. CONCLUSION: Our findings support the study's hypothesis that mixed episodes occur more often in subjects with an inverse temperament (e.g. depressive and anxious), although it cannot be ruled out that subsyndromal features of the bipolar illness had an effect on temperament assessment.     

Impaired Ca-signaling in astrocytes from the Ts16 mouse model of Down syndrome

The trisomy 16 mouse model of Down syndrome has been used to compare calcium (Ca)-homeostasis and Ca-signaling in astrocytes from trisomic mice and from diploid littermates. Ratio calcium-imaging of Fura-2/AM loaded primary astroglial cultures prepared from the hippocampus shows that resting Ca levels are on average significantly higher in trisomic than in the control astrocytes (280 vs. 120 nM). Serotonin (3 μM) and glutamate (30–300 μM) evoked transient Ca-increases from 400 to 600 nM in euploid but from only 20 to 150 nM in trisomic astrocytes. Imaging of ATP-driven Ca-accumulation in cellular organelles revealed a significantly stronger uptake of Ca in trisomic astrocytes that might buffer cytosolic Ca-increases. Our results demonstrate major disturbances in Ca-signaling in trisomic astrocytes that are likely to be of pathophysiological relevance.     

Properties of voltage-gated currents of microglia developed using macrophage colony-stimulating factor

Microglia were isolated from a murine neonatal brain cell culture in which their development had been stimulated by supplementation with the macrophage/microglial growth factor macrophage colony-stimulating factor (M-CSF). Using the whole-cell configuration of the patch-clamp technique, voltage-gated membrane currents were recorded from these microglial cells. Hyperpolarization induced inward rectifying K⁺ currents, as described for microglia from untreated cultures. These currents activated negative to the K⁺ equilibrium potential and, with a strong hyperpolarization, displayed time-dependent inactivation. The inactivation was abolished when extracellular NaCl was replaced by N-methyl-d-glucamine (NMG), thereby indicating a partial block of this K⁺ conductance by Na⁺. Inward rectifying currents were also blocked by extracellularly applied Cs⁺ or Ba²⁺. They were slightly diminished following treatment with extracellular tetraethylammonium chloride (TEA) but were not affected by 4-aminopyridine (4-AP). Upon long lasting depolarizing voltage pulses to potentials positive to 0 mV, the cells exhibited a slowly activating H⁺ current which could be reduced by application of inorganic polyvalent cations (Ba²⁺, Cd²⁺, Co²⁺, La³⁺, Ni²⁺, Zn²⁺) as well as by 4-AP or TEA. Based on their kinetics and pharmacological characteristics, both currents detected on M-CSF-grown microglia are suggested to correspond to the inward rectifier and the H⁺ current of macrophages.     

Synthesis and characterization of monomethacrylate-functionalized self-organizing crown ether compounds

Synthesis and characterization of methacrylate-monofunctionalized crown ether compounds based on derivatives of 2-hydroxymethyl-1,4,7,10,13-pentaoxacyclopentadecane and 4′-hydroxymethyl-1,4,7,10,13-pentaoxabenzocyclopentadecane is described. By differential scanning calorimetry (DSC) and thermooptical analysis (TOA) it is shown that the synthesized compounds and their sodium triflate complexes exhibit columnar mesophases.     

Lectin histochemistry of the lymphoid organs of the chicken

Cellular interactions within the immune system are in part mediated via the carbohydrate-rich coat of the cell membrane, the glycocalyx, of which the terminal carbohydrate residues are of particular functional importance. Thus, these carbohydrate residues from thymus, bursa of Fabricius, spleen and bone marrow of 2- and 30-day-old chickens were investigated by lectin histochemistry. In the thymus, mannose as well as N-acetyl-glucosamine (glcNAc)-specific lectins labelled macrophages, epithelial reticulum cells and lymphocytes within the cortex. In the bursa of Fabricius, the brush border of the lining epithelium, the macrophages and the endothelium were labelled by mannose-specific lectins. The follicle-associated epithelium was labelled by a broad spectrum of lectins. Epithelial cells that separated the cortex from the medulla and large mononuclear cells in the cortex were only being labelled by N-acetyl-galactosamine (galNAc)-specific and glcNAc-specific lectins, respectively. In the spleen, lymphocytes of the peri-ellipsoid lymphocyte sheaths and macrophages of the red pulp were labelled by lectins of nearly all sugar specificities. In general, glycotopes of these organs were more intensively labelled in the 2-day-old chicken than in the 30-day-old chicken, indicating changes in glycotope expression during post-hatching development. Thus, cells of the avian immune system are as rich and diverse in their lectin binding sites as their mammalian counterparts, indicating that similar carbohydrate lectin interactions between cells and matrices take place in birds as well.     

Identification of protein pattern in kidney cancer using ProteinChip arrays and bioinformatics

Tumor biology of renal cell carcinoma (RCC) is not very well understood, although many studies on molecular and cellular biology have been performed. It is accepted now that cancer research has to be performed also with proteomic tools, because proteins are the real actors in the genesis and progression of cancer. Therefore, we used a ProteinChip System(R) (SELDI) which is able to detect minute amounts of protein and moreover to analyze a complex protein pattern. We analyzed 37 cases of clear cell RCC as a training set including corresponding normal tissue. From all samples protein lysates were made and spotted directly on different chip surfaces (SAX2, WCX). After a washing procedure the arrays were analyzed in the ProteinChip Reader. All profiles were subjected to a bioinformatical analysis including normalization, clustering, rule extraction and rating. Defined rules (markers) were evaluated using a test set of 24 samples (13 tumor tissues and 11 normal kidney tissues). The generated rule base for the SAX2 surface showed a sensitivity of 100% and a specificity of 97.3%. For the WCX arrays the optimal rule base showed worse results. A combined rule base for SAX2 and WCX did not result in a higher sensitivity or specificity. Using the optimal rule base for the SAX2 chip in the test set, sensitivity and specificity reached 76.9% and 100%, respectively. The ProteinChip System represents a key technology for the rapid detection of cancer specific proteomic patterns. It is possible to identify clear cell renal cancer with high sensitivity and specificity from minimal amounts of cells.     

Clinical Phenotype and Relevance of LRP5 and LRP6 Variants in Patients With Early-Onset Osteoporosis (EOOP)

Reduced bone mineral density (BMD; ie, Z-score ≤−2.0) occurring at a young age (ie, premenopausal women and men <50 years) in the absence of secondary osteoporosis is considered early-onset osteoporosis (EOOP). Mutations affecting the WNT signaling pathway are of special interest because of their key role in bone mass regulation. Here, we analyzed the effects of relevant LRP5 and LRP6 variants on the clinical phenotype, bone turnover, BMD, and bone microarchitecture. After exclusion of secondary osteoporosis, EOOP patients (n = 372) were genotyped by gene panel sequencing, and segregation analysis of variants in LRP5/LRP6 was performed. The clinical assessment included the evaluation of bone turnover parameters, BMD by dual-energy X-ray absorptiometry, and microarchitecture via high-resolution peripheral quantitative computed tomography (HR-pQCT). In 50 individuals (31 EOOP index patients, 19 family members), relevant variants affecting LRP5 or LRP6 were detected (42 LRP5 and 8 LRP6 variants), including 10 novel variants. Seventeen variants were classified as disease causing, 14 were variants of unknown significance, and 19 were BMD-associated single-nucleotide polymorphisms (SNPs). One patient harbored compound heterozygous LRP5 mutations causing osteoporosis-pseudoglioma syndrome. Fractures were reported in 37 of 50 individuals, consisting of vertebral (18 of 50) and peripheral (29 of 50) fractures. Low bone formation was revealed in all individuals. A Z-score ≤−2.0 was detected in 31 of 50 individuals, and values at the spine were significantly lower than those at the hip (−2.1 ± 1.3 versus −1.6 ± 0.8; p = .003). HR-pQCT analysis (n = 34) showed impaired microarchitecture in trabecular and cortical compartments. Significant differences regarding the clinical phenotype were detectable between index patients and family members but not between different variant classes. Relevant variants in LRP5 and LRP6 contribute to EOOP in a substantial number of individuals, leading to a high number of fractures, low bone formation, reduced Z-scores, and impaired microarchitecture. This detailed skeletal characterization improves the interpretation of known and novel LRP5 and LRP6 variants. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).