2D potential measurements by applying automatic beam adjustment system to heavy ion beam probe diagnostic on the Large Helical Device.

Two-dimensional potential profiles in the Large Helical Device (LHD) were measured with heavy ion beam probe (HIBP). To measure the two-dimensional profile, the probe beam energy has to be changed. However, this task is not easy, because the beam transport line of LHD-HIBP system is very long (∼20 m), and the required beam adjustment consumes much time. To reduce the probe beam energy adjustment time, an automatic beam adjustment system has been developed. Using this system, required time to change the probe beam energy is dramatically reduced, such that two-dimensional potential profiles were able to be successfully measured with HIBP by changing the probe beam energy shot to shot.

MAP2-mediated in vitro interactions of brain microtubules and their modulation by cAMP.

Microtubule-associated proteins (MAPs) are involved in microtubule (MT) bundling and in crossbridges between MTs and other organelles. Previous studies have assigned the MT bundling function of MAPs to their MT-binding domain and its modulation by the projection domain. In the present work, we analyse the viscoelastic properties of MT suspensions in the presence or the absence of cAMP. The experimental data reveal the occurrence of interactions between MT polymers involving MAP2 and modulated by cAMP. Two distinct mechanisms of action of cAMP are identified, which involve on one hand the phosphorylation of MT proteins by the cAMP-dependent protein kinase A (PKA) bound to the end of the N-terminal projection of MAP2, and on the other hand the binding of cAMP to the RII subunit of the PKA affecting interactions between MTs in a phosphorylation-independent manner. These findings imply a role for the complex of PKA with the projection domain of MAP2 in MT-MT interactions and suggest that cAMP may influence directly the density and bundling of MT arrays in dendrites of neurons.

Effects of high-affinity nerve growth factor receptor inhibitors on symptoms in the NC/Nga mouse atopic dermatitis model.

BACKGROUND: Nerve growth factor (NGF) is an important substance in the skin, where it modulates nerve maintenance and repair. However, the direct link between NGF and pruritic diseases such as atopic dermatitis is not yet fully understood. Our previous study showed that NGF plays an important role in the pathogenesis of atopic dermatitis-like skin lesions in NC/Nga mice. NGF mediates its effects by binding to two classes of transmembrane receptors, a high-affinity receptor (tropomyosin-related kinase A, TrkA) and a low-affinity receptor (p75). OBJECTIVES: To determine the significance of NGF receptors in the pathogenesis of atopic dermatitis, the effects of TrkA inhibitors AG879 and K252a on the symptoms of NC/Nga mice were evaluated. METHODS: Male NC/Nga mice with severe skin lesions were used. AG879 or K252a was applied to the rostral part of the back of mice five times a week. The dermatitis score for the rostral back was assessed once a week. The scratching behaviour was measured using an apparatus, MicroAct (Neuroscience, Tokyo, Japan). Immunofluorescence examinations were made in the rostral back skin for nerve fibres, NGF and TrkA receptor. RESULTS: Repeated applications of AG879 or K252a significantly improved the established dermatitis and scratching behaviour, and decreased nerve fibres in the epidermis. NGF was observed more weakly in keratinocytes, and a lower expression of TrkA was observed in stratum germinativum of the epidermis of mice treated with AG879 or K252a compared with those treated with vehicle. CONCLUSIONS: We suggest that NGF plays an important role in the pathogenesis of atopic dermatitis-like skin lesions via the high-affinity NGF receptor. These findings provide a new potential therapeutic approach for the amelioration of symptoms of atopic dermatitis.

A method to induce stable atopic dermatitis-like symptoms in NC/Nga mice housed with skin-lesioned mice.

BACKGROUND: Itching is a characteristic symptom in various forms of dermatosis, especially atopic dermatitis; consequently it is a major diagnostic criterion. All features are similar to events seen in patients, hence NC/Nga mice are considered to be a suitable model of human atopic dermatitis. However, there were data spreads in commencing time and the degree of skin lesions in NC/Nga mice. OBJECTIVES: In the present study, we attempted to improve experimental conditions to induce stable skin lesions and to establish a more appropriate method. Methods NC/Nga mice were kept together with skin-lesioned mice during the experiment period (mixed-NC mice). The dermatitis scores of face, ears and rostral back were assessed. Scratching behaviour was measured using an apparatus, MicroAct (Neuroscience, Tokyo, Japan). Transepidermal water loss (TEWL) and serum total IgE levels were also measured. To observe the presence of mites, the skin of the rostral backs of the mixed-NC mice was stripped using cellulose tape. We also investigated the effects of fipronil (Wako, Osaka, Japan), an acaricidal compound, on skin lesions and scratching behaviour of these mixed-NC mice. RESULTS: In mixed-NC mice, skin lesions appeared from 2 weeks, worsened gradually and reached peak levels of a dermatitis score in 8 weeks. Scratching behaviour increased significantly from day 3. TEWL also increased from day 3, but total IgE increased from day 7. Mites were observed on the rostral backs of mixed-NC mice from day 3, and all mice had these mites on day 28. Giving pretreatment with fipronil (Wako), the skin lesions and scratching behaviour of mixed-NC mice was significantly suppressed. CONCLUSIONS: The findings of the present study suggest that the method of being kept together with skin-lesioned mice can induce stable skin lesions and scratching behaviour at an early stage, without skin lesions. This method could help investigate a more stable evaluation of the effects on symptoms of atopic dermatitis, and mechanisms of the itching. It was considered that parasitism of mites, not allergic reactions, was the pathogenesis of skin lesions and scratching behaviour in mixed-NC mice.

Morphological brain changes associated with Schneider's first-rank symptoms in schizophrenia: a MRI study.

BACKGROUND: Schneider's first-rank symptoms involve an alienated feature of the sense of one's own mental or physical activity. To clarify the brain morphological basis for the production of these symptoms, volumes of the frontal and medial temporal regions and their clinical correlates were examined in patients with schizophrenia. METHOD: Twenty-two patients with schizophrenia and 44 age- and gender-matched healthy control subjects were included. All patients were in their psychotic episodes with definite Schneiderian symptoms, rated by using the Scale for Assessment of Positive Symptoms. Volumetric measurements of high-resolution magnetic resonance imaging were performed in the prefrontal area, cingulate gyrus, and precentral gyrus, and the medial temporal structures such as the amygdala, hippocampus, and parahippocampal gyrus. RESULTS: Patients had significantly decreased volumes in the cingulate gray matter and the amygdala compared to controls. In the patient group, Schneiderian symptom severity showed significant inverse correlations with volumes of the right posterior cingulate gray matter and of the left anterior parahippocampal gyrus. CONCLUSIONS: Schneiderian symptoms may be associated with morphological abnormalities in the limbic-paralimbic regions such as the cingulate gyrus and parahippocampal gyrus, which possibly serve the self-monitoring function and the coherent storage and reactivation of information.

Intra-articular oxidative state correlated with the pathogenesis of disorders of the temporomandibular joint.

We investigated the redox state of albumin in the synovial fluid from patients with temporomandibular joint (TMJ) disorders (TMD) to evaluate the relation between the cause of the TMD and the number of types of oxygen in synovial fluid. The albumin was fractionated into three components, human mercaptalbumin (HMA, reduced form) and two types human non-mercaptalbumin (HNA, oxidized form), by high-performance liquid chromatography (HPLC). The 63 patients were divided into three groups radiologically, and the ratios of the redox state of the synovial fluid in each group were compared. The fraction of HNA was significantly higher in patients with advanced disease than in patients with early disease. This indicates that the TMJ is affected by intra-articlular oxidative stress, and the severity of TMD correlates closely with the number of oxidative factors. Oxidative stress was thought to be responsible for the genesis of TMD.

Gray matter features of schizotypal disorder patients exhibiting the schizophrenia-related code types of the Minnesota Multiphasic Personality Inventory.

OBJECTIVE: Previous studies have suggested that several code types of the Minnesota Multiphasic Personality Inventory (MMPI) are useful markers for identifying schizophrenia. We hypothesized that schizotypal disorder (STD) patients with such schizophrenia-related code types have the morphological brain abnormalities associated with schizophrenia. METHOD: Voxel-based morphometric analysis with statistical parametric mapping (SPM) 99 software was used to investigate the differences in brain morphology between 14 STD patients with the schizophrenia-related code types of the MMPI and 28 normal individuals. RESULTS: The STD patients showed significantly decreased gray matter volume in the insular regions bilaterally and in the left entorhinal cortex, compared with the controls. CONCLUSION: Our findings suggest that STD patients with the schizophrenia-related code types have volume reductions in these regions as an endophenotype that overlaps with schizophrenia.

Magnetic resonance imaging study of the cavum septi pellucidi in patients with schizophrenia.

OBJECTIVE: High-resolution magnetic resonance imaging was used to evaluate the prevalence of the cavum septi pellucidi (CSP) in 79 normal subjects and 86 patients with schizophrenia. METHOD: The CSP was assessed by counting the number of consecutive coronal 1-mm slices containing the CSP. A CSP equal to or greater than 6 mm in length was defined as large. RESULTS: The CSP was found in 74.4% of the patients and 74.7% of the normal subjects, a nonsignificant difference. No difference between groups was found in the prevalence of a large CSP. CONCLUSIONS: The findings support the idea that a small CSP is a normal anatomical variant. More cases of a large CSP are needed to elucidate the implications of this abnormality in schizophrenia.

Enhancement of cognitive performance in schizophrenia by addition of tandospirone to neuroleptic treatment.

OBJECTIVE: The goal of this study was to evaluate the effects of the addition of tandospirone, a serotonin-1A (5-HT(1A)) agonist, to ongoing treatment with typical antipsychotic drugs, on two cognitive domains that are relevant to functional outcome in patients with schizophrenia. METHOD: Twenty-six patients with schizophrenia who were receiving stable doses of typical antipsychotics were randomly assigned to adjunctive treatment with 30 mg/day of tandospirone or placebo for 6 weeks. Executive function and verbal memory as well as psychopathology were assessed at baseline and after 6 weeks. RESULTS: Both cognitive measures improved significantly in the patients who received tandospirone; subjects who did not receive tandospirone showed no change. There was no significant change in psychopathology ratings in either group. CONCLUSIONS: The results suggest the usefulness of 5-HT(1A) agonists for enhancing some types of cognitive performance and possibly social and work function in patients with schizophrenia.

[Ectopic ureter in 54 children].

PURPOSE: We reviewed 54 pediatric patients with ectopic ureter treated at our institution from 1975 to 1999. MATERIALS AND METHODS: Our series comprised 40 female and 14 male children, with age from 1 month to 11 years. Clinical records of the patients were reviewed retrospectively. RESULTS: Chief complaint was urinary incontinence in 24, high fever in 18, abdominal mass in 6, scrotal swelling in 3 and growth retardation in 2 patients. Two patients were found to have ectopic ureters without symptom during urological work-ups for their anorectal anomaly. The ectopic ureters opened into vagina in 19, vestibulum in 8, bladder neck in 7, urethra in 17, seminal vesicle in 2 and ejaculatory duct in 1 patient (s). Treatment was ureterocystoneostomy in 30, nephroureterectomy in 19, hemi-nephroureterectomy in 2, and ureteral ligature in 1 patient (s). Postoperatively, most of the patients became symptom free except for 6 patients in whom urinary incontinence was not cured due to mal-development of the bladder neck and sphincter, and due to Gartner's duct cyst. CONCLUSION: Urinary incontinence and urinary tract infection are most frequent presentations of ectopic ureter in children. Although most of the patients are cured with ureterocystoneostomy or nephroureterectomy, some incontinent girls continue to have urinary incontinence due to mal-development of the bladder neck and sphincter or Gartner's duct cyst.

The effect of tandospirone, a serotonin(1A) agonist, on memory function in schizophrenia.

BACKGROUND: The purpose of this study was to test the hypothesis that the addition of tandospirone, a 5-HT(1A) partial agonist, to ongoing treatment with typical antipsychotic drugs, would improve memory function in patients with schizophrenia. METHODS: Eleven outpatients (male/female = 7/4) with schizophrenia who had been on stable doses of haloperidol and biperiden were given tandospirone, 30 mg/day, for 4 weeks. The Wechsler Memory Scale-Revised (WMS-R) was administered at baseline and 4 weeks after the addition of tandospirone. The Brief Psychiatric Rating Scale (BPRS; Total, Positive, and Negative subscale scores) and the Simpson-Angus Scale for Extrapyramidal Symptoms (SAS) were also completed on the two occasions. To exclude the possibility of a practice effect on the WMS-R test, 11 age-matched patients with schizophrenia (M/F = 7/4) were tested at baseline and after a 4-week interval. RESULTS: Repeated measures analysis of variance revealed a significant time by group (patients with or without tandospirone) effect for the Verbal-, but not the Visual Memory composite scores of the WMS-R test; no significant change was observed in patients without tandospirone, whereas improvement in the Verbal Memory score was noted in patients receiving tandospirone. Moreover, there was improvement in the Inclusion score, an index of memory organization as measured by the Logical Memory subtest of WMS-R, only in patients with tandospirone. Scores on the BPRS and SAS were improved during treatment with tandospirone, but the effects did not reach statistical significance. CONCLUSIONS: The results suggest that adjunctive treatment with 5-HT(1A) agonists may improve some types of memory function in schizophrenia.

Intracerebroventricular administration of NMDA-R1 antisense oligodeoxynucleotide significantly alters the activity of ventral tegmental area dopamine neurons: an electrophysiological study.

In this study, we determined the activity of midbrain dopamine (DA) neurons in male albino rats following the intracerebroventricular (i.c.v.) administration of antisense oligodeoxynucleotide (aODN) against the mRNA for the NR1 subunit of the NMDA receptor. In addition, the effect of aODN on the specific binding of the NMDA receptor ligand [(3)H]MK-801 was also examined in various brain areas, including the midbrain. Antisense ODN against the NR1 mRNA, the corresponding sense ODN (sODN) or saline was continuously administered into the right ventricle of rats by osmotic minipumps for 7 days (20 nmol/day). Autoradiographic binding studies indicated that aODN significantly reduced the density of [(3)H]MK-801 binding by an average of 20-30% in several forebrain regions, including the anterior cingulate cortex, caudate putamen, and nucleus accumbens. However, [(3)H]MK-801 binding was not significantly altered in the ventral tegmental area (VTA) or substantia nigra pars compacta (SNC). Subsequently, using the technique of extracellular single-unit recording, the number, as well as the firing pattern, of spontaneously active DA neurons was determined in the VTA and SNC. The administration of aODN did not significantly alter the number of spontaneously active VTA and SNC DA neurons compared to saline- of sODN-treated animals. Furthermore, the firing pattern of spontaneously active SNC DA neurons was not significantly altered. However, for spontaneously active VTA DA neurons, the administration of aODN significantly decreased the percent events in bursts, number of bursts, and percentage of DA neurons exhibiting a bursting pattern compared to saline- and sODN-treated animals, i.e., neurons show less bursting activity. The present results suggest that subchronic aODN treatment against the mRNA for the NR1 subunit of the NMDA receptors can reduce NMDA receptor number and can result in an altered activity of spontaneously active VTA DA neurons in anesthetized rats.

Nomifensine-induced c-fos mRNA expression in discrete brain areas of the developing rat.

In rats, the subcutaneous injection of a dopamine uptake inhibitor, nomifensine (40 mg/kg), induced a significant increase in the c-fos mRNA levels in the neocortex on postnatal days 23 and 49, in the striatum on days 8, 14, 23 and 49, and in the hippocampus on day 23, when compared with saline administration. The repeated injection with nomifensine (40 mg/kg once daily) from postnatal days 49 to 53 and from 23 to 27, but not from days 8 to 12 and 14 to 18, resulted in an enhanced stereotypy response elicited by a subsequent challenge of the drug (5 mg/kg) 21 days after the last injection (behavioral sensitization). The present results suggest that the neuronal circuits regulated by nomifensine might undergo regionally-different developmental changes, which could be implicated in the development of behavioral expressions including nomifensine-induced stereotypy sensitization.

Sylvian fissure and medial temporal lobe structures in patients with schizophrenia: a magnetic resonance imaging study.

Volumes of the medial temporal lobe structures (i.e. the amygdala, hippocampus, and parahippocampal gyrus), Sylvian fissure, and inferior horn of the lateral ventricle relative to the cerebral hemisphere were measured in 24 patients with schizophrenia and 23 normal controls using magnetic resonance imaging. The patients had significantly larger Sylvian fissures and inferior horns bilaterally than the controls. In the patients the right Sylvian fissure size showed a significant positive correlation with the duration of illness. Moreover, earlier onset of illness was significantly correlated with decreased volume of the left medial temporal lobe structures. These results replicate previous finding of inferior horn enlargement and suggest the significance of the Sylvian fissure and the medial temporal lobe structures in pathophysiology of schizophrenia.

Semantic structure in schizophrenia as assessed by the category fluency test: effect of verbal intelligence and age of onset.

It has been reported that long-term memory function, including the semantic structure of category, is impaired in patients with schizophrenia. The present study was performed to determine: (1) whether the deficit in semantic structure in schizophrenia is independent of cultural backgrounds, and (2) the effect of age of onset and verbal intelligence on the degradation of semantic structure in these patients. Fifty-seven Japanese patients with schizophrenia and 33 normal control subjects entered the study. The semantic structure was derived by Multidimensional Scaling (MDS) analysis based on data from the ANIMAL category fluency test. The semantic structure was compared between: (1) schizophrenic patients as a whole vs. normal control subjects; (2) earlier onset (age of onset <20 years) vs. later-onset groups of patients; and (3) high Vocabulary score (score of the Vocabulary subtest from the WAIS-R>7) vs. low Vocabulary score patient groups. Normal control subjects demonstrated the domestic/size dimension in semantic structure, while no such dimension was obtained in patients with schizophrenia. The subgroup comparisons revealed that the later onset or the high Vocabulary score group maintained a relatively intact semantic structure compared with the earlier onset or the low Vocabulary score group, respectively. These findings suggest that the deficit in semantic structure in patients with schizophrenia is commonly observed irrespective of cultural backgrounds, and that age of onset and the level of verbal intelligence are closely related to severity of degradation of the semantic structure in schizophrenia.

Ventricular enlargement in schizophrenia spectrum patients with prodromal symptoms of obsessive-compulsive disorder.

We hypothesized that male patients with schizophrenia spectrum disorders who have prodromal symptoms of obsessive-compulsive disorder (OCD) have ventricular enlargement compared with non-psychotic OCD patients, and that the difference in the ventricular size would offer a clue to the early detection of schizophrenia spectrum disorders. The ventricle-brain ratios (VBRs) in eight male patients with schizophrenia or schizotypal personality disorder (SPD) who had prodromal symptoms of OCD were compared with eight male patients with non-psychotic OCD and 14 normal male comparison subjects using three-dimensional magnetic resonance imaging (MRI). The VBR of the schizophrenia spectrum group was significantly larger than those of the OCD group or comparison subjects. Even the minimum VBR in the schizophrenia spectrum group was larger than the maximum VBR in the OCD group. These results may suggest the usefulness of three-dimensional MRI for early detection of patients with schizophrenia spectrum disorders who manifest OCD symptoms early in the course of the illness.