Genetic mapping of the beta 1- and gamma-subunits of the human skeletal muscle L-type voltage-dependent calcium channel on chromosome 17q and exclusion as candidate genes for malignant hyperthermia susceptibility.

Malignant hyperthermia susceptibility (MHS) is an autosomal dominant disorder of skeletal muscle which manifests as a life-threatening hypermetabolic crisis triggered by commonly-used inhalation anaesthetics and depolarizing muscle relaxants. Defects in the ryanodine receptor (RYR1) protein have been proposed to underly MHS, but significant genetic heterogeneity in MHS has recently been demonstrated. In order to investigate the potential roles played by other skeletal muscle calcium channels in MHS, we isolated cosmids containing the gene encoding the beta 1-subunit of skeletal muscle L-type voltage-dependent calcium channel (CACNLB1).

Behavioural responses of bicucculline methiodide injections into the ventral hypothalamus of freely moving, socially interacting rats.

Several studies, using electrical stimulation of parts of the hypothalamus, have shown, that different parts of the hypothalamus yield different behavioural responses upon stimulation. In order to differentiate between stimulation of neuronal cell bodies and passing fibres and to investigate the role of GABA in hypothalamically elicited behaviour, 25 local injections with bicucculline methiodide, a GABA antagonist, (35 ng/0.2 microliter) were performed in the ventral parts of the hypothalamus of 16 freely moving rats in a social environment.

Rationing in The Netherlands: the liberal and the communitarian perspective.

In the discussion on rationing health care in The Netherlands, a fundamental tension emerges between two ethical perspectives: liberalism and communitarianism. A Dutch government committee recently issued a report opting for a community-oriented approach. This approach proves less communitarian as compared to the views on rationing elaborated by Callahan.

A new microcannula for injections in rat brains without disturbing social interactions.

A new cannula system is presented that allows intracerebral microinjections of neuroactive substances in freely moving rats in a social environment. By connecting a microcannula to a freely rotating stainless steel spring, small (0.2 microliter) injections can be made without disturbing the ongoing social interaction.

Structure and localization of mRNA encoding a pigment dispersing hormone (PDH) in the eyestalk of the crayfish Orconectes limosus.

The pigment-dispersing hormone (PDH) is produced in the eyestalks of Crustacea where it induces light-adapting movements of pigment in the compound eye and regulates the pigment dispersion in the chromatophores. To study this hormone at the mRNA level, we cloned and sequenced cDNA encoding PDH in the crayfish Orconectes limosus. The structure of the PDH preprohormone consists of a signal peptide, a PDH precursor-related peptide (PPRP) and the highly conserved PDH peptide at the carboxy-terminal end.

Intestinal, segmented, filamentous bacteria in a wide range of vertebrate species.

Segmented, filamentous bacteria (SFBs) form a group of bacteria with similar morphology and are identified on the basis of their morphology only. The relationships of these organisms are unclear as the application of formal taxonomic criteria is impossible currently due to the lack of an in vitro technique to culture SFBs. The intestine of laboratory animals such as mice, rats, chickens, dogs, cats and pigs is known to harbour SFBs.

Ecological aspects, explosive range extension and impact of a mass invader, Corophium curvispinum Sars, 1895 (Crustacea: Amphipoda), in the Lower Rhine (The Netherlands).

A few years after it invaded, the amphipod Corophium curvispinum Sars appeared to be the most numerous macroinvertebrate species in the River Rhine. From 1987 to 1991 the densities of this species on the stones of groins in the Lower Rhine at a depth of 0.5 m increased from 2 to 200000 specimens per m.

Human jaw-elevator muscle activity and food comminution in the dentate and edentulous state.

Masseter and temporal surface electromyograms were obtained from seven dentate subjects and six complete-denture wearers during mastication, maximal voluntary clenching and measurements of bite force. The participants chewed two artificial test foods with different textures. The dentate subjects comminuted both foods much better than the denture wearers.

Sequential assignment of 2D-NMR spectra of proteins using genetic algorithms.

The application of genetic algorithms to the problem of the sequential assignment of two-dimensional protein NMR spectra is discussed. The problem is heavily underconstrained since in most cases more patterns are available than amino acid positions, and uncertainties may exist in the preliminary assignments. The results indicate that relatively large amounts of errors may be present in the input data for the genetic algorithm while useful results may still be obtained.

The effects of haloperidol and raclopride in the paw test are influenced similarly by SCH 39166.

We investigated the role of dopamine D1 and D2 receptors in the paw test, an animal model used to assess both the antipsychotic potential and extrapyramidal side effects of drugs. The dopamine D1 receptor antagonist, SCH 39166, as well as the dopamine D2 receptor antagonist raclopride, increased the hindlimb retraction time (HRT), viz. a parameter that models antipsychotic potential, at doses that were lower than those that increased the forelimb retraction time (FRT), viz.

The effects of atmospheric nitrogen deposition and soil chemistry on the nutritional status of Pseudotsuga menziesii, Pinus nigra and Pinus sylvestris.

The ammonium content and the base cation content, expressed relative to ammonium, are enhanced in the soil of Dutch forests, due to the extremely high deposition of ammonium to the forest floor. A nation-wide investigation was carried out to establish whether and how these changed nitrogen fluxes in deposition and soil affect the nutritional status of coniferous trees. The chemical composition of needles of Douglas fir, Scots pine and Corsican pine showed a regional trend similar to that of deposition and soil solution.

The effects of atmospheric nitrogen deposition on the soil chemistry of coniferous forests in The Netherlands.

Nitrogen fluxes, particularly those of ammonium, are extremely high in Dutch forests. In soils exposed to high ammonium deposition, acidification, eutrophication or a combination of both processes may occur. In addition to the amounts of ammonium deposited, the rate of soil nitrification determines which process takes place.

Localization of the gamma-subunit of the skeletal muscle L-type voltage-dependent calcium channel gene (CACNLG) to human chromosome band 17q24 by in situ hybridization and identification of a polymorphic repetitive DNA sequence at the gene locus.

The skeletal muscle dihydropyridine receptor consists of five subunits and fulfils an essential role in excitation-contraction coupling. A genomic clone for the human gamma subunit was used to map the gene (CACNLG) to chromosome band 17q24 by in situ hybridization. Contained within the gene is a 416-bp polymorphic repetitive DNA element that is potentially useful as a genetic marker.

Treatment of schizophrenia: a clinical and preclinical evaluation of neuroleptic drugs.

Forty years after the first clinical report on the effectiveness of chlorpromazine in psychiatric patients, neuroleptic drugs are still the most widely used drugs in the treatment of schizophrenia. Indeed, there are no other drugs which have proven to be as effective in the treatment of this severe psychiatric disorder. Yet, there are still many unresolved problems relating to neuroleptic drugs.

Different degree of ileal colonization by segmented, filamentous bacteria in two strains of mice.

Segmented, filamentous bacteria (SFBs) are autochthonous, apathogenic inhabitants of the ileum of various animal species. Outbred Swiss (Cpb:SE) mice have significantly higher degrees of SFB colonization than do inbred BALB/c mice. The present studies were carried out to identify determinants of this strain difference.

Localization of messenger RNAs encoding crustacean hyperglycemic hormone and gonad inhibiting hormone in the X-organ sinus gland complex of the lobster Homarus americanus.

The localization of messenger RNAs encoding the crustacean hyperglycemic hormone, involved in regulation of carbohydrate metabolism and the gonad inhibiting hormone, which inhibits vitellogenesis, was studied in the eyestalk of the lobster Homarus americanus using complementary RNA probes for in situ hybridization. For the detection of gonad inhibiting hormone messenger RNA, we cloned and sequenced a partial complementary DNA encoding lobster gonad inhibiting hormone and for crustacean hyperglycemic hormone messenger RNA detection an available complementary DNA was used. This approach reveals that there is a frequent but inconsistent cellular co-localization of the two neurohormones.

High-resolution physical mapping of four microsatellite repeat markers near the RYR1 locus on chromosome 19q13.1 and apparent exclusion of the MHS locus from this region in two malignant hyperthermia susceptible families.

Malignant hyperthermia susceptibility (MHS) is a potentially lethal, hereditary disorder of skeletal muscle that may be triggered by inhalation anesthetics and depolarizing muscle relaxants. Defects in the gene encoding the ryanodine receptor (RYR1) localized on human chromosome 19q13.1 have been proposed to be responsible for MHS.

Immunization against cerebral pathology in Plasmodium berghei-infected mice.

The development of cerebral lesions in Plasmodium berghei-infected mice was dependent on the strain of mice and the size of the infectious inoculum. In particular, C57Bl/6J mice develop cerebral lesions when infected with low numbers of parasitized erythrocytes. By increasing the number of parasites in the infectious inoculum, the percentage of animals that develop cerebral malaria is decreased.

Equity and solidarity: the context of health care in The Netherlands.

The current debate on health care resource allocation in the Netherlands is characterized by a social context in which two values are generally and traditionally accepted as being equally fundamental:solidarity and equity. We will present an outline of the distinctive features of the Dutch health care system, and analyze the present state of affairs in the resource allocation debate. The presuppositions of the political call for constraint and (renewed) government supervision and the role of the specific value context in recent proposals for reconstruction of the Dutch health care system will be evaluated.

The medical exception: physicians, euthanasia and the Dutch criminal law.

The legalization of euthanasia, both in the Netherlands and in other countries is usually justified in reference to the right to autonomy of patients. Utilizing recent Dutch jurisprudence, this article intends to show that the judicial proceedings on euthanasia in the Netherlands have not so much enhanced the autonomy of patients, as the autonomy of the medical profession.

The lethal prune/Killer-of-prune interaction of Drosophila causes a syndrome resembling human neurofibromatosis (NF1).

The eye color mutant prune (pn) of Drosophila melanogaster shows a lethal interaction with the Killer-of-prune (K-pn) allele of the abnormal wing disc (awd) locus. The awd gene is the Drosophila homologue of the mammalian tumor metastasis gene nm23, and it has been postulated that pn encodes a protein with similarity to a GAP, a GTPase-activating protein. Such GAPs potentially control Ras-like proteins, which are important molecular switches.

Intestinal, segmented, filamentous bacteria.

Segmented, filamentous bacteria (SFBs) are autochthonous, apathogenic bacteria, occurring in the ileum of mice and rats. Although the application of formal taxonomic criteria is impossible due to the lack of an in vitro technique to culture SFBs, microbes with a similar morphology, found in the intestine of a wide range of vertebrate and invertebrate host species, are considered to be related. SFBs are firmly attached to the epithelial cells of the distal ileal mucosa, their preferential ecological niche being the epithelium covering the Peyer's patches.

Jaw muscle activity, the nucleus accumbens, and dopaminergic agonists: a new approach.

A method was developed to analyze electromyographic (EMG) signals in terms of power, viz., a measure for overall muscle activity, and number of seconds marked by distinct frequency ranges. With the help of this method, the effects of intraaccumbens administration of distilled water, the D1 receptor agonist SK&F 38393 (SKF; 5 micrograms), the D2 receptor agonist LY 171555 (LY; 10 micrograms), and their combination upon the EMG signals of the masseter and the digastric muscle were analysed in freely moving rats.