Veratridine-stimulated central synapses in culture: A quantitative ultrastructural analysis

Synapses in explant cultures of fetal rat neocortex at day 18 in vitro were stimulated by veratridine (10^?4M) for 20 min. The cultures were subsequently processed for electron microscopy and the synapses were analyzed by quantitative techniques, incorporating set mathematical treatment. The mean values of area, perimeter, and form factor of the presynaptic elements significantly increased following veratridine stimulation, compared to the values of control synapses. The length of the postsynaptic thickening also increased, while synaptic curvature did not change significantly in the veratridine group. A fivefold reduction was observed in the mean number of synaptic vesicles per presynaptic element and in the vesicle-terminal area ratio, following veratridine stimulation. The cytoplasm-terminal area ratio and the occurrence of vacuoles/cisternae significantly increased after veratridine application. Planar measurement of membranes (boundary length) of different presynaptic organelles revealed that the total membrane did not change significantly in the veratridine group. The data indicated an increase in volume and swelling of the pre- and postsynaptic elements, considerable depletion of synaptic vesicles, and preservation of the total presynaptic membrane following veratridine stimulation in nerve tissue culture.     

Evidence supporting tight linkage of X-linked Emery-Dreifuss muscular dystrophy to the factor VIII:C gene.

In a large German family with Emery-Dreifuss muscular dystrophy (EDMD) linkage analysis was performed using the factor IX gene (F9), the factor VIII:C gene (F8), the anonymous DNA probe DXS52, and DXS15 as markers. Tight linkage was found between the EDMD locus and the F8 probe (Zmax = 1.19; theta max = 0.00), DXS15 (Zmax = 1.75; theta max = 0.00) and DXS52 (Zmax = 2.26; theta max = 0.00). Weak linkage was found to F9 (Zmax = 0.02; theta max = 0.43). The data from the literature and our results suggest that the gene locus of EDMD is close to F8 (confidence interval theta = 0-0.07). The new linkage data are useful for carrier detection and diagnosis of EDMD patients before onset of major clinical signs.     

Evidence for linkage of the central core disease locus to the proximal long arm of human chromosome 19

Central core disease of muscle (CCD; MIM 117000) is a rare inheritable myopathy that is frequently found in association with susceptibility to malignant hyperthermia (MHS). This observation has prompted us to perform a linkage study in CCD families using various chromosome 19q probes that are linked to the MHS locus and map close to the ryanodine receptor gene (RYR1), a strong MHS candidate gene. Our genetic linkage data support a location of the CCD gene on proximal 19q13.1 and thus suggest that CCD and MHS may be allelic.     

Plantarum novarum turcicarum breviarium

Ohne Zusammenfassung     

A new species of Wellsopsyllus (Copepoda, Harpacticoida, Paramesochridae) from the deep Southern Ocean and remarks on its biogeography

The new deep-sea copepod species of the family Paramesochridae (Copepoda, Harpacticoida) presented here was collected during the scientific ANtarctic benthic DEEP-sea biodiversity cruise II (ANDEEP II) to the Weddell Abyssal Plain and western Weddell Sea and the CROZet natural iron bloom and EXport experiment (CROZEX cruise) to the Crozet Isles in the Indian Ocean. The new species has been allocated to the subgenus Wellsopsyllus within the genus Wellsopsyllus Kunz, 1981, based on the 1-segmented endopods and 3-segmented exopods of swimming legs 2–4. Furthermore, the new species shows a 1-segmented exopod of the antenna. Wellsopsyllus (W.) antarcticus sp. n. can be distinguished from its congeners by its small body size, the presence of two setae on the distal segment of the endopod of the first swimming leg, by the very small furcal rami, the extremely reduced endopods of second and third swimming legs, the reduced mandibular palp and maxillula, as well as by the size and armature of the fifth and sixth swimming legs in both sexes. Difficulties of the placement of the new species into a suitable genus show an insufficiency in the present family classification. In the future, a revision of the genus Wellsopsyllus is essential. With its presence in the western Weddell Sea and the Indian Ocean, the new species may have a wide distribution range. Furthermore, it is the first abyssal species of the genus Wellsopsyllus sampled outside of the Scotia Sea.     

In vivo phage display — A discovery tool in molecular biomedicine

In vivo phage display is a high-throughput method for identifying target ligands specific for different vascular beds. Targeting is possible due to the heterogeneous expression of receptors and other antigens in a particular vascular bed. Such expression is additionally influenced by the physiological or pathological status of the vasculature. In vivo phage display represents a technique that is usable in both, vascular mapping and targeted drug development. In this review, several important methodological aspects of in vivo phage display experiments are discussed. These include choosing an appropriate phage library, an appropriate animal model and the route of phage library administration. In addition, peptides or antibodies identified by in vivo phage display homing to specific types of vascular beds, including the altered vasculature present in several types of diseases are summarized. Still, confirmation in independent experiments and reproduction of identified sequences are needed for enhancing the clinical applicability of in vivo phage display research.     

Phase-synchronization of daily motor activities can reveal differential circadian patterns

The aim of the study was to determine any alteration of the 24 h motor activity pattern of a bipolar patient in different mood states. Actigraphic records were collected on an outpatient basis for a total of 387 days. The daily actograms were synchronized in phase to the time of morning awakening before averaging, which significantly enhanced the structure of the averaged traces. The actograms were divided into three groups based on total daily count. The daily motor activity patterns of the low- and high-activity days have a different circadian pattern. We propose it may have a relevance to the different mood states. The phase-synchronization of the 24 h actograms to the patient's sleep-wake cycle, specifically to the time of awaking from the nighttime sleep, may help reveal differences in the daily temporal patterns of motor activity.     

High-performance liquid chromatographic assay of metabolites of thioguanine and mercaptopurine in capillary blood

The main metabolites of the cytotoxic drugs thioguanine (6TG) and mercaptopurine (6MP) can be measured conveniently in red blood cells (RBC). Isolation of RBC, however, is laborious and requires some milliliters of blood. This HPLC assay allows measurements of thiopurine metabolites in very small blood samples obtained from the finger-tip. The metabolites, derivatives of 6TG and methylmercaptopurine (6MeMP), were extracted and hydrolized with perchloric acid to liberate the corresponding base. 6MeMP is completely transformed under these conditions to 4-amino-5-(methylthio)carbonyl imidazole. The chromatographic separation of 6TG and this imidazole was performed in a single run under isocratic conditions within 10 min using a 70 mm column. The quantification limit was 0.5 nmol/ml for 6TG and 3 nmol/ml blood for 6MeMP. The accuracy was 83% for 6TG (CV=3%) over the concentration range of 0.5-20 nmol/ml blood and 102% (CV=4%) for 6MeMP over the range of 3-150 nmol/ml blood. The intra-assay CV ranged from 5.4 to 7.4% for 6TG and from 6.2 to 10.6% for 6MeMP. The inter-assay CV was 7.5 and 9.5% in a pooled blood sample. The levels in RBC in whole blood were nearly coincident with those obtained in separated RBC, isolation of RBC therefore is not necessary for these measurements, if the drugs are given per os in the day before blood sampling. The concentration of 6MeMP nucleotides is more dependent on the given 6MP dose than the concentration of 6TG nucleotides. Intraindividual variations were small at unchanged drug doses, interindividual metabolite concentrations were highly variable.