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Biomedical subjects

D Knorr

Publications and source records attributed to D Knorr.

At least 19 recordsLinked to original sources
PubMed1992

Identification of molecular defects causing congenital adrenal hyperplasia by cloning and differential hybridization of polymerase chain reaction-amplified 21-hydroxylase (CYP21) genes.

Congenital adrenal hyperplasia (CAH), one of the most common autosomal recessive disorders, is caused primarily by defects in the gene encoding steroid 21-hydroxylase, CYP21B. The molecular diagnosis of CAH, important for prenatal diagnosis, carrier detection, and a better understanding of the various clinical CAH forms, is complicated by the close proximity of a highly similar pseudogene, CYP21A, containing (and probably donating, by gene conversion-like events) most of the defects underlying CAH. In this study, we describe an efficient strategy to identify molecular defects causing CAH: polymerase chain reaction-amplified CYP21 loci are cloned and hybridized to a set of oligonucleotides, allowing rapid and allele-specific identification of all known CYP21B mutations relevant to 21-hydroxylase function. Possible new mutations can be identified by subsequent nucleic acid sequencing provided they reside within the cloned CYP21B fragment (from the TATA box to the 8th of the 10 CYP21B gene exons). Using this method, the CYP21B gene mutations of a heterozygous carrier and 25 CAH patients have been identified by oligonucleotide hybridization. All disease haplotypes seem to have been generated by recombinational events involving the CYP21A pseudogene. In 5 individuals, these data were subsequently verified by nucleic acid sequencing. The procedure can be used for diagnostic applications and may facilitate identification of new CYP21B defects.

Adrenal Hyperplasia, Congenital↗
PubMed1992

Clinical heterogeneity of 21-hydroxylase deficiency of sibs with identical 21-hydroxylase genes.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a disorder with different clinical manifestations, that results from mutations in the P-450(c21) gene. Direct sequence analysis of P-450(c21) genes in a family demonstrates that patients with different clinical forms of congenital adrenal hyperplasia can have identical P-450(c21) genes, suggesting that other effects play a role in developing the different clinical forms.

Adrenal Hyperplasia, Congenital↗
PubMed1992

[Adrenal cortex carcinoma. A rare cause of a Conn syndrome in childhood].

A 2 1/3 year old girl presented classical Conn-Syndrome as diagnostic feature of an adrenocortical carcinoma. Sonographic diagnosis was confirmed by CT-scan, typical hormonal pattern and subsequent surgical procedure. Without further therapy there has been no relapse with a follow-up of 3 years.

Adrenal Cortex Hormones↗
PubMed1991

Prenatal diagnosis of 21-hydroxylase deficiency by RFLP analysis of the 21-hydroxylase, complement C4, and HLA class II genes.

In 19 pregnancies at risk for 21-hydroxylase deficiency (21OHD) in 18 families with at least one affected child, prenatal diagnosis was performed by RFLP analysis using the enzymes Taq I and EcoRI and the DNA probes specific for the 21OH genes, the closely linked complement C4 genes and the highly polymorphic HLA class II genes DRB, DQB, and DPB. For fetal DNA analysis either chorionic villi or cultivated amniotic cells were used. In all 19 cases, a clear prenatal diagnosis was possible either with the 21OH probe alone or in most cases, by combining the results of the different closely linked loci.

Adrenal Hyperplasia, Congenital↗
PubMed1991

Surgery for benign and malignant diseases of the thyroid gland in childhood.

From 1970 to 1986, 51 children and adolescents aged 5-18 years were operated on for diseases of the thyroid gland, among them 42 with benign diseases (juvenile goiter 21, adenoma 17, Graves' disease 3, Hashimoto's thyroiditis 1) and nine with malignancies (papillary carcinoma 4, follicular carcinoma 3, medullary carcinoma 1, anaplastic carcinoma 1). In benign entities, females were three times as often affected as males, whereas both sexes were equally affected in malignancies. Positive family histories were found in 23.3% of the children with adenomas in 71.4% of the children with juvenile goiters. Subtotal strumectomy was carried out in 30 instances and enucleation in 12. Iodized salt and L-thyroxine were given postoperatively as recurrence prophylaxis. Recurrence was seen in two children (4.8%) who had no recurrence prophylaxis. Symptoms in children with malignancies were palpable cervical lymph nodes and solitary nodes in the thyroid gland. Total thyroidectomy was done in all instances, followed by radio-iodine treatment in eight cases and cobalt 60 irradiation in one case. Two children died, of diffuse metastases and irradiation fibrosis of the lung respectively. The peculiarities of diseases of the thyroid gland in childhood that require surgery are discussed.

Adenocarcinoma↗
PubMed1990

The P30 movement protein of tobacco mosaic virus is a single-strand nucleic acid binding protein.

The P30 protein of tobacco mosaic virus (TMV) is required for cell to cell movement of viral RNA, which presumably occurs through plant intercellular connections, the plasmodesmata. The mechanism by which P30 mediates transfer of TMV RNA molecules through plasmodesmata channels is unknown. We have identified P30 as an RNA and single-stranded (ss) DNA binding protein. Binding of purified P30 to ss nucleic acids is strong, highly cooperative, and sequence nonspecific with a minimal binding site of 4-7 nucleotides per P30 monomer. In-frame deletions across P30 were used to localize the ss nucleic acid binding domain to within amino acid residues 65-86 of the protein. We propose that binding of P30 to TMV RNA creates an unfolded protein-RNA complex that functions as an intermediate in virus cell to cell movement through plasmodesmata.

Chromosome Deletion↗
PubMed1990

Pseudohypoaldosteronism in eight families: different forms of inheritance are evidence for various genetic defects.

Pseudohypoaldosteronism is a rare hereditary disorder presenting in early infancy with renal salt loss leading to hyponatremia and hyperkalemia despite high levels of plasma aldosterone. The patients are insensitive to mineralocorticoids; however, sodium supplementation is able to correct electrolyte abnormalities. Absent or greatly diminished type I aldosterone receptors in peripheral mononuclear leucocytes have been recently demonstrated and explain the lack of response to mineralocorticoids. We have studied the mode of inheritance in eight families with a total of nine patients. There was evidence for an autosomal recessive form of inheritance in four families, while the other four families appeared to have an autosomal dominant mode of transmission. In three families the autosomal recessive form was characterized by normal receptor as well as hormone data in both parents, while in one family receptor levels in both parents were greatly reduced, but hormone levels were normal. In the four families with an autosomal dominant mode of transmission there was always one parent with reduced receptor binding in peripheral mononuclear leucocytes and elevated serum hormone levels. These parents were entirely asymptomatic. In an extended family we were able to study an aunt and her newborn daughter, who were both also biochemically affected but clinically asymptomatic. It, therefore, appears that this dual pattern of genetic transmission may indicate differing genetic defects which cause the same clinical picture of pseudohypoaldosteronism.

Adolescent↗
PubMed1990

HLA class I-, complement C4- and 21-hydroxylase probes in the genetic analysis of 21-hydroxylase deficiency.

In order to develop an optimal strategy for the prenatal diagnosis of steroid 21-hydroxylase (EC 1.14.99.10) deficiency, we investigated 16 affected families with salt wasting syndrome. Genomic DNA derived from peripheral white blood cells was digested with 6 different restriction enzymes. Hybridisation was carried out with DNA-probes of the HLA class I region, the 21-hydroxylase- and the complement C4 genes. All the families were informative in at least three different loci. Twelve out of the 16 families were informative by neutral polymorphisms or disease related variants of the 21-hydroxylase gene or the adjoining C4 locus. The reliability of prediction in these cases exceeded 99%. The remaining 4 families were informative only in the HLA class I region, tantamount to a reliability of prediction of about 98%. In none of the cases did we have to fall back on semiquantitative gene dose assessments. We further describe new polymorphisms in the 21-hydroxylase region for the enzyme Pvu II and EcoR V.

Adolescent↗
PubMed1990

[Experiences with specific screening for early detection of congenital adrenogenital syndrome with 21-hydroxylase defect].

In Southern Bavaria over 32 months a total of 575 newborn babies was selectively screened for CAH due to 21-hydroxylase deficiency. Whenever one of the 3 key symptoms "failure to thrive", "ambiguous or atypical genitalia" and/or "positive family history" were present, a small plasma sample was drawn for the rapid and centralized radioimmunologic determination of 17-hydroxyprogesterone (17-OHP) and cortisol. Pathologically elevated 17-OHP plasma levels were found in 9 babies with CAH in whom adequate replacement therapy with gluco- and mineralocorticoids could be initiated without delay. On the basis of a mean birth rate of 60 000 per year a relatively low prevalence of 1:20 000 was calculated. It is likely that this is due to the fact that such a selective newborn screening program fails to detect the clinically normal male infants with simple virilizing CAH.

Adrenal Hyperplasia, Congenital↗
PubMed1989

Longitudinal study of progestins, mineralocorticoids, and glucocorticoids throughout human pregnancy.

The maternal adrenal cortex seems to be involved in the adaptation to pregnancy. To study in detail adrenocortical secretion during pregnancy, we measured plasma aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, and cortisone simultaneously by RIA after extraction and automated Sephadex LH-20 chromatography of 10 normal pregnant women longitudinally throughout pregnancy at weeks 8-10, 14-17, 21-24, 28-32, and 38 as well as at the time of admission to the delivery room. The mean plasma progesterone and 17-hydroxy-progesterone concentrations increased from 37.2 +/- 6.5 (+/- SE) and 8.2 +/- 1.0 nmol/L, respectively, in early gestation to maximum levels of 138.0 +/- 25.7 and 22.8 +/- 2.2 nmol/L at week 38 (P less than 0.01). Plasma glucocorticoid levels rose 2- to 3-fold (P less than 0.01) from weeks 8-10 (corticosterone, 18.5 +/- 5.4; 11-deoxycortisol, 1.9 +/- 0.2; cortisone, 24.2 +/- 4.2; cortisol, 195.5 +/- 37.6 nmol/L) to week 38 (corticosterone, 42.9 +/- 11.2; 11-deoxycortisol, 4.6 +/- 0.5; cortisone, 71.5 +/- 13.6; cortisol, 420 +/- 63 nmol/L). Similarly, plasma mineralocorticoid levels increased 5- to 7-fold (P less than 0.01) from weeks 8-10 (11-deoxycorticosterone, 0.69 +/- 0.12; aldosterone, 0.41 +/- 0.08 nmol/L) to maximum levels at week 38 (5.3 +/- 0.9 and 2.1 +/- 0.3 nmol/L, respectively). At the time of admission to the delivery room, plasma 11-deoxycortisol, corticosterone, and cortisol concentrations were higher (P less than 0.02) than at 38 weeks, but plasma progestin and mineralocorticoid concentrations were not. We conclude that the source of the elevated maternal corticosteroid levels in pregnancy in addition to the estrogen-mediated rise in corticosteroid-binding globulin is the maternal adrenal cortex itself. The peak glucocorticoid levels at admission to the delivery room reflect increased maternal and fetal stress with the onset of labor.

17-alpha-Hydroxyprogesterone↗
PubMed1987

The effects of cyproterone acetate on statural growth in children with precocious puberty.

Forty-four patients (42 f, 2 m) with precocious puberty (31 idiopathic, 1 familial, 7 cerebral, 5 McCune-Albright) were treated with cyproterone acetate for periods of 1-8.75 years in different (P less than 0.05) daily dosages of 117 +/- 6.1 mg/m2 per day (mean +/- SEM, group A, N = 20) and 60.8 +/- 2.42 mg/m2 per day (group B, N = 24). Thirty-three girls had experienced menarche before therapy at a mean age of 4.89 +/- 0.42 years. Treatment was started at a chronologic age of 5.45 +/- 0.33 years in the girls and 5.74 +/- 1.34 years in the boys. At the time of evaluation, 31 of our patients had reached final height. With respect to the effects of treatment on statural growth, the Standard Deviation Scores were retrospectively determined for height, weight, and growth velocity. The initial Bayley-Pinneau height predictions were compared with final height and target height, and the skeletal maturation was studied. There were no significant differences between those parameters in the patients of group A and B or between treated and untreated subjects as far as final height and target height were concerned. It is concluded that cyproterone acetate administered orally at daily doses from 50-150 mg/m2 does not improve statural growth of patients with precocious puberty.

Body Height↗
PubMed1987

Increased plasma cyclic guanosine monophosphate concentrations in children with high levels of circulating atrial natriuretic peptide.

Simultaneous measurements of plasma atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (GMP) concentrations were performed in children with various forms of cardiac diseases (n = 22) and in control children (n = 29). In healthy children, plasma ANP and cyclic GMP levels ranged between 2.4 and 98.0 (mean 45.8) pg/mL and 0.2 to 2.8 (mean 1.40) pmol/mL, respectively. In children with cardiac diseases, plasma ANP (26.0 to 499.7 [mean 188.7] pg/mL) and cyclic GMP (0.2 to 6.0 [mean 2.9] pmol/mL) levels were significantly higher than in control children (both P less than .0001). There was a linear correlation between the two values in children with cardiac diseases (P less than .01). Because the effects of ANP to target tissues are mediated by cyclic GMP, cyclic GMP appears to be a marker for the cellular responses to ANP. The increased cyclic GMP levels in children with cardiac diseases indicate that ANP exerts its effects on target organs also in states of chronically enhanced ANP levels.

Adolescent↗
PubMed1979

[Maldescensus testis, therapy and prognosis].

Since histologic changes are found in undescended testes after the second year of life, treatment is necessary. Often therapy with human choriongonadotrophin is successful, otherwise operative treamtnet is indicated. Infertility at a high rate is found in boys treated for maldescence of the testicles in later childhood. Therapy before the age of two years improves the prognosis.

Child↗