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Theoretical assumptions regarding the genetic and environmental structure of personality proposed in Cloninger's seven-factor model of temperament and character were verified in a Japanese sample by using the twin method. The Temperament and Character Inventory (TCI) was administered to 296 twin pairs ranging in age from 14 to 28 years old. Among four temperament dimensions (novelty seeking [NS], harm avoidance [HA], reward dependence [RD], and persistence [PS]), HA and PS showed significant additive genetic contributions and no shared environmental effect, supporting the original theoretical assumption. NS and RD could be explained by either genetic or shared environmental factors with nonshared environment. All three character dimensions (cooperativeness [CO], self-directedness [SD], and self-transcendence [ST]) could be explained exclusively by additive contributions and no shared environmental effect. Multivariate genetic analysis indicated that there were no significant associations between NS, HA, and RD, as the theory predicts, and the genetic components of PS, SD, and CO were derived from those of the temperament dimensions. The fourth genetic component, which had a substantial load specifically on ST and overlapped with PS, was identified. Although most of the nonshared environmental effects were trait-specific, the phenotypic correlation between NS and HA could be explained by nonshared environmental overlap.

Inflammatory cytokines stimulate glial cells in vitro to produce nitric oxide (NO) from inducible NO synthase (iNOS). Whether the stimulation with cytokines produces NO derived from iNOS has not hitherto been demonstrated in the vivo brain. Nitrite and nitrate (NOx(-)) levels in the rat paraventricular nucleus (PVN) were measured before and after intraparenchymal microinjection of cytokines with a microdialysis technique. The cytokines, tumor necrosis factor (TNF)-alpha (10 ng), interleukin (IL)-1 beta (2 ng), and interferon (IFN)-gamma (2 ng) were microinjected. None of the cytokines alone had any effect on the NOx(-) levels for 8 h. But a combination of TNF-alpha and IFN-gamma gradually increased NOx(-) levels beginning at 140 min after the microinjection, and NOx(-) levels reached 1.8 times the basal level at 380 min. A combination of TNF-alpha and IL-1 beta increased NOx(-) beginning at 340 min, reaching 1.7 times the basal level at 440 min, whereas a combination of IL-1 beta and IFN-gamma had no effect. Microinjection of a mixture of all three cytokines increased NOx(-) levels beginning at 120 min, reaching 3.3 times the basal level at 400 min. Aminoguanidine, which is a selective inhibitor of iNOS, reduced NOx(-) levels induced by the mixed cytokine treatment. Semi-quantitative RT-PCR for iNOS mRNA was done. The intensity of the iNOS mRNA band for the cytokine-treated PVN was stronger than that for the vehicle-treated PVN. These results suggest that the increased NOx(-) after the treatment with mixed cytokines were dependent on iNOS activity. This is the first report to indicate that only cytokines induce NOS in vivo in the brain.

Background: Previous studies have shown that nitric oxide (NO) synthase inhibitors show preclinical antidepressant-like properties, suggesting that NO is involved in the pathogenesis of depression. The purpose of this study is to examine whether or not NO production increases in depressed patients. Methods: Plasma nitrate concentrations, an index of NO production, were measured by high-performance liquid chromatography in depressed patients (n=17) and compared with patients suffering anxiety (n=6) and with healthy controls (n=12). Results: Plasma nitrate concentrations were significantly higher in depressed patients than in patients with an anxiety disorder (P

Dimensional approaches have been used to describe the fundamental dimensions that underlie the entire domain of normal and pathological personality. We tested the five factor model of personality structure in a sample of Japanese twins, to clarify the contributions of genetic and environment. The revised NEO personality inventory (NEO-PI-R) was administered to 251 twin pairs, ranging in age from 15 to 27 years of age. The NEO-PI-R is a 240-item questionnaire which was developed to assess the dimensions of personality. Univariate genetic analysis showed that the AE model in which phenotypic covariances are explained only by additive genetic (A) and nonshared environment (E) is still a plausible model, and that the relative proportion of genetic influence was comparable to that reported by Loehlin (1992). Multivariate genetic analysis of the Japanese data suggested/revealed that the five factors are genetically dependent on each other and one common genetic factor mediates their interdependence. Previous studies have assumed that they are phenotypically independent and robust. Although there are sampling biases in the present study, it is noteworthy that the results for all five factors depicted by the NEO-PI-R were comparable to those reported by Western researchers, and the genetic structure of the five-factor model is complex.

We performed a study to distinguish the trigger of and the factors maintaining bulimia nervosa (BN). The subjects were BN patients, normal women without diet experiences, and normal women with diet experiences. We used the Temperament and Character Inventory scales (TCI) as the instrument. As a result, a high Novelty Seeking score (NS) is identified as the main characteristic of BN, and a high Harm Avoidance score (HA) is assumed to contribute to maintaining bulimic symptoms. As the sociocultural background for eating disorders (ED), there may be pressure on women to be thin to be attractive. Also, ED patients have often been pointed out as having problems with interpersonal relationships. We assume that under sociocultural pressure those women having disordered interpersonal relationships with certain contributing personality factors may develop a diet and ED including BN. Our result using TCI may show that women with high NS go on a diet and women whose HA is also high develop BN in our modern culture.

Although the ICD-10 and DSM-IV may seem to be adequate for most psychiatric diagnoses, they are far from ideal. The diagnostic process is clinical and relies on psychiatric symptoms that are often subjective and subtle. The classification resorts to a variety of information sources with little biological evidence. When making a diagnosis, other information sources are also necessary. The most important of all may be cultural factors. For example, when examining somatoform disorder in Japan, taijin kyofusho (anthropophobia, morbid fear of interpersonal situations) must be taken into consideration. In this chapter, somatoform disorders in Japan will be discussed. Taijin kyofusho will be taken as an example, although taijin kyofusho is usually categorized as social phobia. Specifically, this paper will discuss: (a) the prevalence of somatoform disorder in a general hospital outpatient clinic in Japan; (b) taijin kyofusho as a “primary” or “secondary” somatoform syndrome; (c) past studies on taijin kyofusho; and (d) Morita theory of taijin kyofusho.

The possibility of an interaction between norepinephrine and NO· or NO·-related molecules in vivo was explored. Bubbling of NO· gas in norepinephrine aqueous solution yielded 6-nitronorepinephrine (6-nitroNE). We also identified 6-nitroNE in the mammalian brain. Amounts of 6-nitroNE in the rat brain were attenuated by administration of an inhibitor of nitric oxide synthase. N G -nitro-l-arginine methyl ester. This was reversed by coadministration of l-arginine, suggesting that nitric oxide synthase participated in the formation of 6-nitroNE. Moreover, we found that 6-nitroNE inhibits the activity of catechol-O-methyl transferase, as well as norepinephrine transport into rat synaptosomes. At values to 100 µM, 6-nitroNE did not displace the binding of αl-, α2-, or β-adrenergic receptor ligand. A rat brain microdialysis experiment showed that perfusion of 6-nitroNE into the rat hypothalamic paraventricular nucleus significantly elevated norepinephrine while decreasing 3-methoxy-4-hydroxyphenylglycol, a metabolite of norepinephrine. We propose that 6-nitroNE is a potential signal molecule linking the actions of NE and NO·.

This study was designed to assess the association between novelty seeking and D4DR gene polymorphism in the Japanese population. The 48 bp repeat polymorphism in the third exon of the dopamine D4 receptor gene of 153 normal female students was correlated with personality feature results from the Japanese version of Cloninger's Temperament and Character Inventory. The Novelty Seeking subscale of Exploratory Excitability had a significant association with long alleles of the polymorphic exon III repeat sequence of D4DR. Our results suggest that there is an association between long alleles of the polymorphic exon III repeat sequence of D4DR and the personality traits of the Novelty Seeking subscale of Exploratory Excitability, regardless of racial differences in the frequencies of D4DR exon III repeat polymorphism.

Transient global amnesia (TGA) is a clinical syndrome characterized by sudden loss of memory (including both anteroand retrograde amnesia), perplexity, and repetitive questioning during an episode, duration of an episode ranges from minutes to several hours, lack of physical or neurological abnormality except amnesia, and complete recovery, termed by Fisher and Adams (Fisher and Adams 1958). Although the etiology of TGA is still unsettled, transient cerebral ischemia, epileptic and/or migralneous event are thought to be the possible causes of TGA (Palmer 1986). These possible mechanisms and psychological factors might lead to such alteration of cognitive function that is manifested by changes of event-related potential (ERP) profile. The auditory P3 ERP during TGA, when compared with the P3 after recovery, is reported not to be decreased (Meador et al 1988; Bokura et ai 1994); however, little is described about the distribution of auditory ERPs during TGA. We made an auditory ERP study on a patient during, and two days after an episode of TGA, and obtained several unexpected findings. We here describe these findings, including the alterations of amplitude and peak distribution of scalp ERPs, which may provide a new viewpoint in the field of TGA research.

In order to investigate the biological mechanisms underlying the clinical efficacy of clozapine, 200 mg/day of clozapine was added to the drug regimens of 19 patients with chronic, anti-psychotic-resistant schizophrenia, and the plasma homovanillic acid (HVA), clozapine concentrations, anti-dopamine D2 and anti-serotonin 5-HT 2 receptor activities were measured. After 28 days, six patients showed an improvement of more than 20% over baseline Brief Psychiatric Rating Scale (BPRS) scores. Mean plasma HVA concentrations and anti-D 2 receptor activities did not change significantly in the entire group or in the six patients showing improvement. However, anti-5-HT 2 receptor activities increased significantly in all 19 patients. Changes in BPRS scores did not correlate significantly with changes in plasma HVA or with changes in clozapine concentrations, or with anti-D 2 and anti-5-HT 2 receptor activities.

We investigated whether psychotropics orally administered to rats affect levels of interleukin-1 beta (IL-1 beta) and interleukin-1 receptor antagonist (IL-1Ra) mRNA in the hypothalamus, hippocampus, frontal cortex, and brain stem, using a reverse transcription-polymerase chain reaction method. The psychotropics tested were chlorpromazine, haloperidol, imipramine, maprotiline, fluvoxamine, and diazepam. Treatment for 28 days raised the levels of both mRNAs. The increase in IL-1Ra mRNA was 6-112 times larger than that of IL-1 beta mRNA in most brain regions examined. These results suggest that chronic treatment with psychotropics causes greater amplifying effects on IL-1Ra mRNA than IL-1 beta mRNA in the brain.

Disturbances in dopaminergic systems have been implicated in the etiology of mood disorders. Although genetic factors also play an important role, no major gene has been identified. We conducted an association study using the dopamine D2, D3 and D4 receptor, and transporter gene polymorphisms, comparing 101 mood-disorder patients (52 bipolar and 49 unipolar) and 100 controls. Our results suggest that there is a significant association between the dopamine D4 receptor gene and mood disorders, especially major depression, but no association between the other polymorphisms and mood disorders. Further investigations are needed to clarify the clinical significance of this association in the pathophysiology of mood disorders.

Norepinephrine (NE) (von Euler, U. S. (1972) in Catecholamines (Blaschko, H., and Muscholl, E., eds.) pp. 186-230, Springer-Verlag, Berlin) and nitric oxide (NO·) function as neurotransmitters in the nervous system. We have shown that NE levels in the rat hypothalamic paraventricular nucleus (Shintani, F., Kato, R., Kinoshita, N., Kanba, S., Asai, M., and Nakaki, T. (1995) Proceedings of the Satellite Symposium, 4th IBRO World Congress on Neuroscience, Otsu, 1995) diminish in the presence of NO·. This observation prompted us to explore the possibility of an in vivo interaction between NE and NO· or NO·-related molecules. In fact, nitration of NE has been shown to occur in vitro (d'Ischia, M., and Costantini, C. (1995) Bioorg. Med. Chem. 3, 923-927). We now report the identification of 6-nitronorepinephrine in the mammalian brain. Amounts of 6-nitronorepinephrine in the rat brain were attenuated by intraperitoneal administration of an inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester (L-NAME). This was reversed by coadministration of L-arginine, suggesting that nitric oxide synthase participated in the formation of 6-nitronorepinephrine. Moreover, we found that 6-nitronorepinephrine inhibits the activity of catechol O-methyltransferase, as well as NE transport into rat synaptosomes. A rat brain microdialysis experiment showed that perfusion of 6-nitronorepinephrine into the rat paraventricular nucleus significantly elevated NE while decreasing 3-methoxy-4-hydroxyphenylglycol and that L-NAME administered intraperitoneally decreased NE and increased 3-methoxy-4-hydroxyphenylglycol. These observations suggest that 6-nitronorepinephrine generated in nuclei containing both adrenergic and nitrergic neurons inhibits NE inactivation. We propose that 6-nitronorepinephrine is a potential signal molecule linking the actions of NE and NO·.

A timing controlled auto-ignition name ``AR combustion`` could improve irregular combustion in the part load operation of conventional two-stroke engines. Their previous papers have suggested its idea and the drastic improvements in fuel consumption and HC emission proven through a bench experiments. This time, form a concept that improvements of a two-stroke engine should be done maintaining its original advantages, an AR combustion engine was developed by using a simple exhaust valve and maintaining engine`s original power output. This engine was mounted on a motorcycle and experimented in the ``Dakar rally``. As the results, good fuel economies exceeding a four-stroke rally model, excellent driveability and durability were proven, because of the improvement in the combustion and engine`s potential for the downsizing. The AR combustion engine, consequently, has good prospects for the practical use.

Parental bonding patterns were studied in 52 female Japanese eating disorder outpatients with and without histories of sexual or physical abuse and with dissociation. Instruments included the Parental Bonding Instrument (PBI), the Dissociative Experiences Scale (DES) and the Dissociative Disorders Interview Schedule (DDIS). Those with physical abuse history, but not sexual abuse history, had significantly different parental bonding scores and higher DES scores compared with subjects without physical abuse. DES scores and PBI scores were not correlated. Although the PBI was useful in discriminating between those with and those without abuse histories, it did not detect differences in degree of dissociation. Lack of association of sexual abuse to PBI and DES scores may have been due to mild abuse.

Metastases to the larynx from distant primaries are very rare. The present article reports a case of metastatic papillary adenocarcinoma of the larynx of lung origin. The patient was a 59-year-old female non-smoker, who had a history of adenocarcinoma of the right lung. For the laryngeal tumor, we performed a partial laryngectomy following biopsy. The tumor of the larynx was a papillary adenocarcinoma resembling the lung tumor, both demonstrating positive immunohistochemical staining for pulmonary surfactant apoprotein. The findings emphatically indicated the laryngeal tumor to be metastasis from the primary papillary adenocarcinoma of the lung. The present case report presents the clinical findings, course of disease and histopathological findings with brief reviews of the literature.

The content of schizophrenic delusions of 150 German patients in the Psychiatrische Universitatsklinik Tubingen and those of 324 Japanese patients (ICD-9:295) were compared according to the classification of Huber and Gross. The comparison revealed significantly higher frequencies of delusions of poisoning (18 vs. 8%; p < 0.01) and jealousy (6 vs. 1.9%; p < 0.05) in the German cases, but there was no significant difference in the incidence of comprehensive injury delusions. There was also no significant difference in the incidence of comprehensive grandeur delusions. However, comprehensive belittlement delusions were more frequent in the German group (24 vs. 13.3%; p < 0.01). Among the delusions of this type, the themes of guilt/sin (15.3 vs. 4.9%; p < 0.001), particularly those related to religion, were more frequent in the German group. Although religious delusions were more frequent in the German group (21.3 vs. 6.8%; p < 0.001), the difference regarding the incidence of 'delusions of world destruction' was not statistically significant. Among the persecution/injury delusions, themes of direct persecution from others (Verfolgungswahn) were conspicuous in the German group, whereas delusions of reference (Beziehungswahn) related to harassment, such as 'being slandered by others' or 'being known', were common in the Japanese group. Namely, the difference in the content of these persecution/injury delusions may derive from the different types of self in the two countries: the individually oriented self in Germany and the group-oriented self in Japan. Delusions of guilt/sin in the German group may reflect the characteristics of sin in Christianity.

Congenital dysplasia of the radiocarpal and talocrural joints is extremely rare except in certain severe congenital disorders. We report on 2 cases of a congenital deformity involving a hyperplastic carpal scaphoid and a hypoplastic styloid process of the radius resulting in limitation of wrist extension in both wrists in a female and her son. The son also had an abnormal accessory bone on the distal end of the medial malleolus in both ankles. This is the first case report of such deformities in these anatomical regions.

Patients with minor psychiatric disorders, including neuroses, situational adjustment reaction or acute emotional reaction, were investigated using symptom questionnaires at five research sites in Asia including: Chiang-Mai, Thailand; Bali, Indonesia; Kao-Hsiung, Taiwan, China; Shanghai, China; and Tokyo, Japan. The results revealed that the symptom profiles differ significantly among groups of different settings indicating that sociocultural background does contribute to the manifestation of neurotic symptomatology. It was also found that numerous and various subtypes of somatic scales were identified through factor analysis of symptoms for these Asian populations. It demonstrates that the spectrum of neurotic symptoms has a different focus for subjects in different sociocultural settings.

We investigated the efficacy of Shakuyaku-kanzo-to (TJ-68) in neuroleptic-induced hyperprolactinemia in 11 treated schizophrenic patients. The mean plasma prolactin level decreased significantly from 28.9 +/- 14.5 ng/mL at baseline to 22.0 +/- 15.2 ng/mL at 4 weeks. Potassium levels did not change significantly. Neither the exacerbation of psychosis nor other adverse effects occurred.

Nilvadipine is a calcium channel inhibitor used commonly for the treatment of cerebrovascular insufficiency. We observed two patients with schizophrenia whose psychiatric symptoms and tardive dyskinesia improved after the addition of nilvadipine to their antipsychotic drug regimen. The total score of the brief psychiatric rating scale (BPRS) in case 1 fell from 56 to 42 after 8 weeks on nilvadipine; while that of case 2 fell from 44 to 32. The total score of the abnormal involuntary movement scale (AIMS) in case 2 decreased from 12 to 7. No adverse effects occurred during treatment. Nilvadipine may thus offer a new approach to the adjunctive treatment of schizophrenia.

A 7-year-old boy who suffered from carpal tunnel syndrome caused by aberrant lumbrical muscles associated with cystic degeneration of the tenosynovium of the left hand is described. Judging from the literature studied, this seems to have a very rare origin. Symptoms subsided, and no recurrence has been noticed after operative removal of these structures.

The dexamethasone suppression test (DST) was administered to 59 patients with major affective disorders and 19 with other psychiatric disorders. The combinations of two dexamethasone doses (1mg vs 0.5mg) and two cortisol criterion levels (5μg/dl vs 4μg/dl) were adopted. The highest sensitivity (43%) was found with 0.5mg DST at the 4μg/dl criterion level for Major Depression. Our study failed to distinguish Melancholia in DSM III.

The dexamethasone suppression test (DST) was performed in 38 patients satisfying the Research Diagnostic Criteria (RDC) for cortisol, human growth hormone (hGH), prolactin, triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) were determined at 4:00 p.m. before the administration of dexamethasone, whereas cortisol, hGH and TSH were determined at 4:00 p.m. the day after. Among hormonal variables, only cortisol index (the ratio of the pre-DST cortisol to the post-DST cortisol) was barely useful for discriminating depression. The cortisol index was also correlated with RDC incapacitating subcategory and with symptoms of affect such as depressed mood and psychic anxiety.

Selective enlargement of the third ventricle was observed when the area and the VBR (ventricle-brain ratio) were measured in 37 chronic schizophrenics (DSM-III criteria) as compared with 37 controls. However, the width or the width to IS (maximum inner skull width) ratio was not significantly different between the two groups. There was no correlation between any measure of the third ventricle and any of the clinical variables. Five patients had VBRs of the third ventricle that were larger than the mean + 2 SD of the control, but there was no significant difference between these five schizophrenics and the others in any of the clinical variables.

The computed tomography (CT) scans of 46 chronic schizophrenic patients and 46 controls were studied using ventricular-brain ratio. Ewans' index, and cella media index. None of the indices used revealed significant differences between the patient and the control groups.