Dysconnectivity of the Agency Network in Schizophrenia: A Functional Magnetic Resonance Imaging Study.

Background: Self-disturbances in schizophrenia have recently been explained by an abnormality in the sense of agency (SoA). The cerebral structures of SoA in healthy people are considered to mainly include the insula and inferior parietal lobule. In contrast, the functional lesion of aberrant SoA in schizophrenia is not yet fully understood. Considering the recent explanation of establishing SoA from the standpoint of associative learning, the "agency network" may include not only the insula and inferior parietal lobule but also the striatum. We hypothesized that aberrant SoA in schizophrenia is based on a deficit in the "agency network." Methods: Functional magnetic resonance imaging data were acquired while patients with schizophrenia (n = 15) and matched controls (n = 15) performed our adaptation method of agency attribution task on a trial-by-trial basis to assess participants' explicit experience of the temporal causal relationship between an action and an external event with temporal biases. Analysis of functional connectivity was done using the right supramarginal gyrus and the right middle frontal gyrus as seed regions. Results: In healthy controls, analyses revealed increased activation of the right inferior parietal lobule (mainly the supramarginal gyrus), right insula, and right middle frontal gyrus as an activation of the agency condition. We defined activated Brodmann areas shown in the agency condition of healthy controls as the seed region for connectivity analysis. The connectivity analysis revealed lower connectivity between the head of the left caudate nucleus and right supramarginal gyrus in the patients compared to healthy controls. Conclusions: This dysconnectivity of the agency network in schizophrenia may lead to self-disturbance through deficits in associative learning of SoA. These findings may explain why pathological function of the striatum in schizophrenia leads to self-disturbance.

Detailed analysis of the Japanese version of the Rapid Dementia Screening Test using Arabic-hiragana conversion.

AIM: The number-transcoding task on the Japanese version of the Rapid Dementia Screening Test (RDST-J) requires conversion between Arabic and Chinese numerals (209 to , 4054 to , to 681, to 2027). In this task, questions and answers are written for Chinese-Arabic conversion. We reported that the RDST-J could distinguish subjects with Alzheimer's disease with a Clinical Dementia Rating Scale score of 0.5 from controls. In this study, we investigated the impact of changing the task to a hiragana-Arabic conversion. METHODS: Participants consisted of 45 patients with a Clinical Dementia Rating Scale score of 0.5 and 52 normal controls. RESULTS: The sensitivity and specificity of total scores ≥9 on the two RDST-J versions for discriminating subjects with a Clinical Dementia Rating Scale score of 0.5 from controls were 73.1% and 75.5%, respectively, on the original version, and 71.8% and 73.0%, respectively, on the revised version. CONCLUSIONS: The sensitivity and specificity of the revised version of the RDST-J was equivalent to those of the original version.

Detailed analysis of the Japanese version of the Rapid Dementia Screening Test, revised version.

AIM: The number-transcoding task on the Japanese version of the Rapid Dementia Screening Test (RDST-J) requires mutual conversion between Arabic and Chinese numerals (209 to , 4054 to , to 681, to 2027). In this task, question and answer styles of Chinese numerals are written horizontally. We investigated the impact of changing the task so that Chinese numerals are written vertically. METHODS: Subjects were 211 patients with very mild to severe Alzheimer's disease and 42 normal controls. Mini-Mental State Examination scores ranged from 26 to 12, and Clinical Dementia Rating scores ranged from 0.5 to 3. RESULTS: Scores of all four subtasks of the transcoding task significantly improved in the revised version compared with the original version. The sensitivity and specificity of total scores ≥9 on the RDST-J original and revised versions for discriminating between controls and subjects with Clinical Dementia Rating scores of 0.5 were 63.8% and 76.6% on the original and 60.1% and 85.8% on revised version. CONCLUSIONS: The revised RDST-J total score had low sensitivity and high specificity compared with the original RDST-J for discriminating subjects with Clinical Dementia Rating scores of 0.5 from controls.

Detailed analysis of error patterns in the number-transcoding task on the Japanese version of the Rapid Dementia Screening Test.

AIM: The number-transcoding task on the Japanese version of the Rapid Dementia Screening Test requires mutual conversion between Arabic and Chinese numerals (e.g. 209 → , 4054 → , → 681, → 2027). During this task, some characteristic errors have been seen among patients with Alzheimer's disease (AD). The objective of this study was to clarify whether the frequency of appearance of error patterns differs between patients with mild and severe AD according to Clinical Dementia Rating (CDR) scores. METHODS: A total of 250 patients with AD were recruited and subsequently categorized into two groups based on CDR scores (mild AD: CDR of 0.5 or 1; severe AD: CDR of 2 or 3). We analyzed 19 qualitative error patterns, including 15 that had been reported to date and 4 previously unreported errors, in each subtest. RESULTS: The frequency of appearance of two previously reported and four previously unreported errors in the mild and severe AD groups, respectively, were statistically significant. CONCLUSIONS: Characteristic error pattern distributions in number transcoding can be observed in patients with mild and severe AD according to CDR scores and offers useful information for interpreting cognitive screening data.

Detailed analysis of the supermarket task included on the Japanese version of the Rapid Dementia Screening Test.

AIM: The supermarket task, which is included in the Japanese version of the Rapid Dementia Screening Test, requires the quick (1 min) generation of words for things that can be bought in a supermarket. Cluster size and switches are investigated during this task. We investigated how the severity of dementia related to cluster size and switches on the supermarket task in patients with Alzheimer's disease. METHODS: We administered the Japanese version of the Rapid Dementia Screening Test to 250 patients with very mild to severe Alzheimer's disease and to 49 healthy volunteers. Patients had Mini-Mental State Examination scores from 12 to 26 and Clinical Dementia Rating scale scores from 0.5 to 3. Patients were divided into four groups based on their Clinical Dementia Rating score (0.5, 1, 2, 3). We performed statistical analyses between the four groups and control subjects based on cluster size and switch scores on the supermarket task. RESULTS: The score for cluster size and switches deteriorated according to the severity of dementia. Moreover, for subjects with a Clinical Dementia Rating score of 0.5, cluster size was impaired, but switches were intact. CONCLUSIONS: Our findings indicate that the scores for cluster size and switches on the supermarket task may be useful for detecting the severity of symptoms of dementia in patients with Alzheimer's disease.

The Japanese version of the Rapid Dementia Screening Test is effective compared to the clock-drawing test for detecting patients with mild Alzheimer's disease.

BACKGROUND: The Japanese version of the Rapid Dementia Screening Test (RDST-J) and the clock-drawing test (CDT) are both brief psychometric screening tools used to detect the severity of Alzheimer's disease. It remains unclear, however, which is more effective when screening for mild Alzheimer's disease. METHODS: We administered the RDST-J and CDT to 250 patients with very mild to severe Alzheimer's disease and to 49 healthy volunteers. Patients with a Mini-Mental State Examination score of 12-26 had Clinical Dementia Rating (CDR) scores from 0.5 to 3. Patients were divided into four groups according to CDR score. We performed one-way factorial anova between the four groups and control subjects based on the CDT and RDST-J scores. RESULTS: Data analysis revealed that RDST-J could distinguish patients with CDR 0.5 from the controls, but CDT could not. Furthermore, the sensitivity of a RDST-J score ≥8 was 57.1%, with a specificity of 81.0%, and the sensitivity of a RDST-J score ≥9 was 79.6%, with a specificity of 55.1% for discriminating CDR 0.5 from controls. CONCLUSIONS: RDST-J is a more effective tool than CDT for distinguishing CDR 0.5 from controls.

Frégoli syndrome accompanied with prosopagnosia in a woman with a 40-year history of schizophrenia.

A 68-year-old woman with schizophrenia after a cerebrovascular accident resulting in right medial temporal and occipital damage developed Frégoli syndrome. Neuropsychological testing revealed that she had impairment in facial recognition compatible with prosopagnosia. The Frégoli syndrome disappeared in three month when, remarkably, her prosopagnosia also disappeared. Our findings are consistent with the hypothesis that combination of hyperactivations of temporo-limbic connection and frontal dysfunction may account for the development of Frégoli syndrome.

Degradation of PrP(Sc) by keratinolytic protease from Nocardiopsis sp. TOA-1.

A keratinolytic alkaline proteae (NAPase) from Nocardiopsis sp. TOA-1 degraded a scrapie prion without any chemical or physical treatment. Optimal temperature and pH were 60 degrees C and above pH 10.0. The scrapie prion was completely degraded within 3 min under optimal conditions.

Family history of alcoholism and cognitive recovery in subacute withdrawal.

A family history of alcoholism has been demonstrated to be an important factor affecting cognitive function. However, no studies have yet been conducted to compare cognitive recovery of family history-positive (FH+) and family history-negative (FH-) alcoholics in the subacute withdrawal period. To tackle this problem, a neuropsychological test battery consisting of six computerized tests was administered to 19 FH+ and 20 FH- alcoholics at 2 and 7 weeks after abstinence. At 2 weeks after abstinence, overall performance of both FH+ and FH- groups was significantly poorer than that of healthy controls. At 7 weeks, these performances tended to recover, but in Trail Making A and Figure Position, performances of FH+ alcoholics remained worse than those of controls, while those of FH- alcoholics did not. Thus cognitive recovery during the subacute withdrawal period was worse among FH+ alcoholics than FH- alcoholics, and this finding should be considered when planning alcohol rehabilitation programs.

Further evidence for a comparable memory advantage of self-performed tasks in Korsakoff's syndrome and nonamnesic control subjects.

Two experiments were carried out to examine memory in persons with amnesia using self-performed tasks. In Experiment 1, persons with Korsakoff's syndrome and nonamnesic participants with alcoholism learned action phrases not involving real objects by either self-performed tasks or verbal tasks. As indexed by free recall and recognition tests, a memory advantage favoring self-performed tasks was confirmed in both participant groups. In Experiment 2, persons with Korsakoff's syndrome, nonamnesic alcoholic participants, and young control participants learned object names under three different study conditions that differed from one another as to whether actions for each name were verbally generated and whether actions actually were performed. Verbal generation with or without performing the action facilitated recognition, whereas recall advantage was found only in the verbal generation-plus performance condition. These findings confirm a comparable memory advantage of self-performed tasks for a group with Korsakoff's syndrome and a group of nonamnesic comparison participants. Action memory therefore has potential therapeutic implications for memory rehabilitation.

Effect of activated protein C on plasma plasminogen activator inhibitor activity in patients with acute myocardial infarction treated with alteplase: comparison with unfractionated heparin.

OBJECTIVES: We examined whether activated protein C (APC) is an effective conjunctive therapy to thrombolysis in patients with ST-segment-elevated acute myocardial infarction (AMl). BACKGROUND: Activated protein C possesses both systemic anticoagulant and anti-inflammatory properties. It has been also shown to enhance fibrinolysis by inhibiting plasminogen activator inhibitor (PAI) activity in vitro. METHODS: After successful thrombolysis with alteplase, study patients were assigned to receive one of the two conjunctive therapies for 48 h intravenously: human plasma-derived APC at 0.06 mg/kg per day (APC group, n = 9) or unfractionated heparin at 100 to 400 U/kg per day, adjusted to maintain an activated partial thromboplastin time at 1.5 to 2 times of the control level (heparin group, n = 10). RESULTS: Adverse events, including reocclusion of the recanalized infarct-related coronary artery and major or minor hemorrhagic complications, occurred more frequently in the heparin group (4 of 10 cases) than in the APC group (none of 9 cases) (p = 0.033). In the heparin group, plasma PAI activity (IU/ml, median value [range]) was increased continuously from 8 to 24 h after thrombolysis and peaked at 24 h (30.9 [11.3 to 38.5]); on the other hand, it was not increased in the APC group at 24 h after thrombolysis (11.3 [0.0 to 31.0], p < 0.01 vs. heparin group). CONCLUSIONS: Administration of APC suppressed increasing of plasma PAI activity observed after thrombolysis in patients with AMI. The effect of APC could be more eligible, compared with heparin, as a conjunctive regimen to thrombolysis in AMI patients.

Executive dysfunction and clinical outcome in chronic alcoholics.

BACKGROUND: The purpose of this study was to investigate which of 12 neuropsychological tests predict alcoholic patients' alcohol-specific and/or alcoholic-nonspecific outcome. Our hypothesis was that the ecologically valid neuropsychological tests that measure executive function are better predictors of alcoholics' functional outcome. METHODS: We administered 12 neuropsychological tests to chronic alcoholics. Included in the tests were tasks of Reaction Time, Symbol Digit Modalities, Figure Position, Digit Span, Block Design, Trail Making, and six subtests of a battery called the Behavioral Assessment of the Dysexecutive Syndrome (BADS). Previous investigators have suggested that the BADS has ecological validity. Twenty-two male alcoholics were compared with 15 nonalcoholic control subjects on these neuropsychological measures 7 weeks after detoxification. Two functional outcome indices, i.e., resumption of drinking and occupation, were evaluated 18 months after discharge. RESULTS: The total profile score and the score on three of the six subtests of the BADS were lower in alcoholics than in nonalcoholic controls. Alcoholics' performance on the BADS predicted alcohol-nonspecific outcome (occupation) but not alcohol-specific (drinking) outcome. In contrast, other neuropsychological tests did not predict either of the two outcome indices. CONCLUSIONS: The BADS total profile score is related to alcohol-nonspecific outcome but not to alcohol-specific outcome.

Increased expression of monocyte chemoattractant protein-1 in atherectomy specimens from patients with restenosis after percutaneous transluminal coronary angioplasty.

The plasma concentration of monocyte chemoattractant protein-1 (MCP-1) antigen is higher in patients with restenosis after coronary angioplasty than in those who do not restenose. In this study the MCP-1 expression of coronary atherectomy specimens was investigated by immunohistochemistry. Samples were obtained from 12 patients with restenosis and 15 with de novo lesions by directional coronary atherectomy. MCP-1 immunoreactivity was found in all patients in the restenosis group and in 8 of the de novo group. The frequency of macrophage expression was higher in the restenosis group than in de novo group. These results indicate that local expression of MCP-1 may be associated with the mechanisms of vascular remodeling after coronary angioplasty.

Validation study of the Japanese version of the Obsessive-Compulsive Drinking Scale.

The Obsessive-Compulsive Drinking Scale (OCDS) is a self-rating questionnaire that measures cognitive and behavioral aspects of craving for alcohol. The OCDS consists of two subscales: the obsessive thoughts of drinking subscale (OS) and the compulsive drinking subscale (CS). This study aims to validate the Japanese version of the OCDS. First, internal consistency and discriminant validity were evaluated. Second, a prospective longitudinal 3-month outcome study of 67 patients with alcohol dependence who participated in a relapse prevention program was designed to assess the concurrent and predictive validity of the OCDS. The OCDS demonstrated high internal consistency. The OS had high discriminant validity, while the CS did not. Twenty-three patients (34.3%) dropped out of treatment. These patients had significantly higher OS scores than those who completed the program. At 3 months, the relapse group had significantly higher OCDS scores than the no relapse group. Also, the OCDS score was higher in subjects who had early-onset alcohol dependence than late-onset dependence. The OCDS is useful for evaluating cognitive aspect of craving and predicts dropout and relapse.

Challenging case of pulse infusion thrombolysis using a unique pump system for a patient with deep vein thrombosis: a case report.

A 69-year-old man presented with chronic deep vein thrombosis due to massive thrombi extending from the inferior vena cava to both femoral veins. He had undergone surgery for prostatic cancer in 1991, and since then he had been taking an artificial estrogen agent. He was successfully treated by pulse infusion thrombolysis using a unique pump system, which we have developed, without complication.

Purification and some properties of a keratinolytic enzyme from an alkaliphilic Nocardiopsis sp. TOA-1.

A novel alkaliphilic Nocardiopsis sp., strain TOA-1, was isolated from a tile-joint of a bathroom. Strain TOA-1 produced a variety of alkaline hydrolytic enzymes. An alkaline protease, designated NAPase, was purified and characterized. NAPase had a very high keratinolytic activity and high stability under acidic conditions.