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D Lindhout

Publications and source records attributed to D Lindhout.

At least 109 records · Page 6Linked to original sources
PubMed1989

Individuals with only one allele for a functional insulin receptor have a tendency to hyperinsulinaemia but not to hyperglycaemia.

Recently, we described a leprechaun patient with a genetically transmitted severe insulin resistance due to the absence of functional insulin receptors as inferred from the loss of insulin binding to the patients' fibroblasts and the impaired autophosphorylation of the beta-chain of the receptor. This patient was homozygous for the genetic defect which was recently found to be a leucine to proline mutation at position 233 in the alpha-chain of the insulin receptor. In the present study we have examined insulin receptor functions in relatives of this patient. Some of these individuals are heterozygous for the genetic defect and have only one allele coding for a functional insulin receptor. Insulin binding to cultured fibroblasts from the heterozygous individuals is only 20-40% of control values indicating a Mendelian mode of inheritance of the binding defect. In contrast, insulin stimulated autophosphorylation of the beta-chain of the insulin receptor shows normal values, indicating compensation mechanisms operating on this process. The stimulation of the basal level of 2-deoxyglucose uptake by insulin in fibroblasts from the homozygous patient is 1.2 fold whereas the heterozygous and control individuals show stimulation values of approximately 1.65 fold. Basal levels of 2-deoxyglucose uptake are similar in these fibroblasts. Oral glucose tolerance tests on the heterozygous individuals indicate an increased requirement for insulin of the target tissues as concluded from the tendency towards hyperinsulinaemia with no observed hyperglycaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The diagnostic management of newborns with congenital contractures: a nosologic study of 75 cases.

A prospective clinical study is presented of 75 patients with multiple congenital contractures. With the data from medical history, child neurologic examinations, laboratory tests including chromosome and dermatoglyphic analysis, and neuropathology in 23 cases with perinatal death, a nosological or syndromal diagnosis was made in 61 cases. These cases were classified by localization of causal pathology in the categories "cerebral dysgenesis", spinal cord defects, neuromuscular disorders and miscellaneous disorders without muscle weakness. Following this concept, the various modes of inheritance of specific disorders presenting with congenital contractures, as well as possibilities for prenatal diagnosis by ultrasonography are discussed. A guideline for the child neurologic evaluation of infants with congenital contractures is proposed. It is concluded that: 1) specification of the causal lesion and proper classification of disorders with congenital contractures is crucial for genetic counseling, (prenatal) diagnosis and management; 2) the analysis of dermatoglyphics in differential diagnosis of congenital contractures should be restudied; and 3) more study and experience is required in the observation of abnormal or decreased fetal movements by ultrasonography.

Brain↗
PubMed1988

Fibroblasts from a leprechaun patient have defects in insulin binding and insulin receptor autophosphorylation.

Leprechaunism is an inherited human disorder associated with an extreme resistance of the target cells towards the action of insulin. We have examined the properties of the insulin receptor in fibroblasts from a leprechaun patient (Geldermalsen, the Netherlands). In vitro, severe insulin resistance is reflected by a low level of insulin stimulated uptake of 2-deoxyglucose by these fibroblasts. This defect seems to be caused by a combination of two factors: a low level of insulin binding to intact cells and a strong decrease of insulin stimulated autophosphorylation of the receptor. The stimulation of autophosphorylation by insulin was approximately six-fold in control subjects and less than two-fold in the patient. No abnormalities were observed in the total number of insulin receptors in these cells and the molecular weights of the receptor subunits. In addition, the insulin concentration required for half maximal autophosphorylation is similar for the solubilised receptor from control and patient fibroblasts.

Cells, Cultured↗
PubMed1988

Ventricular septal defect with overriding aorta in trisomy-18.

In a child with trisomy-18 prenatal echocardiography demonstrated the presence of a ventricular septal defect with overriding aorta. In a previous anatomical study of 18 hearts with this malformation we found a 50% concurrence rate with trisomy-18. In case of prenatal echocardiographic detection of a ventricular septal defect with overriding aorta, we advise thorough ultrasound examination for additional malformations as seen in trisomy-18; subsequently this procedure should be completed by cytogenetic analysis of amniotic cells.

Aorta↗
PubMed1988

The role of ultrasound in the early diagnosis of fetal structural defects following maternal anticonvulsant therapy.

A total of 162 pregnant subjects using anticonvulsant drugs were examined for fetal congenital defects over a period of five years. In 138 of these subjects, alpha-feto-protein (AFP) levels were determined in amniotic fluid at 16 weeks of gestation to rule out spina bifida. In all instances, a fetal anomaly scan was performed between 18 and 20 weeks of gestation. AFP levels were always within the normal range; neonatal examination revealed no spina bifida; however, in seven newborns, a single, or multiple structural defect was established. Apart from cases of severe hydrocephaly, hypospadia, and radius aplasia, the anomalies were too small to be detected by present-day ultrasound equipment. Couples should be informed of the limitations of ultrasound in the early detection of structural defects previously associated with the use of anticonvulsant drugs.

Abnormalities, Drug-Induced↗
PubMed1987

Premature centromere division (PCD): a dominantly inherited cytogenetic anomaly.

We describe a family with an increased frequency of cells with premature centromere division (PCD) of all chromosomes in four phenotypically normal individuals. This familial PCD phenomenon is apparently different from the well-described PCD of the X chromosome and from the centromere splitting in cells of patients with Roberts syndrome. Implications for genetic counseling are discussed.

Centromere↗
PubMed1987

The heterogeneity of the Pena-Shokeir syndrome.

There is evidence that the Pena-Shokeir syndrome is not a specific phenotype but should be regarded as a "fetal akinesia deformation sequence". A neuropathological study of six random new cases was performed to evaluate this theory. Brain pathology observed included persistent fetal meningeal vascularization (two cases), agenesis of the septum pellucidum (one case) and hydranencephaly (one case). Investigation of the spinal cord (in two cases) revealed no abnormalities. Muscle histology (in four cases) was indicative of neurogenic atrophy in two cases. These findings are compared with the data of the 28 cases previously described. It is concluded that the Pena-Shokeir syndrome is a heterogeneous syndrome in which cerebral lesions may play an important role in the pathogenesis. The cerebral malformations may also indicate the time of origin and contribute in the perinatal death of this syndrome.

Abnormalities, Multiple↗
PubMed1986

Concordant cerebral oligodendroglioma in identical twins.

A case of concordant oligodendroglioma in monozygotic twins is reported. The twins were also concordant for uterine leiomyoma and one twin partner had fibroadenoma and lipoma of the breast and myelofibrosis. As very few cases of concordant glioma in monozygotic twins have been published and no such cases in dizygotic twins, a genetic influence in the aetiology of glioma can only be suggested.

Brain Neoplasms↗
PubMed1985

The Pena-Shokeir syndrome: report of nine Dutch cases.

We report on nine individuals with the Pena-Shokeir syndrome. Clinical findings are compared with data on patients from the literature. Emphasis is made on genetic background, neuropathological findings, and (in two cases) on prenatal data. Possible pathogenetic mechanisms are discussed.

Abnormalities, Multiple↗
PubMed1985

Fibrodysplasia ossificans progressiva: current concepts and the role of CT in acute changes.

Fibrodysplasia ossificans progressiva (FOP) may be treated with diphosphonate in an attempt to control the deposition of calcium phosphate. Amounts of calcium deposition may be assayed by plain radiographs and CT. In a sporadic case of FOP treated for 6 years with a diphosphonate (EHDP) we have analyzed the findings from CT. This modality presents a suitable means of monitoring response to new therapeutic agents, but CT also gives insights into the pathogenesis of the disorder.

Child↗