PubMed Health⌕ Search

Biomedical subjects

E Werder

Publications and source records attributed to E Werder.

14 recordsLinked to original sources
PubMed2000

No evidence of uniparental disomy 2, 6, 14, 16, 20, and 22 as a major cause of intrauterine growth retardation.

Intrauterine growth retardation (IUGR) is defined as length and/or weight below the 10th percentile. Etiology and, consequently, long-term outcome are extremely heterogeneous with chromosomal abnormalities found in up to 7%. Recently, uniparental disomy (UPD), i.e. the inheritance of both homologues of one pair of chromosomes from only one parent, was found in an increasing number of children with IUGR. Particularly, UPD of chromosome 7 was found in up to 10% of patients with IUGR and/or a phenotype of primordial growth retardation or Silver-Russell syndrome (SRS), but also UPD of chromosomes 2, 6, 14, 16, 20, and 22 was reported in single cases with IUGR. To evaluate impact and relevance of UPD in children with IUGR we investigated 23 sporadic cases with IUGR subsequently diagnosed as primordial growth retardation (n = 13) or SRS (n = 10) by molecular methods for UPD of chromosomes 2, 6, 14, 16, 20, and 22. No instance of UPD was found. Inheritance of all chromosomes investigated was biparental in all cases. Therefore, we conclude that UPD of these chromosomes is not a major cause of IUGR.

Adult↗
PubMed2000

Abundant defective viral particles budding from microglia in the course of retroviral spongiform encephalopathy.

A pathogenetic hallmark of retroviral neurodegeneration is the affinity of neurovirulent retroviruses for microglia cells, while degenerating neurons are excluded from retroviral infections. Microglia isolated ex vivo from rats peripherally infected with a neurovirulent retrovirus released abundant mature type C virions; however, infectivity associated with microglia was very low. In microglia, viral transcription was unaffected but envelope proteins were insufficiently cleaved into mature viral proteins and were not detected on the microglia cell surface. These microglia-specific defects in envelope protein translocation and processing not only may have prevented formation of infectious virus particles but also may have caused further cellular defects in microglia with the consequence of indirect neuronal damage. It is conceivable that similar events play a role in neuro-AIDS.

Animals↗
PubMed2000

17alpha-hydroxylase/17,20-lyase deficiency as a model to study enzymatic activity regulation: role of phosphorylation.

Cytochrome P450 17alpha-hydroxylase (CYP17) is a single gene-encoded protein with two activities: 17alpha-hydroxylase and 17,20-lyase. The two catalytic activities are differentially regulated in health and disease. We took advantage of naturally occurring human mutations to understand the molecular bases of this differential regulation. We identified eight novel mutations in the CYP17 gene, different in nature and spread throughout the gene. As posttranslational modifications appear to be important for activity control, we investigated the phosphorylation state of wild-type and mutant CYP17 proteins. Although phospholabeled protein was seen when the wild-type and most mutant proteins were expressed, no phosphorylation was detected for the F417C mutant. F417C is the only 17,20-lyase deficiency case confirmed at the molecular level and represents the first phosphorylation CYP17-deficient mutant. In search of the physiological agents involved in this process, the effect of cAMP was tested on activity and phosphorylation state of our mutant CYP17 proteins. cAMP stimulates activity and phosphorylation in all cases, except in the F417C and R35L mutants. The lack of response to the physiological second messenger might explain the different phenotypes. The F417C mutant protein, which is already shown to be associated with the lack of electron transfer, provides for the first time a link between the electron transfer system and the phosphorylation state of the CYP17 enzyme in the control of 17,20-lyase activity.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

[Chronic giardiasis with intestinal dwarfism and delayed puberty in immunoglobulin deficiency syndrome: complete catch-up growth after therapy].

A 10-year-old, previously healthy Swiss boy suffered from repeated episodes of watery diarrhea for some months following a summer camp holiday. No etiology was found, and except for symptomatic treatment no other therapy was necessary. Five years later he was investigated because of growth failure, with a bone age of 11.5 years, but the correct diagnosis was not established. Only when he was reinvestigated at the age of 20 years, because of persistent growth failure and a bone age of 14 years, were Giardia lamblia trophozoites seen microscopically on the surface of duodenal mucosa biopsy specimens. At the same time dysgammaglobulinemia was detected which may have predisposed the gastrointestinal tract to chronic giardiasis. After a 10-day course of metronidazole the patient experienced catch-up growth and completed his pubertal development. The dysgammaglobulinemia persisted after therapy. This case showed that in patients with intestinal growth failure, catch-up growth and completion of pubertal development are possible even after the age of 20 years if nutritional supply is sufficient. Bone age determinations serve to indicate remaining growth potential.

Adolescent↗
PubMed1998

Foamy virus particle formation.

Subgenomic expression plasmids for the so-called human foamy virus (HFV) structural gag, gag/pol, and env genes were constructed and used to analyze foamy virus particle formation by electron microscopy. Expression of an R-U5-gag-pol construct under control of the human cytomegalovirus immediate-early enhancer-promoter resulted in the formation of viral cores with a homogeneous size of approximately 50 nm located in the cytoplasm. Upon coexpression of an envelope construct, particles were observed budding into cytoplasmic vesicles and from the plasma membrane. Expression of the Gag protein precursor pr74 alone led to aberrantly formed viral particles of heterogeneous size and with open cores. Normal-shaped cores were seen after transfection of a construct expressing the p70gag cleavage product, indicating that p70gag is able to assemble into capsids. Coexpression of p70gag and Env resulted in budding virions, ruling out a requirement of the reverse transcriptase for capsid or virion formation. In sharp contrast to other retroviruses, the HFV cores did not spontaneously bud from cellular membranes. Radiochemical labeling followed by protein gel electrophoresis also revealed the intracellular retention of Env-deprived HFV capsids.

Humans↗
PubMed1998

An inherited mutation associated with functional deficiency of the alpha-subunit of the guanine nucleotide-binding protein Gs in pseudo- and pseudopseudohypoparathyroidism.

Pseudohypoparathyroidism type Ia (PSP) is a disorder characterized by Albright's osteodystrophy, secondary hyperparathyroidism, lowered Gs activity, and resistance of the urinary cAMP excretion to exogenous PTH. The patients had raised basal serum levels of TSH and/or excessive TSH response to TRH. Here we have described a 38-bp deletion at the exon 1/intron 1 boundary of one Gs alpha allele in two mothers with pseudo-PSP and in six offsprings with PSP of a kindred with Albright's osteodystrophy. The deletion eliminates the splice donor site of exon 1. The pseudo-PSP patients presented decreased Gs activity, but normal urinary cAMP responses to PTH and normal TSH levels and responses to TRH. As monitored during 22 yr, they had normal serum levels of calcium and PTH. The findings demonstrate the same inherited functional defect of Gs alpha in two female patients with pseudo-PSP and in six of their offspring with PSP. The pathogenesis of clinical hypoparathyroidism remains to be clarified.

Adolescent↗
PubMed1997

[Transitory neonatal hypothyroidism caused by transplacental transfer of anti-receptor antibodies of hypophyseal thyroid simulation. Case report and estimated incidence].

Transient neonatal hypothyroidism induced by transplacental transfer of thyrotropin receptor-blocking antibodies is rare, but should be diagnosed early because its course, treatment, and prognosis are different from the other forms of congenital hypothyroidism. Transient neonatal hypothyroidism should be suspected in infants with a history of maternal autoimmune thyroid disease. We describe two siblings whose mother has been treated for idiopathic primary nongoitrous hypothyroidism since adolescence. High levels of thyrotropin receptor-blocking antibodies were first detected in maternal serum at the time of the first child's birth. At the time of the second child's birth antithyroid peroxidase antibodies were found in addition to the thyrotropin receptor-blocking antibodies. Both children were clinically healthy newborns without evidence of congenital malformations. Thyroid suppression, reflected by high levels of TSH during neonatal screening, was transient in both infants. Hormonal substitution was only necessary in one child for a period of 4 months. When tested at the age of 6-7 months, maternal antibodies had completely disappeared from the infants' sera. At ages 7 and 4 years respectively the 2 children do not require treatment and show normal growth and neurodevelopmental skills. In the north-eastern part of Switzerland congenital hypothyroidism has an incidence of one in 3300 live-born infants, the most frequent form being permanent congenital hypothyroidism (1:4500). In this population, analyzed over a period of 16 years, the two cases reported represent the only observations of transient neonatal hypothyroidism due to thyrotropin receptor-blocking antibodies; the incidence can thus be estimated to be approximately 1:310,000 live newborns. In this rare condition, early recognition is pertinent in order to avoid unnecessary treatment and parental anxiety.

Adolescent↗
PubMed1993

Neurological and adrenal dysfunction in the adrenal insufficiency/alacrima/achalasia (3A) syndrome.

Review of 20 patients with glucocorticoid deficiency (three cases also with salt loss) associated with absent tear secretion (19 cases) and achalasia of the cardia (15 cases) revealed neurological abnormalities in 17 including hyper-reflexia, muscle weakness, dysarthria, and ataxia together with impaired intelligence and abnormal autonomic function, particularly postural hypotension. These findings indicate that significant neurological problems are common in this multisystem disorder.

Addison Disease↗
PubMed1982

Inhibition of cytochemical bioactivity of parathyroid hormone by plasma in pseudohypoparathyroidism type I.

Despite the high circulating levels of immunoreactive PTH in patients with pseudohypoparathyroidism type I (PSPI) the levels of bioactive PTH (bioPTH) have been found to be close to the normal range. To elucidate this dissociation, we have studied the recovery of the biological activity of bovine PTH added to the plasma of patients with either PSPI, or with hypoparathyroidism (PTX), primary hyperparathyroidism (HPT) or of normal subjects. In PSPI (n = 10) the recovery of biological activity was 5.6% +/- 3.6 (mean +/- SEM) whereas in PTX (n = 7), in HPT (n = 4) and in normal subjects (n = 8) it was 79% +/- 5, 75% +/- 9 and 68% +/- 4, respectively. In another PSPI patient, who had undergone total parathyroidectomy, bioPTH was undetectable but the recovery from the plasma of added PTH was 84%. Thus we have found inhibition of PTH bioactivity by plasma of PSPI patients which was absent after parathyroidectomy.

Animals↗