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1.
Front Psychiatry ; 14: 1275043, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38025415

RESUMO

Background: There is a rising interest in perinatal mental health studies, and proper psychometric tools to assess autistic traits among this population in Japan are vital. Objective: This study aimed to clarify the optimal factor structure of the AQ as part of a perinatal mental health research project. Methods: We used the Japanese version of the AQ (AQ-J) to measure autistic-like traits in pregnant women. Participants were 4,287 Japanese women who were pregnant or who had given birth within the last month. We performed exploratory factor analysis (EFA) using the first sample group (n = 2,154) to obtain factor structures for the final item selections. We performed confirmatory factor analysis (CFA) using the second sample group (n = 2,133) to obtain a model with good fit, then compared the model to all previously proposed models to determine the best-fitting model. Results: The EFA analysis identified a model consisting of 25 items distributed across three factors. Cronbach's alpha for the total 25-item AQ-J, 9-item "Social interaction" factor, 11-item "Non-verbal communication" factor, and 5-item "Restricted interest" factor was 0.829, 0.829, 0.755, and 0.576, respectively. McDonald's omega and its 95% confidence interval were 0.826 (0.821-0.836), 0.835 (0.821-0.837), 0.755 (0.744-0.766), and 0.603 (0.556-0.596), respectively. CFA confirmed that the three-factor structure had an acceptable fit (goodness of fit index: 0.900, comparative fit index: 0.860, root mean square error of approximation: 0.066). These findings indicated that the three-factor model was better than the 13 existing models. Conclusion: The findings are discussed in relation to the adequacy of the AQ-J for assessing autistic traits in perinatal women. We recommend the use of this 25-item, three-factor AQ-J model for this population owing to its superiority to all previous models.

2.
Sci Rep ; 13(1): 15684, 2023 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-37735197

RESUMO

This study aimed to determine how paternal and maternal parenting before adolescence affects adult attachment to a partner during the perinatal period, using three different models of attachment. We used the Parental Bonding Instrument (PBI) and the Relationship Questionnaire (RQ) to examine perceived parenting practices and adult attachment styles, respectively. The participants included 4586 Japanese women who were pregnant or who had given birth, up until one month after childbirth. We performed structural equation modeling analysis between PBI and RQ scores with three different category models, including the four-category model (secure, fearful, preoccupied, and dismissive attachment) as Model 1, the two-category model (model of the self and others) as Model 2, and the single-category model (total attachment style) as Model 3. Models 1 and 2 showed a good fit. Both path models showed a significant association between adult attachment style and perceived paternal and maternal parenting before adolescence, where high care and low overprotection from both paternal and maternal parents predicted adult attachment. Our findings indicate that attachment styles are best described using the four-category and two-category models, and suggest that both paternal and maternal overprotection and care influence adult attachment with a partner during the perinatal period.


Assuntos
População do Leste Asiático , Relações Interpessoais , Apego ao Objeto , Poder Familiar , Pais , Gravidez , Adulto , Feminino , Humanos , Gravidez/psicologia , Parto Obstétrico , População do Leste Asiático/psicologia , Medo , Poder Familiar/psicologia , Pais/psicologia , Criança , Período Periparto/psicologia
3.
BMC Psychiatry ; 23(1): 463, 2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-37365599

RESUMO

BACKGROUND: Although several studies have found significant relationships between autistic traits and depression/anxiety, the relationships between autistic traits and postpartum depression/anxiety remain unclear. Moreover, few studies have examined the relationships between autistic traits and mother-infant bonding while considering depression or anxiety. METHODS: This study used a cross-sectional data analysis design. Participants were 2692 women who completed the Autism-Spectrum Quotient (AQ), Hospital Anxiety and Depression Scale (HADS), and Mother-to-Infant Bonding Scale (MIBS) at 1 month postpartum. We performed path analysis that included parity, the five AQ subscales (social skills, attention switching, attention to detail, communication, and imagination), both HADS subscales (anxiety and depression), and the two MIBS subscales (lack of affection and anger and rejection). RESULTS: Our path analysis revealed that higher scores for social skills, attention switching, communication, and imagination were associated with higher scores for depression. Higher scores for social skills, attention switching, attention to detail, and communication were associated with higher scores for anxiety. Moreover, difficulties in social skills and imagination were associated with failure of maternal-infant bonding. However, more attention to detail was associated with better maternal-infant bonding. CONCLUSIONS: This study suggests that maternal autistic traits are related to anxiety and depression to a certain degree, but only slightly related to maternal-infant bonding at 1 month postpartum. To improve autistic women's quality of life and that of their newborns, perinatal mental health issues such as anxiety, depression, and maternal-fetal bonding difficulties should be appropriately addressed.


Assuntos
Transtorno Autístico , Depressão Pós-Parto , Gravidez , Humanos , Feminino , Lactente , Recém-Nascido , Depressão , Estudos Transversais , Qualidade de Vida , Período Pós-Parto , Depressão Pós-Parto/psicologia , Ansiedade/psicologia , Mães/psicologia , Apego ao Objeto , Relações Mãe-Filho
4.
Am J Case Rep ; 24: e939200, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37143323

RESUMO

BACKGROUND Coronary artery pseudoaneurysm is an extremely rare condition. In this report, we describe an 85-year-old hemodialysis male patient who developed a coronary artery pseudoaneurysm due to physical damage associated with coronary artery calcification. CASE REPORT An 85-year-old man on hemodialysis had undergone emergency percutaneous coronary intervention of the left anterior descending artery for acute coronary syndrome 9 years ago. He presented to the emergency room with a fever and chest pain and was admitted to the cardiology department with a urinary tract infection and acute coronary syndrome. On day 21 after admission, when the urinary tract infection had resolved, coronary angiography was performed, which revealed a pseudoaneurysm proximal to the left anterior descending artery stent. The patient was scheduled to undergo surgery due to the pseudoaneurysm's risk of rupture. Surgical manipulation was performed under cardiac arrest using the median sternotomy approach. A highly calcified coronary intima was found inside the pseudoaneurysm, which was completely ruptured on the proximal side of the pseudoaneurysm. The pseudoaneurysm was closed after endarterectomy. A coronary artery bypass graft was also performed in the great saphenous vein graft of the left anterior descending artery. Histopathological examination showed no obvious signs of infection, and a diagnosis of pseudoaneurysm was established. Postoperative contrast-enhanced computed tomography showed patency of the coronary artery bypass graft and no pseudoaneurysm recurrence. CONCLUSIONS Coronary artery pseudoaneurysms are extremely rare, but this case demonstrates that atherosclerotic changes can lead to the formation of a pseudoaneurysm in an elderly hemodialysis patient.


Assuntos
Síndrome Coronariana Aguda , Falso Aneurisma , Doença da Artéria Coronariana , Humanos , Masculino , Idoso , Idoso de 80 Anos ou mais , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/complicações , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Falso Aneurisma/cirurgia , Diálise Renal/efeitos adversos , Ruptura
5.
Sci Rep ; 12(1): 19071, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36351967

RESUMO

The parental bonding instrument (PBI) is often used to examine the perceptions of children and adolescents regarding parenting practices. Previous studies have investigated the factor structure of the PBI. However, although it is important to examine the relationships between the perceived parenting practices and perinatal mental health, few studies have included perinatal women. We aimed to accurately clarify which PBI factor structure was useful in assessing perinatal women (n = 4633). Furthermore, we evaluated the measurement invariance between primipara and multipara groups, and between the paternal and maternal PBI forms. Our exploratory and confirmatory factor analyses revealed that a three-factor PBI structure was most plausible for perinatal women. Moreover, we found complete invariance (residual invariance) of the PBI ratings across primipara and multipara women for the paternal and maternal forms. In contrast, we found weak invariance (metric invariance) of the PBI ratings across the paternal and maternal forms. Our participants tended to rate fathers as less caring and less overprotective than mothers. This three-factor structure shows measurement invariance in perinatal women and can be used to accurately determine how the perceived parenting style before adolescence influences women's mental health in the perinatal period.


Assuntos
Apego ao Objeto , Poder Familiar , Criança , Adolescente , Masculino , Humanos , Feminino , Gravidez , Japão , Inquéritos e Questionários , Poder Familiar/psicologia , Pai , Relações Pais-Filho
6.
Mol Genet Genomic Med ; 10(3): e1884, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35128829

RESUMO

Carney complex (CNC) is a rare hereditary syndrome that involves endocrine dysfunction and the development of various types of tumors. Chromosome 2p16 and PRKAR1A on chromosome 17 are known susceptibility loci for CNC. Here we report a mother and son with CNC caused by an 8.57-kb deletion involving the transcription start site and non-coding exon 1 of PRKAR1A. The proband is a 28-year-old male with bilateral large-cell calcified Sertoli cell testicular tumors and pituitary adenoma. Comprehensive genomic profiling for cancer mutations using Foundation One CDx failed to detect any mutations in PRKAR1A in DNA from the testicular tumor. Single-nucleotide polymorphism array analysis of the proband's genomic DNA revealed a large deletion in the 5' region of PRKAR1A. Genomic walking further delineated the region an 8.57-kb deletion. A 1.68-kb DNA fragment encompassed by the deleted region showed strong promoter activity in a NanoLuc luciferase reporter assay. The patient's mother, who is suffering from recurrent cardiac myxoma, a critical sign for CNC, carried an identical deletion. The 8.57-kb deleted region is a novel lesion for CNC and will facilitate molecular diagnosis of the disease.


Assuntos
Complexo de Carney , Mixoma , Adulto , Complexo de Carney/diagnóstico , Complexo de Carney/genética , Complexo de Carney/patologia , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Éxons , Humanos , Luciferases , Masculino , Mixoma/genética , Mixoma/patologia
7.
Neuropsychiatr Dis Treat ; 17: 3407-3413, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34848961

RESUMO

PURPOSE: Identification of pregnant women with bonding difficulties is important to provide early intervention. However, few studies have examined the utility of self-report questionnaires that assess mother-infant bonding as screening tools for bonding difficulties. This longitudinal study aimed to identify pregnant women with bonding difficulties using the Japanese version of the Mother-to-Infant Bonding Scale (MIBS-J) and to estimate its optimal cutoff points in the peripartum period. PATIENTS AND METHODS: A total of 1301 pregnant women completed the MIBS-J and Hospital Anxiety and Depression Scale (HADS) at three time points: first trimester (T1; approximately 12-15 weeks gestation), third trimester (T2; approximately 30-34 weeks gestation), and postpartum (T3; approximately 4 weeks postpartum). A two-step cluster analysis was conducted to classify pregnant women based on their MIBS-J subscale scores at the three time points. Based on the cluster analysis results, receiver operating characteristic curve analysis was performed to estimate the optimal cutoff scores for the MIBS-J total score at each time point. RESULTS: The two-step cluster analysis produced two clusters: Cluster 1 (n = 824) and Cluster 2 (n = 477). Both the MIBS-J and HADS scores were significantly higher in Cluster 2 than in Cluster 1 at all time points. The MIBS-J tentative cutoff points were 3/4, 3/4, and 2/3 at T1, T2, and T3, respectively. CONCLUSION: We identified two distinct groups across the perinatal period: pregnant women with bonding difficulties and pregnant women with normal bonding. Our findings suggest the usefulness of the MIBS-J as a screening tool to identify bonding difficulties during pregnancy.

8.
Psychiatry Clin Neurosci ; 75(10): 312-317, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34314089

RESUMO

AIM: This study was aimed towards detecting how perceived parenting practices before adolescence affect maternal-infant bonding in the perinatal period, considering factors such as depression, anxiety, and parity. METHODS: We used the Parental Bonding Instrument (PBI) to examine perceived parenting practices. Participants included 1301 pregnant women who completed the Hospital Anxiety and Depression Scale (HADS) and Mother-to-Infant Bonding Scale (MIBS) at three time points: early pregnancy (approximately 12-15 weeks), late pregnancy (approximately 30-34 weeks) and postpartum (4 weeks after childbirth). We performed a path analysis with factors including parity, PBI subscales (paternal care, paternal overprotection, maternal care and maternal overprotection), HADS and MIBS. RESULTS: Perceived paternal or maternal low care parenting predicted higher HADS and MIBS scores in early pregnancy. Moreover, perceived maternal low care parenting predicted higher HADS scores at postpartum and higher MIBS scores in late pregnancy. Perceived paternal or maternal overprotective parenting predicted higher HADS scores in the pregnancy period. Furthermore, perceived maternal overprotective parenting predicted higher MIBS scores in late pregnancy. Being primipara predicted higher HADS scores at postpartum and higher MIBS scores in early pregnancy and at postpartum. Being multipara predicted higher MIBS scores in late pregnancy. CONCLUSION: This study suggests that perceived negative parenting before adolescence has indirect effects (via anxiety and depression) and direct effects on maternal-infant bonding in the perinatal period.


Assuntos
Ansiedade , Depressão , Relações Mãe-Filho/psicologia , Mães/psicologia , Apego ao Objeto , Poder Familiar/psicologia , Paridade , Complicações na Gravidez/psicologia , Adolescente , Adulto , Depressão Pós-Parto/psicologia , Feminino , Humanos , Recém-Nascido , Japão , Masculino , Comportamento Materno , Comportamento Paterno , Gravidez
9.
Nutrients ; 13(4)2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33918430

RESUMO

It is important to clarify how the breastfeeding method affects women's mental health, and how women's mental health affects the breastfeeding method in the early postpartum period when major depression and other psychiatric problems are most likely to occur. This study aimed to examine this bidirectional relationship in the early postpartum period. Participants were 2020 postpartum women who completed the Hospital Anxiety and Depression Scale (HADS) and Mother-to-Infant Bonding Scale (MIBS). We obtained data for participants' breastfeeding method for four weeks after childbirth. We performed a path analysis with factors including breastfeeding method (exclusive breastfeeding or non-exclusive breastfeeding), parity (primipara or multipara), the two HADS subscales (anxiety and depression), and the two MIBS subscales (lack of affection and anger and rejection). The path analysis showed that breastfeeding method did not significantly affect depression, anxiety, and maternal-infant bonding in the early postpartum period. Women with higher anxiety tended to use both formula-feeding and breastfeeding. Our study suggests that exclusive breastfeeding is not associated with maternal-fetal bonding in early postpartum, considering depression, anxiety, and parity.


Assuntos
Ansiedade/psicologia , Aleitamento Materno/psicologia , Depressão Pós-Parto/psicologia , Relações Mãe-Filho/psicologia , Período Pós-Parto/psicologia , Adulto , Feminino , Humanos , Recém-Nascido , Apego ao Objeto , Paridade , Gravidez , Escalas de Graduação Psiquiátrica
10.
Neuropsychiatr Dis Treat ; 17: 221-227, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33531811

RESUMO

PURPOSE: The Hospital Anxiety and Depression Scale (HADS) is a self-report questionnaire widely used to assess anxiety and depression. To the best of our knowledge, only four studies have examined the factor structure of the HADS for assessing pregnant women, with conflicting results. This study aimed to assess the factor structure and measurement invariance of the HADS for use with pregnant Japanese women. PARTICIPANTS AND METHODS: A total of 936 pregnant Japanese women completed the HADS questionnaire at three time points: the first and third trimester of pregnancy, and postpartum. We examined the factor structure of the HADS in Group 1 (n = 466) using exploratory factor analysis (EFA). We then compared the models identified in Group 1 with those from previous studies using confirmatory factor analysis (CFA) in Group 2 (n = 470). We performed multiple-group CFA for Group 2 to test the measurement invariance of the best-fit model across the three time points. RESULTS: The EFA for the Group 1 data at the three time points revealed a two-factor model. In the CFA, the two-factor model from Group 1 showed the best fit with the data at the three time points. In the multiple-group CFA for Group 2, we confirmed the configural and metric invariance of the two-factor model across the three time points. CONCLUSION: Our findings provide evidence for a two-factor structure and weak measurement invariance of the HADS in pregnant Japanese women during the peripartum period.

11.
Neuropsychiatr Dis Treat ; 16: 3117-3122, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33364763

RESUMO

PURPOSE: Postpartum depression is a well-known risk factor, and postpartum anxiety and parity are potential risk factors, for mother-infant bonding disorder. However, few studies have focused on the relationships among these factors and mother-infant bonding. This cross-sectional study explored the associations between depression, anxiety and parity, and mother-infant bonding. MATERIALS AND METHODS: Japanese mothers, both primiparas and multiparas, completed the Mother-to-Infant Bonding Scale (MIBS) and the Hospital Anxiety and Depression Scale (HADS) one month after childbirth. We performed a stepwise multiple regression analysis with the forward selection method to assess the effects of HADS anxiety and depression scores and parity as independent variables on mother-infant bonding as the dependent variable. RESULTS: A total of 2379 Japanese mothers (1116 primiparas and 1263 multiparas) took part in the study. MIBS score (2.89 ± 2.68 vs 1.60 ± 2.11; p < 0.0001) was significantly higher in primiparas than in multiparas. HADS anxiety (6.55 ± 4.06 vs 4.63 ± 3.41; p < 0.0001) and depression (6.56 ± 3.43 vs 5.98 ± 3.20; p < 0.0001) scores were also significantly higher in primiparas than in multiparas. A stepwise multiple regression analysis with the forward selection method revealed that HADS depression and anxiety scores and parity were significantly associated with MIBS score (p = 0.003, 0.015 and 0.023). CONCLUSION: Depression, anxiety and primiparity were negatively associated with mother-infant bonding one month after childbirth.

12.
Molecules ; 25(9)2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32397331

RESUMO

We describe a patterned surface-enhanced Raman spectroscopy (SERS) substrate with the ability to pre-concentrate target molecules. A surface-adsorbed nanosphere monolayer can serve two different functions. First, it can be made into a SERS platform when covered by silver. Alternatively, it can be fashioned into a superhydrophobic surface when coated with a hydrophobic molecular species such as decyltrimethoxy silane (DCTMS). Thus, if silver is patterned onto a latter type of substrate, a SERS spot surrounded by a superhydrophobic surface can be prepared. When an aqueous sample is placed on it and allowed to dry, target molecules in the sample become pre-concentrated. We demonstrate the utility of the patterned SERS substrate by evaluating the effects of inhibitors to acetylcholinesterase (AChE). AChE is a popular target for drugs and pesticides because it plays a critical role in nerve signal transduction. We monitored the enzymatic activity of AChE through the SERS spectrum of thiocholine (TC), the end product from acetylthiocholine (ATC). Inhibitory effects of paraoxon and carbaryl on AChE were evaluated from the TC peak intensity. We show that the patterned SERS substrate can reduce both the necessary volumes and concentrations of the enzyme and substrate by a few orders of magnitude in comparison to a non-patterned SERS substrate and the conventional colorimetric method.


Assuntos
Acetilcolinesterase/química , Carbaril/química , Inibidores da Colinesterase/química , Paraoxon/química , Análise Espectral Raman
13.
Case Rep Obstet Gynecol ; 2019: 6753184, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31662930

RESUMO

BACKGROUND: Fetal akinesia refers to a broad spectrum of disorders with reduced or absent fetal movements. There is no established approach for prenatal diagnosis of the cause of fetal akinesia. Chromosome 1p36 deletion syndrome is the most common subtelomeric terminal deletion syndrome, recognized postnatally from typical craniofacial features. However, the influence of chromosome 1p36 deletion on fetal movements remains unknown. CASE REPORT: A 32-week-old fetus with akinesia showed multiple abnormalities, including fetal growth restriction, congenital cardiac defects, and ventriculomegaly. G-banding analysis using cultured amniocytes revealed 46,XY,22pstk+. Postnatal whole exome sequencing and subsequent chromosomal microarray identified a 3 Mb deletion of chromosomal region 1p36.33-p36.32. These results of molecular cytogenetic analyses were consistent with the fetal sonographic findings. CONCLUSION: Using the exome-first approach, we identified a case with fetal akinesia associated with chromosome 1p36 deletion. Chromosome 1p36 deletion syndrome may be considered for differential diagnosis in cases of fetal akinesia with multiple abnormalities.

14.
Urol Case Rep ; 20: 67-69, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30009133

RESUMO

We report a case with prostate cancer and gastric neuroendocrine carcinoma. A 72-year old male presented with a gastric lesion 5 months after radical prostatectomy. The lesion was immunohistochemically positive for PSA, alpha-methylacyl-CoA racemase, synaptophysin, and chromogranin A, but negative for androgen receptor (AR). Differentiating gastric neuroendocrine carcinoma from gastric metastasis of prostate cancer is difficult, as both lesions exhibit similar acinar cell proliferation with prominent nucleoli.1 We discuss the diagnostic process of this case and how AR was a useful specific marker for diagnosing primary gastric neuroendocrine carcinoma.

15.
J Cardiol Cases ; 2(3): e119-e122, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30532808

RESUMO

A 74-year-old female was admitted to our hospital due to prolonged chest pain that had lasted about 2 h. An electrocardiogram revealed ST-elevation in leads I, aVL, and V3-6, with an increase in myocardial necrosis markers. Emergency coronary angiography was performed, and left ventriculography showed the typical features of apical ballooning, and so a diagnosis of Takotsubo cardiomyopathy (TC) was made. On the 10th day after admission, the patient suddenly went into cardiopulmonary arrest because of a blow-out type left ventricular (LV) free wall rupture. Despite extensive cardiopulmonary resuscitation, the patient died. The autopsy revealed hemopericardium and a perforating wound located in the anterior wall of the LV. It was revealed that the diagonal branch of the coronary artery was occluded, and so a diagnosis of TC coexisting with acute myocardial infarction (AMI) was made. No previous case of TC accompanied by AMI has been reported. We present its clinical course during hospitalization and the result of a histopathologic examination.

17.
J Laryngol Otol ; 120(2): e13, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16917990

RESUMO

We present a patient suffering from salivary duct carcinoma in the mobile portion of the tongue, arising from a minor salivary gland; this condition is extremely rare. The patient was a 64-year-old woman who presented with a nonpainful, hard mass in her tongue. An aspiration smear showed cells with very scant cytoplasm and pale oval nuclei containing small, single nucleoli. Scattered clusters of small cells had darkly stained nuclei. Neither necrosis nor cribriform areas were seen. The smears suggested a salivary gland neoplasm; however, definitive diagnosis of salivary duct carcinoma remained difficult. Partial glossectomy was performed with a wide margin. Macroscopic examination revealed an unencapsulated, submucosal tumour infiltrating underlying muscle. Microscopic examination revealed a salivary duct carcinoma with comedonecrosis and relatively few cribriform and papillary areas. This case suggests that it may not be easy to establish a definitive diagnosis of salivary duct carcinoma from an aspiration smear if the salivary duct carcinoma is composed of comedonecrosis surrounded by solid tissue in a noncribriform pattern.


Assuntos
Ductos Salivares/patologia , Neoplasias das Glândulas Salivares/patologia , Neoplasias da Língua/patologia , Língua/patologia , Carcinoma Ductal/patologia , Carcinoma Ductal/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Necrose , Neoplasias das Glândulas Salivares/cirurgia , Glândulas Salivares Menores/patologia , Língua/cirurgia , Neoplasias da Língua/cirurgia , Resultado do Tratamento
19.
FEBS Lett ; 573(1-3): 226-30, 2004 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-15328002

RESUMO

Human histamine H1 receptor (H1R) contains five possible phosphorylation residues (Thr140, Thr142, Ser396, Ser398 and Thr478) and the substitution of all these five residues to alanine completely impairs agonist-induced receptor downregulation. In the present study, to determine which residue(s) are responsible for receptor downregulation, we used mutant H1Rs in which single or multiple residues were substituted with alanine. The results suggested that two groups, i.e., residues Thr140 and Thr142, and residues Ser396 and Ser398, independently contributed to H1R downregulation. Thr140 and Ser398 mainly contributed to downregulation, and Thr142 or Ser396 had a slight inhibitory effect on Thr140- or Ser398-mediated process, respectively.


Assuntos
Regulação para Baixo , Receptores Histamínicos H1/química , Receptores Histamínicos H1/metabolismo , Serina/metabolismo , Treonina/metabolismo , Sequência de Aminoácidos , Animais , Células CHO , Cricetinae , Regulação para Baixo/efeitos dos fármacos , Histamina/farmacologia , Humanos , Dados de Sequência Molecular , Mutação/genética , Conformação Proteica , Receptores Histamínicos H1/genética , Serina/genética , Treonina/genética
20.
J Pharmacol Sci ; 94(4): 410-9, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15107581

RESUMO

The histamine H(1) receptor (H1R) level is dynamically regulated in vivo under various physiological and pathological conditions. The H1R regulation may consist of various processes, and this study focused on the process of receptor trafficking, that is, receptor internalization to endosomes and the following receptor degradation. First, we identified five possible phosphorylation residues of human H1R, Thr(140), Thr(142), Ser(396), Ser(398), and Thr(478), based on in vitro phosphorylation studies. Then to determine the role of these residues, we constructed a mutant H1R in which all of these five residues were substituted with alanine. Both wild-type and the mutant receptors expressed in Chinese hamster ovary (CHO) cells had similar values of K(d) for [(3)H]mepyramine binding and K(i) for histamine, and these cells showed similar levels of histamine-stimulated inositol phosphate formation. Both types of H1Rs were internalized essentially in the same way upon stimulation with histamine (100 microM) for 30 min. However, down-regulation of the mutant H1R was completely impaired, whereas that of wild-type H1R occurred by approximately 60% by the treatment with 100 microM histamine for 24 h. These results suggest that these residues are responsible for receptor down-regulation but not for receptor internalization. Possibly, phosphorylation of the residues is required for receptor transport from endosomes to lysosomes.


Assuntos
Aminoácidos/química , Aminoácidos/genética , Regulação para Baixo/efeitos dos fármacos , Agonistas dos Receptores Histamínicos/farmacologia , Pirilamina/farmacologia , Receptores Histamínicos H1/química , Receptores Histamínicos H1/metabolismo , Alanina/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Células CHO , Cricetinae , Cricetulus , Endocitose , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Cinética , Dados de Sequência Molecular , Fosforilação , Fosfotransferases/metabolismo , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Pirilamina/metabolismo , Receptores Histamínicos H1/genética , Homologia de Sequência de Aminoácidos
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