Demonstration of competition between endogenous dopamine and [11C]raclopride binding in in vitro brain slices using a dynamic autoradiography technique

Although the basolateral nucleus (BL) of the amygdala is known to contain an abundance of gamma-aminobutyric acid (GABA)ergic neurons that regulate the amygdaloid projection neurons and influence storage and consolidation of memory, it remains to be determined what type of neuronal input controls GABAergic neurons in the BL. We examined the synapses that GABAergic neurons form with GABAergic and noradrenergic neurons and terminals with unknown transmitters by double-labeling immunoelectron microscopy using anti-GABA and dopamine-beta-hydroxylase (DBH) antisera. The medium and small dendrites of the GABAergic neurons were shown to receive symmetric, inhibitory-type synapses from GABAergic axon terminals and asymmetric, excitatory-type synapses from noradrenergic axon terminals. Each segment of the GABAergic neurons from perikarya to dendritic spines received both symmetric and asymmetric synapses from unlabeled axon terminals of various forms and sizes. The incidence rates of the two types of synapses were almost identical. Our results suggest that GABAergic neurons in the BL of the rat amygdala might be affected by the excitatory influence of the noradrenergic system and the inhibitory influence of the GABAergic system. Furthermore, these neurons are also strongly influenced by both excitatory and inhibitory-type synapses from neuronal systems other than the GABAergic and noradrenergic systems.     

Season of birth in Japanese patients with schizophrenia

A number of North American and European studies have observed a higher proportion of winter births in schizophrenia patients. Fewer studies have investigated this issue in Asian populations, and the findings are not as consistent as in the studies of Western populations. A statistically significant excess of winter births has not been observed in Japanese or Korean studies, while some of the studies found a decreased number of summer births among their patients. We further investigated the issue in Japanese patients with schizophrenia (n=2985). No significant excess of winter births was observed. Spearman correlation between schizophrenia births and ambient temperature was not significant. However, a decrease in the summer births was found, consistent with most of the previous Japanese studies. When analyzed by gender, a decrease in summer births was found in males, but not in females. In addition, a trend towards an increase in winter births was observed and Spearman correlation between low ambient temperature and schizophrenia births was significant in male subjects. More significant seasonality of birth in male patients than in female patients might be related to more susceptibility to pre- or perinatal disturbances in neurodevelopment in males than in females.     

A case of long-term remission with salvage surgeries for chemotherapy-resistant germ cell tumor of testis

A patient with non-seminomatous germ cell tumor of testis underwent operations for metastases in the lung and mediastinum three times, when the serum AFP level remained remarkably high despite of intensive chemotherapy, and has been disease-free for three years after the last treatment. Our experience illustrates that the salvage surgery even under high serum marker levels may provide a beneficial outcome for selected cases of chemotherapy-resistant germ cell tumors.     

Origins of surface potentials evoked by electrical stimulation of oculomotor nerves: are they related to electrooculographic or electromyographic events?

OBJECT: Evoked potentials elicited by electrical stimulation of the oculomotor nerve and recorded from surface electrodes placed on the skin around the eyeball reportedly originate in the eye and are represented on electrooculograms. Because evoked potentials recorded from surface electrodes are extremely similar to those of extraocular muscles, which are represented on electromyograms, the authors investigated the true origin of these potentials. METHODS: Evoked potentials elicited by electrical stimulation of the canine oculomotor nerve were recorded from surface electrodes placed on the skin around the eyeball. A thread sutured to the center of the cornea was pulled and the potentials that were evoked during the resultant eye movement were recorded. These potentials were confirmed to originate in the eye and to be represented on electrooculograms because their waveforms were unaffected by the administration of muscle relaxant. To eliminate the influence of this source, the retina, a main origin of standing potentials of the eyeball, was removed. This resulted in the disappearance of electrooculography (EOG) waves elicited by eye movement. Surface potentials elicited by oculomotor nerve stimulation were the same before and after removal of the retina. Again the oculomotor nerve was electrically stimulated and electromyography (EMG) response of the extraocular muscles was recorded at the same time that potentials were recorded from the surface electrodes. In their peak latencies, amplitudes, and waveforms, the evoked potentials obtained from surface electrodes were almost identical to EMG responses of extraocular muscles. CONCLUSIONS: Evoked potentials elicited by electrical stimulation of the oculomotor nerves and obtained from surface electrodes originated from EMG responses of extraocular muscles. These evoked potentials do not derive from the eye.     

Mucin phenotype and microsatellite instability in early multiple gastric cancers

Clinicopathologically, multiple gastric cancers (MGCs) are reported to involve predominantly intestinal-type adenocarcinoma and frequently to be associated with severe intestinal metaplasia. However, there are few reports concerning the characteristic biomarkers of early MGCs. The aim of our study was to identify the cellular lineage defined by mucin phenotypes and the relationships among mucin phenotypes, background mucosa and microsatellite instability (MSI) of early MGCs. We examined mucin phenotypes of 63 surgically resected carcinomas from 25 patients with early MGCs and 39 early solitary gastric cancers (SGCs) by immunohistochemical analysis using a panel of monoclonal antibodies. MSI and the degree of intestinal metaplasia (IM) on the background mucosa were also examined. In early MGCs, the incidence of cancer exhibiting the gastric phenotype (G-type) was 59% (37 of 63 cancers), which was higher than that in early SGCs (23%, 9 of 39 cancers). There was a significant difference between the distributions of mucin phenotypes in early MGCs and early SGCs (p = 0.001). Whereas half of the G-type cancers in early MGCs were related to severe IM, none of the G-type cancers in early SGCs were related to severe IM. In the early MGCs, MSI was observed in 21 of 63 cancers (33.3%). In contrast, MSI was observed in only 3 of the 39 (7.7%) early SGCs, indicating a significant difference between these 2 groups (p < 0.01). Our results suggest that the characteristic features of early MGCs are the gastric mucin dominant phenotype and high frequency of MSI.     

Small-volume image-guided radiotherapy using hypofractionated,coplanar, and noncoplanar multiple fields for patients with inoperable Stage I nonsmall cell lung carcinomas

BACKGROUND: Occasionally, medically compromised and/or elderly patients with nonsmall cell lung carcinomas (NSCLCs) cannot be treated surgically. We investigated small-volume hypofractionated image-guided radiotherapy (IGRT) without the need for breath control in patients with inoperable Stage I NSCLCs. METHODS: Between September 1996 and September 1999, 22 patients with Stage I NSCLCs, including 19 males and 3 females, were treated with IGRT. Among these patients, there were 13 Stage IA and 9 Stage IB tumors. The tumors ranged in size from 14.2 to 58.5 mm, with a median size of 26.7 mm. Of the 22 patients, 19 were unfit for surgical treatment due to poor pulmonary function, complications, and/or advanced age and 3 refused surgery. Computed tomographic scans (CT) of the primary tumor were taken during three respiratory phases and they were analyzed to determine the planning target volume, which included only the primary tumor with allowances for respiratory movement. The radiation doses administered at the edge of the moving tumor during normal breathing were 80% of the prescribed dose, either 48 or 60 Gy given in eight fractions over 2 weeks. Clinical evaluation, chest CT scan, and pulmonary function tests were performed before irradiation and at regular intervals for the post-IGRT follow-up. The median follow-up period was 24 months (range, 2-44 months; mean, 21.8 months) (at least 24 months for survivors). RESULTS: Of 17 tumors assessed at the initial follow-up 2-6 months after treatment (5 complete responses, 11 partial responses, and 1 progressive disease), 16 (94%) were controlled locally. One local recurrence was observed during the follow-up. The lung carcinoma-specific survival rate at 1 year was 94% and the 1-year actuarial recurrence-free survival rate was 71%. The lung carcinoma-specific survival rate at 2 years was 73% and the 2-year actuarial recurrence-free survival rate was 67%. The treatment was well tolerated and no major side effects were observed. Localized radiation pneumonitis was observed in all patients who were examined by CT scan, but the patients were asymptomatic. Parameters of pulmonary function, including vital capacity, total lung capacity, and diffusion capacity for carbon monoxide, decreased very little or not at all, indicating that IGRT rarely deteriorated pulmonary functions. CONCLUSIONS: Small-volume hypofractionated IGRT without breath control is a feasible and beneficial method for the curative treatment of patients with Stage I NSCLCs. It has the potential of a high local tumor control rate and low morbidity.     

Endostatin regulates endothelial cell adhesion and cytoskeletal organization

Endostatin, an endogenous angiogenesis inhibitor, attenuates endothelial cell migration through an unknown mechanism. We show that endostatin induced tyrosine phosphorylation of focal adhesion kinase and paxillin, and promoted formation of focal adhesions and actin stress fibers, similar to fibroblast growth factor-2 (FGF-2). In cells cotreated with endostatin and FGF-2, focal adhesions and actin stress fibers were decreased, indicating that endostatin disturbs cell-matrix adhesion. Reduced tyrosine phosphorylation and cytoplasmic relocalization of beta-catenin in cells treated with FGF-2 and endostatin indicates that loosening of cell-cell adhesion is also disturbed by endostatin. These data provide a molecular basis both for the lack of effect of endostatin on the normal, quiescent vasculature, and its antagonistic effects on stimulated tumor vessels.     

A case of advanced esophageal cancer with multiple lymph node metastases successfully treated with induction chemotherapy consisting of nedaplatin and 5-FU followed by chemoradiotherapy

A 61-year-old male patient had esophageal carcinoma with multiple mediastinal and right supraclavicular lymph node metastases. Chemotherapy consisting of infusion of nedaplatin and continuous infusion of 5-fluorouracil was performed. After three courses of the chemotherapy, the patient was treated with a combination of cisplatin and 5-FU and radiotherapy. However, only radiotherapy was performed after 18 Gy because of grade 3 leukocytonenia during the chemoradiotherapy. The patient achieved a partial response (nearly complete response) for 9 months after the initiation of the treatment. In conclusion, chemotherapy with NDP and 5-FU followed by chemoradiotherapy is effective and safe for patients with esophageal carcinoma with multiple lymph node metastases.     

A trial of continuous and biweekly low-dose cisplatin and 5-FU with UFT chemotherapy for esophageal cancer

A 77-year-old man with advanced esophageal cancer with tracheal and esophageal obstruction underwent continuous low-dose FP chemotherapy for a total of seven weeks, resulting in a complete response (CR) and disappearance of the esophago-tracheal fistula. Since discharge from the hospital, he has maintained a stable good condition for about two years while receiving biweekly low dose FP chemotherapy and oral UFT. Eight patients who had post-operative recurrence and underwent noncurative operation for esophageal cancer were given low-dose FP chemotherapy. The results of this chemotherapy for those 8 patients and the present patient, for a total of 9 patients were 2 CR, 2 PR, 3 NC and 2 PD, with an overall response rate of 44%, and overall one-year and two-year survival rates of 44% and 22%, respectively.     

Mental state as a possible independent prognostic variable for survival in patients with advanced lung carcinoma

BACKGROUND: Although psychologic factors have been reported to influence the progression of cancer, this theory remains controversial. A prospective study of patients with advanced lung carcinoma was performed to explore the influence of the patient's mental state on survival. METHODS: The patient's mental state was assessed with the Tokyo University Egogram. In a preliminary study, the egograms of long-term survivors (survival > 3 years) with TNM Stage IIIB or Stage IV lung carcinoma were compared with the egograms of consecutive, newly diagnosed lung carcinoma patients (controls). Next, in a prospective study, 123 patients with nonsmall cell lung carcinoma and 56 patients with small cell lung carcinoma (Stage IIIB or Stage IV; Eastern Cooperative Oncology Group performance status of 0 or 1) completed the egogram. Based on the results of the preliminary study, the subjects in the prospective study were divided into Group A (Free Child [FC] >or= 50th percentile and Adapted Child [AC] < 50th percentile) and Group B (FC < 50 percentile or AC >or= 50 percentile). The survival of the two groups was compared. The Cox proportional hazards model was used to determine the joint effect of the patient's mental state and other prognostic factors. RESULTS: In the preliminary study, the FC score of the long-term survivors was significantly higher and the AC score was significantly lower than those of the controls. In the prospective study, the survival of Group A was significantly longer than that of Group B both in the nonsmall cell lung carcinoma and small cell lung carcinoma patients (P = 0.002 and P = 0.005, respectively, by the log-rank test). Multivariate analysis demonstrated that after adjustment for clinical factors, being in Group A was a significant predictor of survival both in the nonsmall cell and small cell lung carcinoma patients. CONCLUSIONS: The results of the current study demonstrate that the mental state of the patient as assessed by the egogram may have prognostic significance in patients with advanced lung carcinoma.