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1.
Internet Interv ; 28: 100515, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35242595

RESUMO

Few studies have compared the effectiveness of internet-based cognitive behavior therapy (ICBT) for obsessive-compulsive disorder (OCD) with treatment as usual (TAU). We investigated the effectiveness of guided ICBT for patients with OCD. This prospective, randomized, controlled, assessor-blinded, multicenter clinical trial was conducted at three facilities in Japan from January 2020 to March 2021. Thirty-one patients with OCD as the primary diagnosis participated in the trial and were randomly assigned to either the intervention group or the control group. The primary outcome was the Yale-Brown obsessive-compulsive scale score; the assessors were blinded. Results of the analysis of covariance among the groups were significantly different between the groups (p < 0.01, effect size Cohen's d = 1.05), indicating the superiority of guided ICBT. The results suggest that guided ICBT is more effective than TAU for treating OCD. RCT REGISTRATION: UMIN Clinical Trials Registry (UMIN000039375).

2.
J Agric Food Chem ; 58(21): 11218-25, 2010 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-20931972

RESUMO

The aim of this study is to investigate the biodistribution of phosphatidylinositol (PI) after oral administration and its anti-obesity effect. When a suspension of radiolabeled PI was orally administered to mice and the biodistribution was examined, PI radioactivity accumulated in the liver compared to myo-inositol radioactivity at 48 h or later after administration. Then, a PI suspension was orally administered to diet-induced obesity (DIO) mice every 4 days, and the anti-obesity effect of PI was examined. As a result, PI suppressed the body weight increase of DIO mice and significantly reduced the plasma levels of aspartate aminotransferase (AST) and cholesterol. Furthermore, PI regulated the expression of some genes in the liver involved in lipid synthesis and metabolism. The present study demonstrated that PI accumulated in the liver after oral administration and exerted its anti-obesity effect on DIO by regulating the expression of certain genes involved in lipid metabolism in the liver.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Obesidade/tratamento farmacológico , Fosfatidilinositóis/administração & dosagem , Animais , Fármacos Antiobesidade/farmacocinética , Expressão Gênica/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , Fosfatidilinositóis/farmacocinética , Distribuição Tecidual
3.
Cancer Lett ; 270(2): 260-8, 2008 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-18555591

RESUMO

Previously, we identified angiogenic vessel-homing peptide Ala-Pro-Arg-Pro-Gly (APRPG), and showed that APRPG-modified liposomes could selectively target to tumor neovasculature. Here, we designed an APRPG-modified liposome encapsulating SU5416, an angiogenesis inhibitor, to overcome the solubility problem, and to enhance the antiangiogenic activity of SU5416. Liposomal SU5416 appeared to have the appropriate characteristics, such as particle size and stability in serum. It showed a significantly lower hemoglobin release than SU5416 dissolved in a Cremophor EL-containing solvent. Compared with peptide-unmodified liposomal SU5416, the APRPG-modified liposomal SU5416 significantly suppressed tumor growth and with no remarkable side effects. Thus, targeted delivery of antiangiogenic drugs with tumor vasculature-targeted liposomes may be useful for antiangiogenic cancer therapy.


Assuntos
Inibidores da Angiogênese/farmacologia , Neoplasias do Colo/tratamento farmacológico , Indóis/farmacologia , Pirróis/farmacologia , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/química , Inibidores da Angiogênese/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/irrigação sanguínea , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Relação Dose-Resposta a Droga , Composição de Medicamentos , Estabilidade de Medicamentos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Hemólise/efeitos dos fármacos , Humanos , Indóis/administração & dosagem , Indóis/química , Indóis/metabolismo , Lipídeos/química , Lipossomos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Tamanho da Partícula , Pirróis/administração & dosagem , Pirróis/química , Pirróis/metabolismo , Solubilidade , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/metabolismo
4.
Am J Med Genet A ; 146A(10): 1241-7, 2008 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-18384145

RESUMO

We describe two new cases of pure 1q terminal deletions. BAC FISH analysis precisely defined the size of deletions. The first is a girl with 10.3-Mb deletion showed typical features of 1q43 deletion as well as a simplified gyral pattern, which was rarely found in 1q43 deletion. The other boy also presented with most of 1q43 deletion features but several atypical symptoms were noted including hydrocephalus, adducted thumbs, and flexion restriction of proximal interphalangeal joints in left hand. A concomitant novel missense mutation in L1CAM was identified in addition to 11.5-Mb deletion. Reviewing all the cases of pure 1q terminal deletion in the literature suggests that it is a clinically recognizable syndrome.


Assuntos
Encéfalo/anormalidades , Deleção Cromossômica , Transtornos Cromossômicos , Cromossomos Humanos Par 1/genética , Adulto , Pré-Escolar , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/fisiopatologia , Cromossomos Artificiais Bacterianos , Feminino , Humanos , Hidrocefalia/genética , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Molécula L1 de Adesão de Célula Nervosa/genética
5.
Am J Med Genet A ; 128A(2): 133-7, 2004 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-15214003

RESUMO

We analyzed five patients with inverted duplication deletion of 8p [inv dup del(8p)] using fluorescence in situ hybridization (FISH) and short tandem repeat polymorphism (STRP) analysis. In all patients, inv dup del(8p) consisted of a deleted distal segment, an intact in-between segment, and a duplicated proximal segment. In all of them, the proximal breakpoint of the deletion and one of the breakpoints of the duplication were identical, each located at one of the two olfactory receptor gene clusters at 8p23. FISH analysis showed all their mothers to be heterozygous carriers of an 8p23 inversion [inv(8)(p23)]. STRP analysis indicated that the deletions occurred in maternally derived chromosomes. The duplicated segments had two copies of maternal, either heterozygous or homozygous alleles. These findings support and reinforce those in 16 patients with inv dup del(8p) and their parents by Floridia et al. [1996: Am J Hum Genet 58:785-796] and subsequent additional studies of 10 of them by Giglio et al. [2001: Am J Hum Genet 68:874-883]. Based on these findings, we propose a model for the inv dup del(8p) formation. The inverted segment and its normal counterpart in inv(8)(p23) heterozygous carrier mothers form a loop at the pachytene period of meiosis I. Inv dup del(8p) with heterozygous duplication is formed through at least one meiotic recombination within the loop. Inv dup del(8p) with the homozygous duplication arises through two meiotic recombinations on the inv(8)(p23) chromosome (one within the loop and the other between the loop and centromere). Subsequent rescue by eliminating a part of the duplicated segment and a centromere enables formation of viable inv dup del(8p). The frequency of the inv(8)(p23) allele is 39% in a normal Japanese population, comparable to 26% in Europeans Giglio et al. [2001: Am J Hum Genet 68:874-883]. The proposed mechanism of formation of inv dup del(8p) requires two independent events (a recombination within the loop and subsequent rescue), which may explain its rarity.


Assuntos
Hibridização in Situ Fluorescente , Polimorfismo Genético , Anormalidades Múltiplas/genética , Alelos , Cromossomos Humanos Par 8 , DNA/química , DNA/metabolismo , Feminino , Deleção de Genes , Duplicação Gênica , Frequência do Gene , Genótipo , Heterozigoto , Homozigoto , Humanos , Deficiência Intelectual/genética , Japão , Masculino , Meiose , Modelos Genéticos , Mães , Família Multigênica , Recombinação Genética
6.
Am J Med Genet A ; 120A(4): 557-61, 2003 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-12884439

RESUMO

A 5-year-old girl with developmental and growth retardation is reported with complex chromosome rearrangements consisting of a partial Xq deletion and an abnormal chromosome 3 with multiple breakpoints. GTG-banding, and multiplex and conventional FISH studies showed that a 6.6-Mb Xq22-q23 segment was inserted into 3q, in addition to three intrachromosomal insertions in chromosome 3. Her karyotype was thus interpreted as 46,X,der(X)(Xpter-->Xq22::Xq23-->Xqter),der(3)(3pter-->3p26::3p12-->3q25.3::3p12-->3p26::Xq22-->Xq23::3q25.3-->3qter). Replication R-banding study showed that the der(X) was inactivated in all blood lymphocytes analyzed. Methylation-specific PCR at the androgen receptor gene (HUMARA) locus at Xq11-q12 showed a skewed inactivation pattern with the active/inactive X chromosome ratio of 92/8. These data indicated the presence, in the majority of cells, of a functioning Xq22-q23 segment in both the normal X and the der(3) chromosomes. Her growth retardation, developmental delay, and other minor anomalies were most likely caused by dosage effects of the genes in the functionally disomic Xq22-q23 region. Despite the presence of two active copies of the proteolipid protein 1 gene (PLP1), she did not show the symptoms of Pelizaeus-Merzbacher disease, a subset of which has been known to be caused by the duplication of PLP1.


Assuntos
Anormalidades Múltiplas/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 3 , Cromossomos Humanos X , Aberrações dos Cromossomos Sexuais , Aneuploidia , Pré-Escolar , Bandeamento Cromossômico , Deleção Cromossômica , Mecanismo Genético de Compensação de Dose , Feminino , Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Translocação Genética
7.
Genomics ; 82(2): 238-44, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12837273

RESUMO

To characterize a submicroscopic, common 8p23 polymorphic inversion, we constructed a complete BAC/PAC-based physical map covering the entire 4.7-Mb inversion and its flanking regions. Two low-copy repeats (LCRs), REPD (approximately 1.3 Mb) and REPP (approximately 0.4 Mb), were identified at each of the inversion breakpoints. Comparison of the REPD and REPP sequences revealed that REPD showed high homology to REPP, with complex direct and inverted orientations. REPD and REPP contain six and five olfactory receptor gene-related sequences, respectively. LCRs at 8p23 showed multiple FISH signals from an Old World monkey to the human. Thus, multiplication of the LCR may have occurred at least 21-25 million years ago. We also investigated the frequency of the 4.7-Mb inversion in the general Japanese population and found that the allele frequency for the 8p23 inversion was estimated to be 27%.


Assuntos
Inversão Cromossômica , Mapeamento Cromossômico , Cromossomos Humanos Par 8/genética , Receptores Odorantes/genética , Sequências Repetitivas de Ácido Nucleico/genética , Mapeamento de Sequências Contíguas , Evolução Molecular , Frequência do Gene , Humanos , Hibridização in Situ Fluorescente , Japão
8.
Am J Med Genet ; 111(3): 285-8, 2002 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-12210324

RESUMO

We describe a duplication of the 8p23.2 band in seven individuals from four families. The duplication was recognizable as an enlarged 8p23.2 band on G-banded chromosomes at the 550 band level. It was transmitted from a parent to offspring in three of the four families in which both parents were karyotyped. Each proband in the four families had the enlarged band and showed various phenotypic abnormalities, but the abnormalities were inconsistent. Chromosomal and interphase fluorescence in situ hybridization (FISH) analysis of the enlarged band region defined a 2.5-Mb duplicated segment common to all seven individuals studied. Interphase FISH analysis of peripheral blood lymphocytes from 50 unrelated normal individuals showed the duplication in three individuals. In view of these findings, it is most likely that the 8p23.2 duplication we described is a normal variant.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 8 , Duplicação Gênica , Criança , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Cariotipagem , Masculino
9.
Am J Med Genet ; 108(3): 182-6, 2002 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-11891682

RESUMO

We report on five cases of de novo structural chromosome rearrangements that were difficult to identify by conventional G-banding analysis. In all five cases, differential chromosome painting (DCP) provided evidence for the presence of an additional segment and its origin. A combination of DCP with subsequent conventional fluorescence in situ hybridization (FISH) analysis using adequate locus-specific probes and reexamination of G-banding patterns resulted in successful identification of the rearrangements. Their karyotypes were finally interpreted as 46,XY,der(1)(qter --> q42.1::p36.3 --> qter) in case 1; 46,XY,der(8)(8pter -->8q24.3::8q24.3 --> 8q23.2::?p11.2 --> ?ps) in case 2; 47,XY,+der(10)(pter --> q11) in case 3; 46,XX,der(3)(17pter --> 17p11.2::3p26 --> 3qter) in case 4; and 46,XY,dup(1) (pter --> q32::q25 --> qter) in case 5.


Assuntos
Translocação Genética , Pré-Escolar , Bandeamento Cromossômico , Coloração Cromossômica , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 3/genética , Cromossomos Humanos Par 8/genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
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