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Y Iijima

Publications and source records attributed to Y Iijima.

At least 19 recordsLinked to original sources
PubMed2006

A complex polymorphic region in the brain-derived neurotrophic factor (BDNF) gene confers susceptibility to bipolar disorder and affects transcriptional activity.

Previous studies have suggested that genetic variations in the brain-derived neurotrophic factor (BDNF) gene may be associated with several neuropsychiatric diseases including bipolar disorder. The present study examined a microsatellite polymorphism located approximately 1.0 kb upstream of the translation initiation site of the BDNF gene for novel sequence variations, association with bipolar disorder, and effects on transcriptional activity. Detailed sequencing analysis revealed that this polymorphism is not a simple dinucleotide repeat, but it is highly polymorphic with a complex structure containing three types of dinucleotide repeats, insertion/deletion, and nucleotide substitutions that gives rise to a total of 23 novel allelic variants. We obtained evidence supporting the association between this polymorphic region (designated as BDNF-linked complex polymorphic region (BDNF-LCPR)) and bipolar disorder. One of the major alleles ('A1' allele) was significantly more common in patients than in controls (odds ratio 2.8, 95% confidential interval 1.5-5.3, P=0.001). Furthermore, a luciferase reporter gene assay in rat primary cultured neurons suggests that this risk allele (A1) has a lower-transcription activity, compared to the other alleles. Our results suggest that the BDNF-LCPR is a functional variation that confers susceptibility to bipolar disorder and affects transcriptional activity of the BDNF gene.

Adult↗
PubMed2004

No association found between the type 1 sigma receptor gene polymorphisms and methamphetamine abuse in the Japanese population: a collaborative study by the Japanese Genetics Initiative for Drug Abuse.

It has been suggested that individual genetic factors are involved in susceptibility to drug dependence and the manifestation of drug-induced psychosis. The aim of this study was to examine the relation between methamphetamine abusers/psychosis and the type 1 sigma receptor gene polymorphisms. Subjects comprised 143 MAP abusers and 181 healthy controls. Two polymorphisms in the type 1 sigma receptor gene, GC-241-240TT and A61C (Gln2Pro), were examined in the present study. No significant differences were observed in either polymorphism between healthy controls and MAP abusers/psychosis. In the subgroup analyses, the rate of CC genotype of A61C tended to be higher in MAP patients who had experienced spontaneous relapse without MAP use than in those who had not (P = .06, OR = 3.02 95%CI = 0.92-9.92). However, the level of this significant trend did not remain after the Bonferroni's multiple correction. This study suggests that type 1 sigma receptor gene is unlikely to play a major role in substance abuse liability and/or the development of MAP psychosis.

Adult↗
PubMed2002

Non-typhi salmonella in children with severe malaria.

OBJECTIVE: To determine the association between Plasmodium falciparum malaria and non-typhi Salmonella in children. DESIGN: Cross-sectional hospital based study. SETTING: Kilifi District Hospital (KDH) between January 1997 and June 2001. SUBJECTS: Children aged between three months to 123 months (mean age 28.28 months) and who had been admitted to the paediatric or High Dependency Research Ward (HDRW) of the KDH. METHODS: A total of 19, 118 blood cultures routinely obtained for all admissions and 1,820 clinically indicated stools samples were obtained from 9,147 children admitted with malaria. The specimens were cultured and antibiotic sensitivity done using standard laboratory procedures with stringent internal and external quality control in place. RESULTS: The total bacterial pathogens isolated from blood and stool were 1,395/19,118 (7.3%) and 342/1,820 (19%) respectively. Non-typhi salmonella consisted of 260/1,395 (18.6%) of the positive blood cultures and 92/324 (28.4%) of the stool cultures out of which a total of 101 NTS occurred in children with severe malaria. Out of the 9,147 malaria cases admitted, 101/9,147 (1.10%) had concomitant NTS infection. NTS with severe malaria as a proportion of all malaria admissions for the period varied between 0.8% and 1.5%. There was a significant association (p-value=0.032) between clinical outcome of death and female sex of the patient. The NTS isolates which occurred with severe malaria showed various levels of antibiotic resistance. They were resistant to ampicillin (35%), chloramphenicol (18%), gentamicin (22%), cefuroxime (29%), sulphamethoxazole-trimethoprim (39%), ciprofloxacin (3%), cefotaxime (14%), amoxycillin-clavulanic acid (26%) and tobramycin (18.0%). Multidrug resistance (MDR) was seen in 34 (33.6%) of the isolates. CONCLUSIONS: NTS and severe malaria occurring together are a problem in this area and that a large number of the isolates are MDR. An elaborate case-controlled study is required to elucidate the chain of events of both NTS and malaria parasite co-existence.

Age Distribution↗
PubMed2001

Acid resistance of human enamel in vitro after bicarbonate application during remineralization.

OBJECTIVES: The aim of this study was to investigate the acid resistance of subsurface enamel lesions remineralized with bicarbonate solutions during remineralization. METHODS: Two experiments were carried out. In experiment 1, mineral uptake and acid resistance of remineralized enamel lesions were analyzed quantitatively by microradiography for mineral changes. Bicarbonate solutions of 0.5, 5.0 and 50.0 mM were used. In experiment 2, to clarify acid resistance mechanisms, the pH changes in demineralizing solutions on the remineralized enamel surfaces were measured continuously. Only a bicarbonate solution of 5.0 mM was used. RESULTS: In experiment 1, the bicarbonate-treated groups were more acid resistant than the non-treated groups (p<0.05). However, no statistically significant difference was observed among the different concentrations of bicarbonate. In experiment 2, the pH rise of the bicarbonate group was greater than the other groups. CONCLUSION: It was found that bicarbonate-treated enamel lesions were resistant to acid. It would suggest that bicarbonate ions applied during remineralization may have penetrated into the subsurface lesions. These ions may have worked as buffer agents against the acid challenge and inhibited the decrease in pH.

Acids↗
PubMed2001

Effect of interferon therapy on Japanese chronic hepatitis C virus patients with anti-liver/kidney microsome autoantibody type 1.

AIM: The aim of this study was to determine the prevalence of anti-liver/kidney microsome autoantibody type 1 (anti-LKM-1) among hepatitis C virus (HCV)-infected Japanese patients at various stages (chronic hepatitis, liver cirrhosis and hepatocellular carcinoma), and to assess the influence of anti-LKM-1 on interferon therapy. METHODS: A total of 390 serum samples from 215 HCV-infected patients with chronic hepatitis (HCV-CH), 81 HCV-infected patients with liver cirrhosis (HCV-LC), and 94 HCV-HCC infected patients were subjected to examination. Ninety-one HBsAg-positive patients and 137 healthy subjects served as controls. Anti-liver/kidney microsome autoantibody type 1 was determined by using a newly developed ELISA using recombinant cytochrome P450 IID6 as the antigen. RESULTS: Anti-liver/kidney microsome autoantibody type 1 was detected in six of the 390 (1.5%) chronic HCV-infected patients (four were HCV-CH and two were HCV-LC); in contrast, it was not detected in control groups. Among the 110 HCV-CH patients treated with interferon (IFN), four were positive for anti-LKM-1. No change in anti-LKM-1 immunoreactivity from negative to positive during interferon therapy was observed. Moreover, no increase in the serum alanine aminotransferase level was observed in these four patients with anti-LKM-1. CONCLUSION: Our study indicates that: (i) anti-LKM-1 does not aggravate the liver disease associated with HCV infection; and (ii) no change in anti-LKM-1 immunoreactivity from negative to positive or no aggravations of liver dysfunction were observed among HCV-CH patients during the IFN therapy for Japanese patients with liver disease.

Autoantibodies↗
PubMed2001

Familial gastrointestinal stromal tumor with hyperpigmentation: association with a germline mutation of the c-kit gene.

We describe 2 siblings with multiple gastrointestinal stromal tumors (GISTs) and cutaneous hyperpigmentation. Both had a point mutation of the c-kit gene. The patients were sisters who had exhibited cutaneous hyperpigmentation since their late teens, but the diagnosis of multiple gastrointestinal submucosal tumors was not made until they were 41 and 45 years old. Histologic examination showed that these tumors were GISTs expressing CD34 and Kit protein. Both patients died of GISTs. Single-strand conformation polymorphism analysis showed a mutation of c-kit in tumor DNA extracted from paraffin-embedded specimens. Direct sequencing analysis showed that the point mutation occurred at codon 559 of exon 11 (Val-->Ala). The same single-point mutation was detected in DNA extracted from peripheral leukocytes obtained from the younger sister and her 2 children (who had similar general hyperpigmentation) as well as in DNA from a skin biopsy specimen taken from the older sister. The germline mutation at codon 559 of the c-kit gene found in the present familial GISTs differed from that in a previously reported case of familial GISTs. We propose that GISTs caused by a germline mutation of the c-kit gene should be referred to as GIST-cutaneous hyperpigmentation disease.

Adult↗
PubMed2001

Prevention of bacterial diarrhea by pasteurization of drinking water in Kenya.

Diarrheal disease is one of the major causes of morbidity and mortality in developing countries. Drinking water is a primary transmission route of infectious diarrheagenic bacteria in a rural area of Kenya (Microbiol. Immunol. 41: 773-778, 1997). We tried to prevent diarrhea at villages with approximately 1,500 households in Kenya by pasteurizing drinking water. A durable simple thermoindicator which changes color at 70 C was used as an indicator of pasteurization. The number of households in which drinking water was coliform bacteria-free increased from 10.7% to 43.1% after adoption of a pasteurization practice. Consequently, the incidence of severe diarrhea among people drinking pasteurized water was significantly lower than in people taking raw water (odds ratio=0.55, P=0.0016). The reduction ratio of the incidence after pasteurization was nearly equivalent with that after the adoption of a boiling method. Employment of women leaders as fieldworkers and demonstration of bacterial colony disappearance on agar plates by pasteurization also affected reduction of the diarrheal incidence.

Bacterial Infections↗
PubMed2000

A new ETV6/TEL partner gene, ARG (ABL-related gene or ABL2), identified in an AML-M3 cell line with a t(1;12)(q25;p13) translocation.

The ETV6/TEL gene has been reported to fuse to PDGFRbetab MDS1/EVI1, BTL, ACS2, STL, JAK2, ABL, CDX2, TRKC, AML1, and MN1. Among them, PDGFRbeta, ABL, JAK2, and TRKC are tyrosine kinases (TK). We identified a novel ETV6 partner gene, ARG (ABL-related gene or ABL2), another TK gene in a cell line established from a patient with acute myelogenous leukemia (AML-M3) with a t(15;17)(q22;q11.2) and a t(1;12)(q25;p13), which has the remarkable feature to differentiate to mature eosinophils in culture with all-trans retinoic acid and cytokines. The ETV6/ARG transcripts consisted of exon 1 to 5 of ETV6 and the 3' portion of ARG starting from exon 1B or exon 2, resulting in an open reading frame for a fusion protein consisting of the entire PNT oligomerization domain of ETV6 and all of the functional domains of ARG including the TK domain. This is the same protein structure as identified in the other ETV6 TK fusion proteins. The reciprocal ARG/ETV6 transcript was not expressed, and the normal ETV6 allele was not deleted or rearranged. Although the ABL is known to be involved in various human malignancies, ARG has not been involved in human malignancies despite its high homology to ABL. Thus, this is the first report showing involvement of ARG in human leukemia. The ETV6/ARG protein may be involved in the unique differentiation capacity of this cell line. (Blood. 2000;95:2126-2131)

Adaptor Proteins, Signal Transducing↗
PubMed2000

Isolation of 10-hydroxycoronaridine from Tabernaemontana penduliflora and its estrogen-like activity.

The methanol extract of Tabernaemontana penduliflora was found to appreciably inhibit [3H]-estradiol binding to estrogen receptors. Activity-guided fractionation led to the isolation of two known alkaloids, 10-hydroxycoronaridine (1) and its 10-O-methyl ether, voacangine (2). These alkaloids together with other related alkaloids were tested for their estrogenic activities. Among these molecules, 1 was found to be the most potent estrogen agonist and is distinctly more active than genistein.

Cell Division↗
PubMed2000

A contribution to genome-wide association studies: search for susceptibility loci for schizophrenia using DNA microsatellite markers on chromosomes 19, 20, 21 and 22.

As an initial step for genome-wide association studies, we sought an association between schizophrenia and 34 microsatellite markers on chromosomes 19, 20, 21 and 22 by a case-control design. The samples examined for an association were 168 schizophrenic patients and 146 control subjects in the Japanese population. The allele distribution of the 34 loci differed significantly between Japanese and French populations. Significant deviation from the Hardy-Weinberg equilibrium was observed at D19S209 and D21S1256 in the control subjects. Case-control comparisons of the initial screening revealed a significant difference in allele frequency at D20S95 and a trend of difference at D20S118. To confirm these possible associations, additional samples consisting of 110 schizophrenic patients and 116 control subjects were examined, and an association between D20S95 and schizophrenia was confirmed (corrected P value after Bonferroni correction, 0.00035). D20S95 is located close to the gene (CHGB) encoding chromogranin B. These findings suggest that CHGB could be an important candidate gene involved in the development of schizophrenia.

Case-Control Studies↗
PubMed2000

A functional angiotensin II receptor-GFP fusion protein: evidence for agonist-dependent nuclear translocation.

We constructed an expression vector for a fusion protein [ANG II type 1a receptor-green fluorescent protein (AT(1a)R-GFP)] consisting of enhanced GFP attached to the COOH terminus of the rat AT(1a)R. Chinese hamster ovary (CHO) cells transfected with AT(1a)R-GFP demonstrated specific, high-affinity (125)I-labeled ANG II binding (IC(50) 21 nM). ANG II exposure stimulated sodium-proton exchange and cytoplasmic calcium release to a similar extent in cells transfected with AT(1a)R or AT(1a)R-GFP; these responses were desensitized by prior exposure to ANG II and were sensitive to the AT(1)R blocker losartan. ANG II-driven internalization of AT(1a)R-GFP in transfected CHO cells was demonstrated both by radioligand binding and by laser scanning confocal microscopy. Colocalization of GFP fluorescence with that of the nuclear stain TOTO-3 in confocal images was increased more than twofold after 1 h of ANG II exposure. We conclude that AT(1a)R-GFP exhibits similar pharmacological behavior to that of the native AT(1a)R. Our observations also support previous evidence for the presence of AT(1a)R in the nucleus and suggest that the density of AT(1a)R in the nucleus may be regulated by exposure to its ligand.

Angiotensin II↗
PubMed2000

Stereochemistry of cis- and trans-hinokiresinol and their estrogen-like activity.

Naturally occurring phenylpropanoids, hinokiresinol (trans-hinokiresinol) and nyasol (cis-hinokiresinol) were found to possess appreciable estrogen receptor binding activity. Strong differences in activity were observed between the geometrical isomers and enantiomers. Among these, (3S)-cis-hinokiresinol displayed the highest activity, one order of magnitude greater than the activity of genistein. Furthermore, cis- and trans-hinokiresinol stimulated the proliferation of estrogen-dependent T47D breast cancer cells, and their stimulatory effects were blocked by an estrogen antagonist, indicating that the compounds are estrogen agonists. In addition, the absolute configuration of C-3 in (+)-cis-hinokiresinol has been assigned as S by comparison with the circular dichroism spectra of the hydrogenated products prepared from cis and trans ((3S)-trans-hinokiresinol: previously assigned) isomers. These results incidentally provide us with an unambiguous answer to contradictory reports regarding the assignment of the full stereochemisry of cis- and trans-hinokiresinol that have existed in the literature for more than two decades.

Animals↗
PubMed2000

Structures of 4-aryl-coumarin (neoflavone) dimers isolated from Pistacia chinensis BUNGE and their estrogen-like activity.

Activity-guided fractionation of twigs of Pistacia chinensis resulted in the isolation and characterization of two novel ingredients as potent estrogen agonists. On the basis of spectral analysis and comparison with a related compound their structures were elucidated as 3,3''-dimers of 4-aryldihydrocoumarins (3,4-dihydro-4-(4'-hydroxyphenyl)-7-hydroxycoumarin) differing only in the stereochemical disposition of the linkage between the two 4-arylcoumarin moieties. These compounds are the first examples of bis-flavonoids which have been proven to possess estrogen-like activity.

Animals↗
PubMed1999

Diabetes alters neurite regeneration from mouse retinal explants in culture.

We examined the effect of experimental diabetes on neurite regeneration from adult mouse retinal explants cultured in the presence of different concentrations of glucose. The numbers of regenerating neurites at 3, 6 and 10 days in culture at normal glucose concentration (7 mM) were significantly smaller in streptozotocin-induced diabetic C57BL/6 mice than in normal control mice. In contrast, treatment of retinal explants with high glucose concentration (57 mM) significantly diminished the number of regenerating neurites in the control mice, but not in the diabetic mice. These results suggest that retina in diabetic mice has impaired capability of neurite regeneration in a normal glucose environment, but is adaptable to a high glucose environment in vitro.

Animals↗
PubMed1999

Cell-specific targeting of a thymidine kinase/ganciclovir gene therapy system using a recombinant Sindbis virus vector.

Transfer of the herpes simplex virus type I thymidine kinase (HSV-TK) gene into tumor cells using virus-based vectors in conjunction with ganciclovir (GCV) exposure provides a potential gene therapy strategy for the treatment of cancer. The possibility of using a novel targetable Sindbis virus expression vector containing the HSV-TK gene was examined. Baby hamster kidney (BHK) cells and several human tumor cells infected with a Sindbis virus containing the HSV-TK gene showed strong expression of HSV-TK protein. Cells transduced with the HSV-TK gene exhibited increased TK activity, ranging from 3- to 20-fold over an average baseline level. The human HeLa-CD4+ cells infected with recombinant Sindbis virus containing the HSV-TK gene were sensitive to low concentrations of GCV (0.1-1 microg/ml) and the 50% growth inhibitory concentration (IC50) was 0.6 microg/ml. We also demonstrated applications of cell type-specific Sindbis virus-mediated antigen-antibody targeting of the HSV-TK/GCV system in vitro. Sindbis virus containing the HSV-TK gene packaged in a helper virus displaying the IgG-binding domain of protein A on its envelope could infect various tumor cell lines in the presence of specific antibodies that recognize antigens on their surfaces. HSV-TK-transduced tumor cell lines exhibited sensitivity to GCV. Our data suggest the potential for targeted gene therapy of the HSV-TK/GCV system using a cell type-specific recombinant Sindbis virus vector-antibody system.

Animals↗
PubMed1999

High prevalance of TT virus infection in Japanese patients with liver diseases and in blood donors.

BACKGROUND/AIMS: Although a novel DNA virus, TT virus (TTV), has been isolated from a patient with cryptogenic post-transfusion hepatitis, its pathogenic role remains unclear. To elucidate its prevalence and clinical impact in patients with liver diseases, the presence of TTV DNA was assessed in patients with liver diseases and blood donors (BDs) in Japan using two primer sets, one conventional and the other new and highly sensitive. METHODS: We studied 261 samples, 72 with chronic hepatitis associated hepatitis C virus (HCV-CH), 57 with hepatocellular carcinoma associated HCV (HCV-HCC), 12 with HCC without either HCV or hepatitis B virus (NBNC-HCC), and 120 of BDs. RESULTS: Using two primer sets, TTV DNA was detected in 68 (94.4%), 53 (93.0%), 12 (100%), and 98 (81.7%) HCV-CH, HCV-HCC, NBNC-HCC, and BDs, respectively. The prevalence was not significantly different between HCV-CH and HCV-HCC, or between HCV-HCC and NBNC-HCC. Comparison between patients with and without TTV revealed no significant differences in backgrounds or biochemical findings. Histopathological findings in patients with HCV-CH, and number, maximum diameter, and histological differentiation of HCC also did not demonstrate any relation to TTV infection. TTV strains can be divided into five groups using phylogenetic analysis, but no disease-specific group appears to exist. CONCLUSIONS: Our data suggest that: 1) TTV is very prevalent among patients with liver diseases and even among BDs in Japan, 2) TTV infection does not impact on liver damage with HCV infection, and 3) TTV infection also does not affect the development or progression of HCC.

Adult↗