Several theories regarding pathophysiology of mood disorders (depression or bipolar disorders) and the mechanisms of therapeutic agents (antidepressnts or mood stabilizer) have been proposed. Inhibition of monoamine reuptake into nerve endings by antidepressants is one of the cornerstones of the monoamine hypothesis on depression. Many studies have focused on alterations in levels of monoamines and their receptors. More recent studies have been extended to examination of the post-receptor intracellular targets. These include several classes of the guanosine triphosphate-binding proteins that couple receptors and effectors, adenylate cyclase and the inositol phosphate second messenger system. This review summarizes studies on signal transduction and neural plasticity in terms of mood disorders.

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In patients with cleft lip and palate, a series of treatments have been performed to achieve a normal facial appearance and a good oronasal function. Decisions on timing and the procedure to be performed should always be based on the patient's growth. Despite successful, well-timed surgery and adequate orthodontic treatment, maxillary hypoplasia appears to be unavoidable in some patients with cleft lip and palate. Class III malocclusion and the accompanying facial deformity are treated with Le Fort I maxillary osteotomy after facial skeletal growth is completed. Maxillary osteotomy provides dramatic improvement in patient's facial appearance and occlusion; however, there is a possibility of relapse after surgery. In our retrospective evaluation, there are significant correlations between the amount of surgical movement and relapse in all directions. Because the lip and nose cover the maxilla, the movement of the maxilla influences the appearance of the lip and nose. Therefore, definitive revision of the lip and nose in cleft patients should be performed after maxillary osteotomy. At this stage, all procedures that were not done because of their effects on growth can be performed. For definitive management of the nose and lip, all strategies of reconstructive, plastic, and aesthetic surgery should be considered. A series of treatments as the patient grows after the birth is completed by these revisions.

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To elucidate the association between the duration of untreated psychosis and long-term outcome in schizophrenic patients, we followed up a cohort of first-episode schizophrenic patients in Nagasaki. The present study was conducted in the framework of the World Health Organization Collaborative Study on Determinants of Severe Mental Disorders, which our research group participated in as The Nagasaki World Health Organization Collaborating Center for Research and Training in Mental Health. The cohort was established during the period from 1979 to 1980 and consisted of 107 patients initially diagnosed as schizophrenia according to ICD-9. The subjects of the present study were 97 members of the cohort (54 males and 43 females) in whom we could measure the duration of untreated psychosis. The 97 study subjects were followed up for 15 years since they were enrolled in the cohort and were checked their mental conditions at 1-, 2-, 5-, 10- and 15-year follow-up points. The triplet of the 1st, 2nd and 3rd quartiles of the duration of untreated psychosis in them was (1, 4, 12) months (the mean was 9.9 months). During the whole period of 15-year follow-up, 5 patients died, 40 were lost for follow-up and 52 remained contacted at 15-year follow-up point; out of these 52 patients, 22 were contacted through the whole period. During the first 10 years of the follow-up, the patients diagnosed to have completely been remitted at follow-up point showed a significantly or marginally shorter duration of untreated psychosis as compared to those diagnosed not to have completely remitted; the triplet of the 1st, 2nd and 3rd quartiles of the duration of untreated psychosis in those diagnosed to have completely remitted at 1-year follow-up point was (1, 3, 4) months, while that in those diagnosed not to have completely remitted at the same follow-up point was (2, 6, 12) months and the difference was significant (p=0.036, Wilcoxon rank-sum test). Similarly, the triplets of the 1st, 2nd and 3rd quartiles of the duration of untreated psychosis in the two groups diagnosed with and without complete remission at 2-, 5- and 10-year follow-up points were (1, 3, 4) and (2, 6, 17) months (p=0.021), (1, 3, 8) and (1, 6, 17) months (p=0.149), and (1, 2, 3) and (3, 6, 12) months (p=0.008), respectively. However, no difference was observed between the two groups at 15-year follow-up point; (1, 4, 12) and (1, 4, 9) months (p=0.828). The results of the present study indicate that the duration of untreated psychosis will probably influence on the outcome of schizophrenia at least 10 years.

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Vasospasm sometimes disturbs successful blood access for hemodialysis, and prevention of vasospasm is desirable when constructing arteriovenous fistulae. We first investigated vasospasm of the radial artery in this operation and analyzed factors associated with this phenomenon in 20 patients with end-stage renal disease. Alteration of blood flow in the radial artery was evaluated in them, and intima-media thickness (IMT), endothelial function index (EFI) and laboratory data were analyzed. Vasospasm occurred in 9 of 20 cases (45.0%) at 5 min after anastomosis, and displayed a marginally significant correlation (r=0.31, p=0.081) with EFI. We then conducted a randomized study of 84 patients with end-stage renal disease to examine the effects of administering transdermal glyceryl trinitrate (GTN) in this operation. EFI was significantly correlated with IMT (r= -0.45, p<0.001). At 5 min after anastomosis, vasospasm occurred in 12 (28.6%) of 42 patients who were administered GTN, while it occurred in 20 (47.6%) of 42 patients without GTN administration (controls); the difference was marginally significant (p=0.072). In patients with IMT≤1.1, alteration of diameter (5 min/1 min after anastomosis) was significantly reduced compared with controls (p=0.032). These data suggest that IMT could offer a predictor of vasospasm occurrence during arteriovenous fistula operations. Use of preoperative transdermal GTN may be effective in preventing vasospasm during such surgery.

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Treatment of pulmonary hypertension has not yet been established and effective drug therapies are required. We hypothesized that inhibition of cyclic guanosine monophoshate (cGMP)- phosphodiesterase (PDE) would result in specific vasodilation of the hypertensive pulmonary arteries. This study was carried out to determine whether PDE V inhibitors could dilate pulmonary artery (PA) from monocrotaline-induced pulmonary hypertensive rats. Thirty-six Wistar rats were given either monocrotaline (105 mg/kg) or normal saline (control) subcutaneously. Three weeks later, the PA rings were isolated and mounted in 5-mL organ chambers. After precontraction with norepinephrine (0.1 μmM), one of two PDE V inhibitors, zaprinast and dipyridamole, was added in a cumulative fashion. We also investigated whether nitric oxide synthetase (NOS) inhibitor modifies the effects of the PDE V inhibitors on the PA. Zaprinast and dipyridamole dose-dependently dilated the PA from either saline- or monocrotaline- treated rats. There was no difference in the dilatory effect between monocrotaline and saline rats. Pretreatment of a NOS inhibitor (N^G-nitro-L-arginine methyl ester (0.1 mM)) reduced moderately the vasodilatory effect of zaprinast on the PA from monocrotaline-treated but not saline-treated rats. The results suggest that PDE V inhibitors exert a strong vasodilating effect on PA of pulmonary hypertensive rats as well as on that of normal rats, and that NO plays a role, at least in part, in the effect of PDE V inhibition on PA of pulmonary hypertensive rats.

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A 27-year-old man was hospitalized for an evaluation of a high fever and left hemiparesis. Gadolinium-enhanced MRI disclosed a lesion with ring enhanced areas with marked edema extending from the right basal ganglia and thalamus to the midbrain that appeared to be a brain abscess. The lesion resolved almost completely during the 2 month period after admission. Three weeks after discharge the patient again developed a high fever, and an MRI examination disclosed a large new lesion involving the left thalamus, brainstem and upper pons. No ring enhancement was detected by gadolinium-enhanced MRI, and the new lesion again spontaneously resolved almost completely, but during the second admission the patient also developed oral aphthae and skin eruptions suggesting Behçet's disease. This is a rare case suggesting that the lesions occurring in association with neuro-Behçet disease may resolve spontaneously.

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In this report, we describe a case of recurrent desmoid tumor that was characterized by a novel APC gene mutation and osteopontin (OPN) expression. A 20-year-old female patient with adenomatous polyposis underwent a right colectomy at 13 years of age. Five years later, she developed an abdominal desmoid tumor that was resected. After 2 more years, a recurrent desmoid tumor was found in the same region. This tumor grew rapidly and quickly became massive. The doubling time was estimated to be 122 days, based on the computed tomography findings. When we analyzed the APC gene in the recurrent desmoid tumor, we found a novel frame-shift mutation at codon 1564. This frame-shift mutation changed TTA to TAG, which is a stop codon. Northern blot analysis and immunohistochemical analysis for OPN, a GRGDS (glycine-arginine-glycine-aspartic acid-serine)- containing adhesive molecule, revealed abundant amounts of OPN mRNA and protein expression in this desmoid tumor. We postulated that the truncated APC protein and OPN expression might be involved in the invasive nature of this recurrent desmoid tumor. A primary cell culture derived from the desmoid tumor was assessed for chemosensitivity to 5-fluorouracil, cisplatin, doxorubicin, colchicine, docetaxel, and anti-OPN antibody. Docetaxel was found to have the strongest inhibitory effect on cell growth. As a result, docetaxel was administered to this patient (60 mg/m²/month) for 3 cycles. Over the next 2 years, no detectable recurrences occurred. Thus, docetaxel was clinically effective for the treatment of a recurrent desmoid tumor.

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