RESUMO
AIMS: Poor growth in childhood cancer survivors who undergo haematopoietic stem cell transplant (HSCT) without exposure to radiation is reported anecdotally, although literature to support this is limited. The aims of this study were to assess the change in height standard deviation score (SDS) and the final adult height (FAH) in children who underwent chemotherapy-only conditioned HSCT and to identify predictors of poor growth. MATERIALS AND METHODS: We conducted a retrospective hospital medical record review (1984-2010) of children (1-10 years) who underwent chemotherapy-only conditioned HSCT, noting anthropology measurements at cancer diagnosis, HSCT, 10 years old and FAH. RESULTS: The median age at HSCT of the 53 patients was 4.5 years, 75% had a haematological malignancy and 25% a solid tumour. Half of the cohort underwent allogenic HSCT and most (89%) conditioned with busulphan. The mean change in height SDS from primary cancer diagnosis to FAH was -1.21 (±1.18 SD), equivalent to 7-8.5 cm loss, with a mean FAH of -0.91 SDS (±1.10 SD). The greatest height loss occurred between diagnosis and HSCT (-0.77 SDS, 95% confidence interval -1.42, -0.12, P = 0.01), with no catch-up growth seen by FAH. Patients with solid tumours had the greatest height loss. Overall body mass index SDS did not change significantly over time, or by cancer type. CONCLUSIONS: Chemotherapy-only conditioned HSCT during childhood can impact FAH, with the greatest height loss occurring prior to HSCT and no catch-up growth after treatment finishes. Children transplanted for a solid tumour malignancy seem to be more at risk, possibly due to intensive treatment regimens, both pre-transplant and during conditioning.
Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Adulto , Estatura/efeitos da radiação , Criança , Neoplasias Hematológicas/radioterapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Irradiação Corporal Total/efeitos adversosRESUMO
INTRODUCTION: Adverse neurological events in very low birth weight (VLBW) children with bronchopulmonary dysplasia (BPD) are more frequent than in children without. An understanding of the ages when preterm infants acquire certain motor skills will give parents more appropriate information on motor development. The objective of the present study is to estimate the influence between BPD and the age of acquisition of sitting unsupported and independent walking in VLBW children with normal neurological examination at 2 years of corrected age. PATIENTS AND METHODS: A longitudinal study was conducted on a cohort of 885 children with VLBW, admitted to the Hospital "12 de Octubre" between January 1991 and December 2003. Age for both skills was established by interview with parents. Means were compared with t-test and Bonferroni adjustment where appropriate. RESULTS: Both motor skills were acquired later in the group with BPD (7.8±2m vs. 7.1±1.3m for sitting unsupported and 14.5±3.8m vs. 13.4±2.5m for walking) (P<.001). BPD was associated with delayed acquisition (above p90) of these skills, OR=2.6 (1.6-4.1) for sitting and OR=2.8 (1.6-4.8) for walking. Association was found after adjusting for gestational age (GA) and weight. CONCLUSION: BPD was associated with delayed acquisition of both skills in VLBW children with normal neurological examination at 2 years.
Assuntos
Displasia Broncopulmonar/fisiopatologia , Recém-Nascido de muito Baixo Peso/crescimento & desenvolvimento , Atividade Motora , Feminino , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino , Exame Neurológico , CaminhadaRESUMO
AIMS: The aims of this study is to (i) determine the age of sitting unsupported and independent walking in preterm infants with birth weight under 1500 g (very low birth weight, VLBW); (ii) estimate differences between VLBW children and a reference population and (iii) estimate the association between clinical characteristics and late age at sitting and walking. METHODS: A longitudinal study was conducted of a cohort of 876 children with VLBW. The World Health Organization (WHO) motor development study population was used as a reference. Ages for both skills were established by interview with parents. Means were compared with t-test, ANOVA and Bonferroni adjustment where appropriate. RESULTS: The inclusion criteria were complied with 694 patients; 50% of VLBW sat at 7 m corrected age (CA) and walked at 13 m CA. Both motor skills were acquired later (7.3 +/- 1.5 and 13.6 +/- 2.8 m) compared with the control group (6 +/- 1.1 and 12.1 +/- 1.8 m). Weight or head circumference at birth below the 10th percentile or the presence of bronchopulmonary dysplasia were associated with delayed acquisition of both skills. CONCLUSION: Very low birth weight infants typically sit unsupported and walk later than term infants. Tables describing reference values for milestones acquisition for different categories of infants (gestational age, birth weight and other determinants) may contribute to inform the decision making process on access to available resources.
Assuntos
Desenvolvimento Infantil/fisiologia , Recém-Nascido Prematuro/fisiologia , Recém-Nascido de muito Baixo Peso/fisiologia , Equilíbrio Postural/fisiologia , Caminhada/fisiologia , Fatores Etários , Análise de Variância , Pré-Escolar , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Recém-Nascido de muito Baixo Peso/crescimento & desenvolvimento , Entrevistas como Assunto , Estudos Longitudinais , Destreza Motora , Valores de Referência , Caminhada/estatística & dados numéricosRESUMO
The ribosomal stalk is involved directly in the interaction of the elongation factors with the ribosome during protein synthesis. The stalk is formed by a complex of five proteins, four small acidic polypeptides and a larger protein which directly interacts with the rRNA at the GTPase center. In eukaryotes, the acidic components correspond to the 12 kDa P1 and P2 proteins, and the RNA binding component is protein P0. All these proteins are found to be phosphorylated in eukaryotic organisms. Previous in vitro data suggested this modification was involved in the activity of this structure. To confirm this possibility a mutational study has shown that phosphorylation takes place at a serine residue close to the carboxyl end of proteins P1, P2 and P0. This serine is part of a consensus casein kinase II phosphorylation site. However, by using a yeast strain carrying a temperature sensitive mutant, it has been shown that CKII is probably not the only enzyme responsible for this modification. Three new protein kinases, RAPI, RAPII and RAPIII, have been purified and compared with CKII and PK60, a previously reported enzyme that phosphorylates the stalk proteins. Differences among the five enzymes have been studied. It has also been found that some typical effectors of the PKC kinase stimulate the in vitro phosphorylation of the stalk proteins. All the data available suggest that phosphorylation, although it is not involved in the interaction of the acidic proteins with the ribosome, affects ribosome activity and might participate in some ribosome regulatory mechanism.
Assuntos
Proteínas Fúngicas/metabolismo , Proteínas Ribossômicas/metabolismo , Ribossomos/química , Ribossomos/metabolismo , Leveduras/metabolismo , Sequência de Aminoácidos , Proteínas Fúngicas/química , Regulação da Expressão Gênica , Dados de Sequência Molecular , Fosforilação , Proteínas Quinases/isolamento & purificação , Proteínas Quinases/metabolismo , Proteínas Ribossômicas/química , Proteínas Ribossômicas/genéticaRESUMO
The ribosomal stalk is directly involved in the interaction of the elongation factors with the ribosome during protein synthesis. The stalk is formed by a complex of five proteins, four small acidic polypeptides and a larger protein which directly interacts with the rRNA at the GTPase center. In eukaryotes the acidic components correspond to the 12-kDa P1 and P2 proteins, and the RNA binding component is the P0 protein. All these proteins are found phosphorylated in eukaryotic organisms, and previous in vitro data suggested this modification was involved in the activity of this structure. Results from mutational studies have shown that phosphorylation takes place at a serine residue close to the carboxy end of the P proteins. Modification of this serine residue does not affect the formation of the stalk and the activity of the ribosome in standard conditions but induces an osmoregulation-related phenotype at 37 degrees C. The phosphorylatable serine is part of a consensus casein kinase II phosphorylation site. However, although CKII seems to be responsible for part of the stalk phosphorylation in vivo, it is probably not the only enzyme in the cell able to perform this modification. Five protein kinases, RAPI, RAPII and RAPIII, in addition to the previously reported CKII and PK60 kinases, are able to phosphorylate the stalk proteins. A comparison of the five enzymes shows differences among them that suggest some specificity regarding the phosphorylation of the four yeast acidic proteins. It has been found that some typical effectors of the PKC kinase stimulate the in vitro phosphorylation of the stalk proteins. All the data suggest that although phosphorylation is not involved in the interaction of the acidic P proteins with the ribosome, it can affect the ribosome activity and might participate in a possible ribosome regulatory mechanism.
Assuntos
Biossíntese de Proteínas , Proteínas Ribossômicas/metabolismo , Ribossomos/metabolismo , Sequência de Aminoácidos , Caseína Quinase II , Dados de Sequência Molecular , Fosforilação , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/fisiologia , RNA Mensageiro/metabolismo , Proteínas Ribossômicas/genética , Ribossomos/enzimologia , LevedurasRESUMO
Protein P0, an essential component of the eukaryotic ribosomal stalk, is found phosphorylated in the ribosome. Substitution of serine 302 in the amino acid sequence of the Saccharomyces cerevisiae P0 by either aspartic acid or cysteine abolishes in vitro and in vivo phosphorylation of the protein. On the contrary, the replacement of this serine by a threonine results in an increase in the protein phosphorylation under both sets of conditions. Therefore, this serine residue, which is part of a consensus casein kinase II modification site, SDDD, seems to be the phosphorylation site in protein P0. The effect of the mutations on the protein activity has been tested in S. cerevisiae W303dGP0 and D67dGP0, both of which carry a genomic P0 gene under the control of the GAL1 promoter. Transformation of the mutated genes in S. cerevisiae W303dGP0 allows cell growth at 30 degreesC in glucose-to repress the wild-type P0 expression-at the same rate as controls, and the ribosomes contain a normal amount of the other stalk components. A similar absence of effect of the mutations on growth was found in strain D67dGP0, which has ribosomes deprived of the P1 and P2 proteins. Therefore, P0 phosphorylation is not a requirement for ribosome activity in standard growth conditions either in the presence or in the absence of the other stalk proteins. However, a phenotypic effect is detected in the case of strain D67 transformed with the overphosphorylated threonine containing P0, which contrary to the wild-type and the other mutated proteins is unable to support cell growth at 37 degreesC in the presence of either 0.3 M NaCl or 0.8 M sorbitol. In vitro polymerizing tests indicate that this effect is not due to the thermosensitivity of the mutated protein. The results indicate that although P0 phosphorylation is not required for the overall ribosome activity, it may affect the expression of specific proteins involved in metabolic processes such as osmoregulation.