Toshihiko Hamanaka

Inhibition of tryptophan hydroxylase by (R)- and (S)-1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines (salsolinols)

The (R)- and (S)-enantiomers of salsolinol, the dopamine-derived tetrahydroisoquinolines, were found to inhibit the activity of tryptophan hydroxylase (TPH), prepared from serotonin-producing murine mastocytoma P-815 cells. Inhibition of TPH by salsolinols was found to be non-competitive with the substrate L-tryptophan. Tryptophan hydroxylase is composed of two elements with different kinetic properties in terms of cofactor (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin and these two elements were inhibited by salsolinols in competitive and uncompetitive ways, respectively. Stereoselectivity of salsolinol was not observed, concerning the potency and the type of inhibition on PTH. These data indicate that salsolinols might be naturally occurring inhibitors of indoleamine metabolism.

Semantic priming in patients with Alzheimer and semantic dementia.

Semantic priming for pairs of words having semantic relation (members of the same category) but not associative relation was tested in four patients with mild Alzheimer-type dementia (AD), three patients with semantic dementia (SD) and three normal controls. Priming effects were exhibited by all the AD patients and normal controls but by none of the SD patients. The facilitation did not differ depending on whether words were written in kanji or kana. The nature of semantic deficits in AD and SD is discussed.

Validity of brief intelligence tests for patients with Alzheimer's disease

Abstract The validity of two kinds of brief intelligence tests for patients with Alzheimers disease (AD) was investigated. In study 1, five short forms of the Japanese Wechsler Adult Intelligence Scale‐Revised (JWAIS‐R) were administered to 102 AD patients. The results showed that the intraclass correlation coefficients (ICC) between IQ estimated with the short forms and those obtained by administration of the full JWAIS‐R were satisfactory, ranging from 0.82 to 0.98, and that the abbreviated forms took a shorter time to execute. In study 2, the Ravens Coloured Progressive Matrices (RCPM) and the Mini‐Mental State Examination (MMSE) were administered to 67 AD patients. The ICC between the IQ estimated with these tests and the full‐scale IQ of the JWAIS‐R were both acceptable at 0.57, and each test could be carried out in a very short time. It was concluded that these brief tests, particularly the WAIS‐R short forms, are highly practical for quick measurement of intelligence in AD patients, although they have their respective limitations.

TYPUS MELANCHOLICUS IN LIGHT OF THE FIVE-FACTOR MODEL OF PERSONALITY

Abstract The present paper examines Typus melancholicus (TM), which is widely accepted as premorbid personality of depression in Germany and Japan, from the viewpoint of the five-factor model of personality, which has recently been gaining international popularity as the comprehensive model of personality traits. Two measures of TM, von Zerssen’s F-list and Kasahara’s scale, as well as the personality questionnaire for the five-factor model, NEO Five Factor Inventory, were completed for 140 consecutive psychiatric outpatients by their close relatives. It was found that (a) the two measures of TM had good internal consistency reliability, (b) they had reasonable concurrent validity, and (c) TM was characterized by high Conscientiousness, high Agreeableness and, to a lesser degree, high Extraversion. The results were largely in agreement with theoretical prediction and provide further support to the construct validity of the TM measures. Whether combining the three personality traits into one type is meaningful in depicting a particular premorbid personality constellation awaits further empirical examination.

Two cases of functional focal retrograde amnesia with impairment of object use

We report on two patients, TH and KN, with focal retrograde amnesia (FRA). Their memory loss regarding life events extended to their whole lives, whereas they could acquire and retain new information. They also showed prominent deficits in production and comprehension of common words. In addition, at least in the testing situation, they were impaired in their recognition and use of familiar objects. Although both cases of FRA followed an episode that can cause brain pathology, MRI revealed no structural abnormality in either patient. Stressful situations preceding the onset were evident in KN, but not in TH. We discuss their impairments of object knowledge from a neuropsychological perspective, and we interpret the etiology of their condition as a functional rather than a psychogenic amnesia.

Inhibition of human brain aromatic l-amino acid decarboxylase by cooked food-derived 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and other heterocyclic amines

A carcinogenic, food-derived heterocyclic amine, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), was found to inhibit aromatic L-amino acid decarboxylase isolated from human brainstem. Trp-P-2 inhibited the enzyme activity toward L-DOPA more markedly than that toward 5-hydroxytryptophan. The inhibition was competitive to a cofactor of the enzyme, pyridoxal-5-phosphate, and the Ki value of Trp-P-2 was 163 microM. The enzyme activity could be fully recovered after removal of Trp-P-2 by gel filtration, which indicates that the inhibition was reversible. Among a series of heterocyclic amines examined for their effects on the activity toward L-DOPA, Trp-P-2 was the most potent inhibitor, followed by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, then Trp-P-1. Another heterocyclic amine, 2-amino-3-methyl-9H-pyrido[2,3-b]indole also inhibited the enzyme. The inhibition of the decarboxylase activity by these heterocyclic amines may affect the catecholamine metabolism in human brain.

One hundred years of neuropsychology in Japan: Retrospect and prospect

The development of neuropsychology in Japan since the end of the 19th century will be outlined, including a number of pioneering works that gave a scientific basis to contemporary Japanese neuropsychology. The activities of societies/associations of related disciplines as well as the educational systems of clinical and experimental neuropsychology, which represents in Japan an interdisciplinary field, will be described. After national and international activities are mentioned, a review of significant Japanese contributions to main topics in neuropsychology will be given in some detail: dementia, memory disorders, frontal lobe syndromes, aphasia-alexia-agraphia, callosal syndromes, and specific right hemisphere syndromes. The issues of these interdisciplinary scientific investigations have found application in language and cognitive disabilities of brain-damaged patients, as well as evaluation of medical treatments and comedical rehabilitational efforts, care, and counseling. Finally, some comments will be presented on possible and desirable developments of Japanese neuropsychology in the future.

Knowing Members of the Advisory Board

‘intellectual biography’, I had some reservations, because I was then only 65, an unexceptional age when many are still healthy and working even more brilliantly than in their younger days. However, on reaching 70 it may be justified for me to recall my studies and my work in the field of history of psychiatry. I was born in 1933, the son of a surgical practitioner Shiro Hamanaka (1906–82) in the city of Kishiwada, Japan, near Osaka. One of my high school teachers, a mathematician with extraordinary cosmopolitan erudition, introduced me to European science, history and culture. After graduating from the Faculty of Medicine, Kyoto University, and getting my national licence for medical practice, I was initiated into my specialty in 1961 at the university’s Department of Psychiatry and Neurology, which had been founded in 1903 by Professor S. Imamura (1874–1946); see Kyoto University (2003). Imamura (1903) published a neuropsychological paper in German dealing with the functions of corpus callosum, after completing his experimental work in Vienna with S. Exner, and later he became familiar with Pierre Janet’s medical psychology in Paris. At the time of my novitiate, I found much intellectual nourishment in a school which continued the thinking of Professor Imamura. Professor M. Murakami (1910–2000), the head of the department, performed a number of clinical studies of anthropological psychopathology in accordance with the works of Pierre Janet and Eugène Minkowski, whom he had met during his studies in Paris around 1935. At this time, too, H. Ohashi (1923–86), a lecturer and later professor, published his monumental book on clinical neuropsychology and neuropsychiatry (Ohashi, 1965/1998), which was the first comprehensive monograph in Knowing Members of the Advisory Board