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Biomedical subjects

B D Brown

Publications and source records attributed to B D Brown.

14 recordsLinked to original sources
PubMed1992

Androgen receptor gene mutations identified by SSCP in fourteen subjects with androgen insensitivity syndrome.

The androgen insensitivity syndrome (AIS) is a disorder of male sexual development resulting in a wide range of clinical phenotypes. AIS is classified into two phenotypic forms: complete (CAIS) and partial (PAIS). To determine the molecular basis of the phenotypic diversity in AIS, we have studied 27 subjects (13 CAIS, 14 PAIS), spanning the full range of AIS phenotypes. We report the results of a mutation screen of the androgen receptor gene. The coding regions of the gene were amplified by the polymerase chain reaction and screened for single strand conformation polymorphisms to identify mutations. This was followed by DNA sequencing of putative mutant segments. Androgen receptor gene mutations were identified in nine CAIS and five PAIS subjects. Two of the CAIS mutations in exon A resulted in frameshifts. A third CAIS mutation resulted in the deletion of a single amino acid from the ligand binding domain of the receptor. All other mutations caused single amino acid substitutions in the ligand binding domain. These results suggest that mutations affecting the ligand binding domain of the androgen receptor are the most frequent cause of AIS, although some cases of PAIS may be the result of other, as yet undefined, genetic lesions.

Androgens↗
PubMed1992

Role of the androgen receptor in male sexual differentiation.

The two androgens responsible for all aspects of male sexual differentiation are testosterone and dihydrotestosterone. The action of both these steroids is mediated by a specific intracellular receptor, the androgen receptor, which is a member of the nuclear receptor superfamily. The androgen receptor gene has been cloned and is located on the X chromosome at Xq11-12. Mutations of this gene have been found in subjects with both complete and partial androgen insensitivity. In a study of 27 subjects with the androgen insensitivity syndrome, we have identified mutations in 14, using a rapid mutation screening assay. The same technique has also been used to determine carrier status in an affected family. We have also identified a mutation in two brothers who show perineal hypospadias as the only evidence of undervirilisation. Familial severe hypospadias should therefore be included as part of the phenotypic spectrum of partial androgen insensitivity. The study of naturally occurring mutations of the androgen receptor gene is providing further information on the function of the androgen receptor and its role in normal male sexual differentiation.

Dihydrotestosterone↗
PubMed1990

Antagonism of the anti-conflict effects of phenobarbital, but not diazepam, by the A-1 adenosine agonist l-PIA.

The present study examined the effects of the anxiolytics diazepam and phenobarbital, the A-1 adenosine agonist N6-R-phenylisopropyladenosine (l-PIA), and the A-2 adenosine agonist 5'-N-ethylcarboxamidoadenosine (NECA) on conflict behavior. Water-restricted rats were trained to drink from a tube that was electrified (0.5 mA intensity) on a FI-29s schedule, electrification being signaled by a tone. After 3 weeks of daily 10-min sessions, the animals accepted a stable number of shocks (punished responding) and consumed a consistent volume of water (unpunished responding) per session. Different doses of l-PIA and NECA were then tested separately at weekly intervals. In addition, the effects of diazepam and phenobarbital were determined in animals pretreated with saline, l-PIA, or NECA. Neither l-PIA (15-250 nmole/kg) nor NECA (2.5-20 nmole/kg) produced a significant anti-conflict effect when administered alone. Diazepam (1.25-10 mg/kg) or phenobarbital (10-40 mg/kg) administration to saline-pretreated rats resulted in a dose-dependent increase in punished responding (shocks received) with minimal effects on unpunished responding (water intake). Neither l-PIA nor NECA pretreatment reliably altered the effects of diazepam on conflict behavior. Pretreatment with l-PIA, but not NECA, significantly reduced the anti-conflict effects of phenobarbital on conflict behavior. These data suggest that phenobarbital, but not diazepam, anti-conflict responses may involve interactions with A-1 adenosine receptors.

Adenosine↗
PubMed1990

Endonucleolytic cleavage of a maternal homeo box mRNA in Xenopus oocytes.

We have identified a messenger RNA (mRNA) sequence from a Xenopus homeo box-containing gene that is the target for a sequence-specific endoribonuclease in vivo. Synthetic RNA transcribed from an allele of the maternal gene Xlhbox2B is efficiently cleaved when injected into Xenopus oocytes. The cleavage sequence lies between the protein-coding region and a 600-base 3'-untranslated region. Intermediates in degradation are readily observed: Both the 5' and 3' products of cleavage are recovered, thus showing that the cleavage activity is an endonuclease. When a 90-base region of the Xlhbox2B sequence is inserted into a second homeo box RNA that is normally stable, it is sufficient to confer an identical cleavage reaction on the hybrid RNA. The cleaved region contains a repeated sequence motif and is cut at multiple sites. Inhibition of translation does not affect the rate or extent of cleavage, while the coinjection of antisense RNA complementary to the 90-base region completely blocks the reaction. Because most mRNAs are not found on polysomes during oogenesis, translation-independent cleavage at such sites may provide a novel post-transcriptional mechanism to regulate the amount of mRNA available for embryogenesis.

Alleles↗
PubMed1990

Localization of specific mRNAs in Xenopus embryos by whole-mount in situ hybridization.

We have adapted a non-radioactive technique to detect localized mRNAs in whole-mount Xenopus embryos. Synthetic antisense RNA transcribed in the presence of digoxygenin-UTP is used as a probe and is detected via an anti-digoxygenin antibody. We show that localized mRNAs can be detected from late gastrula to tadpole stages and that high as well as low abundance RNAs can be detected. The method was tested on muscle actin and alpha-globin RNAs, whose localization has previously been characterized. In addition, we used the method to determine the distribution of XA-1 RNA, an anterior ectoderm-specific RNA, which we show is expressed in the periphery of the cement gland as well as in the region of the hatching gland. The sequence of an XA-1 cDNA predicts a protein rich in proline and histidine.

Alpha-Globulins↗
PubMed1977

[Idiopathic intestinal lymphangiectasia with hypoproteinemia. Unusual combination of complete diagnosis and ineffective therapy (author's transl)].

This case illustrates the difficulties which occasionally are encountered in diagnosing and treating small intestinal diseases. The delay in diagnosis was due to the fact that symptoms started in 1950 but the disease was not described until 11 years later. Once the diagnosis was established, there was an unexplained failure of response to appropriate therapy.

Aged↗
PubMed1975

Distribution and age-dependent concentration in brain tissue of glycoproteins containing N-acetylgalactosamine.

Glycoproteins that yield non-dialyzable, alkali-labile, N-acetylgalactosamine-containing heteropolysaccharides upon proteolytic digestion show a threefold enrichment in white matter relative to gray matter. Approximately 50% of these glycoproteins appear in soluble extracts prepared from rat brain. This distribution contrasts with that of the predominant alkali-stable sialoglycopeptides, which account for 60% of the total brain glycoprotein-carbohydrate. The latter glycopeptides showed a twofold enrichment in gray matter compared with white, and only about 10% of the glycoproteins that yield these glycopeptides could be solubilized by extraction with aqueous solvents. The concentration of the N-acetylgalactosamine-containing glycoproteins in the 3-year-old cerebral gray matter from human brain was respectively 7-15 and 15-30 times greater than in 8- and 72-year-old tissue. Electrophoretic analysis of the non-dialyzable, alkali-stable, acidic glycopeptides that contain NANA, fucose, mannose, galactose, and N-acetylglucosamine, obtained from the microsomal and synaptosomal fractions, revealed that the composition of these glycopeptides in the two fractions was identical.

Acetylgalactosamine↗