45 research outputs found
Congenital Diarrhea and Cholestatic Liver Disease: Phenotypic Spectrum Associated with MYO5B Mutations
Myosin Vb (MYO5B) is a motor protein that facilitates protein trafficking and recycling in polarized cells by RAB11- and RAB8-dependent mechanisms. Biallelic MYO5B mutations are identified in the majority of patients with microvillus inclusion disease (MVID). MVID is an intractable diarrhea of infantile onset with characteristic histopathologic findings that requires life-long parenteral nutrition or intestinal transplantation. A large number of such patients eventually develop cholestatic liver disease. Bi-allelic MYO5B mutations are also identified in a subset of patients with predominant early-onset cholestatic liver disease. We present here the compilation of 114 patients with disease-causing MYO5B genotypes, including 44 novel patients as well as 35 novel MYO5B mutations, and an analysis of MYO5B mutations with regard to functional consequences. Our data support the concept that (1) a complete lack of MYO5B protein or early MYO5B truncation causes predominant intestinal disease (MYO5B-MVID), (2) the expression of full-length mutant MYO5B proteins with residual function causes predominant cholestatic liver disease (MYO5B-PFIC), and (3) the expression of mutant MYO5B proteins without residual function causes both intestinal and hepatic disease (MYO5B-MIXED). Genotype-phenotype data are deposited in the existing open MYO5B database in order to improve disease diagnosis, prognosis, and genetic counseling.This research was funded by Jubiläumsfonds der Österreichischen Nationalbank, grant no.16678 (to A.R.J.), grant no. 18019 (to G.-F.V.) and Tiroler Wissenschaftsfonds, grant No. 0404/2386 (toG.-F.V.).info:eu-repo/semantics/publishedVersio
Alberta Infant Motor Scale (AIMS) Performance of Early-Term Greek Infants: The Impact of Shorter Gestation on Gross Motor Development among “Term-Born” Infants
Early-term birth (37+0 to 38+6 gestational weeks) may have a negative impact on infants’ neurodevelopment compared to delivery at 39 weeks or beyond. The purpose of this study was to evaluate the gross motor development of early-term infants using the Alberta Infant Motor Scale (AIMS). A total of 1087 healthy infants (559 early-term and 528 full-term infants born at 39+0 to 41+6 weeks of gestation) were studied. Mean AIMS scores were compared between the two groups at monthly intervals. The impact of gestational age on total AIMS scores was assessed by linear regression, after adjustment for chronological age, sex and SGA. Mean total AIMS scores, albeit within normal range, were significantly lower in early-term than full-term infants at the 2nd, 6th, 7th, 8th and 12th month of age; differences between groups were within three points. In multivariate regression analysis, a longer gestation by one week had a positive impact on total AIMS score during the first year of life (β = 0.90; 95% CI 0.45, 1.35). In conclusion, early-term infants exhibit worse gross motor performance during the first year of life in comparison with their full-term peers; however, the differences between the two groups are small
Alberta Infant Motor Scale (AIMS) Performance of Early-Term Greek Infants: The Impact of Shorter Gestation on Gross Motor Development among “Term-Born” Infants
Early-term birth (37(+0) to 38(+6) gestational weeks) may have a
negative impact on infants’ neurodevelopment compared to delivery at 39
weeks or beyond. The purpose of this study was to evaluate the gross
motor development of early-term infants using the Alberta Infant Motor
Scale (AIMS). A total of 1087 healthy infants (559 early-term and 528
full-term infants born at 39(+0) to 41(+6) weeks of gestation) were
studied. Mean AIMS scores were compared between the two groups at
monthly intervals. The impact of gestational age on total AIMS scores
was assessed by linear regression, after adjustment for chronological
age, sex and SGA. Mean total AIMS scores, albeit within normal range,
were significantly lower in early-term than full-term infants at the
2nd, 6th, 7th, 8th and 12th month of age; differences between groups
were within three points. In multivariate regression analysis, a longer
gestation by one week had a positive impact on total AIMS score during
the first year of life (beta = 0.90; 95% CI 0.45, 1.35). In conclusion,
early-term infants exhibit worse gross motor performance during the
first year of life in comparison with their full-term peers; however,
the differences between the two groups are small
Peptide YY (3-36) represents a high percentage of total PYY immunoreactivity in preterm and full-term infants and correlates independently with markers of adiposity and serum ghrelin concentrations
The gut hormone peptide YY 3-36 [PYY (3-36)] has been suggested to
posses anorexigenic actions in animals and human adults. However, its
circulating concentrations and function have not been studied in
neonates. Serum concentrations of PYY (3-36) were determined by RIA
(RIA) in 62 healthy preterm infants [mean(SD) gestational age,
32.0(2.1) weeks; postnatal age, 40.9(14.8 d)] and 15 healthy fullterm
infants of comparable postnatal age and gender. The correlations between
PYY (3-36) levels and anthropometric characteristics, food intake,
growth rates and circulating concentrations of total PYY, ghrelin,
leptin, insulin and adiponectin were examined. Mean (SD) PYY (3-36)
concentrations were higher in preterm [543.7(157.6) ng/L] than full
term infants [350.9(114.1) ng/L; p < 0.001] and accounted for 48% and
42% of total PYY basal plasma immunoreactivity in preterm and full term
infants, respectively. In multiple regression analysis, PYY (3-36)
concentrations correlated negatively with the infants’ BMI and
positively with serum ghrelin concentrations, but not with caloric
intake, weight gain or concentrations of any other hormone studied. In
conclusion, PYY (3-36) represents almost half of total PYY
immunoreactivity in neonates. It’s correlations with ghrelin and BMI
suggest a role of this peptide in the regulation of energy homeostasis;
however, its specific functions and physiologic significance in neonates
remain to be elucidated
Circulating visfatin levels in healthy preterm infants are independently associated with high-density lipoprotein cholesterol levels and dietary long-chain polyunsaturated fatty acids
The adipokine visfatin has been proposed to exert insulin-mimicking
effects and to play a role in the development of metabolic syndrome.
Preterm infants are at risk for the later development of insulin
resistance and, possibly, for other components of metabolic syndrome.
Dietary long-chain polyunsaturated fatty acids (LCPUFAs) during the
perinatal period may reduce the risk of metabolic syndrome. The authors’
objective was to study the circulating concentrations of visfatin in
preterm infants and to examine associations of visfatin with
anthropometric measurements, metabolic indices, and dietary LCPUFAs.
Serum visfatin concentrations were determined by enzyme-linked
immunosorbent assay at mean (SD) 33.8 (11.7) days of life in 60 healthy
preterm infants (gestational age, 32.7 [1.9] weeks) randomly assigned
to be fed since birth either a formula containing LCPUFA (arachidonic
and docosahexaenoic acid) (+LCPUFA group) or the same formula without
LCPUFA (-LCPUFA group). Associations of visfatin with anthropometric
parameters, serum glucose, insulin, homeostasis model assessment index
of insulin resistance, blood lipids, and adiponectin levels were
examined. Serum visfatin levels were significantly higher in the +LCPUFA
than in the -LCPUFA group (P < .001) and correlated positively with body
weight z score (beta = 0.31, P = .02), total cholesterol (beta = 0.34, P
= .01), high-density lipoprotein cholesterol (HDL-C) (beta = 0.47, P <
.001), and adiponectin levels (beta = 0.29, P = .03), but not with
indices of insulin sensitivity. In multiple regression analysis, HDL-C
and dietary LCPUFAs correlated independently with serum visfatin levels.
Circulating visfatin levels in preterm infants are independently
associated with HDL-C levels and dietary LCPUFAs. Whether the higher
visfatin levels in the +LCPUFA preterm infant group are beneficial for
the later health of these infants remains to be determined. (C) 2011
Elsevier Inc. All rights reserved
Disparity in circulating adiponectin multimers between term and preterm infants
Aims: To study circulating levels and distribution of adiponectin multimers [low molecular weight (LMW)-, medium molecular weight (MMW)- and high molecular weight (HMW)-adiponectin] in preterm and full-term infants. Methods: Total serum adiponectin and its multimers were measured in 40 healthy infants at the age of one month and associations with anthropometric parameters [body weight and length, body mass index (BMI)], weight gain and metabolic indices (glucose, insulin) were examined. Twenty of the infants were born preterm (gestational age 33.2±1.6 weeks). Results: LMW-adiponectin level and its fractional ratio to total adiponectin were significantly higher in full-term than in preterm infants (P<0.001 and P<0.01, respectively), whereas, MMW-adiponectin level and its ratio were significantly lower (P=0.03 and P=0.01, respectively). HMW-adiponectin did not differ significantly between full-term and preterm infants and accounted for almost 60% of total adiponectin levels in both groups. HMW-adiponectin, but not MMW adiponectin or LMW adiponectin, correlated significantly with anthropometric measurements, similarly to total adiponectin; in addition, HMW adiponectin correlated significantly with weight gain. Conclusions: HMW adiponectin is the most prevalent form in infants. Circulating levels and distribution of MMW- and LMW-adiponectin differ between full-term and preterm infants, but the role of these adiponectin multimers needs to be studied further.Peer Reviewe
HNA-1d: a new human neutrophil antigen located on Fc gamma receptor IIIb associated with neonatal immune neutropenia
BackgroundNeonatal immune neutropenia (NIN) is a rare, but potentially
life-threatening, disorder caused by maternal alloantibodies recognizing
paternal neutrophil antigens on fetal cells. Alloantibodies directed
against the human neutrophil alloantigen system (HNA)-1 located on Fc
receptor IIIb (FcRIIIb) are most frequently implicated in NIN. In this
report, we describe two cases of NIN with alloantibodies against
FcRIIIb, which did not match one of the known HNA-1a, -1b, or -1c
specificities, but define a new antigen, HNA-1d.
Study Design and MethodsNeutrophil-reactive antibodies were detected by
agglutination, microscopic immunofluorescence, and monoclonal antibody
(MoAb)-specific immobilization of neutrophil antigens (MAIGA) assay. For
epitope mapping of FcRIIIb-reactive antibodies, recombinant chimeric
variants of FcRIIIb were used in the MAIGA assay. Genotyping of FCGR3B
was performed by allele-specific polymerase chain reaction.
ResultsBoth mothers were typed FCGR3B*01+, *02-, *03+. Antibody
screening revealed the presence of alloantibodies reactive with FcRIIIb
encoded by FCGR3B*02, but not with FcRIIIb encoded by FCGR3B*03.
MAIGA with recombinant, partly chimeric FcRIIIb variants demonstrated
that the antigen recognized by maternal antibodies is characterized by
two amino acids, Ala78 and Asp82. Among the FCGR3B alleles, the sequence
Ala78—Asn82 is exclusively encoded by FCGR3B *02.
ConclusionA previously unrecognized second antigen, HNA-1d, is present
on FcRIIIb encoded by FCGR3B*02. This antigen is characterized by the
sequence Ala78—Asn82. It appears that only individuals carrying the
HNA-1c phenotype can form anti-HNA-1d alloantibodies. The HNA-1 system
now consists of four antigens encoded by three alleles
Association of Plasma Irisin Levels with Circulating Endothelial Microparticles (EMPs) and Endothelial Progenitor Cells (EPCs) in Children Born Prematurely
Prematurity has been linked with endothelial dysfunction in later life. The purpose of this study was to evaluate the association between plasma irisin, an adipomyokine reported to protect the functional integrity of vascular endothelium, and circulating endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs), consisting early biomarkers of endothelial dysfunction, in preterm-born children. We studied 131 prepubertal children; 61 preterm and 70 born at term (controls). Plasma irisin was determined by ELISA. Circulating CD62E(+), CD144(+) and CD31(+)/CD42b(-) EMPs, and CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs, were determined by flow cytometry. Body mass index, waist-to-hip ratio, neck circumference, systolic and diastolic blood pressure, and biochemical parameters (glucose, lipids, insulin, HOMA-IR) were also evaluated. Plasma irisin was significantly lower (p = 0.001), whereas circulating EMPs and EPCs were higher, in children born prematurely compared to controls. Irisin was recognized as independent predictor for CD144(+) and CD31(+)/CD42b(-) EMPs, CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs in the total study population, and for CD31(+)/CD42b(-) EMPs in the preterm group. In conclusion, plasma irisin correlates independently with circulating EMP and EPC subpopulations in prepubertal children and in preterm-born ones. Further studies in children will potentially elucidate the link between irisin and the primary stages of prematurity-related endothelial dysfunction