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C Van Dop

Publications and source records attributed to C Van Dop.

At least 55 records · Page 3Linked to original sources
PubMed1987

Prevalence of polymorphic 21-hydroxylase gene (CA21HB) mutations in salt-losing congenital adrenal hyperplasia.

Using genomic restriction analysis of 14 unrelated patients with salt-losing congenital adrenal hyperplasia, we identified three different CA21HB mutation patterns: no detectable restriction fragment abnormalities (16/28 haplotypes), deletion of the active CA21HB gene (9/28), and apparent conversion of the active CA21HB gene to the pseudogene CA21HA (3/28). CA21HB gene deletion was associated with HLA-Bw47 in 6 haplotypes and with absent C4B expression in 7. A variety of HLA and C4 types was associated with the other mutations. Apparent conversion of CA21HB to CA21HA was identified by the disparity between the intensity ratios for the major TaqI and BglII hybridization fragments.

Adrenal Hyperplasia, Congenital↗
PubMed1987

Isolated gonadotropin deficiency in boys: clinical characteristics and growth.

Analysis of the clinical findings and growth in 20 boys with isolated gonadotropin deficiency revealed a heterogeneous group of physical abnormalities. Ten of these patients were hyposmic or anosmic (Kallmann syndrome). Abnormalities found in our patients included undescended testes, gynecomastia, and ocular or skeletal anomalies. Regardless of the presence of hyposmia, patients without testicular enlargement (less than 2 cm3), had serum luteinizing hormone (LH) responses to luteinizing hormone-releasing factor (LRF) that were the same as in prepubertal boys. By contrast, five boys with testicular enlargement (greater than 2 cm3), some of whom had hyposmia, had a greater serum LH response to LRF than did prepubertal boys. Adrenarche was moderately delayed; although all boys initially had normal serum levels of dehydroepiandrosterone-sulfate, four boys eventually developed elevated serum levels. Bone ages were delayed compared with chronologic age in boys who had the condition after 15 years of age. The rate of linear growth was normal, and final adult heights were normal with testosterone therapy, although linear growth continued longer in these boys than in boys with normal pubertal progression. Although none of the patients was obese at the time of diagnosis, three patients developed obesity after initiation of testosterone therapy.

Adolescent↗
PubMed1987

Coupling of HLA-A3,Cw6,Bw47,DR7 and a normal CA21HB steroid 21-hydroxylase gene in the Old Order Amish.

HLA-Bw47, a rare human histocompatibility antigen, occurs in strong linkage disequilibrium with HLA-A3,Cw6,DR7 and salt-losing congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency and is associated with a contiguous deletion of the active CA21HB gene and the C4B complement gene. We studied the HLA-A3,Cw6,Bw47,DR7 haplotype in 10 subjects of the Old Order Amish of Lancaster County in Pennsylvania and found that this haplotype, which occurs with a similar frequency in this group as in the general caucasoid population, has C4B and Ca21HB genes. These C4B and CA21HB genes are expressed as assessed by C4 typing and iv ACTH testing, respectively. Serological studies indicate that the HLA-D loci of this Amish haplotype are the same as those in patients with HLA-Bw47 and CAH, but different from HLA-D loci coupled to HLA-B13, which some workers have proposed is the progenitor genotype for HLA-Bw47. Our studies demonstrate that 1) HLA-Bw47 is not an invariant marker for salt-losing CAH due to 21-hydroxylase deficiency, and 2) the HLA-Bw47 phenotype coupled to CAH is not derived from the HLA-B13 genotype by a single mutation.

Adrenal Hyperplasia, Congenital↗
PubMed1986

McCune-Albright syndrome. Long-term follow-up.

This article describes clinical follow-up of 15 patients--13 females and two males--with McCune-Albright syndrome. Osseous fractures occurred only during childhood, while hearing impairment due to temporal bone involvement occurred in four of six adults. Four females with precocious puberty had final heights that were not different from the mean for normal females; they eventually developed regular menses, and two had children. Persistent hyperthyroidism requiring ablative therapy occurred in three subjects, while hypophosphatemia occurred in three subjects. The protean manifestations of this disorder suggest that it results from a basic defect of cellular regulation. We postulate that its varied endocrine abnormalities result from altered regulation of intracellular cyclic adenosine monophosphate effects.

Acromegaly↗
PubMed1986

Spermatozoa contain a guanine nucleotide-binding protein ADP-ribosylated by pertussis toxin.

Spermatozoa from invertebrates (sea urchin, starfish) and vertebrates (trout, guinea pig, bull, pig, human) contain a membrane-bound protein that is ADP-ribosylated by pertussis toxin but not by cholera toxin. The Mr of this protein is 39,000 in invertebrate sperm and 41,000 in mammalian sperm, but 40,000 in trout spermatozoa. The pertussis toxin substrate from sea urchin sperm copurified with [gamma-35S]GTP binding activity. Chymotryptic maps of this ADP-ribosylated protein from sea urchin sperm were the same as those of alpha-subunit of Go from rat brain. Antiserum to the beta-subunit of bovine retinal transducin bound to a sperm protein with Mr approximately 35,000. These studies are the first describing a guanine nucleotide-binding coupling protein in sperm.

Adenosine Diphosphate Ribose↗
PubMed1986

Restriction maps and restriction fragment length polymorphisms of the human 21-hydroxylase genes.

Restriction maps were constructed for the two human 21-hydroxylase genes (21-OHA and 21-OHB) by using DNA from subjects homozygous for a deletion of each gene. Comparing the patterns of these two genes, a KpnI restriction site occurred in the 21-OHA gene in place of a TaqI site in the 21-OHB gene about 1-kb from the 5' end of the gene, and an extra EcoRI site was located 500 bp 5' to the common EcoRI site. The DNA of fourteen unrelated normal subjects was digested with nine restriction endonucleases (AccI, BamHI, BgIII, EcoRI, HindIII, KpnI, MspI, SacI and TaqI). Restriction fragment length polymorphisms were found with EcoRI, HindIII and AccI that resulted from polymorphic endonuclease sites outside the genes.

Adrenal Hyperplasia, Congenital↗
PubMed1986

Go, a guanine nucleotide-binding protein: immunohistochemical localization in rat brain resembles distribution of second messenger systems.

We have localized a guanine nucleotide-binding protein, Go, in rat brain by immunohistochemistry with a selective polyclonal antiserum to the alpha 39 subunit of Go. Specific staining is widely distributed, abundant in neuropil, absent from neuronal cell bodies, and displays regional heterogeneity. Staining is enriched in cerebral cortex, particularly the molecular layer, neuropil of the hippocampal formation, striatum, substantia nigra pars reticulata, molecular layer of the cerebellum, substantia gelatinosa of the spinal cord, and posterior pituitary. High density staining in the substantia nigra reflects a Go-containing striatonigral pathway since striatal lesions reduce ipsilateral immunostaining in the pars reticulata. Confirming immunostaining, quantitative [32P]ADP-ribosylation of nigral membranes with pertussis toxin indicates a 66% +/- 11% (mean +/- SEM) reduction of Go ipsilateral to striatal lesions. Go may be associated with Purkinje cells in the cerebellum since membranes from mutant mice (Nervous), which postnatally lose Purkinje cells, are markedly depleted in pertussis toxin substrate. The localizations of Go correspond in many areas with those of protein kinase C, a component of the phosphatidylinositol cycle, suggesting a major role for Go in the brain related to regulation of the phosphatidylinositol cycle.

Adenosine Diphosphate Ribose↗
PubMed1986

Congenital adrenal hyperplasia: molecular mechanisms resulting in 21-hydroxylase deficiency.

21-Hydroxylase deficiency resulting in congenital adrenal hyperplasia (CAH) is a HLA-linked autosomal recessive disorder that has a wide range of phenotypic expression. Two homologous 21-hydroxylase genes (21-OHA and 21-OHB) occur within the Class III region of the major histocompatibility complex, but only one (21-OHB) appears to function in adrenal steroidogenesis. Our restriction maps, and initial sequence data from White et al. (Pediatr Res 20:274A (1986)) for the two human 21-OH genes reveal a high degree of homology between these genes and a reading frame shift mutation in the 21-OHA gene respectively. Among fourteen control subjects, the intragenic restriction patterns of the 21-OHA and 21-OHB genes are invariant. The few restriction fragment length polymorphisms (RFLPs) found in some controls result from polymorphic restriction sites outside the 21-OH genes. In patients with CAH, several different mechanisms for mutation of the 21-OHB gene have been described: deletion of the unique sequences of the 21-OHB gene, conversion of the unique sequences of the 21-OHB gene to those of 21-OHA, and mutations of 21-OHB which do not result in a detectable alteration of restriction pattern (e.g., point mutations). Duplication of the 21-OHA gene has been found in some patients with attenuated CAH; however, the significance of this finding remains unclear.

Adrenal Hyperplasia, Congenital↗
PubMed1985

Differential diagnosis in young women with oligomenorrhea and the pseudo-pseudohypoparathyroidism variant of Albright's hereditary osteodystrophy.

Oligomenorrhea was the reason for consultation in three individuals (two sisters and one unrelated woman) with the pseudo-pseudohypoparathyroidism (PPHP) variant of Albright's hereditary osteodystrophy (AHO). All had short stature, Ullrich-Turner-like signs, acral anomalies typical of AHO/brachydactyly E, and hypogonadism. One of the three individuals also had reduced erythrocyte NS (a membrane nucleotide regulatory protein that is required for functional coupling of stimulatory hormone receptors and catalytic adenylate cyclase) activity as described in the pseudohypoparathyroidism variant of AHO. The differential diagnosis of young women with the PPHP phenotype is discussed with special reference to Ullrich-Turner syndrome, brachydactyly E, the "resistant ovary" syndrome, and acrodysostosis.

Adolescent↗
PubMed1985

Amino acid sequence of the alpha subunit of transducin deduced from the cDNA sequence.

Transducin, a GTP-binding protein involved in phototransduction in the vertebrate retina, belongs to a family of homologous coupling proteins that also includes Gs and Gi, the regulatory proteins of adenylate cyclase. Here we report the cDNA sequence and deduced amino acid sequence of transducin's alpha subunit (T alpha). The cDNA was isolated, by screening with an antibody probe, from a bovine retinal cDNA library in the expression vector lambda gt11. The 2.2-kilobase cDNA insert hybridized to a single 2.6-kilobase poly(A)+ RNA species present in extracts of bovine retina but not of bovine heart, liver, or brain. The nucleotide sequence of the cDNA revealed an open reading frame long enough to encode the entire 39-kDa T alpha polypeptide. The polypeptide sequence deduced from the cDNA would be composed of 350 amino acids and have a molecular weight of 39,971. Portions of the sequence matched reported amino acid sequences of T alpha tryptic fragments, including sites specifically ADP-ribosylated by cholera and pertussis toxins. The predicted sequence also includes four segments, ranging from 11 to 19 residues in length, that exhibit significant homology to sequences of GTP-binding proteins, including the ras proteins of man and yeast and the elongation factors of ribosomal protein synthesis in bacteria, EF-G and EF-Tu. In combination with previous functional studies of tryptic fragments of T alpha, the deduced amino acid sequence makes it possible to predict which portions of the polypeptide interact with other molecules involved in retinal phototransduction.

Amino Acid Sequence↗
PubMed1984

Partial cDNA sequence of the gamma subunit of transducin.

A 151 bp cDNA segment that encodes the amino-terminal portion of the gamma subunit of bovine transducin was isolated from a retinal cDNA library constructed in the expression vector lambda gt11. The base sequence of this cDNA confirms the sequence of the first 39 amino-terminal amino acids reported for the native protein (McConnell et al. (1984) Fed. Proc. 43, 1585). Northern blot analysis indicates that the complete mRNA is approximately 650 bases long and that its expression is limited to the retina.

Amino Acid Sequence↗
PubMed1984

Amino acid sequence of retinal transducin at the site ADP-ribosylated by cholera toxin.

Transducin was [32P]ADP-ribosylated by cholera toxin in bovine retinal rod outer segments and then partially purified on omega-amino octyl agarose to remove other ADP-ribosylated proteins. Trypsin digestion of the ADP-ribosylated transducin and further purification using boronate-polyacrylamide beads and high performance liquid chromatography yielded a single radiolabeled tetrapeptide, Ser-Arg-Val-Lys. The ADP-ribose is linked to the guanidinium group of arginine.

Adenosine Diphosphate Ribose↗
PubMed1984

ADP-ribosylation of transducin by pertussis toxin blocks the light-stimulated hydrolysis of GTP and cGMP in retinal photoreceptors.

Cholera toxin and pertussis toxin catalyze ADP-ribosylation of the alpha-subunits of the GTP-binding stimulatory (Ns) and inhibitory (Ni) coupling components, respectively, of adenylate cyclase. Cholera toxin also catalyzes the ADP-ribosylation of transducin, the GTP-binding signal-coupling protein of retinal rod outer segments, and thereby reduces its light-stimulated GTPase activity. We show here that pertussis toxin also ADP-ribosylates transducin. Illumination markedly inhibits the ADP-ribosylation of transducin by pertussis toxin. ADP-ribosylation by this toxin in the dark is also lessened by prior incubation with hydrolysis-resistant GTP analogs. These inhibitory effects indicate that the GDP complex of transducin is the preferred form for ADP-ribosylation by pertussis toxin. Transducin modified by this toxin has a lower affinity for photoexcited rhodopsin than does unmodified transducin. ADP-ribosylation inhibits the light-stimulated GTPase activity of rod outer segments and blocks the signal-coupling activity of transducin in photoactivation of the phosphodiesterase. These and previous results show that cholera and pertussis toxins preferentially ADP-ribosylate the active (GTP-binding) and inactive (GDP-binding) conformations, respectively, of transducin. Correspondingly, ADP-ribosylation by these toxins inhibits GTPase activity by stabilizing transducin in the preferred active (GTP-binding) or inactive (GDP-binding) conformation. The actions of pertussis toxin on retinal rod outer segments provide further evidence for a high degree of homology between retinal transducin and the N proteins of the adenylate cyclase system.

Adenylate Cyclase Toxin↗
PubMed1984

Father to son transmission of decreased Ns activity in pseudohypoparathyroidism type Ia.

We found both renal resistance to endogenous and exogenous PTH and reduced activity of the stimulatory guanine nucleotide-binding regulatory protein (Ns) of adenylate cyclase in a man with clinical signs of pseudohypoparathyroidism type Ia (PHP-Ia). Both of his children also had reduced Ns levels and short stature. The girl, 11 yr old, had evidence of partial resistance to PTH, while the son, age 7 yr, had no apparent abnormalities in calcium metabolism or response to administered PTH. Variable expression of the metabolic abnormalities of PHP during childhood has been previously described. The occurrence of reduced Ns activity in father and son is consistent with autosomal dominant inheritance for the primary biochemical defect of PHP-Ia in this family.

Adult↗