In order to study the antineoplastic effect of Prostaglandin (PG) derivatives on the tumors in the central nervous system, basic experiments were carried out in in vitro and in vivo system. PGs used were PGD2, PGJ2, and 412PGJ2. The subjects were an established brain tumor cell line, U373MG, and T9 rat glioma cell line. The aim of the present study was to stud y whether these derivatives possessed antitumoral effect on brain tumors and, if so, to clarify the mechanism of their antineoplasticity. Established T9 cell line derived from rat glioma and U373MG derived f rom human glioma were used as the target cells. All derivatives, PGD2, PGJ2, and Δ12PGJ2, showed significant growth inhibitions on cultured cells dose-dependently, and Δ12PGJ2 was most effective, followed by PGJ2 and then PGD2. In chronological observation of the growth inhibition and changes in the viabilitiy, early growth inhibition and decrease of the viability were observed in the order of Δ12PGJ2, PGJ2 and then PGD2. At low concentration, however, regrowth of the cells was observed somehow as time passed. Changes of the DNA-histogram were studied using flow cytometer (FCM). Cells at the G2 -FM phase and S phase decreased in number, while rate of the cells at G0/G1 phase increased. At low concentration the cell returned to the proliferative pattern as before as time passed, while at high concentration such tendency was not observed, suggesting stop of the cell cycle. Antineo plastic effect appeared at rather earlier phase,6 to 9 hours after contact with Δ12PGJ2, and the author could confirm that G1 phase blocking started prior to decrease of the viability. According to the study of the effect of PG derivatives on the cell kinetics of the established brain tumor cell lines by the double staining method with bromodeoxyuridine (BrdU)and DNA, it was clearly shown that cells at the S and G2 M phase decreased, while rate of those at G0/G1 phase increased in all three prostaglandins, PGD2, PGJ2, and Δ12 PGJ2h. e decrease of the cells at the S phase in which BrdU was taken was clarified by the present study. Morphologically, different from the changes due to other antineoplastic agents such as ACNU, changes of the cytoplasm such as vacuolization of the cytoplasm or disappearance of the cell processes were prominent but changes of the nuclei were rare. Growth inhibition on subcutaneously transplanted brain tumor cell s was studied in rats. In the group receiving intratumoral injection of Δ12PGJ2 (4mg/kg), antineoplastic effect was observed, while no effect was observed in the intraperitoneally injected group. From above results, the author concluded that Prostaglandin had significant antineoplastic effect on cultured brain tumor cells, and the essential substance for the action of the antineoplastic effect was Δ12PGJ2. Clinical application of Δ12PGJ2 among other PG derivatives was expected for the treatment of malignant brain tumor patients.
In the present article, the authers have studied a family case of mental and nervous disorders which might indicate a close relationship of heredity of extapyramidal fragility to psychotic state. The prob and was a 52-year-old married female patient with Parkinson's disease, and she had been suffered from various extrapyramidal symptoms such as tremor, muscle rigidity, mild postural disorders and some other autonomic failures for last 12 years. She has been medically treated with antiparkinsonian drugs since 1985, and the most of symptoms were not disappeared but slightly improved. In 1987 during the treatment, she showed a psychotic episode with insomnia, loss of appetite, delusions of persecution, visual and auditory hallucinations. Her daughter,25-year-old unmarried girl at home, presented agitation, auditory hallucinations and delusions of persecution, and she was admitted in 1987 when she showed psychomotor excitements. She was diagnosed as schizophrenia, paranoid type and began to receive neuroleptics medication since then. As soon as the medication had started, she developed extrapyramidalism such as tremor, rigidity, gait and postural disturbances. Her psychotic symptoms have disappeared and the neuroleptic medication was discontinued. The majority of her extrapyramidal symptoms have been improved but mild tremor has still remained unchanged, even under anti-parkinsonian medications. It is interesting that the daughter's extra pyramidalism resembled closely to the mother's symptoms, in spite of their etiologies are apparently different. Extrapyramidalism and paranoid-hallucinatory state are considered as a result of disturbances of dopaminergic regulation. Therefore, it occurs as the side effect or poisoning of neuroleptic substance. In our cases, however, it is important to realize that the evolutions of the disturbances in the two cases are unusual and that both the cases possess a common hereditary factors. Then, their psychotic states and nervous disorders might be establised on a certain common background. Anyway, this case may be a clue to solve the missing link between psychiatry and neurology.
Striato-nigral degeneration (SND) was first described by Adams et al, in 1960 as a new nosological unit. In the present paper, the authors have studied a case of SND with a special reference to the associated mental deteriorations. A 49-year-old female without any family history had been suffering from various progressive extrapyramidal symptoms such as tremor, rigidity, hypo- and brady-kinesia and mild disturbance of oral speech for five years. She had also been noticed cerebellar ataxia and vesical disturbance. A cerebellar atrophy was pointed out on cranial X-ray CT. At the age of 46, she was clinically diagnosed as SND. Besides the typical neurological symptoms she presented several psychic symptoms, mental deteriorations in particular, during the long term drug treatment. It is well known that SND shows the extrapyramidal disturbances usually accompanied by cerebellar disorders and autonomic failures, but in some cases there are more or less intellectual impairments as are in other spinocerebellar degenerations. Though the memory impairment, characterized by the word “forgetfulness”, is easily noticed in the clinical observation of SND, it seems not so easy to find out mental deteriorations such as motivational disturbance, bradyphrenia and uncontrollable moodiness as seen in our patient. These mental deteriorations could be considered as “subcortical dementia”. How ever, there are certain difficulties, which have not yet been solved, in clinical diagnosis of SND and in intellectual evaluation. Therefore, we have to take account not only of the main neurological symptoms like extrapyramidal disturbances but also of the associated psychiatric symptoms including mental deteriorations in the case of patient with SND.
In this communication, the present authors have studied on a case of the submissive female partner of induced psychosis, of which her lover was the dominant partner and she developed an identical psychophathology to the partner after having been influenced by his psychotic state. The dominant partner (proband) was 21-year-old male student and he had some delusions of possession, that he was possessed by fox and ox, with ideas of persecution, and he was involved in religious activities. He was suspected as paranoid type of schizophrenia in the psychiatric interview, but the diagnosis was not confirmed because he refused to take either further examinations or psychological testings. The submissive partner, who was a 21- year-old female and working in an insurance company, at first made a tout resistance to his delusional ideas, but she was gradually influenced by her lover's psychotic state, particularly after she became interested in spiritual phenomina. Finally she became to share the delusions and the common ideas with him after their cohabitation for several days. The cohabitation was forcibly discontinued by her father, and she was seperated from him, but her state of possession remained unchanged therafter until her emergency admission to our university hospital. Almost complete remission from her psychotic state was after two months' treatment in our inpatient ward. In the present case, the persistent repetitions of unitary spiritual idea by the dominant partner and the entire dependence due to love relationship of the submissive partner appear to be the most important factors for induction of the psychotic state. Recently, spiritual phenomena have come into nation-wide fashion and a large number of people seem to have special interests in the spiritual world etc., so that the possible prevalence of "spiritually"induced psychoses including folie A deux might be expected more frequently among adolescence in particular.
A 58-year-old housewife, who had been suffering from depressive mood, psychomotor inhibition and sleep disturbance since April,1988, was admitted to our clinic in Juiy, when she attempted suicide. First, she was given antidepressant drugs, which produced several side effects and aggravated she depressive symptoms. At the same time, extrapyramidal disturbances such as muscular rigidity and festinating gait associated with bradyphrenia appeared and comiplicated. Then, as the antidepressant medcation was discontinued and replaced with levodopa product, the symptoms mentioned above have gradually been subsided and disappeared. It is well known that depressive mood is usually observed in case of parkinsonism inculuding drug induced extrapyramidalism and their causality and correlation are not yet clear. It is, however, considered that there is a certain reactive factor to the physical disorders and also shat there is a common biochemical basis consisting of metabolic dysfunctions of intracerebral monoamines behind the depression and parkinsonism. In the present case, the existence of the biochemical background common to the mental and nervous disorders has to the considered, particularly because the depression appeared to preceded she appearance of extraoyramidal disturbances. By the way, antidepressants were not so effective to the depressive symptoms as expected, while levodopa has improved not only extrapyramidal disturbances but also various psychiatric disorders. It is quite possible that the extrapyramidal disturbances were induced and aggravated under the antidepressant medications in the present case.
A case of 47-year-old man was admitted to the Kansal Medical University Hospital in March 1981, for progressive dementia, progressive neurogenic muscule atrophy and bulbar palsy. In September 1980, he had made many mistakes in his job. He had a disregard for traffic signal, and he was forgetful remarkably. On his first medical examination, memory disturbance, personality disturbance, poor understanding, hyperkineticus and exasperation of tendon reflexes on extremities were indicated. Hoffmann's reflex was positive at bilatral. Thereafter perseveration and hand tremor were indicated. In 1982, echolalla, stehende Redensarten and triebhafte Hemmungslosigkeit were appeared. After them bilateral muscule atrophy and fascicullation of upper limbs were. Disturbance of swallowing and articulation, atrophy of tongue as symptom in bulbar palsy were appeared. He did not speach, and sucking reflex and forced grasping were noticed. There were continued dementia and generalized muscule atrophy. A severe pneumonia led to death, two years after the onset in March 1983. At autopsy, the brain weighed 1000g. Base of frontal and temporal lobes atrophied. Dilatation of the latral ventricules was appeared. On histrogic examination, neuronal loss was indicated in the frontal lobe and base of the temporal lobe. No specific structural changes such as senile plaques, Pick body, Pick cell or spongy state were formed. There was a slight distruction of myelin seathes and axons in the white matter of the cerebrum. Astroglial proliferation was prominent in the border zone between the cortex and white matter on the frontal and the temporal lobes, and in the innerside of thalamus. In the dorsal lateral part of pallidum, there were demyelination and neuronal loss. Neuronal loss and fibrillary gliosis were noticed in the center of the nigra. There was pallor of the white matter in the peduncles and pyramidal tract of the pons. No change in the cerebellum. In the facial nucleus and the hypoglossal nucleus, neuronal loss was appeared. In the cervical and thoraceal spinal cord, neuronal loss was noticed severely in the anterior horn. Many spheroids were in the lumbar. Pallor was appeared in the lateral spinal tract. Generalized skeletal muscules atrophied neurogenicaly.