Molecular basis of perinatal hypophosphatasia with tissue-nonspecific alkaline phosphatase bearing a conservative replacement of valine by alanine at position 406. Structural importance of the crown domain.

Hypophosphatasia, a congenital metabolic disease related to the tissue-nonspecific alkaline phosphatase gene (TNSALP), is characterized by reduced serum alkaline phosphatase levels and defective mineralization of hard tissues. A replacement of valine with alanine at position 406, located in the crown domain of TNSALP, was reported in a perinatal form of hypophosphatasia. To understand the molecular defect of the TNSALP (V406A) molecule, we examined this missense mutant protein in transiently transfected COS-1 cells and in stable CHO-K1 Tet-On cells.

Effect of liver transplantation on transthyretin Tyr114Cys-related cerebral amyloid angiopathy.

Objective: Patients with amyloidogenic transthyretin (ATTR) Tyr114Cys develop amyloid deposits in cerebral blood vessels, cerebral hemorrhage, and rapidly progressive dementia that presents with hereditary cerebral amyloid angiopathy (CAA). However, no treatment has been identified for CAA. Although liver transplantation has become an acceptable treatment of TTR-related amyloidosis, liver transplantation may not successfully treat CNS manifestations of the disorder.

The interaction of two tethering factors, p115 and COG complex, is required for Golgi integrity.

The vesicle-tethering protein p115 functions in endoplasmic reticulum-Golgi trafficking. We explored the function of homologous region 2 (HR2) of the p115 head domain that is highly homologous with the yeast counterpart, Uso1p. By expression of p115 mutants in p115 knockdown (KD) cells, we found that deletion of HR2 caused an irregular assembly of the Golgi, which consisted of a cluster of mini-stacked Golgi fragments, and gathered around microtubule-organizing center in a microtubule-dependent manner.

[Astasia in a patient with unilateral thalamic infarction: clinical and MRI study].

We report a 82-year-old woman who developed difficulty in standing and sitting in the morning. She had no other complaints and stayed in the bed. The next day, she was admitted to the hospital and neurological examination revealed that she was alert, with no other motor or sensory abnormalities.

Modulation of D-serine levels via ubiquitin-dependent proteasomal degradation of serine racemase.

Mammalian serine racemase is a brain-enriched enzyme that converts L- into D-serine in the nervous system. D-Serine is an endogenous co-agonist at the "glycine site" of N-methyl D-aspartate (NMDA) receptors that is required for the receptor/channel opening. Factors regulating the synthesis of D-serine have implications for the NMDA receptor transmission, but little is known on the signals and events affecting serine racemase levels.

[Seizure-induced transient brain edema in the medial temporal lobe].

We reported a patient with sudden onset seizure resulting in prolonged amnesia. MRI revealed a T2 high signal lesion with swelling in the right medial temporal lobe. Because the MRI lesion remained to be the same in size for two months, biopsy specimens were obtained under informed consent to rule out the brain tumor.

Depletion of vesicle-tethering factor p115 causes mini-stacked Golgi fragments with delayed protein transport.

Depletion of p115 with small interfering RNA caused fragmentation of the Golgi apparatus, resulting in dispersed distribution of stacked short cisternae and a vesicular structure (mini-stacked Golgi). The mini-stacked Golgi with cis- and trans-organization is functional in protein transport and glycosylation, although secretion is considerably retarded in p115 knockdown cells. The fragmented Golgi was further disrupted by treatment with breferdin A and reassembled into the mini-stacked Golgi by removal of the drug, as observed in control cells.

[Diagnostic validity of sensorimotor stroke].

Background: In the clinical practice, "sensorimotor stroke" (SMS) do not always correspond to the diagnosis of small-vessel occlusion (SVO, lacune). We aimed to evaluate diagnostic validity of acute SMS with the use of diffusion-weighted MR imaging (DWI).

Methods: We analyzed 57 consecutive patients with first-ever acute ischemic stroke presenting with SMS.

Direct interaction of N-ethylmaleimide-sensitive factor with GABA(A) receptor beta subunits.

GABA(A) receptors mediate most of the fast inhibitory neurotransmission in the brain, and are believed to be composed mainly of alpha, beta, and gamma subunits. It has been shown that GABA(A) receptors interact with a number of binding partners that act to regulate both receptor function and cell surface stability. Here, we reveal that GABA(A) receptors interact directly with N-ethylmaleimide-sensitive factor (NSF), a critical regulator of vesicular dependent protein trafficking, as measured by in vitro protein binding and co-immunoprecipitation assays.

[A case of interhemispheric subdural empyema with sinusitis diagnosed by diffusion-weighted MRI].

The patient was a 29-year-old man with sinusitis. He was admitted with high grade fever, headache, vomiting and disturbance of consciousness. Neurological examination revealed nuchal rigidity, aphasia, right hemiparesis, right sensory disturbance and bilateral Babinski signs.

High-efficiency and minimum-waste continuous kinetic resolution of racemic alcohols by using lipase in supercritical carbon dioxide.

A novel continuous-flow scCO(2) process for kinetic resolution of racemic alcohols can be performed with an immobilized lipase to lead to a quantitative mixture of the corresponding optically active acetates with up to 99% ee and unreacted alcohols with up to 99% ee, in which the productivity of the optically active compounds was improved by over 400 times compared to the corresponding batch reaction using scCO(2).

Diabetes mellitus decreases hippocampal release of neurotransmitters: an in vivo microdialysis study of awake, freely moving rats.

Possible diabetes mellitus-induced changes in hippocampal monoaminergic activities were studied to understand the relationships between neurotransmitter levels and various abnormalities in freely moving diabetic rats. We used both experimentally (STZ rats) and spontaneously diabetic rats (WBN/Kob rats) as the diabetic animal model, and compared the findings with those obtained from non-diabetic rats (C rats). Measurement of neurotransmitters (serotonin and dopamine) was carried out using an in vivo microdialysis method.

Effects of ethanol on the induction of uncoupling protein-1 (UCP1) mRNA in the mouse brown adipose tissue.

Expression of uncoupling protein-1 (UCP1) is increased by cold acclimation and overfeeding, and reduced in fasting and genetic obesity. It is known that the mitochondrial UCP1 in the brown adipose tissue (BAT) is an important key molecule for non-shivering thermogenesis. On the other hand, ethanol (EtOH) alters thermoregulation in humans and laboratory animals.

Dynamics of Golgi matrix proteins after the blockage of ER to Golgi transport.

When the ER to Golgi transport is blocked by a GTP-restricted mutant of Sar1p (H79G) in NRK-52E cells, most Golgi resident proteins are transported back into the ER. In contrast, the cis-Golgi matrix proteins GM130 and GRASP65 are retained in punctate cytoplasmic structures, namely Golgi remnants. Significant amounts of the medial-Golgi matrix proteins golgin-45, GRASP55 and giantin are retained in the Golgi remnants, but a fraction of these proteins relocates to the ER.

Rax1, a protein required for the establishment of the bipolar budding pattern in yeast.

In Saccharomyces cerevisiae, cell type determines two distinct spatial budding patterns. Haploid cells exhibit an axial pattern, whereas diploid cells exhibit a bipolar pattern. Axl1, a member of the insulin-degrading enzyme (IDE) family, is the key morphological determinant for the haploid axial pattern.

Identification and characterization of GCP16, a novel acylated Golgi protein that interacts with GCP170.

GCP170, a member of the golgin family associated with the cytoplasmic face of the Golgi membrane, was found to have a Golgi localization signal at the NH2-terminal region (positions 137-237). Using this domain as bait in the yeast two-hybrid screening system, we identified a novel protein that interacted with GCP170. The 2.

Direct interaction of the Golgi membrane with the endoplasmic reticulum membrane caused by nordihydroguaiaretic acid.

Nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenase, blocks protein transport from the endoplasmic reticulum (ER) to the Golgi complex and induces the redistribution of Golgi proteins into the ER. We investigated characteristics of NDGA-induced retrograde movement of the Golgi proteins to the ER. At an early stage of incubation of cells with NDGA, the Golgi complex formed convoluted membrane aggregates.

The CD26-related dipeptidyl aminopeptidase-like protein DPPX is a critical component of neuronal A-type K+ channels.

Subthreshold-activating somatodendritic A-type potassium channels have fundamental roles in neuronal signaling and plasticity which depend on their unique cellular localization, voltage dependence, and kinetic properties. Some of the components of A-type K(+) channels have been identified; however, these do not reproduce the properties of the native channels, indicating that key molecular factors have yet to be unveiled. We purified A-type K(+) channel complexes from rat brain membranes and found that DPPX, a protein of unknown function that is structurally related to the dipeptidyl aminopeptidase and cell adhesion protein CD26, is a novel component of A-type K(+) channels.

Localization of the PP2A B56gamma regulatory subunit at the Golgi complex: possible role in vesicle transport and migration.

The BL6 subline was derived from the F10 line, which was derived from the B16 mouse melanoma cell line. BL6 cells are more invasive than F10 cells and differ genetically from F10 cells by an alteration of the gene encoding the B56gamma regulatory subunit of protein phosphatase 2A (PP2A). This alteration results in the transcription of mRNA encoding a truncated variant of the B56gamma1 isoform (Deltagamma1).

Structural characterization of non-native states of sperm whale myoglobin in aqueous ethanol or 2,2,2-trifluoroethanol media.

The effects of aqueous ethanol or 2,2,2-trifluoroethanol media on the structure of sperm whale myoglobin have been investigated by absorption, CD, and NMR spectra. The structural properties of myoglobin such as heme environments, helix contents, protein folding, and interactions between heme and the protein moiety have been sharply manifested in these spectra. The characterization demonstrated that alcohol-induced conformational change of myoglobin depends on the nature of alcohol and its concentration.

Modulation of the stress response by coffee: an in vivo microdialysis study of hippocampal serotonin and dopamine levels in rat.

We studied whether coffee and its components (caffeine and chlorogenic acid) have stress-relaxing effects. In vivo brain microdialysis was used to characterize the effects of coffee, stress, and their interaction on the serotonergic and dopaminergic systems in the rat hippocampus. Restraint stress for 100 min caused a marked increase in dopamine and serotonin (5-HT) levels in the hippocampus, and then, 100 min resting (freely-moving) time reduced them to basal levels.

Role of the PLC-related, catalytically inactive protein p130 in GABA(A) receptor function.

The protein p130 was isolated from rat brain as an inositol 1,4,5-trisphosphate-binding protein with a domain organization similar to that of phospholipase C-delta1 but lacking PLC activity. We show that p130 plays an important role in signaling by the type A receptor for gamma-aminobutyric acid (GABA). Yeast twohybrid screening identified GABARAP (GABA(A) receptor-associated protein), which is proposed to contribute to the sorting, targeting or clustering of GABA(A) receptors, as a protein that interacts with p130.

[A case of inflammatory endotracheal polyps in an asthmatic subject].

A 60-year-old asthmatic woman was admitted to our department because of bloody sputum and pneumonia. She had been treated with inhaled becromethasone dipropionate (800 micrograms/day) on an outpatient basis for 3 years. Fiberoptic bronchoscopy revealed polypoid lesions in the trachea, most of which were removed with forceps during the procedure.