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Biomedical subjects

Naoko Takeuchi

Publications and source records attributed to Naoko Takeuchi.

15 recordsLinked to original sources

Association study of polymorphisms in the glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 with schizophrenia.

Based on the glutamatergic dysfunction hypothesis for schizophrenia pathogenesis, we have been performing systematic association studies of schizophrenia with the glutamate receptor and transporter genes. We report here association studies of schizophrenia with three glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 encoding the glutamate transporters EAAT3, EAAT1, and EAAT4, respectively. We initially performed the screening of the total 25 single nucleotide polymorphisms (SNPs) distributed in the three gene regions using 100 out of 400 Japanese cases and 100 out of 420 Japanese controls. After controlling the false discovery rate (FDR) at level 0.05, we observed significant associations of schizophrenia with a genotype of SNP4 (rs2097837, P = 0.007) and with haplotypes of SNP2-SNP5 (P = 7.5 x 10(-5)) and SNP3-SNP5 (P = 9.0 x 10(-4)) in the SLC1A6 region. The haplotype of SNP2-SNP5 of SLC1A6 even showed marginally significant association with the disease in the full-size sample (400 cases and 420 controls, P = 0.031). We concluded that at least one susceptibility locus for schizophrenia may be located within or nearby SLC1A6, whereas SLC1A1 and SLC1A3 are unlikely to be major susceptibility genes for schizophrenia in the Japanese population.

Adult↗

Aqueous-aqueous two-phase systems composed of low molecular weight of polyethylene glycols and dextrans for counter-current chromatographic purification of proteins.

New aqueous-aqueous two-phase systems composed of relatively low molecular weight polymers such as polyethylene glycol (PEG) (Mr: 1000-4000) and dextran (Mr: 10,000 and 40,000) were evaluated for purification of proteins by counter-current chromatography (CCC). The compositions of aqueous two-phase systems were optimized by measuring parameters such as viscosity and volume ratio between the two phases. CCC purification of a glucosyltransferase (GTF) from Streptococcus mutans (SM) cell-lysate was successfully demonstrated with a 7.5% PEG 3350-10% dextran T40 system containing 10mM potassium phosphate buffer at pH 9.0. After CCC purification, both PEG and dextran contained in the CCC fractions were easily removed by ultrafiltration in a short period of time. The fractionated column contents containing GTF were analyzed by enzymatic activity as well as sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. The recovery of the enzyme from CCC fraction was over 95% as estimated by enzymatic activities.

Countercurrent Distribution↗

Distorted perception of smell by volatile agents facilitated inhalational induction of anesthesia.

BACKGROUND: Unpleasant smell of halogenated volatile agents is one of the frustrating factors for inhalational induction. We developed a new modification that might enable children to enjoy the smell itself while incrementally elevating sevoflurane concentration. Troposmia is usually a pathological quality change of smell perception and an olfactory stimulus is distortedly perceived in this state, which we applied to inhalational induction. METHODS: At the preoperative visit an anesthetist told the children that the smell of a facemask could be magically changed from strawberry into anything and promised to change the smell as they requested. In the operating room, a strawberry scented facemask was fitted to the face and the anesthetist announced to them that the magical change of the smell would begin when sevoflurane was added. Whether children perceived the change of the smell as they requested was investigated in the troposmia group, and resistance to fit a facemask was compared between the troposmia group and a control group. RESULTS: Significantly fewer children resisted the facemask in the troposmia group (1 of 32 vs 9 of 32; P = 0.0059). In the troposmia group 18, 22 and 25 of the 32 children said the smell of the facemask changed as they requested before they fell asleep, at the postoperative visit or both, respectively. CONCLUSIONS: Troposmia can be intentionally induced to perceive the smell of sevoflurane on request. Troposmia might contribute to promote children's participation in anesthesia induction and facilitate inhalational induction.

Anesthesia, General↗

Allelic loss during progression of follicular lymphoma.

We performed loss of heterozygosity (LOH) analysis on matched lymph nodes before and after progression of follicular lymphoma (FL), and found novel LOH on chromosome arm 12p. This LOH has not been previously reported in association with FL transformation. Other sites of frequent LOH include chromosome arms 6q and 9p. LOH was observed in both transformed FL and relapse FL. These data suggest that altered tumor suppressor genes exist on 6q, 9p, and 12p that have an important role in the progression of FL. Genetic changes accumulated in relapsed FL in the absence of histological changes compared to initial diagnosis.

Chromosomes, Human, Pair 12↗

Methylenetetrahydrofolate reductase genotype does not play a role in adult T-cell leukemia/lymphoma pathogenesis among human T-lymphotrophic virus type 1 carriers.

Human T-lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukemia/lymphoma (ATL). However, the incidence of ATL is low among HTLV-1 carriers suggesting additional mechanisms are involved in the progression of the disease. A recent study found that polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene influence the susceptibility to malignant lymphoma. We have analyzed the MTHFR genotype in 81 HTLV-1 carriers and 87 ATL patients. No statistically significant associations were found between MTHFR genotype and development of ATL. These data suggest that genetic polymorphisms in the MTHFR locus do not play a role in ATL pathogenesis among HTLV-1 carriers.

Carrier State↗

Electrogastrography abnormality in eating disorders.

Eating disorders are common psychiatric disorders in young women. The aim of the present study was to evaluate the gastric electrical activity of patients with eating disorders and its relation to their symptoms. The electrogastrography (EGG) was performed before and after a water load test for outpatients with eating disorders (n = 36; 14 anorexia nervosa, 14 bulimia nervosa, eight eating disorder not otherwise specified) and healthy women (n = 19). A structured interview (Eating Disorder Examination) was used to assess clinical symptoms. The percentage of normal gastric myoelectrical power was significantly smaller in the eating disorder patients (44.5% vs 74.2%; P < 0.05), while the percentage of bradygastric power was significantly greater, both before and after the water load test compared with the control subjects (30.4% vs 10.4%; P < 0.05). In addition, moderate correlation was found between the duration of illness and the percentage of bradygastria (P < 0.05). In conclusion, it is suggested that longstanding abnormal eating in patients with eating disorders may induce disturbances to gastric motor function, resulting in their abnormal, eating-related behavior, and form a symptomatic vicious circle. The EGG may be a promising method for determining the pathophysiology of eating disorders and for developing effective therapeutic approaches.

Adolescent↗

[Successful corticosteroid treatment of thrombocytopenia in a pregnant woman with myelodysplastic syndrome (refractory anemia)].

A 31-year-old pregnant woman was referred to our hospital due to anemia and thrombocytopenia, and was diagnosed as having myelodysplastic syndrome (refractory anemia) with autoimmune thrombocytopenia. Administration of high dose methylprednisolone and gamma-globulin did not raise her platelet count, and she subsequently delivered a healthy baby after the transfusion of a large amount of platelets. Although the anemia spontaneously improved after delivery, the platelet count remained unchanged. Prednisolone was thus administered a second time, which did finally increase the platelet count. This is the first reported case of a pregnant woman with myelodysplastic syndrome in whom corticosteroid administration was effective for thrombocytopenia.

Adult↗

[Second hematologic response and disappearance of the ABL gene mutant clone by cessation of imatinib in a CML patient with resistance to imatinib].

A seventy-six year old female patient with chronic myelogenous leukemia (CML), (chronic phase), was treated with imatinib and obtained a major cytogenetic response after 6 months of treatment. However, resistance to imatinib appeared 9 months later due to an ABL gene point mutation, and the patient's platelet count and BCR/ABL positive rate had remarkably increased. We discontinued imatinib and used IFNalpha or hydroxyurea, resulting in the disappearance of the ABL gene mutation clone. After that, we obtained a secondary hematologic response with the administration of imatinib.

Aged↗

Allelotype analysis in relapsed childhood acute lymphoblastic leukemia.

We performed for the first time the allelotype of relapsed childhood acute lymphoblastic leukemia (ALL). A total of 38 cases were screened for loss of heterozygosity (LOH) using 71 markers. In all, 26 (68%) patients showed LOH on at least one chromosomal arm, indicating that LOH is a frequent event at relapse. The most frequent loss was found on chromosomal arm 9p at the p16/INK4a locus (39%). LOH at the TEL gene locus on chromosomal arm 12p also occurred often (25%). Frequent loss was observed on chromosome arms 4q (20%), 6q (21%), and 17q (20%). Sequential analysis (i.e. samples obtained from both initial diagnosis and relapse) shows that some patients (63%) have the identical LOH status at both phases, suggesting the presence of the same clone. Other samples (37%) showed distinct LOH alterations, indicating clonal evolution at relapse. Despite the heterogeneous and complex changes, some shared LOH loci occurred in these matched samples, suggesting that many of the same tumor-suppressor genes are aberrant at both phases. In summary, novel tumor-suppressor genes on chromosome arms 4q, 6q, and 17q, as well as the p16 and TEL genes, have an important role in the relapse of childhood ALL.

Adolescent↗

Frameshift mutations in caspase-5 and other target genes in leukemia and lymphoma cell lines having microsatellite instability.

Microsatellite instability (MSI) was examined in 49 lymphoid leukemia/lymphoma cell lines. Frameshift mutations within eight MSI target genes were analyzed in the 12 cell lines and nine childhood acute lymphoblastic leukemia (ALL) samples with MSI. Six cell lines (50%) showed mutations within the coding repeats of the BLM, caspase-5, TCF-4, and PTEN genes. No mutations were identified in the nine childhood ALL samples with MSI. This is the first report that describes mutations of these genes in hematological malignancies. Mutations, presumably caused by an abnormality of the DNA repair genes, may be selected for during the establishment of cell lines.

Adenosine Triphosphatases↗

Mutations in the retinoblastoma-related gene RB2/p130 in adult T-cell leukaemia/lymphoma.

The retinoblastoma (Rb) family consists of the tumor suppressor Rb/p105 and related proteins p107 and Rb2/p130. Although the involvement of the RB/p105 gene in Adult T-cell leukaemia/lymphoma (ATL) has been studied, no mutational data is reported regarding the RB2/p130 gene in ATL. We screened for mutations of the RB2/p130 gene. Mutation was detected in 1 of 41 primary ATL sample. This is the first report describing mutation of the RB2/p130 gene in ATL, suggesting that RB2/p130 may be involved in the development of ATL, and may behave as a tumor suppressor gene in T lymphocytes.

Cell Cycle↗

Genetic polymorphisms in the tumour necrosis factor locus in childhood acute lymphoblastic leukaemia.

Genetic polymorphisms in the tumour necrosis factor (TNF) locus influence the outcome of non-Hodgkin's lymphoma (NHL). We investigated whether these polymorphisms might contribute to the clinical course of childhood acute lymphoblastic leukaemia (ALL). Genomic DNA from 214 childhood ALL patients was analysed. Patients with a high-risk haplotype were older than patients with low-risk haplotype (P = 0.024). No statistically significant associations were found between TNF haplotype and sex, WBC counts, central nervous system involvement, immunophenotype, response to chemotherapy, and event-free survival. These data suggest that genetic polymorphisms in the TNF locus have a limited effect on the outcome of childhood ALL.

Age Factors↗

Scintigraphic prediction of response to chemotherapy in patients with breast cancer: Technetium 99m-tetrofosmin and thallium-201 dual single photon emission computed tomography.

We have investigated the usefulness of dual-isotope single photon emission computed tomography (SPECT) for predicting the response to chemotherapy in patients with breast cancer. Twenty-five patients with breast cancer were analyzed by SPECT using both 99m-technetium-tetrofosmin (99mTc-TF) and 201-thallium-chloride (201Tl). The relationship between response to chemotherapy and retention of each tracer was analyzed. 99mTc-TF retention was significantly higher in responders (42.0+/-37.9) than in non-responders (-11.3+/-34.6) (p=0.003). Ten of 13 patients (76.9%) with high 99mTc-TF retention (>15%) showed good response to chemotherapy, whereas 11 of 12 patients (91.7%) with low 99mTc-TF retention (<15%) did not respond to the therapy. The overall predictability to the response to chemotherapy was 84.0%. 201Tl retention (responders, 47.5+/-60.2% vs. non-responders, 55.8+/-45.0%; p=0.443) was not useful in therapeutic prediction, but was required to identify the lesion on the SPECT image. This is the first report to find that dual-isotope SPECT using 99mTc-TF and 201Tl is useful in predicting the response to chemotherapy in patients with breast cancer. Low 99mTc-TF retention is a strong predictor of therapeutic resistance, and high 99mTc-TF retention suggests a favorable response to chemotherapy.

Adult↗

Tamoxifen-induced non-alcoholic steatohepatitis in patients with breast cancer: determination of a suitable biopsy site for diagnosis.

We have evaluated the distribution of fatty infiltration in the liver for determination of a suitable biopsy site for diagnosis of tamoxifen-induced non-alcoholic steatohepatitis (NASH) in patients with breast cancer. Thirty-eight consecutive breast cancer patients undergoing tamoxifen treatment were analyzed by CT to identify hepatic steatosis (HS) via calculation of the liver/spleen CT ratio in Couinaud's 8 areas. We defined hepatic fatty infiltration as a liver/spleen ratio of less than 0.9. The extent and distribution of the fatty infiltration was assessed using the liver/spleen ratio of the patients who had the lowest CT ratio below 0.9 in the 8 areas. Thirteen (34.2%) of the 38 patients had hepatic fatty infiltration. The liver/spleen ratios of each area differed significantly in all patients (p<0.0001). The CT ratio of these 13 patients was significantly lower in the right lobe than the left lobe (p<0.0001), although the ratios did not differ significantly among the 4 areas of the right lobe (p=0.52). Needle biopsy for diagnosis of NASH should be performed at the right lobe, which contains significantly more infiltrated fat than the left lobe in the liver.

Adult↗