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1.
Child Care Health Dev ; 50(1): e13153, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37460209

RESUMO

BACKGROUND: This study aims to determine the extent to which preschool teachers and childcare workers are aware of the presence of developmental problems among children and to what extent they share information with parents about their concerns regarding a child's development or diagnosis of neurodevelopmental disorders (NDDs). METHODS: We wrote to all 924 preschools and childcare centres in Japan's Nagano and Yamanashi prefectures to request participants. We then sent survey forms to the preschools and childcare centres that agreed to cooperate for three grades comprising 3-, 4- and 5-year-olds in the school year 2020. We asked the staff member in charge of each child to complete the survey. The survey included questions about the teacher's concerns regarding the possibility of an NDD and whether the matter had been shared with the children's parents. RESULTS: We obtained data for 10 354 children from 206 preschools and childcare centres (response rate = 22.3%). Among these children, 457 (4.4%) had an NDD diagnosis that their parents shared with the teachers. However, the teachers of 1274 children (12.3%) had concerns regarding their development but were not informed by the parents about the diagnosis, if any. These 1274 children included 775 (60.8%) cases where the teachers failed to share their concerns with parents because (1) the teachers could not communicate with parents (n = 119), (2) the teachers were not sure if there was a neurodevelopmental problem (n = 360) and (3) the parents were not aware of the problem (n = 296). CONCLUSIONS: Preschool teachers and childcare workers had concerns about the development of a substantial proportion of children in their charge. However, teachers and childcare workers did not share their concerns regarding many children's developmental problems with their parents. The findings suggest that there are challenges in information-sharing between teachers/childcare workers and parents.


Assuntos
Cuidado da Criança , Professores Escolares , Criança , Humanos , Pré-Escolar , Japão , Instituições Acadêmicas , Pais
2.
Intern Med ; 62(7): 1031-1035, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36070937

RESUMO

A 47-year-old man was complaining of consciousness disorder. He had acute kidney injury, hypokalemia, and severe metabolic alkalosis. Initial treatment using intravenous infusion of 0.9% saline and potassium chloride improved his consciousness. It was clarified that he was a severe alcohol abuser who habitually self-vomited. We diagnosed him with volume depletion and pseudo-Bartter's syndrome due to loss of chloride by habitual vomiting. Gastrointestinal endoscopy demonstrated pyloric stenosis, which was ameliorated by Helicobacter pylori eradication therapy. We should consider volume depletion and pseudo-Bartter's syndrome as differential diagnoses when we encounter patients with acute kidney injury and severe metabolic alkalosis.


Assuntos
Injúria Renal Aguda , Alcalose , Síndrome de Bartter , Hiperaldosteronismo , Hipopotassemia , Estenose Pilórica , Masculino , Humanos , Pessoa de Meia-Idade , Síndrome de Bartter/complicações , Síndrome de Bartter/diagnóstico , Síndrome de Bartter/metabolismo , Hipopotassemia/complicações , Estenose Pilórica/complicações , Estenose Pilórica/diagnóstico por imagem , Alcalose/complicações , Alcalose/diagnóstico , Injúria Renal Aguda/complicações , Etanol , Vômito/complicações , Hiperaldosteronismo/complicações
3.
Diagn Cytopathol ; 51(1): E1-E5, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36040850

RESUMO

Pituicytoma is a rare neoplasm, arising in the posterior pituitary or in the hypophyseal stalk, and its cytological findings have not yet been well-described. We have experienced a case of pituicytoma, which was difficult to diagnose intraoperatively, because of its cellular pleomorphism. A tumor measuring 18 mm in maximum diameter was found at the sella turcica in a Japanese woman in her forties. Both intraoperative crush cytology and histology of the resected tumor showed pleomorphic spindle or round cells, including multinucleated cells. Tumor cells were positive for TTF-1, S-100 protein, and vimentin, partially positive for glial fibrillary acidic protein and epithelial membrane antigen, and negative for synaptophysin, hormones of the anterior pituitary gland, CD34, Olig2, PAX8, and napsin A. Ki-67 labeling index was 2.0%. Tumors included in the differential diagnosis in general are pituitary adenoma, craniopharyngioma, germinoma, and metastatic tumor on the radiological standpoint, and pilocytic astrocytoma and meningioma on the cytological standpoint. However, our case was difficult to differentiate especially from high-grade glioma only by morphology, and immunohistochemistry including TTF-1 was helpful.


Assuntos
Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/diagnóstico
4.
Cancer Med ; 10(20): 7174-7183, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34505396

RESUMO

BACKGROUND: The incidence and risk factors of severe anaphylaxis by intravenous anti-cancer drugs are unclear, whereas those of milder reactions have been reported. STUDY DESIGN: Electronic medical charts of cancer patients who have undergone intravenous chemotherapy between January 2013 and October 2020 in a university hospital were retrospectively reviewed. Non-epithelial malignancies were also included in the analysis. "Severe anaphylaxis" was judged using Brown's criteria: typical presentation of anaphylaxis and one or more of hypoxia, shock, and neurologic compromise. (UMIN000042887). RESULTS: Among 5584 patients (2964 males [53.1%], 2620 females [46.9%], median age 66 years), 88,200 person-day anti-cancer drug administrations were performed intravenously, and 27 severe anaphylaxes were observed. The causative drugs included carboplatin (14 cases), paclitaxel (9 cases), and cisplatin, docetaxel, trastuzumab, and cetuximab (1 case each). The person-based lifetime incidence of severe anaphylaxis for patients who received at least one intravenous chemotherapy was 0.48% (27/5584, 95% confidence interval (CI) 0.30%-0.67%) and the administration-based incidence was 0.031% (27/88,200, 95% CI 0.019%-0.043%). Among 124 patients who received at least 10 carboplatin administrations, 10 patients experienced carboplatin-induced severe anaphylaxis (10/124, 8.1%, 95% CI 3.0%-13.1%). Carboplatin caused severe anaphylaxis after at least 9-min interval since the drip started. Thirteen out of 14 patients experienced carboplatin-induced severe anaphylaxis within a 75-day interval from the previous treatment. Paclitaxel infusion caused severe anaphylaxis after a median of 5 min after the first drip of the day at a life-long incidence of 0.93% (9/968, 95% CI 0.27%-1.59%). CONCLUSION: We elucidated the high-risk settings of chemotherapy-induced severe anaphylaxis.


Assuntos
Anafilaxia/induzido quimicamente , Antineoplásicos/efeitos adversos , Administração Intravenosa , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
5.
Nihon Ronen Igakkai Zasshi ; 57(3): 316-320, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32893214

RESUMO

He was a 92-year-old male patient with mild cognitive impairment while preserved activity of daily life. His renal dysfunction gradually increased due to the nephrosclerosis accompanied by systemic edema and water retention. We eventually decided to initiate peritoneal dialysis instead of standard hemodialysis for his end-stage renal dysfunction refractory to optimal medical therapy, given his preserved cognitive function and family support. He underwent an established therapeutic program for the peritoneal dialysis at home with an Information and Communication Technology (ICT).Given the increase in age of the patients with renal dysfunction, peritoneal dialysis has been receiving great attention as a home care strategy. The recent improvement in the device technology and ICT that enables us remote monitoring would reduce patients' effort in the management of peritoneal dialysis. Collaboration with home nursing and care workers would also be warranted for successful home care.


Assuntos
Serviços de Assistência Domiciliar , Falência Renal Crônica , Diálise Peritoneal , Idoso de 80 Anos ou mais , Cognição , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Diálise Renal
6.
JMIR Res Protoc ; 9(4): e15164, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32254045

RESUMO

BACKGROUND: Evidence shows that computerized self-help interventions are effective for reducing symptoms of depression. One such intervention, SPARX, is a gamified mobile computerized cognitive behavioral therapy (cCBT) developed for adolescents in New Zealand, which was shown to be as effective as usual care for young people with mild-to-moderate symptoms of depression. However, gamified cCBT has not yet been tested in Japan. OBJECTIVE: This trial is designed to investigate whether a Japanese-adapted version of SPARX improves depressive symptoms in Japanese university students with mild-to-moderate depressive symptoms. METHODS: In this 7-week, multicenter, stratified, parallel-group, superiority randomized trial, participants will be allocated to either a treatment condition (SPARX) or a wait-list control condition. SPARX is a fully automated program, which will be delivered to the mobile phone or tablet device of the participants. SPARX is designed as an interactive fantasy game to guide the user through seven modules that teach key CBT strategies. All participants will be recruited from universities via advertisements on online bulletin boards, the campus newspaper, and posters. Participants in the treatment condition will use the SPARX program weekly. The primary outcome is the reduction of depressive symptoms (using Patient Health Questionnaires-9) measured at baseline and weekly: once after the 7-week intervention and once at a 1-month follow-up. Secondary outcomes include satisfaction with the program and satisfaction with life, measured by the Satisfaction With Life Scale; positive and negative moods, measured by the Profile of Mood States Second Edition; social functioning, measured by the EuroQol Instrument; rumination, measured by the Ruminative Responses Scale; and coping, measured by the Brief Coping Orientation to Problem Experienced Inventory. RESULTS: This study received funding from The Research Institute of Personalized Health Sciences, Health Sciences University of Hokkaido, and obtained institutional review board approval in September 2019. Data collection began in April 2019. CONCLUSIONS: Results of this trial may provide further evidence for the efficacy of gamified cCBT for the treatment of depression and, specifically, provide support for using SPARX with Japanese university students. TRIAL REGISTRATION: Japan Primary Registries Network UMIN000034354; https://tinyurl.com/uu7xd77. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15164.

7.
J Vet Med Sci ; 82(5): 678-680, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32213730

RESUMO

Here, we investigated the prevalence of Salmonella enterica, with and without resistance to 17 common antimicrobial agents, in 706 green anoles (Anolis carolinensis) that were collected in Naha and Tomigusuku Cities, Okinawa Main Island, Japan, between 2009 and 2014. Salmonella strains, including S. enterica Weltevreden and Enteritidis serovars, were identified in the large intestinal content samples extracted from 15 (2.1%) of the analyzed green anoles. No antimicrobial resistance was detected. Thus, the present study demonstrates that although the prevalence of Salmonella and the risk of its transmission from the green anoles to humans or other animals on Okinawa Main Island are relatively low, the green anole population nevertheless represents a potential source of Salmonella infection that could affect human health in this region.


Assuntos
Intestino Grosso/microbiologia , Lagartos/microbiologia , Salmonella/isolamento & purificação , Animais , Resistência Microbiana a Medicamentos , Espécies Introduzidas , Japão , Prevalência , Salmonella/classificação
8.
Urol Oncol ; 37(6): 353.e9-353.e15, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30737158

RESUMO

OBJECTIVE: In rare cases, differential diagnosis between bladder cancer (BC) and gynecological tract cancer (GTC) is difficult because of anatomical proximity and morphological similarity. We analyzed expression status of sex steroid hormone receptors in BC in this study. First, we investigated their usefulness as a histological marker for differential diagnosis. Second, we considered their roles in BC histogenesis. METHODS: Estrogen receptor α (ERα) and progesterone receptor (PgR) expression was investigated by immunohistochemistry in 125 BCs obtained by transurethral resection or biopsy, then in nonneoplastic background mucosa (trigone, fundus, and dome) of 33 total cystectomy samples. They were evaluated as positive when ≥ 1% of 500 subject cells were immunoreactive with moderate or strong intensities. RESULTS: ERα and PgR were positive in 38.4% and 3.2% of BCs, respectively, suggesting that ERα status alone could not definitely differentiate between BC and GTC. ERα expression was not significantly associated with age and sex of BC patients and histopathology of BCs. Although not significant, ERα expression was more frequent in higher grade (G1/G2 vs. G3/G4; P = 0.143) and marginally associated with advanced stage of BCs (pTis/pTa/pT1 vs. pT2/pT3, P = 0.056). ERα expression was significantly more frequent in background mucosa with ERα-positive BC (In the epithelium and stroma; both P < 0.001). ERα expression was continuously observed from normal to malignant epithelium in some cases. Although not significant, Brunn's nest or cystitis glandularis was more frequent in background mucosa with ERα-positive BC (P = 0.218). Analyses of nonneoplastic mucosa in cystectomy revealed that ERα was more frequently positive in urothelium of trigone, a predilection site for cystitis glandularis, than those of fundus and dome, with a significant difference between trigone and dome (P = 0.034). These data suggest that chronic inflammation may up-regulate ERα in the background epithelium, especially in trigone, and ERα expression in BC might be the reflection of bladder epithelium from which BC arose. CONCLUSIONS: Usefulness of ERα was limited in differential diagnosis between BC and GTC. ERα up-regulation might not play a critical role in the development of BC because it was already noted in the background bladder mucosa.


Assuntos
Receptor alfa de Estrogênio/análise , Receptores de Progesterona/análise , Neoplasias da Bexiga Urinária/química , Neoplasias da Bexiga Urinária/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Receptor alfa de Estrogênio/biossíntese , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Progesterona/biossíntese , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
9.
Bioorg Med Chem Lett ; 27(20): 4626-4629, 2017 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-28935264

RESUMO

Neuromedin U (NMU) mediates various physiological functions via NMUR1 and NMUR2 receptors. NMUR2 has been considered a promising treatment option for diabetes and obesity. Although NMU-8, a shorter peptide, has potent agonist activity for both receptors, it is metabolically unstable. Therefore, NMU-8 analogs modified with long-chain alkyl moieties via a linker were synthesized. An octadecanoyl analog (17) with amino acid substitutions [αMePhe19, Nle21, and Arg(Me)24] and a linker [Tra-γGlu-PEG(2)] dramatically increased NMUR2 selectivity, with retention of high agonist activity. Subcutaneous administration of 17 induced anorectic activity in C57BL/6J mice. Owing to its high metabolic stability, 17 would be useful in clarifying the physiological role and therapeutic application of NMU.


Assuntos
Depressores do Apetite/metabolismo , Peptídeos/metabolismo , Receptores de Neurotransmissores/metabolismo , Alquilação , Sequência de Aminoácidos , Animais , Depressores do Apetite/química , Depressores do Apetite/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peptídeos/agonistas , Receptores de Neurotransmissores/antagonistas & inibidores , Relação Estrutura-Atividade
10.
Bioorg Med Chem Lett ; 27(15): 3542-3545, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28596054

RESUMO

The natriuretic peptide (NP) system is a critical endocrine, autocrine, and paracrine system and has been investigated for potential use against cardiovascular and metabolic diseases. The clearance of NPs is regulated by the proteolysis of neutral endopeptidase (NEP) and by endocytosis via natriuretic peptide receptor-3 (NPR3). A linear NPR3-selective peptide, [Cha8]-ANP(7-16)-NH2 (1), showed potent binding affinity for NPR3 but poor predicted chemical stability due to its free thiol group. A 12-mer peptide (9) without a thiol group was designed by the hybridization of two NPR3-binding peptides: a linear ANP fragment peptide analog and musclin, a murine member of the bHLH family of transcription factors, possessed high binding affinity and strict selectivity for NPR3. To increase the proteolytic resistance of 9, amino acid substitutions at the cleavage sites led to hydroxyacetyl-[d-Phe5,d-Hyp7,Cha8,d-Ser9,Hyp11,Arg(Me)14]-ANP(5-15)-NHCH3 (23), showing high and selective binding affinity for NPR3 over NPR1 and excellent stability in mouse serum. Compound 23 increased intracellular cGMP concentrations in primary cultured adipocytes, and continuous administration induced substantial plasma cGMP elevation in mice, suggesting its potential to clarify the physiological role of NPR3 and its therapeutic application.


Assuntos
Fator Natriurético Atrial/farmacologia , Proteínas Musculares/farmacologia , Fragmentos de Peptídeos/farmacologia , Receptores do Fator Natriurético Atrial/antagonistas & inibidores , Fatores de Transcrição/farmacologia , Sequência de Aminoácidos , Animais , Fator Natriurético Atrial/administração & dosagem , Fator Natriurético Atrial/sangue , Fator Natriurético Atrial/química , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Musculares/administração & dosagem , Proteínas Musculares/sangue , Proteínas Musculares/química , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/química , Receptores do Fator Natriurético Atrial/metabolismo , Fatores de Transcrição/administração & dosagem , Fatores de Transcrição/sangue , Fatores de Transcrição/química
11.
Biochem Biophys Res Commun ; 483(1): 101-106, 2017 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-28043792

RESUMO

Tropomyosin receptor kinase B (TrkB) is a known receptor of brain-derived neurotrophic factor (BDNF). Because it plays a critical role in the regulation of neuronal development, maturation, survival, etc., TrkB is a good target for drugs against central nervous system diseases. In this study, we aimed to generate peptidic TrkB agonists by applying random peptide phage display technology. After the phage panning against recombinant Fc-fused TrkB (TrkB-Fc), agonistic phages were directly screened against TrkB-expressing HEK293 cells. Through subsequent screening of the first-hit BM17 peptide-derived focus library, we successfully obtained the BM17d99 peptide, which had no sequence similarity with BDNF but had TrkB-binding capacity. We then synthesized a dimeric BM17d99 analog peptide that could phosphorylate or activate TrkB by facilitating receptor homodimerization. Treatment of TrkB-expressing HEK293 cells with the dimeric BM17d99 analog peptide significantly induced the phosphorylation of TrkB, suggesting that homodimerization of TrkB was enhanced by the dimeric peptide. This report demonstrates that our approach is useful for the generation of artificial peptidic agonists of cell surface receptors.


Assuntos
Glicoproteínas de Membrana/agonistas , Peptídeos/farmacologia , Sequência de Aminoácidos , Bacteriófago T7 , Avaliação Pré-Clínica de Medicamentos , Células HEK293 , Humanos , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/metabolismo , Biblioteca de Peptídeos , Peptídeos/síntese química , Peptídeos/química , Fosforilação , Ligação Proteica , Multimerização Proteica , Proteínas Tirosina Quinases/química , Proteínas Tirosina Quinases/metabolismo , Receptor trkB
12.
Biometals ; 28(4): 669-77, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25850340

RESUMO

We previously developed a chelating ligand, 1-(2-hydroxy-3-methoxybenzaldehyde)-4-aminosalicylhydrazone (HMB-ASH), which can chelate Fe(III) to form a complex. The HMB-ASH-Fe(III) complex exhibits a dose-dependent anti-proliferative effect in HepG2 cells, whereas the ligand, HMB-ASH, and Fe(III) alone had no considerable effect. The HMB-ASH-Fe(III) complex was composed of Fe(III):HMB-ASH (1:2), as determined by high-performance liquid chromatography with high-resolution mass spectrometry. The IC50 value was approximately 20 µM, which was comparable to those of the anti-cancer drugs oxaliplatin (OXP) and etoposide (ETP) under the same conditions. Similar to OXP and ETP, HMB-ASH-Fe(III) induced apoptosis in HepG2 cells, as revealed by terminal deoxynucleotidyl transferase fluorescein-12-dUTP nick end labeling assay.


Assuntos
Benzaldeídos/farmacologia , Compostos Férricos/farmacologia , Células Hep G2/citologia , Células Hep G2/efeitos dos fármacos , Hidrazonas/farmacologia , Apoptose/efeitos dos fármacos , Benzaldeídos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Compostos Férricos/síntese química , Compostos Férricos/química , Humanos , Hidrazonas/química , Células MCF-7 , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais Cultivadas
13.
J Clin Invest ; 124(5): 2099-112, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24713652

RESUMO

Brown adipose tissue (BAT) is a highly vascularized organ with abundant mitochondria that produce heat through uncoupled respiration. Obesity is associated with a reduction of BAT function; however, it is unknown how obesity promotes dysfunctional BAT. Here, using a murine model of diet-induced obesity, we determined that obesity causes capillary rarefaction and functional hypoxia in BAT, leading to a BAT "whitening" phenotype that is characterized by mitochondrial dysfunction, lipid droplet accumulation, and decreased expression of Vegfa. Targeted deletion of Vegfa in adipose tissue of nonobese mice resulted in BAT whitening, supporting a role for decreased vascularity in obesity-associated BAT. Conversely, introduction of VEGF-A specifically into BAT of obese mice restored vascularity, ameliorated brown adipocyte dysfunction, and improved insulin sensitivity. The capillary rarefaction in BAT that was brought about by obesity or Vegfa ablation diminished ß-adrenergic signaling, increased mitochondrial ROS production, and promoted mitophagy. These data indicate that overnutrition leads to the development of a hypoxic state in BAT, causing it to whiten through mitochondrial dysfunction and loss. Furthermore, these results link obesity-associated BAT whitening to impaired systemic glucose metabolism.


Assuntos
Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/irrigação sanguínea , Mitocôndrias/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Adipócitos Marrons/patologia , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/patologia , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Glucose/genética , Glucose/metabolismo , Hipóxia/genética , Hipóxia/metabolismo , Hipóxia/patologia , Hipóxia/fisiopatologia , Camundongos , Camundongos Knockout , Mitocôndrias/genética , Mitocôndrias/patologia , Mitofagia/genética , Obesidade/genética , Obesidade/fisiopatologia , Espécies Reativas de Oxigênio/metabolismo , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genética
15.
Photodermatol Photoimmunol Photomed ; 29(3): 132-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23651273

RESUMO

BACKGROUND: Xeroderma pigmentosum (XP) is a photosensitive genodermatosis with increased susceptibility to skin cancers. Patients are typically diagnosed with XP when they consult a dermatologist for skin cancers. CASE/METHODS: The genetic analysis and 2-8 years of follow-up for three school-age patients with XP-V is described. The patients were referred to us because of increased pigmented freckles; they had not experienced abnormal sunburn or developed skin cancer at their first visit. All patients harbored a genetic mutation in the POLH gene. XPV9KO was diagnosed at age 13 with a homozygous del1661A that creates a stop codon in the non-catalytic domain of POLH. The patient practiced sun protection, effectively preventing the development of skin cancer by age 21. XPV19KO was diagnosed at age 11 with a compound heterozygous mutation of G490T and C1066T, causing POLH truncation in the catalytic domain. This patient developed basal cell carcinoma at ages 12 and 13. XPV18KO was referred to us at age 11 and diagnosed with compound heterozygous variants of c.1246_1311del66 (exon 9 skipping), a novel mutation, and c.661_764 del104 (exon 6 skipping). CONCLUSION: Freckle-like pigmentation on sun-exposed skin is sometimes the only sign of XP-V, and early diagnosis is extremely important for children.


Assuntos
Códon de Terminação , DNA Polimerase Dirigida por DNA/genética , Heterozigoto , Mutação Puntual , Xeroderma Pigmentoso/genética , Adolescente , Criança , DNA Polimerase Dirigida por DNA/metabolismo , Éxons , Feminino , Seguimentos , Humanos , Masculino , Estrutura Terciária de Proteína , Xeroderma Pigmentoso/enzimologia , Xeroderma Pigmentoso/patologia
16.
Circulation ; 124(25): 2920-32, 2011 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-22144572

RESUMO

BACKGROUND: The calcium-binding proteins myeloid-related protein (MRP)-8 (S100A8) and MRP-14 (S100A9) form MRP-8/14 heterodimers (S100A8/A9, calprotectin) that regulate myeloid cell function and inflammatory responses and serve as early serum markers for monitoring acute allograft rejection. Despite functioning as a proinflammatory mediator, the pathophysiological role of MRP-8/14 complexes in cardiovascular disease is incompletely defined. This study investigated the role of MRP-8/14 in cardiac allograft rejection using MRP-14(-/-) mice that lack MRP-8/14 complexes. METHODS AND RESULTS: We examined parenchymal rejection after major histocompatibility complex class II allomismatched cardiac transplantation (bm12 donor heart and B6 recipients) in wild-type (WT) and MRP-14(-/-) recipients. Allograft survival averaged 5.9±2.9 weeks (n=10) in MRP-14(-/-) recipients compared with >12 weeks (n=15; P<0.0001) in WT recipients. Two weeks after transplantation, allografts in MRP-14(-/-) recipients had significantly higher parenchymal rejection scores (2.8±0.8; n=8) than did WT recipients (0.8±0.8; n=12; P<0.0001). Compared with WT recipients, allografts in MRP-14(-/-) recipients had significantly increased T-cell and macrophage infiltration and increased mRNA levels of interferon-γ and interferon-γ-associated chemokines (CXCL9, CXCL10, and CXCL11), interleukin-6, and interleukin-17 with significantly higher levels of Th17 cells. MRP-14(-/-) recipients also had significantly more lymphocytes in the adjacent para-aortic lymph nodes than did WT recipients (cells per lymph node: 23.7±0.7×10(5) for MRP-14(-/-) versus 6.0±0.2×10(5) for WT; P<0.0001). The dendritic cells (DCs) of the MRP-14(-/-) recipients of bm12 hearts expressed significantly higher levels of the costimulatory molecules CD80 and CD86 than did those of WT recipients 2 weeks after transplantation. Mixed leukocyte reactions with allo-endothelial cell-primed MRP-14(-/-) DCs resulted in significantly higher antigen-presenting function than reactions using WT DCs. Ovalbumin-primed MRP-14(-/-) DCs augmented proliferation of OT-II (ovalbumin-specific T cell receptor transgenic) CD4(+) T cells with increased interleukin-2 and interferon-γ production. Cardiac allografts of B6 major histocompatibility complex class II(-/-) hosts and of B6 WT hosts receiving MRP-14(-/-) DCs had significantly augmented inflammatory cell infiltration and accelerated allograft rejection compared with WT DCs from transferred recipient allografts. Bone marrow-derived MRP-14(-/-) DCs infected with MRP-8 and MRP-14 retroviral vectors showed significantly decreased CD80 and CD86 expression compared with controls, indicating that MRP-8/14 regulates B7-costimulatory molecule expression. CONCLUSIONS: Our results indicate that MRP-14 regulates B7 molecule expression and reduces antigen presentation by DCs and subsequent T-cell priming. The absence of MRP-14 markedly increased T-cell activation and exacerbated allograft rejection, indicating a previously unrecognized role for MRP-14 in immune cell biology.


Assuntos
Calgranulina A/imunologia , Calgranulina B/imunologia , Rejeição de Enxerto/metabolismo , Transplante de Coração/imunologia , Animais , Antígenos B7/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Calgranulina A/genética , Calgranulina A/metabolismo , Calgranulina B/metabolismo , Citocinas/genética , Citocinas/metabolismo , Sobrevivência de Enxerto/imunologia , Histocompatibilidade/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Complexo Antígeno L1 Leucocitário/genética , Complexo Antígeno L1 Leucocitário/imunologia , Complexo Antígeno L1 Leucocitário/metabolismo , Teste de Cultura Mista de Linfócitos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores do Ácido Retinoico/imunologia , Receptores do Ácido Retinoico/metabolismo , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Transplante Homólogo , Receptor gama de Ácido Retinoico
17.
Am J Med Genet A ; 152A(12): 3143-7, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21108399

RESUMO

We describe two patients with Pallister-Hall syndrome (PHS) with genital abnormalities: a female with hydrometrocolpos secondary to vaginal atresia and a male with micropenis, hypoplastic scrotum, and bilateral cryptorchidism. Nonsense mutations in GLI3 were identified in both patients. Clinical and molecular findings of 12 previously reported patients who had GLI3 mutations and genital abnormalities were reviewed. Genital features in the male patients included hypospadias, micropenis, and bifid or hypoplastic scrotum, whereas all the females had hydrometrocolpos and/or vaginal atresia. No hotspot for GLI3 mutations has been found. The urogenital and anorectal abnormalities associated with PHS might be related to dysregulation of SHH signaling caused by GLI3 mutations rather than hormonal aberrations. We recommend that clinical investigations of genital abnormalities are considered in patients with PHS, even those without hypopituitarism.


Assuntos
Anormalidades Múltiplas/genética , Síndrome de Pallister-Hall/diagnóstico , Anormalidades Urogenitais/diagnóstico , Anormalidades Urogenitais/genética , Criança , Pré-Escolar , Códon sem Sentido , DNA/genética , DNA/isolamento & purificação , Éxons , Feminino , Mutação da Fase de Leitura , Genes Dominantes , Heterozigoto , Humanos , Fatores de Transcrição Kruppel-Like/genética , Masculino , Proteínas do Tecido Nervoso/genética , Técnicas de Amplificação de Ácido Nucleico , Reação em Cadeia da Polimerase , Proteína Gli3 com Dedos de Zinco
19.
J Anesth ; 22(4): 341-6, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19011770

RESUMO

PURPOSE: Several reports indicate that a neutrophil elastase inhibitor, sivelestat, may have prophylactic efficacy against a systemic inflammatory response after cardiovascular surgery with cardiopulmonary bypass (CPB). We evaluated the clinical pulmonary and cardiac effects of sivelestat. METHODS: We performed a retrospective study of 25 pediatric patients who underwent elective cardiovascular surgery with CPB for ventricular septal defect with pulmonary hypertension. Ten patients received 0.2 mg x kg(-1) x h(-1) sivelestat; the other is patients were the control group. There were no significant differences in demographic characteristics between the two groups. The P(a)O(2)/fractional inspired oxygen (F(I)O(2); P/F) ratio, the respiratory index (RI), and the fractional area change (FAC) of the left ventricle (LV) in the postoperative course were measured. RESULTS: The P/F ratio was higher in the sivelestat group compared with the control group and there were significant differences between the two groups immediately after weaning form CPB, and at 12 h after weaning from CPB (P < 0.05). The RI was lower in the sivelestat group compared with the control group and there were significant differences between the two groups at immediately after weaning from CPB, and at 6 h and 12 h after CPB (P < 0.05). The FAC of the LV was significantly better in the sivelestat group and there was a significant difference between the two groups on postoperative day (POD) 3 (P < 0.05). CONCLUSION: We have shown that pediatric patients who underwent cardiovascular surgery with CPB who received sivelestat had a higher P/F ratio, a lower RI, and better FAC of the LV in the postoperative course.


Assuntos
Ponte Cardiopulmonar , Glicina/análogos & derivados , Coração/efeitos dos fármacos , Proteínas Secretadas Inibidoras de Proteinases/farmacologia , Mecânica Respiratória/efeitos dos fármacos , Sulfonamidas/farmacologia , Procedimentos Cirúrgicos Vasculares , Anestesia por Inalação , Feminino , Glicina/farmacologia , Comunicação Interventricular/complicações , Comunicação Interventricular/cirurgia , Hematócrito , Humanos , Hipertensão Pulmonar/complicações , Lactente , Unidades de Terapia Intensiva Pediátrica , Contagem de Leucócitos , Masculino , Oxigênio/sangue , Respiração Artificial , Estudos Retrospectivos , Função Ventricular Esquerda/efeitos dos fármacos
20.
J Anesth ; 22(2): 182-5, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18500619

RESUMO

We performed anesthetic management for a patient with severe Williams-Campbell syndrome, which is a congenital deficiency of cartilage in the subsegmental bronchial tree. An 11-year-old girl with this syndrome had labored breathing because of abdominal distension caused by a giant ovarian tumor, and removal of the tumor was scheduled. Because she had been receiving home oxygen therapy for 10 years due to hypoxia, it was possible that positive-pressure ventilation may have increased the risk of perioperative pulmonary complications. So we selected combined spinal and epidural anesthesia with general anesthesia, using a ProSeal (Laryngeal Mask Company, Henley on Thames, UK) laryngeal mask airway. We placed an epidural catheter and induced spinal anesthesia blockade under general anesthesia as the main analgesia technique, in order to maintain spontaneous breathing. The surgery was completed uneventfully and the patient emerged from anesthesia without dyspnea. She had an uneventful recovery and was discharged home.


Assuntos
Anestesia Epidural/métodos , Anestesia Geral/métodos , Raquianestesia/métodos , Neoplasias Ovarianas/cirurgia , Teratoma/cirurgia , Brônquios/anormalidades , Cartilagem/anormalidades , Criança , Feminino , Humanos , Intubação Intratraqueal/métodos , Monitorização Intraoperatória , Neoplasias Ovarianas/complicações , Síndrome , Teratoma/complicações , Resultado do Tratamento
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