Biomedical subjects

Tsukasa Sasaki

Publications and source records attributed to Tsukasa Sasaki.

At least 19 recordsLinked to original sources

PubMed2004

Association between the neurofibromatosis-1 (NF1) locus and autism in the Japanese population.

Autistic patients have a 100 to 190-fold increased risk of neurofibromatosis compared to the general population. This suggests that the two diseases may share a common etiological background. Recently, a new allele (or the six-repeat allele) of the (AAAT)(n) repeat polymorphism in an Alu sequence in the neurofibromatosis-1 (NF1) gene was observed exclusively in severe autistic patients, not in controls, in Caucasians of French ancestry. This suggests a role of the NF1 gene in the development of autism. We investigated three microsatellite polymorphisms within the intron-27b and intron-38 of the NF1 region, including the (AAAT)(n) and two (CA)n repeat polymorphisms, in Japanese subjects with autism (n = 74) and controls (n = 122). The six-repeat allele of the (AAAT)(n) polymorphism was not found either in patients or controls, possibly indicating an ethnic difference in the polymorphism. However, significant differences were observed in the allele distributions of the (AAAT)(n) and a (CA)(n), which were located at intron-27b, between patients and controls, although an association was not significant between autism and another polymorphism at intron-38. This may suggest an involvement of the NF1 locus in susceptibility to autism, although further investigations are recommended.

Adolescent↗

PubMed2004

Season of birth effect on personality in a general population.

Seasonality of births in schizophrenia and other mental disorders has been consistently observed. This may be through effects of unknown environmental factors that seasonally fluctuate on the brain development. The effects may affect cognitive function of the brain and behavioral characteristics that might be correlated with the development of personality not only in patients with mental disorders but also in healthy subjects. We, therefore, investigated the effects of season of birth on personality traits in healthy Japanese adults (n = 397). Personality traits were evaluated using the NEO Personality Inventory-Revised (NEO PI-R). A trend for lower Agreeableness in subjects born during winter (December to February) than other subjects was observed (P = 0.036, after correction for the multiple testing, multiple regression analysis adjusting for age and sex). Other major factors of the NEO PI-R, including Neuroticism, Extraversion, Openness and Conscientiousness, were not affected by season of birth. Further studies may be recommended to confirm the results, considering the relatively limited sample size. Evaluation of cognitive functions and behaviors using other measures including event-related potentials and functional MRI may also help the interpretation of the present result.

Adult↗

PubMed2004

Mitochondrial DNA polymorphisms and extraversion.

Mitochondria is the major site of energy production in cells, therefore, mitochondrial abnormality may affect functions of organs including the brain, which constantly requires high levels of energy consumption. Previous studies have suggested a role of mitochondria and their DNA polymorphisms in neuro-psychiatric disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia and bipolar mood disorder. Thus, we hypothesized that mitochondrial DNA polymorphisms might be related with the development of personality. The present study investigated a role of two mitochondrial DNA polymorphisms, the C5178A and A10398G, in personality traits evaluated using the NEO PI-R scores in 238 healthy Japanese volunteers. Subjects with the 5178A genotype showed significantly higher extraversion score than those with the 5178C genotype (P = 0.027), while no significant association was observed between the C5178A polymorphism and other scores. No significant association was found between the A10398G polymorphism and any scores. Regarding the 5178-10398 haplotype, the score of extraversion, not other scores, was significantly associated with the A-G haplotype (P = 0.042). Although further studies are recommended for the confirmation, the result may suggest a role of the mitochondrial DNA polymorphism in the personality trait.

Adult↗

PubMed2004

Association of six polymorphisms of the NOTCH4 gene with schizophrenia in the Japanese population.

The NOTCH4 gene is located at 6p21.3 and involved in the development and patterning of the central nervous systems. Recently, Wei and Hemmings [2000] observed that the gene was associated with schizophrenia. Subsequent to the report, several studies investigated the gene in schizophrenia, with controversial and inconclusive results. In the present study, we investigated six polymorphisms (SNPs 1-5 and a CTG repeat) of the gene in Japanese subjects with schizophrenia (n = 284) and the same number of controls. The polymorphisms include SNP5, which has been observed to be associated with schizophrenia in a Chinese population and two new SNPs 3-4 adjacent to SNP5, in addition to the SNPs 1-2 and the CTG repeat, which were suggested for the association with the disease in the previous study. As a result, no significant difference in genotypic distributions or allelic frequencies of the six polymorphisms of the gene was observed between the patients and the controls. Also, no significant difference was found in frequencies of haplotypes of the six polymorphisms between the patients and the controls. However, the distribution of SNP2 was significantly deviated from Hardy-Weinberg equilibrium in the patients (P = 0.000986), not in the controls, which could be a chance or due to an association of SNP2 with the disease. In conclusion, the present study provided no clear evidence for an association between the NOTCH4 gene and schizophrenia in the Japanese population.

Adult↗

PubMed2004

Cyclic ADP-ribose, a putative Ca2+-mobilizing second messenger, operates in submucosal gland acinar cells.

Cyclic ADP-ribose (cADPR), a putative Ca(2+)-mobilizing second messenger, has been reported to operate in several mammalian cells. To investigate whether cADPR is involved in electrolyte secretion from airway glands, we used a patch-clamp technique, the measurement of microsomal Ca(2+) release, quantification of cellular cADPR, and RT-PCR for CD38 mRNA in human and feline tracheal glands. cADPR (>6 microM), infused into the cell via the patch pipette, caused ionic currents dependent on cellular Ca(2+). Infusions of lower concentrations (2-4 microM) of cADPR or inositol 1,4,5-trisphosphate (IP(3)) alone were without effect on the baseline current, but a combined application of cADPR and IP(3) mimicked the cellular response to low concentrations of acetylcholine (ACh). Microsomes derived from the isolated glands released Ca(2+) in response to both IP(3) and cADPR. cADPR released Ca(2+) from microsomes desensitized to IP(3) or those treated with heparin. The mRNA for CD38, an enzyme protein involved in cADPR metabolism, was detected in human tissues, including tracheal glands, and the cellular content of cADPR was increased with physiologically relevant concentrations of ACh. We conclude that cADPR, in concert with IP(3), operates in airway gland acinar cells to mobilize Ca(2+), resulting in Cl(-) secretion.

ADP-ribosyl Cyclase↗

PubMed2004

What causes seasonality of birth in schizophrenia?

An excess of winter-spring births (and/or a decrease of summer births) has consistently been observed in schizophrenia (SCZ). This observation may provide a significant clue about the causes of the disease if specific factors which cause the phenomenon can be determined. This paper reviews several studies which investigated factors correlated with this observation in SCZ, in an attempt to determine which factors more likely cause the seasonality. Among the candidates of the factors are meteorological variables (such as ambient temperature), several infections, maternal hormones, sperm quality, nutrition and external toxins. A variation of procreation might also have an effect. Among the factors, the most extensively studied are temperature and viral infections. Some of them have appeared promising, but further studies are definitely required. Several challenges, including complicated correlations of the factors and determination of the susceptible period during pregnancy, need to be overcome. Comparisons of the data from areas and cohorts with different patterns of the candidate factors may be helpful. Animal studies may also help investigate the molecular and physiological mechanisms of the phenomenon.

Animals↗

PubMed2004

Gastrin-releasing peptide receptor (GRPR) locus in Japanese subjects with autism.

Gastrin-releasing peptide receptor (GRPR) gene is considered a candidate locus for infantile autism for several reasons. The present study investigated two polymorphic sites (C/450/T and C/661/T) in the second exon of the GRPR gene in Japanese patients with autism (DSM-IV) and healthy subjects. The two polymorphic sites were at high linkage disequilirium, consistent with a previous study in a North American population. The C450-C661 allele, which was observed in one-third of the chromosomes from the North American subjects, was less frequent (6-7%) in the Japanese subjects, suggesting a large ethnic difference in the frequency of the polymorphism. The allele frequencies and genotype distributions were not significantly different between the patients and controls. However, further studies are required to exclude the GRPR locus as a candidate locus for autism, considering the low frequency of the polymorphism in the Japanese subjects.

Adolescent↗

PubMed2004

Prevalence of post-traumatic stress disorder in incarcerated juvenile delinquents in Japan.

The present study investigated frequency of post-traumatic stress disorder (PTSD) in incarcerated juvenile delinquents in Japan. The presence of overwhelming traumatic experiences, which fulfilled the DSM-IV criterion A for PTSD, was evaluated using a self-report questionnaire in 251 delinquents (206 males and 45 females). The structured interview using the Clinician-administered PTSD Scale for DSM-IV (CAPS) was administered to those with the experiences. A substantial portion (36%) of the delinquents reported experiences of exposure to such overwhelming traumatic events, which fulfilled the criterion A. Among those who met the criterion A, 48 subjects (40 males and eight females) received the CAPS interview. Ten (21%) out of 48 were diagnosed with current or past history of full PTSD. Three subjects out of the 10 were currently diagnosed with full PTSD. Another 10 subjects out of 48 (21%) had fulfilled the criteria for current or past history of partial PTSD. Among the 10, one was diagnosed as currently suffering from partial PTSD. In females, frequencies of the past history were quite high (50% for full PTSD and 25% for partial PTSD in the eight subjects), while none was currently diagnosed with PTSD.

Adolescent↗

PubMed2004

Association of the XBP1-116C/G polymorphism with schizophrenia in the Japanese population.

Schizophrenia and bipolar disorder share some clinical features and linkage studies have shown that several loci are common. Recently, the authors found that the -116C-->G substitution in the promotor region of XBP1, a pivotal gene in endoplasmic reticulum (ER) stress response, causes the impairment of ER stress response, and that the -116C/C genotype is a protective factor; in other words the presence of the G allele increases the risk for bipolar disorder. The gene is located on 22q12.1, which is also linked with schizophrenia. The polymorphisms were investigated in 234 schizophrenic patients as compared with controls. Significant difference of genotype distribution was observed, which suggested that the -116C/C genotype is a protective factor for both of the major mental disorders.

Alleles↗

PubMed2003

Smoking habits in Japanese patients with schizophrenia.

Studies from North America and Western Europe have observed a marked increase of smoking in schizophrenia. This preliminary study investigated smoking habits in Japanese patients with schizophrenia (n=137). The prevalence of smokers (34%) was not higher than in the general Japanese population (37%). Variables associated with smoking were also different from those reported in the Western literature. Different cultural backgrounds may underlie the differing results in Western and Japanese populations.

Adult↗

PubMed2003

Hypoactivation of the prefrontal cortex during verbal fluency test in PTSD: a near-infrared spectroscopy study.

Several studies have suggested that there is frontal dysfunction in subjects with posttraumatic stress disorder (PTSD). We investigated the relationship between alterations of the hemodynamic response of the prefrontal cortex during a cognitive task (verbal fluency task; VFT) and memory function measured using the Wechsler Memory Scale-Revised (WMS-R). The subjects were victims of the Tokyo Subway Sarin attack with (n = 8) or without (n = 26) PTSD. Hemodynamic response in the prefrontal cortex was measured using a 24-channel near-infrared spectroscopy (NIRS) system. Subjects with PTSD had a significantly smaller response of oxygenated hemoglobin and total hemoglobin during the VFT compared with those without PTSD, although there was no significant difference in performance on the VFT. Subjects with PTSD had significantly lower scores on attention and concentration in the WMS-R, which was positively correlated with the increase of total hemoglobin during the VFT. The 'frontal dysfunction' observed in subjects with PTSD may be a secondary phenomenon to reduced attentional capacity.

Adult↗

PubMed2003

Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder.

The pathophysiology of bipolar disorder is still unclear, although family, twin and linkage studies implicate genetic factors. Here we identified XBP1, a pivotal gene in the endoplasmic reticulum (ER) stress response, as contributing to the genetic risk factor for bipolar disorder. Using DNA microarray analysis of lymphoblastoid cells derived from two pairs of twins discordant with respect to the illness, we found downregulated expression of genes related to ER stress response in both affected twins. A polymorphism (-116C-->G) in the promoter region of XBP1, affecting the putative binding site of XBP1, was significantly more common in Japanese patients (odds ratio = 4.6) and overtransmitted to affected offspring in trio samples of the NIMH Bipolar Disorder Genetics Initiative. XBP1-dependent transcription activity of the -116G allele was lower than that of the -116C allele, and in the cells with the G allele, induction of XBP1 expression after ER stress was markedly reduced. Valproate, one of three mood stabilizers, rescued the impaired response by inducing ATF6, the gene upstream of XBP1. These results indicate that the -116C-->G polymorphism in XBP1 causes an impairment of its positive feedback system and increases the risk of bipolar disorder.

Base Sequence↗

PubMed2003

Serotonin transporter-linked promoter region polymorphism and personality traits in a Japanese population.

Serotonin transporter gene may play a critical role in a regulation of mood and other aspects of mental status. A large number of association studies have investigated a correlation between the polymorphism in the serotonin transporter-linked promoter region (5-HTTLPR) and anxiety-related personality traits. The results, however, have been inconsistent. Heterogeneity of subjects regarding gender, occupation, social-class and other environmental factors, in addition to effects of other genes, might have confounded the results. Here, we studied an association between the 5-HTTLPR polymorphism and personality traits in primarily female (78%) healthy subjects (n=244), who had homogeneous backgrounds regarding ethnicity (Japanese) and occupation. Personality traits of the subjects were assessed with the revised NEO Personality Inventory. No significant association was observed between the polymorphism and neuroticism or other personality traits, in all subjects, all females (n=190) or female nurses (n=159). Thus, our findings provided no evidence for an association between the 5-HTTLPR polymorphism and anxiety-related or other personality traits.

Adult↗

PubMed2003

Psychological factors and survival after bone marrow transplantation in patients with leukemia.

Psychological factors may be associated with the outcome of cancer treatment, including bone marrow transplantation (BMT). However, studies on the issue have provided controversial results. In the present study, effects of mood status on the outcome was studied through a follow-up period of 1-3 years as well as in shorter periods (3 and 8 months) post-BMT in 72 Japanese patients with leukemia. Psychological status was evaluated 2 weeks before BMT using Profile of Mood States (POMS). The most major factor abstracted from the POMS subscales (Factor 1, mainly comprising anxiety, depression, anger, fatigue and confusion) was associated with disease-free survival rate at 3 months post-BMT. However, the factor most significantly associated with the outcome was gender. Females had better outcome than males through the period of 1-3 years as well as at 8 months post-BMT. When analyzed by gender, Factor 1 was associated with poor prognosis at 3 and 8 months in males. In females, however, Factor 1 was not significantly associated with the prognosis. The present results suggest an association between mood status pre-BMT and prognosis post-BMT in a gender-specific manner.

Adolescent↗

PubMed2003

Bone marrow transplantation in subjects with mental disorders.

Bone marrow transplantation (BMT) is a critical treatment of malignant illnesses including leukemia and others. Successful achievement of BMT requires the patients to tolerate isolation for several weeks to avoid infections. They are also required to follow several regulations and instructions to survive the treatment because the patients' physical condition is complicated due to the malignant illness, preparatory treatment and transplant of bone marrow from other subjects. These could be a significant challenge for patients with mental disorders. Here the cases are reported of seven leukemia patients who were referred to the Metropolitan Komagome Hospital for BMT from April 1996 through May 2000, who had been suffering from mental disorders, including schizophrenia, bipolar I mood disorder, panic disorder, dysthymic disorder, autistic disorder, and borderline personality disorder, prior to the treatment. The BMT was achieved in six out of the seven subjects; the exception was a subject with borderline personality disorder. Psychiatric treatments, including medication, to improve and maintain mental status appeared to be critical for the achievement of BMT in several patients. Understanding of the status of the malignant disease and the role of BMT was another significant issue. Test admission seemed to be helpful to reduce concerns and anxiety both in the patients and hospital staff.

Adult↗

PubMed2003

Activation of the prefrontal cortex to trauma-related stimuli measured by near-infrared spectroscopy in posttraumatic stress disorder due to terrorism.

To develop a noninvasive method for psychophysiological assessment of posttraumatic stress disorder (PTSD), 34 victims of the Tokyo Subway Sarin Attack in 1995 including 8 diagnosed as PTSD and 12 controls were examined by a multichannel near-infrared spectroscopy (NIRS) system. Hemodynamic response in the prefrontal cortex was monitored during the presentation of trauma-related and control stimuli by video images. Skin conductance response (SCR) was also examined. Oxygenated hemoglobin significantly increased during the trauma-related image in the victims with or without PTSD. Deoxygenated hemoglobin significantly decreased only in victims with PTSD. No significant alteration was found in controls. Significantly enhanced SCR was also observed in the victims with PTSD during trauma-related stimuli. The findings suggest that measurement of cerebral hemodynamic response by NIRS is useful for psychophysiological assessment of PTSD.

Adult↗

PubMed2002

Differential effect of epidermal growth factor on serous and mucous cells in porcine airway submucosal gland.

Using a patch-clamp technique, we found that the fresh porcine submucosal gland acinar cells contained two functionally distinct cell populations, i.e. physiologically relevant concentration of acetylcholine (ACh, 30 nM) induced two distinct patterns of electric response in tracheal gland acinar cells. One was characterized by an outstanding oscillatory Cl(-)-current activity, and the other was with poor Cl(-)-current response but with a comparable K(+)-current. We examined the effect of epidermal growth factor (EGF) on the ACh-induced electric responses in these cells. EGF affected only the latter (K(+)-prominent) cell type to potentiate significantly the ACh-induced K(+)-current. An immunohistochemistry revealed that the receptor for EGF was identified preferentially on the mucous, but not serous, cells. Genistein, one of the tyrosine-kinase inhibitors, abolished the augmentation effect of EGF on the ACh-induced current. Thus, we identified the serous cell with a Cl(-)-rich current in response to ACh and the mucous cell with a K(+)-dominant response. Moreover, EGF affected the mucous cells alone to potentiate the ACh-induced electric response. EGF may contribute to the pathophysiological alterations in chronic inflammatory airways both in morphological (mucous cell hypertrophy/hyperplasia) and functional (thick viscous hypersecretion) ways.

Acetylcholine↗

PubMed2002

Human leukocyte antigen-A specificities and its relation with season of birth in Japanese patients with schizophrenia.

Several studies, including one from Japan, have observed an increase of Human Leukocyte Antigen (HLA)-A24 and A26 in schizophrenia, although others failed to observe the increase. No use of systematic diagnostic criteria and a not-adequately reliable typing technique might have affected the results in the previous studies. We investigated HLA-A specificities in Japanese patients with schizophrenia (DSM-IV), recruited from the same area as in the early Japanese study. A DNA-based technique (polymerase chain reaction-microtiter plate hybridization) was employed. No significant difference was observed in frequencies of any HLA-A specificities between patients and controls, including A24 and A26. No significant association was found between the HLA-A and birth-season in patients. Thus, no evidence was obtained for an association between HLA-A and schizophrenia from the Japanese population.

Adult↗