Association between Malnutrition Severity and Swallowing Function in Convalescent Rehabilitation Wards: A Multi-Center Cohort Study in Malnourished Patients with Sarcopenic Dysphagia.

OBJECTIVES: To evaluate the characteristics of sarcopenic dysphagia (SD) and the prognosis of swallowing function in convalescent rehabilitation hospital patients; and to investigate the association between malnutrition severity and SD. DESIGN: A prospective, multi-center, cohort study. SETTING: We extracted registry data from the Japanese Sarcopenic Dysphagia Database, focusing on patients admitted to convalescent rehabilitation hospitals. PARTICIPANTS: A total of 207 participants were recruited and stratified according to the presence or absence of SD. Next, the participants were divided into groups based on nutrition status using the Global Leadership Initiative on Malnutrition criteria: normal nutrition, moderate malnutrition, and severe malnutrition. We also compared the outcomes between patients with SD (SD group) and those without SD (no-SD group) according to malnutrition status. MEASUREMENTS: The Food Intake LEVEL Scale (FILS) score was the outcome measure. Higher scores on the FILS indicate better swallowing function. We compared the patient characteristics between the SD and non-SD groups among all patients and then according to the severity of malnutrition. RESULTS: A total of 207 patients were recruited. 11 were diagnosed with normal nutrition, 72 with moderate malnutrition, and 124 with severe malnutrition. There were 128 participants with SD and 79 participants without SD; the prevalence of SD was 61.8%. Hip fracture was the most common disease among the SD patients (34.4%). The median time to the end of follow-up was 73.5 days for the SD group and 84.0 days for the no-SD group. There was no significant difference in the FILS score between the SD and no-SD groups, but the increase in the FILS score was significantly lower in the SD group than the no-SD group among patients with severe malnutrition after adjusting for confounding factors (age, sex, FILS at admission, BMI, cognitive functional independence measure, and care level before onset) (ß = -0.206, p = 0.011, 95% confidence interval = -0.723, -0.098). CONCLUSION: Orthopedic diseases are the most common type of disease among SD patients in convalescent rehabilitation hospitals. Swallowing dysfunction was particularly severe in malnourished patients with SD. This result suggests the importance of the definition of SD for malnourished patients. We should practice nutritional management as soon as possible in severely malnourished patients diagnosed with SD.

Aberrant microRNA expression in the brains of neurodegenerative diseases: miR-29a decreased in Alzheimer disease brains targets neurone navigator 3.

AIMS: MicroRNAs (miRNAs) are small non-coding RNAs that regulate translational repression of target mRNAs. Accumulating evidence indicates that various miRNAs, expressed in a spatially and temporally controlled that manner in the brain plays a key role in neuronal development. However, at present, the pathological implication of aberrant miRNA expression in neurodegenerative events remains largely unknown. To identify miRNAs closely associated with neurodegeneration, we performed miRNA expression profiling of brain tissues of various neurodegenerative diseases. METHODS: We initially studied the frontal cortex derived from three amyotrophic lateral sclerosis patients by using a microarray of 723 human miRNAs. This was followed by enlargement of study population with quantitative RT-PCR analysis (n = 21). RESULTS: By microarray analysis, we identified up-regulation of miR-29a, miR-29b and miR-338-3p in amyotrophic lateral sclerosis brains, but due to a great interindividual variation, we could not validate these results by quantitative RT-PCR. However, we found significant down-regulation of miR-29a in Alzheimer disease (AD) brains. The database search on TargetScan, PicTar and miRBase Target identified neurone navigator 3 (NAV3), a regulator of axon guidance, as a principal target of miR-29a, and actually NAV3 mRNA levels were elevated in AD brains. MiR-29a-mediated down-regulation of NAV3 was verified by the luciferase reporter assay. By immunohistochemistry, NAV3 expression was most evidently enhanced in degenerating pyramidal neurones in the cerebral cortex of AD. CONCLUSIONS: These observations suggest the hypothesis that underexpression of miR-29a affects neurodegenerative processes by enhancing neuronal NAV3 expression in AD brains.

Insomnia in Japanese peri- and postmenopausal women.

OBJECTIVE: To determine the prevalence and to identify the correlates of insomnia in Japanese peri- and postmenopausal women. METHOD: We retrospectively analyzed the records of 1451 peri- and postmenopausal women enrolled in the Systematic Health and Nutrition Education Program, conducted at the Menopause Clinic of the Tokyo Medical and Dental University Hospital, between 1995 and 2009. RESULTS: The prevalence of insomnia was 50.8%. The severity of insomnia correlated negatively with health-related quality of life (HR-QOL) scores on all the four domains assessed: physical health, mental health, life satisfaction and social involvement. With regard to other menopausal symptoms, insomnia correlated more strongly with depressed mood than with vasomotor symptoms, and one-third of insomniac women were seriously depressed. On categorizing the participants into four groups--not insomniac or depressed, N; insomniac but not depressed, I; not insomniac but depressed, D; insomniac and depressed, ID--the HR-QOL scores were observed to worsen in order N > I > D > ID. No significant difference was detected between groups I and ID with regard to their sleep quality measures. The number of heavy smokers was high in groups I and ID. With regard to the effect of the combination of medication and health/nutrition education, hormone therapy and nightly hypnotics significantly improved the insomnia symptoms, but hypnotics administered 'as needed' did not. CONCLUSIONS: Insomnia in Japanese peri- and postmenopausal women correlates more strongly with depressed mood than with vasomotor symptoms. Cessation of smoking may improve the women's sleep quality, and hormone therapy and nightly hypnotics are both effective treatments.

Protein microarray analysis identifies human cellular prion protein interactors.

AIMS: To obtain an insight into the function of cellular prion protein (PrPC), we studied PrPC-interacting proteins (PrPIPs) by analysing a protein microarray. METHODS: We identified 47 novel PrPIPs by probing an array of 5000 human proteins with recombinant human PrPC spanning amino acid residues 23-231 named PR209. RESULTS: The great majority of 47 PrPIPs were annotated as proteins involved in the recognition of nucleic acids. Coimmunoprecipitation and cell imaging in a transient expression system validated the interaction of PR209 with neuronal PrPIPs, such as FAM64A, HOXA1, PLK3 and MPG. However, the interaction did not generate proteinase K-resistant proteins. KeyMolnet, a bioinformatics tool for analysing molecular interaction on the curated knowledge database, revealed that the complex molecular network of PrPC and PrPIPs has a significant relationship with AKT, JNK and MAPK signalling pathways. CONCLUSIONS: Protein microarray is a useful tool for systematic screening and comprehensive profiling of the human PrPC interactome. Because the network of PrPC and interactors involves signalling pathways essential for regulation of cell survival, differentiation, proliferation and apoptosis, these observations suggest a logical hypothesis that dysregulation of the PrPC interactome might induce extensive neurodegeneration in prion diseases.

Enhancement of antitumor activity of herpes simplex virus gamma(1)34.5-deficient mutant for oral squamous cell carcinoma cells by hexamethylene bisacetamide.

Current oncolytic viruses exert only limited antitumor activity on their own. There is a need to increase their oncolytic capability. We evaluated the effect of a differentiating reagent, hexamethylene bisacetamide (HMBA), on the antitumor activity of a gamma(1)34.5-deficient herpes simplex virus type 1 (HSV-1) R849 for human oral squamous cell carcinoma (SCC) cells. Hexamethylene bisacetamide increased the viral yield, especially at a low input multiplicity of infection (MOI), and the transcription of immediate early genes of HSV-1. Hexamethylene bisacetamide treatment promoted the cytopathic effect of R849 and increased the proportion of dead cells. Hexamethylene bisacetamide produced more apoptotic cells in R849-infected cells as compared with parental HSV-1(F)-infected cells. The growth of oral SCC xenografts in nude mice was markedly suppressed by treatment with R849 in combination with HMBA, and the survival of the co-treated animals was significantly prolonged as compared with that of animals treated with R849 only. Herpes simplex virus type 1 mRNA was expressed in tumors and trigeminal neurons, but not in brain, lung, liver, and kidney. These results indicate that HMBA enhances the antitumor activity of R849 through the expression of immediate early genes without increasing its toxicity. Hexamethylene bisacetamide can be used as an enhancing agent for oncolytic therapy with HSV-1 mutants.

Proper Orthogonal Decomposition Methods for the Analysis of Real-Time Data: Exploring Peak Clustering in a Secondhand Smoke Exposure Intervention.

This work explores a method for classifying peaks appearing within a data-intensive time-series. We summarize a case study from a clinical trial aimed at reducing secondhand smoke exposure via the installation of air particle monitors in households. Proper orthogonal decomposition (POD) in conjunction with a k-means clustering algorithm assigns each data peak to one of two clusters. Aversive feedback from the monitors increased the proportion of short-duration, attenuated peaks from 38.8% to 96.6%. For each cluster, a distribution of parameters from a physics-based model of airborne particles is estimated. Peaks generated from these distributions are correctly identified by POD/clustering with >60% accuracy.

Role of endothelium in the human uterine arteries during normal menstrual cycle.

1. The present experiments were designed to investigate the role of endothelium in the human uterine arteries during the normal menstrual cycle. 2. Acetylcholine (ACh) produced a concentration-dependent relaxation response during the higher level of plasma 17 beta-oestradiol (E2) (follicular and luteal phases, E2 = 131.9 +/- 15.9 pg ml-1, n = 13; group I). However, the agent did not produce a definite relaxation, but produced a slight contraction during the ovulatory and menstruation phases (E2 = 19.8 +/- 2.9 pg mg-1, n = 5; group II). During the follicular and luteal phases (E2 = 181.1 +/- 9.0 pg ml-1, n = 6), ACh produced a slight contraction, but not relaxation in 6 cases (group III). Relaxation in response to A23187 in group II was not different from that in group I, while it was significantly (P < 0.05 and P < 0.005) reduced in group III. Sodium nitroprusside (SNP)-induced relaxation was similar in the three groups. 3. Correlation between the maximum response to ACh and the plasma E2 was highly significant (gamma = 0.8142, P < 0.001) in 18 cases of groups I and II, but not in all 24 cases including group III (gamma = 0.1183, NS). 4. Relaxations in response to ACh in group I or A23187 in all groups were abolished after removal of the endothelium. In group I, ACh- and A23187-induced relaxations were greatly inhibited by methylene blue or NG-nitro-L-arginine (L-NOARG) and partially inhibited by indomethacin. None of these treatments except for methylene blue modified the SNP-induced relaxation, which was significantly inhibited by methylene blue.5. The A23187-induced relaxation was hardly affected by methylene blue or L-NOARG in group III,but was partially inhibited by these agents in group II. The effect of indomethacin in inhibiting the A23187 induced-relaxation was most potent (58.9%) in group III and least (16.9%) in group I.6. There were no histological changes in 14 cases out of 18 (groups I and II), but very slight intimal thickening was observed in 4 cases in group I. On the other hand, severe intimal thickening was observed in all 6 cases in group III.7. These results indicate that, in human uterine artery strips, ACh and A23187 cause endothelium dependent relaxations, which are mediated mainly through EDRF/NO in group I, mainly prostacyclin(PGI2) in group III, or both in group II. It is suggested that lack of the production/release of EDRF/NO and/or of interaction between EDRF/NO and PGI2 might play a role in the formation of intimal thickening in human uterine arteries.

Intimal hyperplasia in human uterine arteries accompanied by impaired synergism between prostaglandin I2 and nitric oxide.

1. The present experiments were designed to investigate the mechanisms causing intimal hyperplasia in connection with the impaired synergism between prostaglandin I2 (PGI2) and nitric oxide (NO) in human uterine arteries (UAs). 2. In order to assess the magnitude of intimal hyperplasia, the intima:media ratio (%) was estimated with the aid of an image analyser. Human UAs were classified into two groups, I and II on the basis of the ratio and the degree of elastin deposition of histologically normal specimens. The intima:media ratio in group II was determined to be 38.9 +/- 7.7% (n = 6), which was significantly (P < 0.01) higher than that in group I (16.5 +/- 1.5%, n = 7). Less deposition of elastin was found in group I than in group II. 3. The relaxation activities of iloprost (IP) as a stable analogue of PGI2 and sodium nitroprusside (SNP) as a NO donor were not different between the two groups. When the minimum concentrations (Cmin) of IP and SNP in producing relaxation were applied together to the UA strips, these compounds interacted synergistically in group I. The observed relaxation (48.7 +/- 8.8%, n = 7) in this group was significantly (P < 0.01) greater than the predicted value of 18.8 +/- 3.1% (n = 7) (the mathematical sum of the relaxations caused by IP and SNP alone). By contrast, these agents interacted in an additive manner in group II. The observed relaxation (20.8 +/- 9.5%, n = 6) was not significantly different from the predicted value (18.6 +/- 2.4%, n = 6) in this group. 4. During the relaxation produced by the addition of IP and SNP alone or in combination, the changes in cyclic nucleotides (cyclic AMP and cyclic GMP) contents (pmol mg-1 protein) were assayed. When IP and SNP at Cmin were applied together to the UA strips, these compounds interacted synergistically in increasing cyclic nucleotides in group I. The observed net increase in the content was determined to be 1.46 +/- 0.30 (P < 0.05 vs. the predicted value of 0.67 +/- 0.12) in this group (n = 7). By contrast, the observed net increase (0.40 +/- 0.07, n = 6) did not exceed the predicted value (0.65 +/- 0.07, n = 6) in group II. 5. These results suggest that the formation of intimal hyperplasia in group II may be closely related to the impaired synergism between PGI2 and NO in the human UAs.

Accumulation of endogenous inhibitors for nitric oxide synthesis and decreased content of L-arginine in regenerated endothelial cells.

1. We examined regeneration of endothelial cells (ECs), neointima formation, decreased endothelium-dependent relaxation (EDR) and changes in the contents of L-arginine, NG-monomethyl-L-arginine (L-NMMA), asymmetrical NG, NG-dimethylarginine (ADMA) and symmetrical NG,NG-dimethylarginine (SDMA) in the regenerated ECs, 6 weeks after balloon denudation of the rabbit carotid artery. 2. Regeneration of ECs was completed in 6 weeks and a significant neointima formation accompanied by the decreased EDR was observed. 3. L-NMMA and ADMA contents in the regenerated ECs (23.5 +/- 4.3 and 21.2 +/- 2.0 pmol mg-1 DNA, respectively) were significantly (P < 0.05 and P < 0.01) higher than those in the control ECs (8.8 +/- 3.0 and 7.4 +/- 1.9 pmol mg-1 DNA, respectively), whereas L-arginine was significantly (P < 0.005) decreased in the regenerated ECs (31,470 +/- 1,050 pmol mg-1 DNA) as compared to that in the control ECs (47,870 +/- 1,890 pmol mg-1 DNA). SDMA content was below the assay limits. 4. L-NMMA and ADMA, but not SDMA, inhibited the EDR induced by acetylcholine in a concentration-dependent manner. The inhibition with L-NMMA and ADMA was prevented by an addition of L-arginine, but not by D-arginine. 5. These results suggest that the accumulation of endogenous inhibitors for nitric oxide synthesis and decreased L-arginine content are associated with decreased NO production/release from regenerated ECs and neointima formation.

Subjective image of invisible hand coded by monkey intraparietal neurons.

Humans can perform purposeful hand actions even blindly in the dark, perhaps using mental images of the hand. To demonstrate such subjective body images, this study describes the activities of bimodal (somatosensory and visual) neurons in the monkey intraparietal cortex. Visual stimuli moving into the space encompassing their somatosensory receptive fields (s-RFs) on the hand activated these neurons, forming visual receptive fields (v-RFs) as if coding a hand-image. After the hand was hidden by covering it with an opaque plate, the v-RF persisted over the plate above the invisible s-RF. Furthermore, when the hand was moved invisibly under the plate, the v-RF moved over the plate to follow the invisible s-RF. Thus, monkeys can maintain and update subjective body images in the mind, and they are coded by intraparietal bimodal neurons.

Self-images in the video monitor coded by monkey intraparietal neurons.

When playing a video game, or using a teleoperator system, we feel our self-image projected into the video monitor as a part of or an extension of ourselves. Here we show that such a self image is coded by bimodal (somatosensory and visual) neurons in the monkey intraparietal cortex, which have visual receptive fields (RFs) encompassing their somatosensory RFs. We earlier showed these neurons to code the schema of the hand which can be altered in accordance with psychological modification of the body image; that is, when the monkey used a rake as a tool to extend its reach, the visual RFs of these neurons elongated along the axis of the tool, as if the monkey's self image extended to the end of the tool. In the present experiment, we trained monkeys to recognize their image in a video monitor (despite the earlier general belief that monkeys are not capable of doing so), and demonstrated that the visual RF of these bimodal neurons was now projected onto the video screen so as to code the image of the hand as an extension of the self. Further, the coding of the imaged hand could intentionally be altered to match the image artificially modified in the monitor.

Exploratory eye movement dysfunctions in patients with schizophrenia: possibility as a discriminator for schizophrenia.

In our previous studies patients with schizophrenia and their parents had less frequent eye fixations and a more limited area of inspection than normal controls while freely viewing stationary S-shaped figures. The present study attempted to discriminate schizophrenics from non-schizophrenics using exploratory eye movements. Two groups (A and B) were formed, each comprising 30 schizophrenic and 70 non-schizophrenic subjects (10 each of patients with depression, methamphetamine psychosis, alcohol psychosis, anxiety disorder, temporal lobe epilepsy, frontal lobe lesions and healthy normal controls). Discriminant analysis was performed on group A to obtain a discriminant. The validity of applying this discriminant to group B was investigated. By focussing on exploratory eye movements, schizophrenics could be discriminated from non-schizophrenics with a sensitivity of 76.7% and a specificity of 81.4%. These results show that exploratory eye movements are a useful discriminator for schizophrenia.

[When do strokes occur?--analysis of diurnal variation and activity during the onset].

The diurnal variation and activity during the onset of stroke were examined in more than 700 consecutive patients. 304 cases with hypertensive intracerebral hemorrhage (HIH), 214 cases with subarachnoid hemorrhage (SAH) and 201 cases with obstructive cerebrovascular disease (OCVD) were investigated about the time of onset. Concerning the activity during the onset, 296 cases with HIH, 215 cases with SAH and 198 cases with OCVD were examined. HIH occurred frequently between 1500-1800 hours, 0600-0900 hours and 1800-2100 hours. SAH occurred frequently between 0900-1200 hours, 1500-1800 hours and 1800-2100 hours. Both HIH and SAH were least likely to occur between 0000-0300 hours. OCVD exhibited a small peak incidence between 0900-1200 hours, but there were no differences between the groups for the other time periods. Both HIH and SAH were likely to occur frequently in the lavatory, while bathing and during meals. HIH also occurred frequently during physical work, while SAH occurred as frequently during mental work or housework as during hard physical labor. OCVD commonly occurred during sleep or relaxation. The relationship between diurnal variation in stroke and the circadian variation of blood pressure is discussed. The incidence of all three types of strokes during work was higher in the non-aged group (patients under 66 years) than in the aged group (patients over 66 years). HIH and SAH occurred associated with alcohol consumption more frequently in the non-aged group than in the aged group. It is likely that the difference of the time and of the activity during the onset between aged group and non-aged group reflects the difference of life-style between aged and non-aged people.

[Study of recombinant human erythropoietin treatment on the anemia of predialysis patients].

We conducted a multiple-center joint study on the effects of recombinant human erythropoietin (rEPO) for predialysis patients. rEPO was intravenously administered to 42 predialysis patients (13 males and 29 females) with hematocrit (Ht) levels of less than 30%. The subjects were divided into group A (28 cases) in which rEPO was administered twice a week, and group B (14 cases) with rEPO administration once a week. The initial administration dosage was 6000IU/week. The Ht levels were 22.6 +/- 3.3% for group A and 23.2 +/- 2.7% for group B before the administration of rEPO, and increased to 31.0 +/- 4.0% and 27.7 +/- 3.7% respectively twelve weeks after initiating administration. The levels of effective improvement on anemia included 'markedly effective' in 17 cases (80.9%) and 'effective' in 2 cases (9.5%) in group A, and 'markedly effective' in 5 cases (41.7%) and 'effective' in 3 cases (25.0%) in group B. No significant change was seen in serum creatinine (Cr) levels during the study period. In the evaluation of renal function by reciprocal serum creatinine (1/Cr), a consistent tendency was not recognized; thus, suggesting that the rEPO administration had no effect on the renal function. No variation of blood pressure was seen. As far as side effects were concerned, headache and heavy headedness were recognized in four cases. There were, however, no cases in which the severity of the side effects dictated the discontinuation of the rEPO administration. In conclusion, rEPO was judged to be a safe and effective treatment for the anemia of predialysis patients.

Different localization of ETA and ETB receptors in the hyperplastic vascular wall.

We investigated which subtypes of endothelin-1 (ET-1) receptors are involved in the pathogenesis of angioplasty-induced lesion formation in the rabbit carotid artery. Four weeks after removing endothelial cells (EC), we noted a marked intimal hyperplasia. The Bmax values for [125I]ET-1 and [125I]IRL1620 (an agonist for the ETB receptors) bindings were greater in the hyperplastic artery, without changes in Kd values. [125I]ET-1 binding was completely inhibited by unlabeled ET-1 and Ro 46-2005, a mixed-type antagonist for the ETA and ETB receptors, but partially by BQ123, a selective antagonist for ETA receptors, and IRL1620. The [125I]ET-1 binding sites not inhibited with BQ123 were significantly increased in the hyperplastic artery. The binding study suggested the presence of non-ETA/non-ETB receptors. The rank order of the increasing ratio in the density of receptors was ETB > putative non-ETA/non-ETB > total ET-1 receptors > ETA. The histochemical experiments with biotinylated ET-1 at lysine-9 side chain alone or in combination with unlabeled ET-1, BQ123, Ro 46-2005, or IRL1620, showed the ETA receptors to be localized mainly in the media, whereas the ETB receptors localized mainly in the neointima. These results suggest that the increased ET-1 receptors, especially ETB and/or putative non-ETA/non-ETB, are closely related to the occurrence of the intimal hyperplasia after endothelial removal.

The mechanism of myometrial contractions induced by endothelin-1 in rat.

Experiments were performed to characterize endothelin-1-induced contractions and the role of endothelin (ET) receptor subtypes in rat myometrium. The binding sites of [(125)I]-ET-1 were saturable with high affinity. Scatchard plot analysis revealed that ET-1 binding sites in the myometrium constituted a single population. The dissociation equilibrium constant (Kd) and the maximum binding sites (Bmax) were determined to be 48.9+/-3.0 pM and 1364.0+/-210.3 fmol/mg protein respectively. Specific [(125)I]-ET-1 binding was inhibited completely by unlabelled ET-1 and Ro 46-2005 (mixed-type ET receptor antagonist), but not fully (90.7+/-1.4%) by BQ 123 (a selective ETA receptor antagonist), and not at all by RES 701-1 (a selective ETB receptor antagonist). ET-1 induced myometrial contractions were composed of two types, an increase in resting tone and rhythmic contractions. These contractions were inhibited by BQ 123 and Ro 46-2005, but not by RES 701-1. ET-1-induced contractions were greatly reduced in Ca2+-free Krebs' solution. Nifedipine abolished the rhythmic contractions without affecting the increase in resting tone. These results suggest that ETA receptors are predominantly localized in rat myometrium and that excitation of ETA receptors evokes two types of contractions by increasing the cytoplasmic Ca2+ concentration.

17 Beta-estradiol increases nitric oxide and prostaglandin I2 production by cultured human uterine arteries only in histologically normal specimens.

These experiments were designed to investigate whether 17beta-estradiol (E2) modulates the endothelial function of perimenopausal human uterine arteries. After the artery specimen was cultured in the presence or absence of E2 at a physiologic concentration of 200 pg/ml, changes in isometric tension and cyclic nucleotide production were determined. Degree of intimal hyperplasia was assessed histologically and expressed as intima-to-media ratio. Acetylcholine produced an endothelium-dependent relaxation in six specimens (group I) of 12, which was inhibited by NG-nitro-L-arginine or indomethacin. However, the agonist failed to produce a definite relaxation in the remaining 6 (group II). The endothelium-dependent relaxation was significantly augmented after incubating with E2 only in group I specimens. Cyclic nucleotide production was significantly increased after E2 incubation only in group I specimens, whereas it was inhibited by NG-nitro-L-arginine or indomethacin. Histologic study revealed that the six specimens of group I had normal intima (intima-to-media ratio = 19.1+/-1.8%) and the remaining six of group II had intimal hyperplasia (intima-to-media ratio = 53.6+/-5.3%). Increased production of cyclic nucleotides occurred in uterine arteries with normal intima but not in arteries with intimal hyperplasia derived from perimenopausal women.

Effect of endogenous dopamine on extrastriatal [¹¹C]FLB 457 binding measured by PET.

Central dopaminergic systems are known to be implicated in the pathophysiology of schizophrenia and recent in vivo dopamine receptor imaging studies have focused on the measurement of extrastriatal dopamine receptor. However, there are only a limited number of ligands that can measure the low-density D2 receptor in extrastriatal regions and their sensitivity to endogenous dopamine in extrastriatal regions has not yet been fully examined. In this study, the effect of endogenous dopamine on the extrastriatal binding of [11C]FLB 457 was examined in the rhesus monkey after facilitation with 1 mg/kg of methamphetamine (MAP) and was compared with the effect on the striatal binding of [11C]raclopride. The indices of receptor binding were obtained by four methods using cerebellum as a reference region. The bindings of [11C]FLB 457 in the frontal cortex, temporal cortex, and thalamus were not significantly changed after MAP treatment, while the striatal binding of [11C]raclopride was decreased by more than 20%. These results suggest that [11C]FLB 457 is not sensitive to endogenous dopamine in the extrastriatal regions of rhesus monkeys, despite a sufficient dose of MAP to decrease the binding of [11C]raclopride in the striatum.

Relationship between exploratory eye movements and clinical course in schizophrenic patients.

Exploratory eye movements are psychophysiological indicators of schizophrenia as well as smooth pursuit eye movements. To investigate whether these eye movements change in accordance with the clinical course of the condition in schizophrenia, exploratory eye movements (number of eye fixations, mean eye scanning length, responsive search score, evaluation of reproduced Fig. 1 and 2) of 28 schizophrenic patients were evaluated in repeat test design, conducted an average of 8 months apart. Subjects were first-medicated schizophrenics, half were outpatients and the remaining half were inpatients at the Neuropsychiatry ward of Tokyo Medical and Dental University Hospital. Exploratory eye movement patterns did not improve despite an improvement in clinical symptoms of schizophrenia. This result and those of previous studies of the exploratory eye movements of schizophrenic patients' families suggest that exploratory eye movements reflect a schizophrenic vulnerability marker. Furthermore, decreased mean eye scanning length (MESL) values were observed in subjects who showed unimproved symptoms, particularly negative symptoms over an extended period of time. The result suggests that a decrease in the MESL value may be the most sensitive indicator in the development of chronicity in schizophrenia.