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Biomedical subjects

D Dobbelaere

Publications and source records attributed to D Dobbelaere.

At least 19 recordsLinked to original sources
PubMed2005

[Fatal neonatal respiratory distress in Niemann-Pick C2 and prenatal diagnosis with mutations in gene HE1/NPC2].

UNLABELLED: We report the fifth case of neonatal form of type C2 (NP-C2) Niemann-Pick disease with early and fatal respiratory distress. Eleven families presenting such cases are known to date in the world. Since December 2000, isolation of the underlying gene HE1/NPC2 and its mutations has allowed major advances in diagnosis. CASE REPORT: Elisa was born in May 2000. NP-C2 disease was associated with severe respiratory distress leading to death at the age of four months. On the next pregnancy in September 2000, prenatal diagnosis was performed by means of biological tests that required four weeks response time. In December 2000, isolation of the HE1/NPC2 gene located to 14q24.3 and of some of its mutations allowed to characterize the patient as being homozygote for the nonsense mutation E20X. On the the two next pregnancies, prenatal diagnosis was performed at 12 SA, in 48 hours, by the means of mutation analysis. The last fetus was heterozygote for the mutation E20X, allowing the birth at term of a healthy male newborn baby. CONCLUSION: Niemann-Pick type C disease is a rare lysosomal lipid storage disease with severe prognosis. It is characterized by abnormalities of intracellular transport of endocytosed cholesterol. Diagnosis relies on biological tests that require cultured cells. Genetic heterogeneity defines two different genetic complementation groups C1 and C2. Severe and early respiratory distress is more likely to be associated with the rare type C2. Since December 2000, after identification of the disease-causing mutations in the proband, mutation analysis of gene HE1/NPC2 on direct chorionic villus samples allows early and fast (48 hours) prenatal diagnosis.

Carrier Proteins↗
PubMed2005

Reduced nuclear translocation of nuclear factor (NF)-kappaB p65 in the footpad epidermis of dogs infected with distemper virus.

Infection of canine footpads with the canine distemper virus (CDV) can cause massive epidermal thickening (hard pad disease), as a consequence of increased proliferation of keratinocytes and hyperkeratosis. Keratinocytes of canine footpad epidermis containing detectable CDV nucleoprotein antigen and CDV mRNA were shown previously to have increased proliferation indices. Because various proteins that play a role in the proliferation of epidermal cells are viral targets, the potential participation of such proteins in CDV-associated keratinocyte proliferation was investigated. Transforming growth factor-alpha (TGF-alpha), cell cycle regulatory proteins p21, p27 and p53, and nuclear factor (NF)-kappaB transcription factor components p50 and p65 were studied in the footpad epidermis from the following groups of dogs inoculated with CDV: group 1, consisting of seven dogs with clinical distemper and CDV in the footpad epidermis; group 2, consisting of four dogs with clinical distemper but no CDV in the footpad epidermis; group 3, consisting of eight dogs with neither clinical distemper nor CDV in the footpad epithelium. Group 4 consisted of two uninoculated control dogs. The expression of TGF-alpha, p21, p27 and p53, and p50 in the basal layer, lower and upper spinous layers, and in the granular layer did not differ statistically between CDV-positive (group 1) and CDV-negative (groups 2-4) footpad epidermis. However, there were differences in the levels of nuclear and cytoplasmic p65 expression between group 1 dogs and the other three groups. Thus, footpads from group 1 dogs had more keratinocytes containing p65 in the cytoplasm and, conversely, fewer nuclei that were positive for p65. These findings indicate that p65 translocation into the nucleus is reduced in CDV-infected footpad epidermis. Such decreased translocation of p65 may help to explain increased keratinocyte proliferation in hard pad disease and suggests interference of CDV with the NF-kappaB pathway.

Animals↗
PubMed2005

[Vitreous hemorrhage in a neonate with galactosemia. A case report].

Galactosemia is an inherited metabolic disorder due to a defect in one of the three enzymes required to fully metabolize the galactose in glucose: the galactose 1-phosphate uridyltransferase. Because this enzyme is present in the normal foetal liver since the tenth week of gestation, its defect cause congenital abnormality due to galactose accumulation, when the mother had taken milk during the pregnancy. It is mainly a liver pathology whereas the foetal cataract is rare. This latter is usually considered as the sole ophthalmic consequence of this disorder but exceptional ocular haemorrhages have also been described. We report the case of a neonate with galactosemia free from foetal cataract but presenting an unilateral vitreous haemorrhage. Retinal anomalies seen after vitrectomy are probably the source of the vitreous blood favoured by the coagulopathy associated with the neonatal disease. The causes of infant vitreous haemorrhages are often debated and their complications, especially severe amblyopia, require vitrectomy within the month following their discovery. In galactosemia, vitreous haemorrhage can be prevented by an early diagnosis and an appropriate treatment of the liver pathology.

Galactosemias↗
PubMed2004

[Gluthathion synthetase deficit in a newborn infant].

CASE REPORT: We report an observation of a triplet newborn presenting with haemolysis, metabolic acidosis with no lactic acidosis revealing a glutathione synthetase deficiency. These biological signs were associated with multiple malformations (IUGR, toes hypoplasia and cerebral ventricular anomalies), not described in this disease. CONCLUSION: This rare diagnosis can be confirmed by elevation of urinary 5-oxoproline. Prognosis is linked to diagnosis and treatment precocity. We have no argument to think that the malformations we found are related to a glutathione synthetase deficiency. However, as the neurological evolution is often unfavourable, neuroradiological explorations could give information about the location and severity of potential cerebral lesions.

Abnormalities, Multiple↗
PubMed2003

Evaluation of nutritional status and pathophysiology of growth retardation in patients with phenylketonuria.

Recent European studies have shown that growth retardation is com-mon in people with phenylketonuria (PKU) during the first years of life while they receive a low-phenylalanine (Phe) diet. The aims of the present study were to assess the growth of our PKU patients and to search for nutritional and hormonal explanations for the growth delay. Twenty PKU patients aged 8 months to 7 years entered the study. The design was cross-sectional, a longitudinal study having already been performed in our centre. The following data were recorded: weight/height (W/H), height/age (H/A), and weight/age (W/A) Z-scores; fat-free mass (measured from bioelectrical impedometry (FFM1), and skinfold thickness (FFMA). Thyroid hormones, insulin-like growth factor I (IGF1), insulin-like growth factor binding protein (IGFBP3), selenium, zinc, and Phe blood levels were measured. Dietary intake was also recorded over 4 days. PKU patients were moderately but significantly shorter (H/A Z-score varied from -2.12 to 1.61; mean -0.49) and lighter (W/A Z-score varied from -2.58 to 1.49; mean -0.71) than the French reference population. Body composition was not different from that of controls matched for age and sex. IGF1, IGFBP3, and thyroid hormone levels were within normal range. All children received more than two-thirds of the recommended daily allowances for energy (91% +/- 18%) and for proteins (146% +/- 26%). The mean daily intake of our patients was sufficient in selenium, but markedly deficient in zinc (2.4 +/- 2.2 mg/day). No correlation was found between zinc daily intake or zinc plasma levels and growth retardation. Moreover, no relation was found between the plasma Phe concentrations, protein or caloric intake and the presence of growth retardation. Our results show that growth retardation in PKU patients is not related to hormonal or caloric deficiencies. Further studies are needed to investigate the effect of various nutrient supplementation regimens (especially zinc) on the growth of PKU patients.

Aging↗
PubMed2002

Neonatal cholestasis and infantile Gaucher disease: a case report.

AIM: To report on clinical complications of liver disease occurring during Gaucher disease. METHODS: A case of Gaucher disease was revealed by neonatal cholestasis and early onset of portal hypertension. RESULTS: At 7 d of age, a newborn was admitted for cholestasis associated with hepatosplenomegaly and thrombocytopenia. At that time, bone marrow aspirate and liver biopsy did not reveal any engorged cells. The clinical course was marked by early progressive portal hypertension, and the patient died of uncontrollable upper gastrointestinal bleeding. The histological results of the postmortem showed that Gaucher cells were present in the liver, spleen and bone marrow. The diagnosis was confirmed by enzymatic studies. CONCLUSION: Isolated neonatal cholestasis could be the first sign of Gaucher disease. Gaucher disease should always be considered in such circumstances, even if, initially, the bone marrow aspirate and liver biopsy do not reveal any engorged cells.

Age of Onset↗
PubMed2001

Soluble interleukin-1 receptor--reverse signaling in innate immunoregulation.

Interleukin-1 (IL-1) is one of the most important proinflammatory cytokines, regulating immunological and inflammatory processes. It induces a very efficient and self-amplifying cytokine-network. The action of IL-1 must, therefore, be under tight control. Soluble IL-1 receptor was thought to be an efficient negative regulator of the IL-1 signaling system. However, recent studies in vitro and in vivo demonstrate that soluble IL-1 receptor can act as an agonist as well, inducing intracellular signaling events. This feature of soluble IL-1 receptor adds a new level of complexity to our understanding of ligand-receptor cross-talk and cell-to-cell communication.

Adjuvants, Immunologic↗
PubMed2001

Apolipoprotein B Arg3500Gln mutation prevalence in children with hypercholesterolemia: a French multicenter study.

BACKGROUND: Familial defective apolipoprotein B-100, a dominantly inherited form of hypercholesterolemia caused by a single Arg3500Gln mutation, is silent in childhood but may confer a high risk of cardiovascular disease in adulthood. The objective was to determine the prevalence of familial defective apolipoprotein B-100 in hypercholesterolemic French children and to provide a basis for targeting screening efforts in this population. METHODS: One hundred ninety children attending 13 pediatric clinics distributed throughout France were included based on the presence of type IIa hypercholesterolemia with a plasma low-density lipoprotein-cholesterol level of more than 130 mg/dL. The Arg3500Gln mutation was detected in dried blood spots using a polymerase chain reaction assay combined with enzymatic restriction. RESULTS: Three hyperlipidemia phenotypes were found: monogenic dominant pure hypercholesterolemia (n = 117), polygenic hypercholesterolemia (n = 43), and combined hyperlipidemia (n = 11). Three unrelated children were heterozygous for the Arg3500Gln mutation; all three had monogenic dominant pure hypercholesterolemia (3/94 families; 3.2%), yielding a prevalence of 1.83% (3/164) in hypercholesterolemic children, which is similar to prevalences reported in European adults. CONCLUSIONS: The familial defective apolipoprotein B-100 mutation was common (1/31) in children with a phenotype of familial hypercholesterolemia, supporting screening in this population with the goal of preventing premature cardiovascular events.

Adolescent↗
PubMed2001

Neonatal severe intractable diarrhoea as the presenting manifestation of an unclassified congenital disorder of glycosylation (CDG-x).

A case of severe and protracted diarrhoea is reported, which started in the neonatal period and progressively associated with neurological impairment, dysmorphy, hepatosplenomegaly, and hepatic insufficiency, from which the patient died at 2 years of age. Isoelectric focusing of serum transferrin showed a congenital disorder of glycosylation type I pattern but the basic defect could not be identified. This observation shows that congenital disorder of glycosylation is a cause of intractable diarrhoea in neonates.

Congenital Disorders of Glycosylation↗
PubMed1999

Interference by the intracellular parasite Theileria parva with T-cell signal transduction pathways induces transformation and protection against apoptosis.

The intracellular parasite Theileria parva transforms bovine T-lymphocytes, inducing uncontrolled proliferation. Upon infection, cells cease to require antigenic stimulation and exogenous growth factors to proliferate. Earlier studies have shown that pathways triggered via stimulation of the T-cell receptor are silent in transformed cells. This is reflected by a lack of phosphorylation of key signalling molecules and the fact that proliferation is not inhibited by immunosuppressants such as cyclosporin and ascomycin that target calcineurin. This suggests that the parasite bypasses the normal T-cells activation pathways to induce proliferation. Among the MAP-kinase pathways, ERK and p38 are silent, and only Jun N-terminal kinase is activated. This appears to suffice to induce constitutive activation of the transcription factor AP-1. More recently, it could be shown that the presence of the parasite in the host cell cytoplasm also induces constitutive activation of NF-kappaB, a transcription factor involved in proliferation and protection against apoptosis. Activation is effectuated by parasite-induced degradation of IkappaBs, the cytoplasmic inhibitors which sequester NF-kappaB in the cytoplasm. NF-kappaB activation is resistant to the antioxidant N-acetyl cysteine and a range of other reagents, suggesting that activation might occur in an unorthodox manner. Studies using inhibitors and dominant negative mutants demonstrate that the parasite activates a NF-kappaB-dependent anti-apoptotic mechanism that protects the transformed cell form spontaneous apoptosis and is essential for maintaining the transformed state of the parasitised cell.

Animals↗
PubMed1999

Transformation of leukocytes by Theileria parva and T. annulata.

Theileria parva and T. annulata provide intriguing models for the study of parasite-host interactions. Both parasites possess the unique property of being able to transform the cells they infect; T. parva transforms T and B cells, whereas T. annulata affects B cells and monocytes/macrophages. Parasitized cells do not require antigenic stimulation or exogenous growth factors and acquire the ability to proliferate continuously. In vivo, parasitized cells undergo clonal expansion and infiltrate both lymphoid and non-lymphoid tissues of the infected host. Theileria-induced transformation is entirely reversible and is accompanied by the expression of a wide range of different lymphokines and cytokines, some of which may contribute to proliferation or may enhance spread and survival of the parasitized cell in the host. The presence of the parasite in the host-cell cytoplasm modulates the state of activation of a number of signal transduction pathways. This, in turn, leads to the activation of transcription factors, including nuclear factor-kappa B, which appear to be essential for the survival of Theileria-transformed T cells.

Animals↗
PubMed1998

AP-1 and ATF-2 are constitutively activated via the JNK pathway in Theileria parva-transformed T-cells.

Bovine T-cells infected by the protozoan parasite Theileria parva undergo lymphoblastoid transformation, and proliferate in an uncontrolled manner. While it has been established that the transcription factor NF-kappa B is constitutively activated in T. parva-infected T-cells, little is known about other transcription factors such as AP-1 and ATF-2. We demonstrated increased binding activity to the AP-1 and CREB/ATF-2 consensus binding sites and show that the AP-1 complex is composed of c-Jun, JunD, c-Fos, and ATF-2. The transcription factors c-Jun and ATF-2 are constitutively phosphorylated in a parasite-dependent manner. Both transcription factors can be phosphorylated by jun-NH2-terminal kinase (JNK), but ATF-2 is also a substrate for p38. We determined whether p38 is activated in T. parva-infected cells. Immunoblot analysis and inhibitor studies indicate that JNK, but not p38, is involved in ATF-2 phosphorylation. Based on these results and previous studies, we conclude that parasite interference with mitogen-activated protein kinase pathways is restricted to constitutive activation of JNK.

Activating Transcription Factor 2↗
PubMed1998

A DNA probe for the detection of Dicrocoelium dendriticum in ants of Formica spp. and Lasius spp.

Repetitive DNA sequences present in the genome of Dicrocoelium dendriticum were identified by hybridization of genomic DNA that had been digested with different restriction enzymes with 32P-labeled genomic D. dendriticum DNA. DNA fragments containing repetitive sequences were isolated from PstI-digested D. dendriticum DNA and were subcloned into a plasmid vector. Plasmids containing repetitive sequences were identified by colony hybridization. One of these plasmids, designated Ddr-IV, was isolated and used as a probe in further studies. Ddr-IV is specific for D. dendriticum since it does not hybridize to DNA isolated from other trematodes. In addition, Ddr-IV was capable of detecting D. dendriticum metacercariae in ants (Formica cunicularia, F. rufibarbis, and Lasius sp.), which act as second intermediate hosts in the parasite's life cycle. Since metacercariae constitute the infectious stage of the parasite for grazing animals, Ddr-IV will provide a useful tool for epidemiology studies of dicrocoeliosis.

Animals↗