A new disorder of praxis in neurodegenerative disease that may be part of Alzheimer's disease.

Apraxia is a well-known disorder of praxis and is caused mainly by damage to the left parietal lobe. We presented two cases of neurodegenerative disease with a distinct disorder of praxis, predominantly involving left parietal lobe. While both patients could understand what they should do, they were not able to initiate action and often stopped during execution of actions. They had no apraxia and no temporal and spatial errors on praxis. Magnetic resonance imaging of both patients showed atrophy of the left parieto-occipital and temporo-occipital lobes, and single photon emission computed tomography showed hypoperfusion in the same lobes. Moreover, one of our cases, using [11C] PIB PET, demonstrated increased uptake in the cerebral cortices, suggesting Alzheimer's disease. The symptoms described are different from other disorders of praxis and similar to bradyphrenia or freezing.

A case of musical agraphia.

Damage to the left upper parietal lobule causes pure agraphia. However, we experienced a patient who exhibited musical agraphia following such a lesion after the agraphia improved. The patient was a 53-year-old female piano teacher. After surgery, she exhibited agraphia and musical agraphia. There was no expressive amusia, receptive amusia, aphasia, agnosia or apraxia. Fifteen months post-surgery, when her agraphia had resolved, her abilities to read, write, and copy music were evaluated. She could read and write single notes and musical signs, but her ability to write a melody was seriously impaired. Furthermore, the salient impairment was in writing rhythm rather than pitch. She could copy music, but only slowly. We consider her a case of pure musical agraphia.

Cerebral localization of the center for reading and writing music.

The mechanisms that underlie the ability to read and write music remain largely unclear compared to those involved in reading and writing language. We had the extremely rare opportunity to study the cerebral localization of the center for reading and writing music in the case of a professional trombonist. During rehearsal immediately before a concert, he suffered a hemorrhage that was localized to the left angular gyrus, the area that has long been known as the center for the ability to read and write. Detailed tests revealed that he showed symptoms of alexia with agraphia for both musical scores and language.

[Stability studies on 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate (FUT-187) in aqueous solution].

FUT-187 (I), 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino] benzoate dimethanesulfonate, is a new synthesized proteinase inhibitor. Decomposition kinetics and photoreactivity of I in aqueous solution were studied. In aqueous solution, I was hydrolyzed to its moieties, [4-(4,5-dihydro-1H-imidazol-2-yl)amino]benzoic acid (IABA) and 6-amidino-2-naphthol (AN). The hydrolysis followed a pseudo-first order reaction. I was stable under acidic condition between pH 2 and pH 3 and decomposed by irradiation from xenon light to form IABA, AN and compound II. The structure of II was studied by nuclear magnetic resonance, infrared, mass and ultraviolet spectra and identification tests. It was shown that II was 6-amidino-2-hydroxy-1-naphthyl[4-(4,5-dihydro-1H-imidazol-2-yl)amino]- phenyl ketone, benzophenone derivative, produced by photorearrangement reaction of I.

Does the brain prefer geometrical homogeneity?

Some patients with frontotemporal lobar degeneration (FTLD) have shown the development of painting or musical abilities after the onset of the disease. In this report, we present another emergent ability. A female patient with FTLD showing dense atrophy of the bilateral anterior lobes and a loss of voluntary activity in aspects of daily living, presented with the characteristic behaviours when given a paper and a pair of scissors. When a shape was already drawn on the paper, she showed reasonable skills with the scissors, cutting without any hesitation. When she cut a blank piece of paper, she showed quite unique geometrical preferences. Her severely degenerated brain combined with her geometrical abilities suggests that the human brain is naturally affected by geometrical homogeneity.

Inhibitory effects of newly synthesized active center-directed trypsin-like serine protease inhibitors on the complement system.

OBJECTIVE: To obtain a synthetic anti-complement inhibitor which has stronger activity than FUT-175 (nafamostat mesilate), as a synthetic ester derivative containing amidino and guanidino groups. METHODS: We synthesized several modified compounds of FUT-175. The anti-complement activities were measured using synthetic substrates and complement-mediated hemolysis in vitro. The anti-complement activity in vivo was evaluated via Forssman systemic shock in guinea pigs. RESULTS: FUT-175 inhibited C1r and C1s with IC50s of 1.7x10(-6) and 3.2x10(-7) M, respectively. Inhibitory activities were decreased by substitution of the amidino group with a hydrogen atom (compound 2), but not the guanidino group with a hydrogen atom (compound 3). Compound 6, in which the benzene ring of compound 3 was substituted with a furan ring, inhibited C1r and the complement-mediated hemolysis in high-diluted serum with higher potency than FUT-175. The inhibitory activity of compound 6 in hemolysis was weakened in low diluted serum. Compound 7 had a guanidino group inserted into compound 6; however, Compound 7 strongly inhibited hemolysis even in low-diluted serum, and suppressed Forssman systemic shock more potently than both FUT-175 and compound 6. CONCLUSIONS: These data suggest that the 2-furylcarboxylic acid derivatives have a strong potential for inhibiting the activities of the complement, and the guanidino group was required to retain high inhibitory activities in vivo, and compound 7 is a hopeful anti-complement agent.