Comparing Medial Temporal Atrophy Between Early-Onset Semantic Dementia and Early-Onset Alzheimer's Disease Using Voxel-Based Morphometry: A Multicenter MRI Study.

Background: Early-onset Semantic dementia (EOSD) and early-onset Alzheimer's disease (EOAD) are often difficult to clinically differentiate in the early stages of the diseases because of the overlaps of clinical symptoms such as language symptoms. We compared the degree of atrophy in medial temporal structures between the two types of dementia using the voxel-based specific regional analysis system for Alzheimer's disease (VSRAD).

Methods: The participants included 29 (age: 61.

Assessment of Amyloid Deposition in Patients With Probable REM Sleep Behavior Disorder as a Prodromal Symptom of Dementia With Lewy Bodies Using PiB-PET.

Dementia with Lewy bodies (DLB) often exhibits REM sleep behavior disorder (RBD) at its prodromal stage. Meanwhile, DLB is often comorbid with Alzheimer's disease (AD)-type pathology. In typical AD, amyloid-β deposition begins considerably before the onset of dementia and has already reached a plateau at the stage of mild cognitive impairment.

Intravenously administered 2'-deoxycytidine suppresses mouse myeloma tumor growth.

We examined the in vivo effects of intravenously administered 2'-deoxycytidine (dCyd) on tumor growth and survival time in mice bearing SP2/0-Ag14 (SP2/0) myeloma tumors. Administration of dCyd tended to decrease the tumor volume and significantly decreased the tumor weight. A single intravenous administration of dCyd significantly increased survival time of the tumor-bearing mice.

Changes in 2'-deoxycytidine levels in various tissues of tumor-bearing mice.

The nucleoside 2'-deoxycytidine (dCyd) increases in the plasma of cancer patients with poor prognoses. 5-fluorouracil (5FU) is one of the anti-cancer agents used in chemotherapy for patients whose plasma dCyd is elevated. We examined the free dCyd level in various tissues of mice, with and without tumors, and in mice with and without the administration of 5FU or of dCyd, and investigated the effects of dCyd in tumor-bearing animals.

2'-Deoxycytidine decreases the anti-tumor effects of 5-fluorouracil on mouse myeloma cells.

2'-Deoxycytidine (dCyd), a pyrimidine nucleoside found at high concentrations in the plasma of cancer patients with a poor prognosis after chemotherapy, is considered to be a biomarker for breast cancer. 5-Fluorouracil (5FU) is a nucleoside analog and is used as an anti-tumor agent in patients whose plasma dCyd concentrations are increased. Because both dCyd and 5FU are pyrimidine analogues, it is possible that they have pharmacokinetic/ pharmacodynamic interaction, by which the anti-cancer efficacy of 5FU would be reduced.

S-sulfonation of transthyretin is an important trigger step in the formation of transthyretin-related amyloid fibril.

Senile systemic amyloidosis and familial amyloid polyneuropathy are caused by oxidative deposition of conformationally altered transthyretin (TTR). We identified oxidative modification of the 10th cysteine of TTR through S-sulfonation in vitro. Based on mass spectrometric analysis, we determined the spectrophotometric, western blotting, and fluorescent microscopic properties of TTR incubated with and without cysteine-S-sulfonate in acidic (pH 4) and alkaline (pH 8) conditions at 37 degrees.

[Oxidative precipitation of transthyretin--a clue to elucidate amyloidosis].

Common precipitation of amyloid proteins occurs in amyloidosis such as dementia and prion diseases. The precipitates are characteristically stained with congo red, although it is not yet known why this occurs. We have found a kind of amyloid protein, transthyretin(TTR), that is S-sulfonated at the residue of cysteine in blood from patients with deficiency of molybdenum cofactor, which is essential to sulfite oxidase.

Modification of cysteine residue in transthyretin and a synthetic peptide: analyses by electrospray ionization mass spectrometry.

Cysteine and cystine in protein are modified to various derivatives in vitro and in vivo. By electrospray ionization mass spectrometry (ESI-MS), we previously found derivatives of serum transthyretin (TTR) in which cysteine residue at position 10 was changed to glycine residue and sulfocysteine residue. The change, cysteine to glycine, was unique and the origin of the sulfonic acid group was controversial.

A screening system of prodrugs selective for MAO-A or MAO-B.

We synthesized several prodrugs of glycine and gamma-aminobutyric acid. In order to establish a screening system from the prodrugs of selective activity to MAO-A or MAO-B, we examined purification conditions such as solubilization with Triton X-100, precipitation with ammonium sulfate, gel filtration and anion exchange chromatography. MAO-B was purified from various tissues such as guinea pig brain, kidney and spleen.

The peak height ratio of S-sulfonated transthyretin and other oxidized isoforms as a marker for molybdenum cofactor deficiency, measured by electrospray ionization mass spectrometry.

Molybdenum cofactor deficiency is a fatal neurological disorder, which follows an autosomal-recessive trait and is characterized by combined deficiency of the enzyme, sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase. Early detection of molybdenum cofactor-deficient patients is essential for their proper care and genetic counseling of families at risk. We demonstrate the use of S-sulfonated transthyretin (TTR) as a marker for molybdenum cofactor deficiency.