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1.
Mol Psychiatry ; 20(4): 447-53, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25070538

ABSTRACT

The neuropeptide oxytocin may be an effective therapeutic strategy for the currently untreatable social and communication deficits associated with autism. Our recent paper reported that oxytocin mitigated autistic behavioral deficits through the restoration of activity in the ventromedial prefrontal cortex (vmPFC), as demonstrated with functional magnetic resonance imaging (fMRI) during a socio-communication task. However, it is unknown whether oxytocin exhibited effects at the neuronal level, which was outside of the specific task examined. In the same randomized, double-blind, placebo-controlled, within-subject cross-over clinical trial in which a single dose of intranasal oxytocin (24 IU) was administered to 40 men with high-functioning autism spectrum disorder (UMIN000002241/000004393), we measured N-acetylaspartate (NAA) levels, a marker for neuronal energy demand, in the vmPFC using (1)H-magnetic resonance spectroscopy ((1)H-MRS). The differences in the NAA levels between the oxytocin and placebo sessions were associated with oxytocin-induced fMRI signal changes in the vmPFC. The oxytocin-induced increases in the fMRI signal could be predicted by the NAA differences between the oxytocin and placebo sessions (P=0.002), an effect that remained after controlling for variability in the time between the fMRI and (1)H-MRS scans (P=0.006) and the order of administration of oxytocin and placebo (P=0.001). Furthermore, path analysis showed that the NAA differences in the vmPFC triggered increases in the task-dependent fMRI signals in the vmPFC, which consequently led to improvements in the socio-communication difficulties associated with autism. The present study suggests that the beneficial effects of oxytocin are not limited to the autistic behavior elicited by our psychological task, but may generalize to other autistic behavioral problems associated with the vmPFC.


Subject(s)
Aspartic Acid/analogs & derivatives , Autistic Disorder/drug therapy , Autistic Disorder/pathology , Oxytocin/administration & dosage , Prefrontal Cortex/metabolism , Recovery of Function/drug effects , Administration, Intranasal , Adult , Aspartic Acid/metabolism , Double-Blind Method , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Male , Oxygen/blood , Oxytocics/administration & dosage , Oxytocics/pharmacology , Oxytocin/pharmacology , Prefrontal Cortex/blood supply , Prefrontal Cortex/drug effects , Protons , Retrospective Studies , Time Factors , Young Adult
2.
Transl Psychiatry ; 4: e379, 2014 Apr 08.
Article in English | MEDLINE | ID: mdl-24713860

ABSTRACT

Few biomarkers have been known that can easily measure clinical conditions in mental illnesses such as schizophrenia. Capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) is a new method that can measure ionized and low-molecular-weight metabolites. To explore global metabolomic alterations that characterize the onset of schizophrenia and identify biomarkers, we profiled the relative and absolute concentrations of the plasma metabolites from 30 patients with first-episode schizophrenia (FESZ, four drug-naïve samples), 38 healthy controls and 15 individuals with autism spectrum disorders using CE-TOFMS. Five metabolites had robust changes (increased creatine and decreased betaine, nonanoic acid, benzoic acid and perillic acid) in two independent sample sets. Altered levels of these metabolites are consistent with well-known hypotheses regarding abnormalities of the homocysteine metabolism, creatine kinase-emia and oxidative stress. Although it should be considered that most patients with FESZ received medication, these metabolites are candidate biomarkers to improve the determination of diagnosis, severity and clinical stages, especially for FESZ.


Subject(s)
Child Development Disorders, Pervasive/metabolism , Electrophoresis, Capillary/methods , Mass Spectrometry/methods , Plasma/metabolism , Schizophrenia/metabolism , Adult , Biomarkers/blood , Biomarkers/metabolism , Child Development Disorders, Pervasive/blood , Female , Humans , Male , Schizophrenia/blood , Young Adult
3.
Transl Psychiatry ; 2: e178, 2012 Oct 23.
Article in English | MEDLINE | ID: mdl-23092982

ABSTRACT

Atypical trajectory of brain growth in autism spectrum disorders (ASDs) has been recognized as a potential etiology of an atypical course of behavioral development. Numerous neuroimaging studies have focused on childhood to investigate atypical age-related change of brain structure and function, because it is a period of neuron and synapse maturation. Recent studies, however, have shown that the atypical age-related structural change of autistic brain expands beyond childhood and constitutes neural underpinnings for lifelong difficulty to behavioral adaptation. Thus, we examined effects of aging on neurochemical aspects of brain maturation using 3-T proton magnetic resonance spectroscopy ((1)H-MRS) with single voxel in the medial prefrontal cortex (PFC) in 24 adult men with non-medicated high-functioning ASDs and 25 age-, IQ- and parental-socioeconomic-background-matched men with typical development (TD). Multivariate analyses of covariance demonstrated significantly high N-acetylaspartate (NAA) level in the ASD subjects compared with the TD subjects (F=4.83, P=0.033). The low NAA level showed a significant positive correlation with advanced age in the TD group (r=-0.618, P=0.001), but was not evident among the ASD individuals (r=0.258, P=0.223). Fisher's r-to-z transformation showed a significant difference in the correlations between the ASD and TD groups (Z=-3.23, P=0.001), which indicated that the age-NAA relationship was significantly specific to people with TD. The current (1)H-MRS study provided new evidence that atypical age-related change of neurochemical aspects of brain maturation in ASD individuals expands beyond childhood and persists during adulthood.


Subject(s)
Aging/metabolism , Aspartic Acid/analogs & derivatives , Asperger Syndrome/metabolism , Autistic Disorder/metabolism , Prefrontal Cortex/metabolism , Adult , Age Factors , Aspartic Acid/metabolism , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Male , Multivariate Analysis
4.
Kyobu Geka ; 62(9): 839-41, 2009 Aug.
Article in Japanese | MEDLINE | ID: mdl-19670792

ABSTRACT

A 50-year-old man was found to have a chest abnormal shadow during a check-up and visited our hospital in 1991. Tumor shadow was observed in the anterior mediastinum. Resection of the tumor was performed by partial thymectomy. The pathological diagnosis was a thymoma type B1 and stage I based on Masaoka' s classification. In 2004, he underwent radical thymectomy and partial resection of the lung to remove the local recurrent tumor followed by postoperative radiation therapy. In 2006, 3rd operation was performed and the tumor in the superior mediastinum was resected. Since then, the patient is well without signs of recurrence. We experienced a case of thymoma with long-term survival treated by polysurgery.


Subject(s)
Thymoma/surgery , Thymus Neoplasms/surgery , Humans , Male , Middle Aged , Reoperation , Thymectomy , Thymoma/mortality , Thymus Neoplasms/mortality
5.
Surg Today ; 27(2): 149-53, 1997.
Article in English | MEDLINE | ID: mdl-9017993

ABSTRACT

This study was designed to reexamine the healing process of expanded polytetrafluoroethylene (EPTFE) grafts with standard porosity (30 microm) and high porosity (60 microm) in portal vein replacement, and to evaluate the effect of an omentum wrap, which has certain functions that promote healing, on graft healing. These grafts, either wrapped by the omentum or not, were placed as portal vein replacements in 24 mongrel dogs. After 1 month, the grafts were retrieved and examined for patency, thrombus-free areas, thickness of the pseudointima, and the total number of cells growing into the graft wall. There were no statistical differences in the patency rates. The high-porosity grafts had a significantly larger thrombus-free area, a thicker pseudointima, and a larger growth of cells than the standard-porosity grafts. The omentum wrap significantly increased the thrombus-free area and stimulated a larger growth of cells in both grafts. The high-porosity grafts plus omentum demonstrated a thrombus-free area of 82.2% vs 27.3% in the standard-porosity grafts. In addition, the migration of fibroblasts and macrophages was most evident in the high-porosity grafts wrapped by the omentum. In conclusion, graft healing enhancement was observed in the high-porosity EPTFE grafts wrapped by the omentum. It is thus suggested that transmural cellular migration plays an important role in the process of graft healing.


Subject(s)
Blood Vessel Prosthesis/standards , Omentum , Polytetrafluoroethylene , Portal Vein/surgery , Vascular Patency , Wound Healing/physiology , Animals , Dogs
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