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The central histaminergic neuron system modulates the wakefulness, sleep-awake cycle, appetite control, learning and memory, and emotion. Previous studies have reported changes in neuronal histamine release and its metabolism under stress conditions in the mammalian brain. In this study, we examined, using positron emission tomography (PET) and [(11)C]-doxepin, whether the histaminergic neuron system is involved in human depression. Cerebral histamine H1 receptor (H(1)R) binding was measured in 10 patients with major depression and in 10 normal age-matched subjects using PET and [(11)C]-doxepin. Data were calculated by a graphical analysis on voxel-by-voxel and ROI (region of interests) basis. Binding potential (BP) values for [(11)C]-doxepin binding in the frontal and prefrontal cortices, and cingulate gyrus were significantly lower in the depressed patients than those in the normal control subjects. There was no area of the brain where [(11)C]-doxepin binding was significantly higher in the depressed patients than in the controls. ROI-based analysis also revealed that BP values for [(11)C]-doxepin binding in the frontal cortex and cingulate gyrus decreased in proportion to self-rating depressive scales scores. The results of this study demonstrate that depressed patients have decreased brain H(1)R binding and that this decrease correlates with the severity of depression symptoms. It is therefore suggested that the histaminergic neuron system plays an important role in the pathophysiology of depression and that its modulation may prove to be useful in the treatment of depression.

Objectives: Since patients manifesting behavioral and psychological symptoms of dementia (BPSD) are a burden for their families and caregivers, the underlying neurobiological mechanism of this condition should be clarified. Using positron emission tomography (PET), we previously reported that wandering behavior in dementia was associated with a disturbed dopaminergic neuron system. We herein investigated the relationship between the severity of BPSD and the striatal D2 receptor density in Alzheimer's disease (AD)., Methods: Ten patients with probable AD as per the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the AD and Related Disorders Association (ADRDA) criteria and five normal subjects were examined with PET. The tracer used was [11C]raclopride (D2 antagonist). The uptake of [11C] raclopride was calculated as the estimation of binding potential (BP) of the striatum to the cerebellum. The AD patients were institutionalized in multiple nursing homes, and their BPSD were evaluated by the Behavioral Pathology in AD Frequency Weighted Severity Scale (BEHAVE-AD-FW) scale (Reisberg)., Results: There was a significant inverse Spearman's correlation between BEHAVE-AD-FW score and the BP, especially between the score of the behavioral domain and the BP values. The BP was found to be lower in severer BPSD patients., Conclusions: Patients with AD who manifest severe BPSD may have some dysfunction of striatal dopamine metabolism compared with those without BPSD.

Background and Aim: Antral somatostatin interacts with gastric acid secretion. We aimed to investigate the effect of eradication on gastric acid, somatostatin secretion and mucosal histology in gastric ulcer patients with Helicobacter pylori (H. pylori) infection., Methods: Twenty-eight patients (21 male, 7 female) with H. pylori-positive gastric ulcer were treated with dual therapy. Before and 4-8 weeks after the therapy, the histology of biopsy specimens, basal acid output (BAO) and maximal acid output (MAO) after stimulation with tetragastrin were assessed. Somatostatin concentration in the gastric juice was measured by radioimmunoassay, and somatostatin output during either the basal or gastrin-stimulated period was also examined., Results: Eradication was successful in 22 patients. Before treatment, the acid and somatostatin output were inversely related to the severity of neutrophil infiltration in the corpus and antrum, respectively. After successful eradication, improvement of histological inflammation and an increase in BAO, basal and gastrin-stimulated somatostatin output were observed. Eradication had no effect on atrophy and MAO. There was a positive correlation between gastric acid and somatostatin output in the basal or stimulated condition, irrespective of H. pylori infection., Conclusions: The present results suggest that recovery of gastric BAO may be caused by an improvement in corpus neutrophil infiltration, but not by an increase in parietal cell volume or a change in atrophy. Also, there was an increase in basal and gastrin-stimulated somatostatin-containing cell activity accompanied by improved antral neutrophil infiltration in the early phase after H. pylori eradication in gastric ulcers., (Copyright 2003 Blackwell Publishing Asia Pty Ltd)

Donepezil, an acetylcholinesterase (AChE) inhibitor, has not been evaluated for its binding characteristics using a radioactive tracer, although its inhibitory action on AChE has been studied. The aim of this research is to examine whether AChE can be visualized in vivo and in vitro with [(11)C]donepezil. [5-(11)C-methoxy]Donepezil was synthesized by O-methylation using [(11)C]methyl triflate. The binding of [(11)C]donepezil to brain homogenates was higher in the brain stem and striatum, and it was lowest in the cerebellum. The in vitro autoradiographic study successfully demonstrated the specific binding of [(11)C]donepezil to AChE in the rat brain. The IC(50) value of binding was approximately 10 nM, which is comparable to the reported value for inhibiting enzyme activity (6 nM). Saturation experiments revealed that the B(max) and K(d) of [(11)C]donepezil binding in vitro are 65 fmol/mg tissue and 39.8 nM, respectively. In accordance with the in vitro bindings, the in vivo distribution of [(11)C]donepezil was heterogeneous in the rat brain. In the blocking experiments, the heterogeneous distribution disappeared in the presence of a large amount of unlabeled donepezil. These data suggest that [5-(11)C-methoxy]donepezil can be potentially useful to image AChE non-invasively in the human brain by positron emission tomography.

We report an unusual case of synchronous triple early cancers of the stomach, gallbladder and sigmoid colon. The patient was a 70-year-old man. Gastrointestinal endoscopy at a medical check-up initially revealed early gastric cancer. A thorough preoperative investigation showed a gallbladder tumour and early colon cancer. Endoscopic mucosal resection was performed for the colon cancer. Microscopically, the specimen showed well-differentiated adenocarcinoma involving the submucosal layer. Distal partial gastrectomy (D1) and simple cholecystectomy with lymph node dissection were also performed. The histopathological diagnosis was well-differentiated adenocarcinoma in the stomach (T1, N0, M0; Stage IA) and poorly differentiated papillary adenocarcinoma (T1, N0, M0; Stage I) in the gallbladder. The patient was doing well with no evidence of recurrence 6 months after surgery.

We investigated the influence of anesthesia on the brain distribution of [11C]methamphetamine (MAP) obtained by the positron emission tomography (PET) using the normal rhesus monkeys. We clarified that the brain uptake of [11C]MAP under halothane anesthesia was faster and higher than that under pentobarbital. The difference of the effect of anesthesia is an important problem in pharmacokinetic study in PET with experimental animals.

Although endoscopic hemostasis is an effective treatment for acute upper gastrointestinal bleeding, permanent hemostasis may be difficult to achieve by conventional endoscopic treatment alone in some patients. In addition, conventional hemostatic endoscopic therapy is limited in patients with a risk of gastrointestinal ulcer perforation. We tried endoscopic fibrin glue injection in 21 patients as a new approach to control severe upper gastrointestinal bleeding. A new type of coaxial double lumen needle was used in the last 15 patients. Hemostasis was obtained immediately by fibrin glue injection in all 7 patients after unsuccessful attempts using conventional methods, including absolute alcohol or epinephrine injection, clipping, or electrocoagulation. There were no episodes of rebleeding in this group. In 10 of the 14 patients who underwent endoscopic fibrin glue injection as the primary therapy, complete hemostasis was achieved with the initial treatment. The remaining 4 required a second injection within 48 hours. There were no treatment-related complications. None of the patients required an additional surgical operation for bleeding, and the period of hospitalization was reduced after the introduction of fibrin glue injection. Considering the effect on acceleration of ulcer healing, endoscopic fibrin glue injection is an effective treatment with no risk of tissue injury. This technique can be used as the first choice or after failure of conventional endoscopic hemostatic methods.

Repeated administration of methamphetamine (MAP) causes behavioral sensitization in animals. We previously reported that the maximum accumulation level of [11C]MAP in the MAP-sensitized dog brain was 1.4 times higher than that in the control. In behavioral studies, haloperidol (a dopamine D2 receptor antagonist) prevents MAP-induced behavioral sensitization, and cocaine (a dopamine reuptake blocker) has the cross-behavioral sensitization with MAP. In the present study, to elucidate the relation between the MAP-induced behavioral sensitization and the pharmacokinetics of MAP, we investigated the effects of haloperidol and cocaine pretreatments on brain regional distribution and kinetics of [11C]MAP using positron emission tomography (PET). A significant increase of [11C]MAP uptake into the sensitized dog brain was prevented by haloperidol and cocaine pretreatments. These pharmacokinetic changes were not due to the changes in the rate of MAP metabolism. These results suggest haloperidol and cocaine can change the cerebral pharmacokinetic profile of MAP in the behavioral-sensitized dog. The variations of MAP-accumulation may affect the development or expression of MAP-induced behavioral sensitization.

We have characterized a new tumor-associated antigen defined by monoclonal antibody (MAb) generated against HMA-1 breast cancer cell line. MAb AM-1 was selected based on its preferential reactivity to breast cancer cells versus to normal or benign epithelial cells by immunofluorescence and immunohistochemical assays of cultured, or fresh specimens. AM-1 demonstrated strong reactivity to breast cancer cell lines including HMA-1, YMB-1-E, YMB-1 and MDA-MB-231 in flow cytometry. In immunoprecipitation, AM-1 recognized high molecular weight components of 160-210 kDa and > 370 kDa. Reactivity with HMA-1 cells was diminished markedly when treated by heat, protease or periodate, suggesting that the antigenic epitope is composed with carbohydrates and peptides. Enzyme digestion of precipitated antigens demonstrated that the antigen contains O-linked and N-linked carbohydrates with neuraminic acid structures. Furthermore, binding inhibition and sandwich ELISA assays using MAbs reactive with known breast cancer-associated antigens and synthetic MUC1 core peptide (PDTRPAPGSTAPPAHGVTSAPDTR) demonstrated that the antigen is distinct from CEA, TAG-72 or MUC1, while the antigen conjoins with MUC1 and TAG-72 as a trimmer form in HMA-1 cells. These results suggest that AM-1 recognizes a novel glycoprotein which is abundant in breast cancer, and may be utilized in the management of breast cancer patients.

We newly prepared a MAP-sensitized dog by repeated MAP treatment and studied the brain distribution of [11C]MAP in the normal and the MAP-sensitized dog using PET. The maximal level of accumulation of [11C]MAP in the sensitized dog brain was 1.4 times higher than that in the control. No difference was found in the metabolism of MAP between the two conditions. The significant increase of [11C]MAP in the MAP-sensitized brain indicates that subchronic MAP administration causes some functional change in the uptake site of MAP. The pharmacokinetic change may, in part, account for behavioral sensitization.

[11C]Methamphetamine ([11C]MAP) was synthesized by an automated on-line [11C]methylation system for positron emission tomography (PET) study. We newly produced a MAP sensitized dog by repeated MAP treatment and studied the brain distribution of [11C]MAP in the normal and the MAP sensitized dog. The maximal level of accumulation of [11C]MAP in the sensitized dog brain was 1.4 times higher than that in the control. No difference was found in the metabolism of MAP between the two conditions. The significant increase of [11C]MAP in the MAP sensitized brain indicates that subchronic MAP administration causes some functional change in uptake site of MAP.

Tricuspid insufficiency is not infrequent in combined valvular diseases. We used Carpentier's De Vega's or Bex's annuloplasty with our own modification in combined tricuspid insufficiency and found the results much more satisfactory compared with previous methods. Of 152 patients with acquired valvular disease, 24 with combined valvular disease underwent one of these procedures. During the same period, three tricuspid valve replacements, using a glutaraldehyde-treated xenograft, were performed in patients with severly damaged tricuspid valves. Simultaneous procedures for other valves were open mitral commissurotomy in 14, mitral valve replacement in 9 and aortic and mitral valve replacement in 4 patients. Despite the seriousness of their preoperative condition, 25 of 27 patients survived, resulting in a mortality rate of 7.4%. We believe that these annuloplasty methods represent a remarkable progress in the treatment of tricuspid valve insufficiency in combined valvular diseases.

A pancreatic endocrine tumor measuring 1.5 X 1.0 X 1.0 cm in a 67-year-old man with recurrent hypoglycemic attacks was examined by immunohistochemistry and electron microscopy. The tumor cells were relatively uniform, and almost all of them were immunoreactive to insulin. A few calcitonin-positive cells could be identified scattering in tumor cell strands, and the content of calcitonin in the tumor was 85 ng/g wet tissue. Coexistence of insulin and calcitonin in tumor cells was demonstrated by using adjacent semithin sections of the Epon-embedded material. Electron microscopically, the tumor consisted of a single type of cells with secretory granules identical to B-cell granules in the normal counterpart.

Effect of methylprednisolone on the emesis of patients treated with CDDP was examined by randomized control trial. Methylprednisolone showed no effect on the frequency of vomiting on the day of CDDP administration as well as on the duration of nausea and anorexia after CDDP treatment.

The effect of high-dose metoclopramide (2 mg/kg, 4 times every 2 hours) on the emesis of patients treated with CDDP (80 mg/m2) was examined by randomized control trial. The above metoclopramide regimen significantly suppressed the frequency of vomiting on the day of CDDP administration. The duration of nausea and anorexia after CDDP treatment was also shortened by high-dose metoclopramide administration.