Enhanced head-twitch response to 5-HT-related agonists in thiamine-deficient mice.

While many studies suggest an involvement of brain serotonergic systems in neuro-psychiatric disorders such as schizophrenia and depression, their role in Wernicke-Korsakoff syndrome (WKS) remains unclear. Since dietary thiamine deficiency (TD) in mice is considered as a putative model of WKS, it was used in the present study to investigate the function of serotonergic neurons in this disorder. After 20 days of TD feeding, the intensity of tryptophan hydroxylase immunofluorescence was found to be significantly decreased in the dorsal and medial raphe nuclei. In addition, the head-twitch response (HTR) elicited by the intracerebroventricular administration of the 5-HT(2A) agonist 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) was significantly increased in TD versus control mice, whereas the injection of ketanserin, a 5-HT(2A) receptor antagonist, prevented this enhancement. A single injection of thiamine HCl on the 19th day of TD feeding did not reduce the enhanced DOI-induced HTR. On the other hand, the administration of d-fenfluramine, a 5-HT releaser, did not enhance the HTR in TD mice. Together, our results indicate that TD causes a super-sensitivity of 5-HT(2A) receptors by reducing presynaptic 5-HT synthesis derived from degenerating neurons projecting from the raphe nucleus.

Identification of proteins whose amounts are altered by mutation in the pgsA gene of Escherichia coli.

We identified proteins whose amounts were altered in an Escherichia coli pgsA3 mutant lacking the potential to synthesize phosphatidylglycerolphosphate, a precursor of phosphatidylglycerol. Proteins whose amounts were increased in the mutant were protease Do, periplasmic oligopeptide-binding protein, tryptophanase, and an unidentified protein, while the decreased one was flagellin. Transformation of the mutant with a plasmid containing the wild type pgsA gene complemented the phenotype, indicating that the pgsA3 mutation is responsible for the phenotype.

Site-directed mutational analysis for the membrane binding of DnaA protein. Identification of amino acids involved in the functional interaction between DnaA protein and acidic phospholipids.

DnaA protein, the initiator of chromosomal DNA replication in Escherichia coli, interacts with acidic phospholipids, such as cardiolipin, and its activity seems to be regulated by membrane binding in cells. In this study we introduced site-directed mutations at the positions of hydrophobic or basic amino acids which are conserved among various bacteria species and which are located in the putative membrane-binding region of DnaA protein (from Asp357 to Val374). All mutant DnaA proteins showed much the same ATP and ADP binding activity as that of the wild-type protein. The release of ATP bound to the mutant DnaA protein, in which three hydrophobic amino acids were mutated to hydrophilic ones, was stimulated by cardiolipin, as in the case of the wild-type protein. On the other hand, the release of ATP bound to another mutant DnaA protein, in which three basic amino acids were mutated to acidic ones, was not stimulated by cardiolipin. These results suggest not only that the region is a membrane-binding domain of DnaA protein but also that these basic amino acids are important for the binding and the ionic interaction between the basic amino acids and acidic residues of cardiolipin and is involved in the interaction between DnaA protein and cardiolipin.

Amounts of proteins altered by mutations in the dnaA gene of Escherichia coli.

We identified proteins whose amounts were altered in a temperature-sensitive dnaA46 mutant of Escherichia coli. Proteins whose amounts were increased in the mutant were serine hydroxymethyltransferase, beta-ketoacyl [acyl carrier protein] synthase II, long-chain fatty acid transport protein, and UDP-glucose 4-epimerase, while the decreased ones were flagellin and D-ribose-binding protein. Transformation of the mutant with a plasmid containing the wild type dnaA gene complemented the phenotype. As pulse-labeling experiments revealed that the rates of synthesis of the proteins were altered in the mutant, DnaA protein may be involved in expression of these proteins.

Comparison of disposition behavior and de-coppering effect of triethylenetetramine in animal model for Wilson's disease (Long-Evans Cinnamon rat) with normal Wistar rat.

The disposition behaviors and de-coppering effect of triethylenetetramine dihydrochloride (trientine), a selective chelating agent for copper and an 'orphan drug' for Wilson's disease, have been evaluated in an animal model, Long-Evans Cinnamon (LEC) rats, and normal rats (Wistar). In LEC rats, urinary excretion of trientine was remarkably lower than that of Wistar rats. The absorption rates from the jejunal loop and in vitro metabolism in the liver S9 fraction (supernatant of 9000 x g) were approximately the same for both strains. The decline of urinary excretion of trientine in LEC rats is thought to be due mainly to the lowering of the functional activity of the kidney, because urinary excretion of creatinine and phenolsulfonphthalein were significantly lower in LEC rats than those in Wistar rats. Both acceleration of urinary excretion of copper and reduction of hepatic copper levels were observed with treatment of trientine in LEC rats aged 6 weeks. In LEC rats aged 13 weeks, however, no de-coppering effect from the liver was observed, though urinary excretion of copper was increased. These results suggest that trientine has a pharmacological effect in disease state, especially in the early stages of hepatitis.

Reflection polarizing holographic optical element for compact magnetooptical disk heads.

A reflection polarizing holographic optical element with sinusoidal surface-relief has been developed for compact magnetooptical (MO) disk heads. The element has the polarizing beam splitter function as well as the focusing and tracking error signal detection functions. To produce the sinusoidal surface-relief structure with photolithography, a new fabrication process, which includes procedures for converting a rectangular profile into a sinusoidal profile, is introduced. Replicas were also fabricated with high replication fidelity using the photopolymerization method. The developed element was used in an MO disk head. A 57-dB C/N ratio, which is sufficient value for practical use was achieved for a 1-MHz readout signal.

An analytic study of epileptic falls.

The subject of this study was a total of 48 epileptic falls or drop attacks in 15 children, captured by a self-tracking video monitoring system. A fall was defined as a complete loss of the maintenance of either standing or sitting posture, which took place within 1 s. The patients with epileptic falling attacks thus defined fulfilled the diagnostic criteria of Lennox-Gastaut syndrome. Through precise analysis of the ongoing sequence from the onset to the completion of the fall, it was possible to classify them into the following four types: (a) tonic type, 9 falls in five patients; (b) flexor spasms type, 25 falls in eight patients; (c) myoclonic-atonic type, 12 falls in three patients; and (d) atonic type, 2 falls in one patient. In contrast to the generally accepted view, it was found that atonic or myoclonic-atonic falls were rather exceptional. Seven of eight children whose falls were categorized as the flexor spasms type, which is reminiscent of infantile spasms in terms of clinical as well as EEG expressions, in fact experienced in their individual history West syndrome before it evolved to Lennox-Gastaut syndrome. In particular, the extreme pathophysiological complexity of epileptic falls or drop attacks is stressed.