Predominant presence of Streptococcus anginosus in the saliva of alcoholics.

Chronic alcohol consumption is known to be a major risk factor for cancers of the upper aerodigestive tract. The incidence of esophageal cancer (4.4%) in alcoholics is reported to be much higher than that in the Japanese population as a whole (0.0001%). This suggests the presence of specific factors in chronic alcohol consumption-related carcinogenesis. Recently, data showing a significant correlation between Streptococcus anginosus and carcinogenesis in the upper aerodigestive tract have been reported. In this study, the ratio of S. anginosus to oral bacteria in the saliva of 38 alcoholic patients was investigated to determine if there is an association between alcoholic patients and S. anginosus infection. The level of S. anginosus in the saliva from 22 healthy people, 41 esophageal cancer patients, 32 gastritis patients, and 24 periodontitis patients was also investigated and compared to the level in alcoholic patients. In the saliva from esophageal cancer patients, the level of S. anginosus was not significantly different from that of healthy people. The levels of S. anginosus in periodontitis and gastritis patients were also similar. In alcoholics, however, there was an extremely high level of S. anginosus, suggesting that they, rather than healthy people and general esophageal cancer patients, have a high risk for S. anginosus infection.

Personality and cancer survival: the Miyagi cohort study.

We tested the hypothesis that personality plays a role in cancer outcome in a population-based prospective cohort study in Japan. In July 1990, 41 442 residents of Japan completed a short form of the Eysenck Personality Questionnaire-Revised and a questionnaire on various health habits, and between January 1993 and December 1997, 890 incident cases of cancer were identified among them. These 890 cases were followed up until March 2001, and a total of 356 deaths from all causes was identified among them. Cox proportional-hazards regression was used to estimate the hazard ratio (HR) of death according to four score levels on each of four personality subscales (extraversion, neuroticism, psychoticism, and lie), with adjustment for potential confounding factors. Multivariable HRs of deaths from all causes for individuals in the highest score level on each personality subscale compared with those at the lowest level were 1.0 for extraversion (95% CI=0.8-1.4; Trend P=0.73), 1.1 for neuroticism (0.8-1.6; Trend P=0.24), 1.2 for psychoticism (0.9-1.6; Trend P=0.29), and 1.0 for lie (0.7-1.5; Trend P=0.90). The data obtained in this population-based prospective cohort study in Japan do not support the hypothesis that personality is associated with cancer survival.

Postural effects on brain hemodynamics in unilateral cerebral artery occlusive disease: a positron emission tomography study.

To investigate effect of assuming of upright posture on brain hemodynamics in patients with unilateral internal carotid or middle cerebral artery occlusion (MCAO), local tissue oxygen extraction fraction (OEF), and postural changes in regional cerebral blood flow (rCBF) during supine and sitting conditions were examined using positron emission tomography (PET) with (15)O-gas steady-state method and H(2)(15)O autoradiographic method. A total of 22 minor stroke patients at relatively early stages participated. The regions of interest method was used for analyzing levels of perfusion and oxygen metabolic parameters, and postural rCBF change within MCAO group was investigated using statistical parametric mapping. Region of interest analyses showed significant rCBF reduction in the cortical and subcortical regions distal to the artery occlusion in CAO patients during sitting. Regression analyses showed that magnitudes of rCBF reduction in those areas were correlated positively with OEF values and inversely with metabolic rates of oxygen (P < 0.05). Statistical parametric mapping for MCAO patients demonstrated further rCBF reduction by sitting in the occlusion-side MCA territory. The current study suggested that assumption of upright posture could exert an adverse effect on local perfusion in hemodynamically compromised patients with major cerebral vessel occlusion, possibly caused by impairment of local autoregulation.

Methamphetamine-related psychiatric symptoms and reduced brain dopamine transporters studied with PET.

OBJECTIVE: A positron emission tomography (PET) study has suggested that dopamine transporter density of the caudate/putamen is reduced in methamphetamine users. The authors measured nucleus accumbens and prefrontal cortex density, in addition to caudate/putamen density, in methamphetamine users and assessed the relation of these measures to the subjects' clinical characteristics. METHOD: PET and 2-beta-carbomethoxy-3beta-(4-[(11)C] fluorophenyl)tropane, a dopamine transporter ligand, were used to measure dopamine transporter density in 11 male methamphetamine users and nine male comparison subjects who did not use methamphetamine. Psychiatric symptoms in methamphetamine users were evaluated by using the Brief Psychiatric Rating Scale and applying a craving score. RESULTS: The dopamine transporter density in all three of the regions observed was significantly lower in the methamphetamine users than the comparison subjects. The severity of psychiatric symptoms was significantly correlated with the duration of methamphetamine use. The dopamine transporter reduction in the caudate/putamen and nucleus accumbens was significantly associated with the duration of methamphetamine use and closely related to the severity of persistent psychiatric symptoms. CONCLUSIONS: These findings suggest that longer use of methamphetamine may cause more severe psychiatric symptoms and greater reduction of dopamine transporter density in the brain. They also show that the dopamine transporter reduction may be long-lasting, even if methamphetamine use ceases. Further, persistent psychiatric symptoms in methamphetamine users, including psychotic symptoms, may be attributable to the reduction of dopamine transporter density.

Psychiatric disorders in cancer patients: descriptive analysis of 1721 psychiatric referrals at two Japanese cancer center hospitals.

BACKGROUND: Although a diagnosis of cancer today may no longer be considered to be the equivalent of a death sentence, many previous studies in Western countries have revealed that such a diagnosis places many kinds of emotional burden on a patient. However, few studies have focused on the nature of psychiatric disorders in Japanese cancer patients. METHODS: We investigated the characteristics, reason for psychiatric consultation and psychiatric diagnosis of cancer patients by analyzing the database of patients referred to the Psychiatry Divisions at the National Cancer Center Hospital and the National Cancer Center Hospital East, Japan. RESULTS: Among a total of 1721 referrals, most of the cancer patients (78%) were inpatients. Patients with lung cancer (19%) were the most common, followed by patients with breast cancer (13%) and with head and neck cancer (10%). More than half of the patients had recurrent and/or metastatic cancer and 60% of the patients had pain. The most common reason for the consultation was psychiatric evaluation (35%), followed by sleep disorders (19%), anxiety or fear (18%) and depression (18%). Regarding the psychiatric diagnosis, adjustment disorders were the most common (34%), followed by delirium (17%) and major depression (14%). The diagnosis of cancer had been disclosed to more than 99% of the patients. CONCLUSION: The common psychiatric disorders observed in Japanese cancer patients were similar to those in the Western countries provided the cancer diagnosis is disclosed.

Absolute changes in regional cerebral blood flow in association with upright posture in humans: an orthostatic PET study.

UNLABELLED: To determine whether hemodynamic parameters are changed by upright posture in healthy middle-aged humans, absolute values of regional cerebral blood flow (rCBF) were investigated for three different orthostatic conditions. METHODS: PET with [15O]H2O and arterial blood sampling were performed on eight middle-aged healthy volunteers while they were sitting passively or standing actively. Absolute rCBF values estimated by the autoradiographic method in regions of interest were compared using ANOVA, and relative changes in rCBF were also analyzed voxel by voxel using statistical parametric mapping (SPM). RESULTS: Physiologic data remained unchanged for different conditions. ANOVA and SPM showed that absolute and relative rCBF levels were significantly elevated in the cerebellar vermis in the standing position compared with those in the supine and sitting positions. In contrast, ANOVA showed that rCBF in the frontal and parietal cortices tended to be lower in the sitting and standing positions than in the supine position. Regression analysis showed that the frontal rCBF measured during standing tended to be inversely correlated with age. CONCLUSION: The results showed that cerebellar vermis activation was more marked in the standing position than in the sitting or supine positions, indicating that the vermis is a neural substrate for controlling voluntary upright posture. Brain perfusion in the distal internal carotid artery region may be subject to orthostatic postural changes in healthy middle-aged humans.

Changes in dopamine availability in the nigrostriatal and mesocortical dopaminergic systems by gait in Parkinson's disease.

The basal ganglia play a role in controlling movement during gait. The aim of the present study was to investigate changes in dopamine transporter (DAT) availability in the striatum and extrastriatal region in association with walking exercise in six normal subjects and seven age-matched unmedicated patients with Parkinson's disease. This was done by comparing DAT radioligand uptake in the dopaminergic projection areas after gait with that under the resting condition using a DAT probe, 11C-labelled 2-beta-carbomethoxy-3beta-(4-fluorophenyl) tropane ([11C]CFT) and PET. Physiological parameters were stable during and after gait in both groups. The regions of interest method for measuring differences in [11C]CFT uptake level and voxel-based statistical parametric mapping (SPM96) showed that [11C]CFT uptake in the striatum (specifically the putamen) was decreased by gait to a greater extent in normal subjects, whereas a significant reduction in [11C]CFT uptake was not found in the putamen but in the caudate and orbitofrontal cortex in Parkinson's disease patients. These results are the first in vivo evidence that DAT availability is reduced in the nigrostriatal projection area by basic human behaviour, i.e. gait. Alterations in this availability in Parkinson's disease suggested that shifted activation in the medial striatum and the mesocortical dopaminergic system might reflect the pathophysiology of parkinsonian gait.

Cancer regression induced by modified CTL therapy is regulated by HLA class II and class I antigens in Japanese patients with advanced cancer.

Autologous cancer-specific bulk CTLs are unlikely to be induced by in vitro CTL generation (ivtCTLG) using peripheral blood mononuclear cells (PBMCs) of cancer patients when autologous cancer cells are used as in vitro stimulators. However, autologous cancer-specific bulk CTLs are frequently activated when allogeneic cancer cells are used as in vitro stimulators, regardless of the type of cancer cell. We have developed a cancer-specific immunotherapy called modified CTL therapy, which involves adoptive immunotherapy of autologous cancer-specific bulk CTLs after active immunization of autologous or allogeneic cancer cells screened as in vitro stimulators according to their ability to induce autologous cancer-specific CTLs (ACS. CTLs). Cancer did not regress in patients in whom ACS.CTLs were not induced by ivtCTLG using the patients' PBMCs in therapy. Cancer regression, albeit temporary, occurred solely in patients under the immunological condition that ACS.CTLs were induced by ivtCTLG using PBMCs through the therapy. The induction of ACS.CTLs by ivtCTLG using patient PBMCs in therapy was related to patients' HLA class II antigens. HLA DR8 was seen more frequently in ACS.CTL-inducible patients than in ACS.CTL-uninducible patients (P=0.051). On the contrary, HLA DQ3 was seen more frequently in ACS.CTL-uninducible patients (P=0.055). On the other hand, the success in therapy, albeit temporary, was related mainly to patients' HLA class I antigens. HLA B61 was seen more frequently in patients whose therapy proved effective than in patients whose therapy proved ineffective (P=0.018). HLA Cw7 was seen more frequently in therapy-ineffective patients (P=0.040).

Short dynamic FDG-PET imaging protocol for patients with lung cancer.

This positron emission tomography (PET) study was designed to compare 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) kinetic parameters of tumours derived from imaging frames of 0-60 min post FDG injection with those derived from shorter imaging frames of 0-30 min. Dynamic FDG-PET scans were performed on 20 patients with primary lung cancers for 1 h after intravenous injection of FDG. Images were reconstructed with attenuation correction using transmission images obtained with a germanium-68 ring source immediately before FDG injection. A region of interest (ROI) was placed on the plane of the maximal tumour FDG uptake. Arterial input function was estimated from an ROI defined in the left atrium. Based on the standard three-compartment metabolic model, we calculated the rate constants (K1-k3) and influx constant Ki = K1k3/(k2+k3) using the imaging frames for 60 min and 30 min post FDG injection. The standardized uptake value (SUV) of tumour was measured using the imaging frame of 50-60 min post injection. High correlations were observed between kinetic parameters (K1, k2, k3 and Ki) derived from imaging frames of 0-60 min and 0-30 min [0.231+/-0.114 vs 0.260+/-0.174 (r=0.958), 1.149+/-1.038 vs 1.565+/-2.027 (r=0.968), 0.259+/-0.154 vs 0.311+/-0.194 (r=0.886) and 0.044+/-0.022 vs 0.048+/-0.023 (r=0.961), respectively, P<0.001]. Ki showed an excellent agreement between the two methods (y=-0.0041+0.9831x). Mean SUV of the lung cancers was 6.58+/-2.85. It is concluded that the briefer 30-min acquisition may yield essentially the same results as the standard 60-min imaging protocol, thus offering a time saving in dynamic PET studies in which the model parameters are desired.

Palladium-Catalyzed Intermolecular Controlled Insertion of Benzyne-Benzyne-Alkene and Benzyne-Alkyne-Alkene-Synthesis of Phenanthrene and Naphthalene Derivatives.

Aryne reagents, unlike alkynes, undergo insertion by allyl palladium complexes. The verification of the conversion described here is shown using Equation (1) as an example. The reaction proceeds in a few hours in refluxing acetonitrile to give the phenanthrene derivative in up to 71 % yield.

Presynaptic and postsynaptic dopaminergic binding densities in the nigrostriatal and mesocortical systems in early Parkinson's disease: a double-tracer positron emission tomography study.

To investigate changes in the relation between presynaptic and postsynaptic dopaminergic functions in vivo in both nigrostriatal and mesocortical systems in Parkinson's disease (PD), 10 drug-naive early PD patients were studied twice using positron emission tomography with [11C]CFT (dopamine transporter probe) followed by [11C]SCH 23390 (D1 receptor probe). Regional binding potentials (k3/k4) of [11C]CFT and [11C]SCH 23390 in the striatum (nigrostriatal system) and the orbitofrontal cortex (mesocortical system) were estimated by compartment analyses. Levels of [11C]CFT k3/k4 in the two projection areas were shown to be significantly lower in PD, whereas [11C]SCH 23390 levels remained unchanged. Regression analysis showed that estimates of CFT k3/k4 were positively correlated with those of SCH 23390 k3/k4 in the striatum in normal control, whereas the two binding estimates were less positively correlated in the caudate and inversely correlated in the putamen in PD. No significant correlation was observed in the orbitofrontal cortex in both groups. These results indicated that dopamine transporters and D1 receptors change in parallel in the normal striatal synapses, but the association becomes asymmetrical because of reduction in presynaptic and relative elevation in postsynaptic markers in PD. Alterations in synaptic parallel regulation in the nigrostriatal system might reflect early pathophysiology in the parkinsonian brain.

Human cortical areas activated in relation to vergence eye movements-a PET study.

Human cortical areas activated in relation to vergence eye movements were determined using positron emission tomography. Binocular disparity-driven visual stimuli were presented using a head-mounted display. Eye movements were monitored continuously by an infrared limbus tracker. A combination of a bar and a cross was used as the target. In the vergence task, subjects were instructed to follow an approaching bar, while ignoring a stationary cross. Activation in relation to vergence eye movement was discriminated from activation in relation to motion vision by using the ignore-bar task as the control. In the ignore-bar task, subjects were instructed to fixate on a stationary cross, while ignoring an approaching bar. The fixation task was used as the basic control for both the vergence and the ignore-bar tasks. Areas of activation in relation to vergence eye movements were found in the bilateral temporooccipital junction, the left inferior parietal lobule, and the right fusiform gyrus by comparing regional cerebral flow between the vergence and ignore-bar tasks and by the conjunctive analyses of vergence-vs-ignore comparison with vergence-vs-fixation comparison.

Alterations in binding site density of dopamine transporter in the striatum, orbitofrontal cortex, and amygdala in early Parkinson's disease: compartment analysis for beta-CFT binding with positron emission tomography.

We investigated changes in the kinetics in the binding of the dopamine transporter probe 2-beta-carbomethoxy-3beta-(4-[11C]fluorophenyl)tropane (beta-CFT) in living brain by compartmental analysis, using positron emission tomography in unmedicated patients with Parkinson's disease (PD) (Hoehn and Yahr stages I-II). With dynamic positron emission tomographic data from 90-minute acquisitions and metabolite-corrected arterial input functions, binding potentials (k3/k4) were calculated by using estimated rate constants (K1 - k4). In this analysis, the magnitude of the distribution volume (K1/k2) measured in the cerebellum, in which specific binding is negligible, was used as a constrained value for fitting in binding regions. Statistics showed that k3/k4 values in the striatum, the orbitofrontal cortex, and the amygdala were significantly lower in PD patients than in normal controls, whereas there were no differences in K1/k2 ratios and structural volumes between the groups. Correlation analysis showed that the putaminal and orbitofrontal binding levels were correlated positively with motor and mentation scores, respectively, of the Unified Parkinson's Disease Rating Scale. These results indicated that not only the striatal but also the orbitofrontal and amygdalar presynaptic dopaminergic functions were altered in early PD. The reductions in these mesocortical/mesolimbic functions might contribute to the mental and behavioral impairment observed in PD.

Brain activation during maintenance of standing postures in humans.

The regulatory mechanism of bipedal standing in humans remains to be elucidated. We investigated neural substrates for maintaining standing postures in humans using PET with our mobile gantry PET system. Normal volunteers were instructed to adopt several postures: supine with eyes open toward a target; standing with feet together and eyes open or eyes closed; and standing on one foot or with two feet in a tandem relationship with eyes open toward the target. Compared with the supine posture, standing with feet together activated the cerebellar anterior lobe and the right visual cortex (Brodmann area 18/19), and standing on one foot increased cerebral blood flow in the cerebellar anterior vermis and the posterior lobe lateral cortex ipsilateral to the weight-bearing side. Standing in tandem was accompanied by activation within the visual association cortex, the anterior and posterior vermis as well as within the midbrain. Standing with eyes closed activated the prefrontal cortex (Brodmann area 8/9). Our findings confirmed that the cerebellar vermis efferent system plays an important role in maintenance of standing posture and suggested that the visual association cortex may subserve regulating postural equilibrium while standing.

Altered glucose metabolism in the hippocampal head in memory impairment.

OBJECTIVE: To evaluate the relevance of hypometabolism in the hippocampal head to the pathophysiology of memory impairment. BACKGROUND: Neurofunctional imaging studies with an image reslicing technique provided by using software suggest that dysfunction of the amygdalohippocampal system causes memory impairment. However, metabolic and morphologic profiles of the whole hippocampal formation have not been evaluated in detail. METHODS: By tilting the gantry of a high-resolution PET scanner in a plane parallel to the hippocampal longitudinal axis determined beforehand by MRI, we performed quantitative measurement of glucose metabolism in the subdivisions of the hippocampal formation (head, body, tail) in 10 patients of normal intelligence with pure amnesia, in eight patients with AD, and in eight normal subjects. RESULTS: Although the volumes of the amygdala and hippocampal formation in pure amnesics were not different significantly from those of normal subjects, glucose metabolism in the head of the hippocampus was significantly lower in pure amnesics. In patients with AD, marked hypometabolism was found extending to the amygdala, the hippocampal head, and the parietotemporal cortex, along with amygdalohippocampal atrophy. CONCLUSION: Hippocampal head dysfunction plays an important role in memory impairment in amnesic patients. Further metabolic impairment over the amygdalohippocampal system and the surrounding association cortex reflects the pathophysiology of AD.

Antibiotic susceptibility of enterohemorrhagic Escherichia coli O157:H7 isolated from an outbreak in Japan in 1996.

The antibiotic susceptibilities of 43 strains of Escherichia coli O157:H7 identified in the summer of 1996 in Japan were investigated. Growth of 90% of O157 strains was inhibited at a concentration of < or = 0.5 micro/ml by several agents including fosfomycin with glucose-6-phosphate.

Application of a beta microprobe for quantification of regional cerebral blood flow with (15)O-water and PET in rhesus monkeys.

A beta microprobe was successfully applied to monitor arterial input function for quantification of regional cerebral blood flow (rCBF) in the monkey brain with (15)O-water and positron emission tomography (PET). The sensitivity of the probe was approximately 0.83 to 1.67 cps/kBq/ml depending on the studies. A preliminary study was performed to find a suitable use and to evaluate the performance of the system and data analysis procedure. The results showed that dispersion correction of measured input function was unnecessary if microprobes were connected directly to the arterial catheter. Then multiple CBF measurements were done in three monkeys under anesthesia. Identical regions of interest were placed with the aid of magnetic resonance imaging (MRI) of each monkey and rCBF values were estimated. Estimated rCBFs were reproducible for several measurements. The mean CBF value for a pentobarbital anesthetized monkey was 46.0 ml/min/100 g (PaCO2 = 46.3 mmHg). This shows that the use of the beta microprobe for quantification of rCBF with PET was validated. The lack of a need for dispersion correction of observed input function is an advantage with the beta microprobe system because the probes are small enough to be placed near the arterial sampling site.