Development of DARPP-32-positive parts of fetal pig ganglionic eminence and ventral mesencephalon in organotypic slice co-cultures.

Neurons from the fetal pig dopaminergic ventral mesencephalon (VM) and basal ganglia anlage (the ganglionic eminence) were co-cultured as organotypic slice cultures to study the development of the two interconnected brain areas. During a short developmental period (E35-E42), a groove separates the ganglionic eminence into a lateral and a medial part. This was used (a) to study the developmental expression of the striatal marker protein, dopamine and adenosine 3,5-monophosphate regulated phospho-protein (DARPP-32) in the two parts and (b) to compare innervations of the two parts by tyrosine hydroxylase (TH)-positive, dopaminergic fibers from co-cultured slices of the ventral mesencephalon.

Directionality of the lizard ear.

Lizards have highly sensitive ears, but most lizard heads are small (1-2 cm in diameter) compared to the wavelengths of sound of frequencies to which they are most sensitive (1-4 kHz, wavelengths 34-8.5 cm). Therefore, the main cues to sound direction that mammals use - binaural time and intensity cues due to arrival-time differences and sound shadowing by the head--will be very small in lizards.

Leprosy and mortality in the Medieval Danish village of Tirup.

Leprosy was a well-recognized and dreaded disease in Denmark in the Middle Ages (AD 1000-1536). A large fraction of the population was affected by leprosy in the 13th century. This paper analyzes the correlation between signs of leprosy and risk of dying in the small Danish village of Tirup (AD 1150-1350).

GDNF pre-treatment aggravates neuronal cell loss in oxygen-glucose deprived hippocampal slice cultures: a possible effect of glutamate transporter up-regulation.

Besides its neurotrophic and neuroprotective effects on dopaminergic neurons and spinal motoneurons, glial cell line-derived neurotrophic factor (GDNF) has potent neuroprotective effects in cerebral ischemia. The protective effect has so far been related to reduced activation of N-methyl-D-aspartate receptors (NMDAr). This study tested the effects of GDNF on glutamate transporter expression, with the hypothesis that modulation of glutamate transporter activity would affect the outcome of cerebral ischemia.

Quantitative on-line monitoring of hippocampus glucose and lactate metabolism in organotypic cultures using biosensor technology.

Quantitative glucose and lactate metabolism was assessed in continuously perfused organotypic hippocampal slices under control conditions and during exposure to glutamate and drugs that interfere with aerobic and anaerobic metabolism. On-line detection was possible with a system based on slow perfusion rates, a half-open (medium/air interface) tissue chamber and a flow injection analytic system equipped with biosensors for glucose and lactate. Under basal conditions about 50% of consumed glucose was converted to lactate in hippocampal slice cultures.

Signal detection theory, detectability and stochastic resonance effects.

Stochastic resonance is a phenomenon in which the performance of certain non-linear detectors can be enhanced by the addition of appropriate levels of random noise. Signal detection theory offers a powerful tool for analysing this type of system, through an ability to separate detection processes into reception and classification, with the former generally being linear and the latter always non-linear. Through appropriate measures of signal detectability it is possible to decide whether a local improvement in detection via stochastic resonance occurs due to the non-linear effects of the classification process.

3-Nitropropionic acid neurotoxicity in hippocampal slice cultures: developmental and regional vulnerability and dependency on glucose.

We investigated whether neurotoxic effects of the mitochondrial toxin 3-nitropropionic acid (3-NP) in hippocampal slice cultures are dependent on glucose levels in the culture medium and whether such effects occur via apoptosis or necrosis. In addition, 3-NP toxicity was investigated at two developmental stages of the cultures, prepared from rat brain at postnatal day 5-7 and grown in Neurobasal medium for 1 or 3 weeks. Cultures were exposed to 3-NP in the presence of high (25 mM), normal (5 mM), or low (3 mM) glucose for 48 h, followed by 48 h incubation in medium without 3-NP.

Glutathione depletion in nigrostriatal slice cultures: GABA loss, dopamine resistance and protection by the tetrahydrobiopterin precursor sepiapterin.

Dopaminergic neurons in culture are preferentially resistant to the toxicity of glutathione (GSH) depletion. This effect may be due to high intrinsic levels of tetrahydrobiopterin (BH(4)). Here we studied the effects of manipulating GSH and/or BH(4) levels on selective neurotoxicity in organotypic nigrostriatal slice cultures.

Direct observation of syringeal muscle function in songbirds and a parrot.

The role of syringeal muscles in controlling the aperture of the avian vocal organ, the syrinx, was evaluated directly for the first time by observing and filming through an endoscope while electrically stimulating different muscle groups of anaesthetised birds. In songbirds (brown thrashers, Toxostoma rufum, and cardinals, Cardinalis cardinalis), direct observations of the biomechanical effects of contraction largely confirm the functions of the intrinsic syringeal muscles proposed from indirect studies. Contraction of the dorsal muscles, m.

Chronic exposure of kainate and NBQX changes AMPA toxicity in hippocampal slice cultures.

Receptor agonist/antagonist mediated modulation of the excitotoxic effect of AMPA was studied in organotypic hippocampal slice cultures. Treatment of developing cultures for 2 weeks with a subtoxic dose of 2 microM kainate reduced the toxicity of 3 microM AMPA, applied for 48 h with 24 h of recovery, as measured by cellular uptake of the fluorescent dye propidium iodide. In contrast long-term treatment with 0.

Comparison of excitotoxic profiles of ATPA, AMPA, KA and NMDA in organotypic hippocampal slice cultures.

The excitotoxic profiles of (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propionic acid (ATPA), (RS)-2-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), kainic acid (KA) and N-methyl-D-aspartate (NMDA) were evaluated using cellular uptake of propidium iodide (PI) as a measure for induced, concentration-dependent neuronal damage in hippocampal slice cultures. ATPA is in low concentrations a new selective agonist of the glutamate receptor subunit GluR5 confined to KA receptors and also in high concentrations an AMPA receptor agonist. The following rank order of estimated EC(50) values was found after 2 days of exposure: AMPA (3.

Uptake, metabolism and excretion of bisphenol A in the rainbow trout (Oncorhynchus mykiss).

The uptake, metabolism and excretion of the oestrogenic chemical bisphenol A (BPA) were studied in juvenile rainbow trout (Oncorhynchus mykiss). BPA was detectable in plasma, liver and muscle after 2 h of water exposure at 0.44 microM (100 microg BPA/l), and a steady state was reached within 12-24 h.

Epidemiological approach to the paleopathological diagnosis of leprosy.

In paleopathology it is usually assumed that modern diagnostic criteria can be applied to infectious diseases in the past. However, as both the human species and populations of pathogenic microorganisms undergo evolutionary changes, this assumption is not always well-founded. To get valid estimates of the frequency (the point prevalence at death) of leprosy in skeletal samples, sensitivity, specificity, and sample frequency must be estimated simultaneously.

Melatonin activates the peroxidase-oxidase reaction and promotes oscillations.

We have studied the peroxidase-oxidase reaction with NADH and O2 as substrates and melatonin as a cofactor in a semibatch reactor. We show for the first time that melatonin is an activator of the reaction catalyzed by enzymes from both plant and animal sources. Furthermore, melatonin promotes oscillatory dynamics in the pH range from 5 to 6.

The metabotropic glutamate receptor agonist 1S,3R-ACPD stimulates and modulates NMDA receptor mediated excitotoxicity in organotypic hippocampal slice cultures.

The potential toxic effects of the metabotropic glutamate receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) and its interactions with the N-methyl-D-aspartate (NMDA) receptor were studied in hippocampal brain slice cultures, using densitometric measurements of the cellular uptake of propidium iodide (PI) to quantify neuronal degeneration. Cultures exposed to ACPD, showed a concentration (2-5 mM) and time (1-4 days) dependent increase in PI uptake in CA1, CA3 and dentate subfields after 24 h and 48 h of exposure, with CA1 pyramidal cells being most sensitive. The neurodegeneration induced by 2 mM ACPD was completely abolished by addition of 10 microM of the NMDA receptor antagonist (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), while 20 microM of the 2-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainic acid receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) had no effect.

Biocompatibility of silicon-based arrays of electrodes coupled to organotypic hippocampal brain slice cultures.

In this study we examined the passive biocompatibility of a three-dimensional microelectrode array (MEA), designed to be coupled to organotypic brain slice cultures for multisite recording of electrophysiological signals. Hippocampal (and corticostriatal) brain slices from 1-week-old (and newborn) rats were grown for 4-8 weeks on the perforated silicon chips with silicon nitride surfaces and 40 microm sized holes and compared with corresponding tissue slices grown on conventional semiporous membranes. In terms of preservation of the basic cellular and connective organization, as visualized by Nissl staining, Timm sulphide silver-staining, microtubule-associated protein 2 (MAP2) and glial fibrillary acidic protein (GFAP) immunostaining, the slice cultures grown on chips did not differ from conventionally grown slice cultures.

GDNF and neublastin protect against NMDA-induced excitotoxicity in hippocampal slice cultures.

The potential neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF) and neublastin (NBN) against NMDA-induced excitotoxicity were examined in hippocampal brain slice cultures. Recombinant human GDNF (25-100 ng/ ml) or NBN, in medium conditioned by growth of transfected, NBN-producing HiB5 cells, were added to slice cultures I h before exposure to 10 microM NMDA for 48h. Neuronal cell death was monitored, before and during the NMDA exposure, by densitometric measurements of propidium iodide (PI) uptake and loss of Nissl staining.

Cost implications of routine mammography screening of women 50-69 years in the county of Funen, Denmark.

In order to estimate the net costs of introducing mammography screening to women 50-69 years of age, unit costs of all relevant activities related to detection and treatment of breast cancer were estimated using activity based costing methods. In order to determine the overall impact of mammography screening, activity data collected from the second screening round (1996-1997) were compared with expected activity levels in the case no screening had taken place in this time period. The direct health care costs associated with the screening activity, excluding effects on treatment and diagnostics but including women's transport and time costs, were estimated at DKK 305 per attendee.

Pyruvate protects against 3-nitropropionic acid neurotoxicity in corticostriatal slice cultures.

Previously, we have shown that 3-nitropropionic acid (NPA) neurotoxicity in organotypic corticostriatal slice cultures is dependent on glucose and glutamate. Here we studied the neuroprotective potential of agents improving mitochondrial function, including creatine, malate, oxaloacetate, Pyruvate and L-lactate in NPA-treated slice cultures. pyruvate provided the best protection against the loss of glutamic acid decarboxylase activity, depletion of GABA levels, increased propidium iodide uptake and increased glial fibrillary acidic protein levels.

Localization of human serum amyloid P component and heparan sulfate proteoglycan in in vitro-formed Abeta fibrils.

Ultrastructural studies of the localization of serum amyloid P component (SAP) in amyloid fibrils have given divergent results. We here report for the first time that electron microscopy of SAP coincubated with Abeta1-42 peptides or with mature Abeta1-42 fibrils, revealed SAP molecules coating the surface of the mature fibrils and that protofibrils of Abeta1-42 did not bind SAP. Also when incubated with extracted amyloid light chain (AL)-fibrils the SAP molecules aligned on the fibril surface.

Neurotoxic interactions of industrially used ketones.

Occupationally workers are most often exposed to a mixture of solvents. Exposure limits are, however, usually set separately for single solvents. So we reviewed the present knowledge about possible neurotoxic interactions of the industrially most used ketones acetone (ACE), methyl ethyl ketone (MEK) and methyl isobutyl ketone (MIBK) with solvents in general.

Plasmid and chromosome segregation in prokaryotes.

Recent major advances in the understanding of prokaryotic DNA segregation have been achieved by using fluorescence microscopy to visualize the localization of cellular components. Plasmids and bacterial chromosomes are partitioned in a highly dynamic fashion, suggesting the presence of a mitotic-like apparatus in prokaryotes. The identification of chromosomal homologues of the well-characterized plasmid partitioning genes indicates that there could be a general mechanism of bacterial DNA partitioning.

Improved survival of embryonic porcine dopaminergic neurons in coculture with a conditionally immortalized GDNF-producing hippocampal cell line.

Transplantation of embryonic nigral tissue is used as an experimental therapy for patients with Parkinson's disease but is hampered by a limited survival rate of dopaminergic neurons. Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor for nigrostriatal dopaminergic neurons, and the present in vitro study aimed at improving the survival of dopaminergic neurons in porcine mesencephalic brain slice cultures by adding transfected, immortalized, temperature-sensitive GDNF-releasing HiB5 cells (HiB5-GDNF). Embryonic (E27/28) porcine ventral mesencephalic brain slices were placed on membrane inserts in six-well plates with serum-containing medium, and HiB5-GDNF, nontransfected HiB5 cells (HiB5-control), or green fluorescent protein-producing HiB5 cells (HiB5-GFP) were seeded onto each tissue slice.

No association between birth weight and Type 1 diabetes mellitus--a twin-control study.

Aims: To investigate, by means of a twin-control study, whether there is a relationship between birth weight and Type 1 diabetes mellitus.

Methods: In the youngest part (n = 20 888 pairs) of the Danish Twin Register, 95 twin pairs (26 monozygotic and 69 dizygotic) with Type 1 diabetes were identified. Information about birth weight and birth length, prematurity, maternal age and parity was obtained from midwives' records and from the Danish Medical Birth Registry and analysed using Student's two-sided t-test, Chi-square test and logistic regression.

Pigments and proteins in green bacterial chlorosomes studied by matrix-assisted laser desorption ionization mass spectrometry.

We have used matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for mass determination of pigments and proteins in chlorosomes, the light-harvesting organelles from the photosynthetic green sulfur bacterium Chlorobium tepidum. By applying a small volume (1 microL) of a concentrated suspension of isolated chlorosomes directly to the target of the mass spectrometer we have been able to detect bacteriochlorophyll a and all the major homologs of bacteriochlorophyll c. The peak heights of the different bacteriochlorophyll c homologs in the MALDI spectra were proportional to peak areas obtained from HPLC analysis of the same sample.