Masanori Shimoyama

Genetic and clinical studies of japanese patients with familial amyloid polyneuropathy

We examined the DNA analysis of familial amyloid polyneuropathy (FAP) patients and their families from Nagano and Hiroshima prefectures in Japan using recombinant DNA techniques and compared the results with the clinical features. This study indicated that the valine-methionine change prealbumin gene was closely related to the clinical features of type 1 FAP. The DNA analysis was valuable for the definite diagnosis of type 1 FAP even in sporadic and asymptomatic cases. FAP patients from Iiyama city and Ogawa village area in the Nagano prefecture had the same mutation despite differences in clinical features. The onset of the sporadic FAP cases was later than that of the FAP patients who had family histories.

Effect of cerulein on in vivo release of acetylcholine from the rat striatum

An effect of cerulein on in vivo release of acetylcholine (ACh) from the rat striatum was examined by means of intracerebral dialysis. Intraperitoneal administration of cerulein (25-200 micrograms/kg) enhanced a spontaneous release of ACh in a dose-dependent manner. Intraperitoneal administration of cerulein (100 micrograms/kg) also enhanced the K+-evoked (30 mM) release of ACh. Bilateral subdiaphragmatic vagotomy reduced the increase of both K+-evoked and that of spontaneous release of ACh induced by cerulein administration. Pretreatment with haloperidol (0.5 mg/kg, i.p.) had no effect on increase in spontaneous release of ACh brought about by cerulein administration (100 micrograms/kg, i.p.). These results suggested that peripherally administered cerulein stimulated striatal cholinergic neurons, that its stimulatory effect on striatal ACh release was not mediated by striatal dopamine D2 receptors and that the action of cerulein was, in part, mediated via vagal afferent impulses.

Cardiac Disorders and Autonomic Nervous System Involvement in Familial Amyloidosis

To clarify the pathogenesis of cardiac involvement in familial amyloidosis, the authors studied histological changes of the autonomic nervous system and conduction system of the heart in seven cases with this disease. Postmortem examination revealed that the autonomic innervation of the heart was impaired in both sympathetic and parasympathetic nervous system. The specialized conduction system was involved most severely and regularly in the sinus node, and to a lesser extent, in the atrioventricular node, His bundle and its periphery. Dual damage to the sinus node through autonomic denervation and degeneration of the specialized conduction system accounts for arrhythmias and conduction disturbances frequently associated with this disease.

Natural History of Ogawa Village Type Familial Amyloid Polyneuropathy in Japan

Clinical studies were made on 118 cases of familial amyloid polyneuropathy (FAP) originated from Ogawa Village, Japan. The age of onset ranged from 17 to 72 years, and the mean age of onset was 32.1 years in males and 38.4 years in females. One family was unique in that ages of onset of 6 affected members were in their seventh decade. There were 3 exceptional cases in which the disease remained stationarily for more than 10 years with normal activities of daily living (ADL) functions. Developement of the disease was progressive. The progression was not steadily, but stepwise. Clinically presumed causes of death were various including sudden cardiac death, renal failure and sepsis. The average duration of the illness was 10 years. In general, clinical pictures of Ogawa Village cases showed a broader spectrum than those from other areas of the world. For a therapeutic purpose, DMSO was administered to 40 patients orally and/or cutaneously. DMSO administration alleviated gastrointestinal, sensory disturbances and dysuria. When DMSO was discontinued, the phenomena of the “rebound” progression were sometimes observed.

Diagnosis of Familial Amyloid Polyneuropathy by Recombinant DNA Techniques in Relation with Clinical Features

Andrade (1952) type familial amyloid polyneuropathy (FAP) is a disease inherited by autosomal dominance. Serum prealbumin variant with a substitution of methionine (Met) for valine (Val) at position 30 is known to be etiologically related to Andrade type FAP (Tawara et al., 1983; Nakazato et al., 1984; Dwulet and Benson, 1984). With the recent advances in gene manipulation techniques, methods of diagnosis of Andrade type FAP at the DNA level have been established(Sasaki et al., 1984; Mita et al., 1984). The diagnosis is based on the fact that a nucleotide substitution responsible for Val-Met interchange results in formation of new restriction sites for Nsi 1 and Bal 1. Kito et al. (1973) discovered the second largest conglomeration of the disease of the world in Nagano Prefecture, Japan. Since that time, we have carried out long-term epidemiological, neurological and biochemical studies on a group of FAP families in Nagano Prefecture.

Pathological Sutdies on Familial Amyloidosis

Although familial amyloidosis of Andrade type is mainly manifested by polyneuropathy, it is complicated with involvement of multiple visceral organs including the heart, kidney, intestine and so on (Andrade, 1952, 1965). We have reported some clinicopathological aspects of the disease. In this paper, through the analysis of clinical and pathological findings of autopsy cases, the factors leading to the cause of death are clarified.