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1.
Eur J Pediatr ; 175(3): 433-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26459154

RESUMO

UNLABELLED: Hypophosphatasia (HPP) is a rare metabolic bone disease caused by loss-of-function mutations in the gene ALPL encoding the tissue nonspecific alkaline phosphatase (TNSALP). There is a broad range of severity in the phenotype of HPP, and the most severe form exhibits perinatal lethality without mineralization of the skeleton. Here, we describe a female infant with perinatal lethal HPP diagnosed in utero. She was treated with a recombinant ALP (asfotase alfa) as an enzyme replacement therapy (ERT), which started from 1 day after birth. She required invasive ventilation immediately upon birth and demonstrated severe hypomineralization of whole body bone. Severe respiratory insufficiency was controlled by intensive respiratory care with high-frequency oscillation ventilation and nitric oxide inhalation and deep sedation just after birth. Bone mineralization improved with treatment; improvements were visible by 3 weeks of age and continued with treatment. Serum calcium levels decreased following treatment, resulting in hypocalcemia and convulsion, and calcium supplementation was required until 3 months of treatment. She was weaned from mechanical ventilation and has now survived more than 1 year. CONCLUSION: This case demonstrates the success of ERT in treating the severest HPP and highlights the importance of early diagnosis and intervention for these patients.


Assuntos
Fosfatase Alcalina/uso terapêutico , Terapia de Reposição de Enzimas/métodos , Hipofosfatasia/tratamento farmacológico , Imunoglobulina G/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Insuficiência Respiratória/complicações , Fosfatase Alcalina/efeitos adversos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Cálcio/metabolismo , Terapia de Reposição de Enzimas/efeitos adversos , Feminino , Humanos , Imunoglobulina G/efeitos adversos , Lactente , Recém-Nascido , Proteínas Recombinantes de Fusão/efeitos adversos , Respiração Artificial , Insuficiência Respiratória/terapia
2.
J Perinat Med ; 43(2): 239-43, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24968403

RESUMO

AIMS: Neurological outcomes differ considerably between symptomatic and asymptomatic infants with congenital cytomegalovirus (CMV) infection. Our objective was to characterize laboratory markers in symptomatic newborns in comparison with asymptomatic newborns with congenital CMV infection. METHODS: Ten newborns with symptomatic and 13 newborns with asymptomatic congenital CMV infection were included in this 3-year prospective cohort study. Total immunoglobulin M (IgM), CMV-IgM, CMV antigenemia, and CMV-DNA in blood and urine were measured and their positive rates and quantitative values compared between the symptomatic and asymptomatic groups. RESULTS: Fifty percent of newborns in the symptomatic group were positive based on total IgM; this was significantly lower than in the asymptomatic group (100%). Quantitative total IgM values were significantly lower, and there were significantly more copies of CMV-DNA in the blood of symptomatic newborns than in asymptomatic newborns (median values for total IgM: 14 vs. 43 mg/dL and blood CMV-DNA: 3.2×102 vs. 3.5×101 copies/106 white blood cells). CMV-IgM, CMV antigenemia, and urine CMV-DNA did not differ significantly between groups. CONCLUSION: Low total IgM values and high blood CMV loads were associated with the presence of symptoms in newborns with congenital CMV infection.


Assuntos
Infecções por Citomegalovirus/congênito , DNA Viral/sangue , Imunoglobulina M/sangue , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/imunologia , DNA Viral/urina , Humanos , Recém-Nascido , Estudos Prospectivos
3.
Pediatr Int ; 55(2): 169-76, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23163603

RESUMO

BACKGROUND: We define clinical predictors of neurological outcome in neonates with hypoxic-ischemic encephalopathy undergoing hypothermia therapy. METHODS: Twenty-one neonates who underwent selective head cooling between 2004 and 2010 and were followed neurologically for ≥ 24 months were investigated retrospectively. Patients were divided according to the neurological outcome at 2 years of age into group A (n = 11), patients with normal neurological function, and group B (n = 10), patients with neurological disabilities (n = 9) or those who died (n = 1). Predictors were determined by χ(2) and Mann-Whitney U-tests, anova, Spearman rank correlations and receiver-operator curves. RESULTS: Group B showed higher average blood lactate levels during the first day, particularly at 24 h of life; lower day-3 cerebral blood flow resistance index; higher maximum dobutamine dose used; higher rate of thiamylal sodium used; more severe background electroencephalogram suppression during the first week (group A: 11/11 cases ≤ grade 3; group B: 7/9 cases at grade 4-5) and higher rate of cerebral lesions on magnetic resonance imaging in the second week (group A: 1/11 case; group B: 9/10 cases) than group A. The most useful predictor of poor prognosis was cerebral parenchymal lesions on magnetic resonance imaging with 90%, 90% and 90% of sensitivity, specificity and accuracy, followed by week-1 background electroencephalogram ≥ grade 4 with 70%, 100% and 85% and day-3 cerebral blood flow resistance index < 0.46 with 71%, 88% and 80%, respectively. CONCLUSIONS: Prediction of post-cooling neurological outcome could be improved substantially by evaluating multiple factors.


Assuntos
Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/terapia , Encéfalo/patologia , Encéfalo/fisiopatologia , Pré-Escolar , Eletroencefalografia , Feminino , Seguimentos , Cabeça , Humanos , Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/fisiopatologia , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
4.
Cancer Genet ; 241: 72-76, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31353165

RESUMO

Acute myeloid leukemia (AML) with an inv(16)(p13q22) or t(16;16)(p13;q22) chromosomal abnormality represents one of the most common subtypes of de novo cases. These chromosomal rearrangements result in multiple CBFB-MYH11 fusion transcripts, with type-A being the most frequent. We here describe a unique case of de novo AML-M1, with inv(16)(p13q22), leading to an unusual CBFB-MYH11 fusion transcript, and der(7)t(7;11)(q31;q21). The fusion transcript involves a CBFB exon 5 with a breakpoint at nucleotide 754, an insertion of a 13-bp sequence of CBFB intron 5 at the fusion point, and the MYH11 exon 27 with a breakpoint at nucleotide 3464. To our knowledge, this CBFB-MYH11 fusion transcript has never been reported previously. The clinical characteristics of the present case are in line with previous reports suggesting that rare CBFB-MYH11 fusion transcripts lead to aberrant characteristics such as an atypical cytomorphology and additional cytogenetic abnormalities.


Assuntos
Cromossomos Humanos Par 16/genética , Rearranjo Gênico , Leucemia Mieloide Aguda/genética , Proteínas de Fusão Oncogênica/genética , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Cariotipagem Espectral , Resultado do Tratamento
5.
Int J Hematol ; 102(6): 713-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26342691

RESUMO

We report here the first case of NPM1/RARA-positive acute promyelocytic leukemia (APL) preceded by myeloid sarcoma (MS) in the vertebra. A 52-year-old man was diagnosed with MS, as the tumor cells were positive for myeloperoxidase and CD68 but negative for CD163. After treatment with steroids and radiation, the size of the tumor was markedly reduced and peripheral blood count was normal. Bone marrow examination showed 89.2% consisted of unclassified promyelocytes characterized by round nuclei and abundant small azurophilic granules but no Auer rods. The results of chromosome analysis showed 46,XY,t(5;17)(q35;q12). Reverse-transcription polymerase chain reaction amplified the NPM1/RARA fusion transcripts derived from a combination of NPM1 exon 4 and RARA exon 5, or of NPM1 exon 1 and RARA exon 5; the latter of these has not been reported previously. Electron microscopic examination of the promyelocyte nuclei showed they were oval with mild nuclear chromatin condensation and small- to medium-sized nucleoli. Hematological and molecular complete remission was attained after induction therapy including all-trans retinoic acid. As MS was also diagnosed in two of the seven other reported cases of APL with NPM1/RARA, MS may occur more frequently in APL with NPM1/RARA than APL with PML/RARA.


Assuntos
Fusão Gênica , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/patologia , Proteínas Nucleares/genética , Receptores do Ácido Retinoico/genética , Nucléolo Celular/patologia , Nucléolo Celular/ultraestrutura , Núcleo Celular/ultraestrutura , Cromatina/patologia , Cromatina/ultraestrutura , Éxons/genética , Células Precursoras de Granulócitos/citologia , Humanos , Quimioterapia de Indução , Leucemia Promielocítica Aguda/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Nucleofosmina , Receptor alfa de Ácido Retinoico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sarcoma Mieloide/diagnóstico , Sarcoma Mieloide/terapia , Tretinoína/uso terapêutico
6.
Hum Genome Var ; 2: 15017, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-27081530

RESUMO

Severe congenital protein C (PC) deficiency is an autosomal recessive hereditary thrombophilia caused by mutations in PROC. The case manifested severe purpura fulminans, intracranial thrombosis or hemorrhage within 4 days after birth, resulting in blindness. We report the identification of inherited compound heterozygous mutations, including a novel nonsense mutation in PROC, and a prenatal genetic test for a subsequent pregnancy. Prenatal diagnosis may facilitate preemptive and radical therapy for severe PC deficiency.

7.
J Microbiol Immunol Infect ; 36(3): 218-22, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14582570

RESUMO

While the eradication of Helicobacter pylori has been reported to reduce the frequency of ulcer relapse, the preventative mechanism remains unknown. We investigated the changes in the level of gastric colonization 140 days after inducing gastric ulcer by acetic acid in the antral mucosa of a miniature pig infected with H. pylori. The gastric ulcer was induced endoscopically with 1 mL of 40% acetic acid 12 days after inoculation of H. pylori in a 3-month-old miniature pig. Gastric ulcer was healed by 30 days after ulcer induction and the levels of H. pylori in cardiac and antral mucosa increased gradually from 30 to 71 days. The peak bacterial counts in the cardia and antrum were 6.1 and 6.6 log10 cfu/g, respectively, or about 100-fold higher than the initial levels. The levels of H. pylori in cardiac and antral mucosa steadily decreased until reaching the initial levels at 127 days, while that in the fundic mucosa remained constant throughout the observation period. No ulcer recurrence was detected by endoscopy. These results suggested that the levels of H. pylori colonization increased temporally after healing of the acetic acid-induced gastric ulcer in the miniature pig.


Assuntos
Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Úlcera Gástrica/microbiologia , Ácido Acético/toxicidade , Animais , Contagem de Colônia Microbiana , Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Masculino , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/complicações , Úlcera Gástrica/patologia , Suínos , Porco Miniatura , Fatores de Tempo
8.
Microbiol Res ; 158(1): 69-75, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12608582

RESUMO

This study was designed to determine whether magnesium ion in water would influence the colonization of Helicobacter pylori in 2-week-old miniature pigs. Groups A (2 pigs) and B (1 pig) were both fed a milk diet dissolved in drinking water, Group C (2 pigs) was fed a milk diet dissolved in deionized distilled water (DDW), and Group D (1 pig) was fed a milk diet dissolved in DDW supplemented with MgCl2. Groups B, C, and D were all challenged with H. pylori, and Group A was not. Necropsy was performed on the pigs on postinfection Day 5, and biopsy specimens were taken from 16 sites of the stomach. H. pylori were recovered from 11 of 16 sites in Group B, 1 of 32 sites in Group C, and 13 of 16 sites in Group D. On the other hand, the degree of lymphocyte infiltration increased in the order of Group A < Group B < Group C < Group D. These observations suggest that magnesium ion in drinking water is essential for the colonization of H. pylori in the pig stomach. Possible mechanisms for the lymphocyte infiltration are discussed.


Assuntos
Mucosa Gástrica/microbiologia , Helicobacter pylori/crescimento & desenvolvimento , Magnésio/farmacologia , Porco Miniatura/microbiologia , Abastecimento de Água/análise , Animais , Cárdia/efeitos dos fármacos , Cárdia/microbiologia , Cárdia/patologia , Contagem de Colônia Microbiana/métodos , Fundo Gástrico/efeitos dos fármacos , Fundo Gástrico/microbiologia , Fundo Gástrico/patologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Helicobacter pylori/efeitos dos fármacos , Linfócitos/patologia , Masculino , Antro Pilórico/efeitos dos fármacos , Antro Pilórico/microbiologia , Antro Pilórico/patologia , Suínos
9.
Microbiol Res ; 157(4): 323-30, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12501997

RESUMO

Our previous study showed that the colonization levels of Helicobacter pylori were higher in the stomachs of 5-day-old miniature pigs than in 2-week-old ones. As dietary factors can cause these differences, we compared two diets, i.e., Weanymilk and a similar formula with a higher concentration of Fe(II), Weanylobulin. The colonization levels in the fundic mucosa were significantly higher in 2-week-old pigs fed Weanylobulin than in those fed Weanymilk. Supplementing Weanylobulin with an iron chelator, deferoxamine mesylate, significantly lowered the bacteria counts in the gastric mucosa. Normal diets supplemented with Fe(II) in 2-month-old pigs caused significantly more sites of bacteria in the antrum compared with normal diets alone. In addition, ranitidine, an inhibitor of gastric acid secretion that reduces Fe(III) to Fe(II) in the stomach, decreased the bacteria counts in 10-month-old pigs. These results suggested that Fe(II) maintained the colonization levels of H. pylori in the stomach of the miniature pigs.


Assuntos
Compostos Ferrosos/farmacologia , Mucosa Gástrica/microbiologia , Helicobacter pylori/crescimento & desenvolvimento , Animais , Contagem de Colônia Microbiana , Desferroxamina/farmacologia , Complexo Ferro-Dextran/farmacologia , Masculino , Ranitidina/farmacologia , Suínos , Porco Miniatura
10.
Brain Dev ; 36(6): 472-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23860386

RESUMO

BACKGROUND: Raised nucleated red blood cell (NRBC) counts in neonates may indicate in utero hypoxia and brain damage. OBJECTIVE: The study aimed to examine the use of NRBC counts as a predictor of brain injury and neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy (HIE) treated under current cooling-based strategy. METHODS: Forty-three neonates with asphyxia between 2004 and 2010 were retrospectively investigated. Twenty neonates with moderate/severe HIE underwent hypothermia (HT), and 23 with mild HIE were treated in normothermia (NT). Neonates were divided into groups according to the presence of cerebral parenchymal lesions on magnetic resonance imaging (MRI) at 2 weeks after birth. All patients were followed-up neurologically for ⩾ 24 months. NRBC counts during the first 3 days were compared between groups. RESULTS: Eleven HT (HT-N) and 21 NT (NT-N) neonates had normal MRI, and 9 HT (HT-L) and 2 NT (NT-L) neonates had parenchymal lesions. NRBC counts, both absolute and /100 white blood cells (WBC) counts, during the first 3 days in HT-L and NT-L were significantly higher than those in HT-N and NT-N, particularly within 6 hours after birth (HT-N: 502 [0-3060]/mm(3) vs HT-L: 2765 [496-6192]; 0 [0-3417] vs NT-L: 4384 [3978-4789], median [range]). Neonates with /100 white blood cells ⩾ 6/mm(3) and absolute NRBC counts ⩾ 1324/mm(3) within 6 hours of birth had high risks of abnormal MRIs and 2-year outcomes. CONCLUSIONS: NRBC counts can predict brain injury and neurological outcomes in cooled and non-cooled asphyxiated neonates.


Assuntos
Asfixia Neonatal/fisiopatologia , Asfixia Neonatal/terapia , Eritroblastos/fisiologia , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/fisiopatologia , Hipóxia-Isquemia Encefálica/terapia , Asfixia Neonatal/diagnóstico , Asfixia Neonatal/patologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Pré-Escolar , Contagem de Eritrócitos , Feminino , Seguimentos , Humanos , Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/patologia , Recém-Nascido , Contagem de Leucócitos , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
11.
FEBS J ; 279(19): 3639-3651, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22831795

RESUMO

The substrate-binding mode of a 26-kDa GH19 chitinase from rye, Secale cereale, seeds (RSC-c) was investigated by crystallography, site-directed mutagenesis and NMR spectroscopy. The crystal structure of RSC-c in a complex with an N-acetylglucosamine tetramer, (GlcNAc)(4) , was successfully solved, and revealed the binding mode of the tetramer to be an aglycon-binding site, subsites +1, +2, +3, and +4. These are the first crystallographic data showing the oligosaccharide-binding mode of a family GH19 chitinase. From HPLC analysis of the enzymatic reaction products, mutation of Trp72 to alanine was found to affect the product distribution obtained from the substrate, p-nitrophenyl penta-N-acetyl-ß-chitopentaoside. Mutational experiments confirmed the crystallographic finding that the Trp72 side chain interacts with the +4 moiety of the bound substrate. To further confirm the crystallographic data, binding experiments were also conducted in solution using NMR spectroscopy. Several signals in the (1) H-(15) N HSQC spectrum of the stable isotope-labeled RSC-c were affected upon addition of (GlcNAc)(4) . Signal assignments revealed that most signals responsive to the addition of (GlcNAc)(4) are derived from amino acids located at the surface of the aglycon-binding site. The binding mode deduced from NMR binding experiments in solution was consistent with that from the crystal structure.


Assuntos
Quitina/metabolismo , Quitinases/química , Quitinases/metabolismo , Secale/enzimologia , Sementes/enzimologia , Sequência de Aminoácidos , Sítios de Ligação , Catálise , Domínio Catalítico , Quitinases/genética , Cromatografia Líquida de Alta Pressão , Cristalografia por Raios X , Hidrólise , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Mutação/genética , Ressonância Magnética Nuclear Biomolecular , Ligação Proteica , Estrutura Terciária de Proteína , Homologia de Sequência de Aminoácidos , Especificidade por Substrato
13.
J Antimicrob Chemother ; 50(1): 133-6, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12096020

RESUMO

Plaunotol, a cytoprotective anti-ulcer agent, has antibacterial activity against Helicobacter pylori. The purpose of the present study was to investigate the effect of plaunotol when combined with clarithromycin or amoxicillin against H. pylori. When combined with clarithromycin, plaunotol showed synergic activity against 11 of 14 strains, and additive activity against the other three strains, by chequerboard titration. When combined with amoxicillin, plaunotol showed additive activity against 10 of 14 strains. No antagonistic effects were seen against any of the strains tested. The interactions between plaunotol and either clarithromycin or amoxicillin were determined by time-kill assay against the Sydney Strain (strain SS1) of H. pylori. The combination of plaunotol with clarithromycin showed synergic activity and with amoxicillin showed additive activity. In a C57BL/6 mouse gastritis model infected with H. pylori SS1, the plaunotol-clarithromycin and plaunotol-amoxicillin combinations both exhibited synergic effects, which allowed the effective dose of clarithromycin to be reduced when co-administered with plaunotol. These results suggest that plaunotol may have a useful role in combination with anti-H. pylori drugs in the treatment of H. pylori-associated diseases.


Assuntos
Amoxicilina/farmacologia , Antibacterianos/farmacologia , Claritromicina/farmacologia , Álcoois Graxos/farmacologia , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Amoxicilina/uso terapêutico , Animais , Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Diterpenos , Sinergismo Farmacológico , Quimioterapia Combinada , Álcoois Graxos/uso terapêutico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Estômago/efeitos dos fármacos , Estômago/microbiologia
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