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Biomedical subjects

J A Donald

Publications and source records attributed to J A Donald.

At least 37 records · Page 2Linked to original sources
PubMed1998

A susceptibility locus for bipolar affective disorder on chromosome 4q35.

Bipolar affective disorder (BAD) affects approximately 1% of the population and shows strong heritability. To identify potential BAD susceptibility loci, we undertook a 15-cM genome screen, using 214 microsatellite markers on the 35 most informative individuals of a large, statistically powerful pedigree. Data were analyzed by parametric two-point linkage methods under several diagnostic models. LOD scores >1.00 were obtained for 21 markers, with four of these >2.00 for at least one model. The remaining 52 individuals in the family were genotyped with these four markers, and LOD scores remained positive for three markers. A more intensive screen was undertaken in these regions, with the most positive results being obtained for chromosome 4q35. Using a dominant model of inheritance with 90% maximum age-specific penetrance and including bipolar I, II, schizoaffective/mania, and unipolar individuals as affected, we obtained a maximum two-point LOD score of 2.20 (theta = .15) at D4S1652 and a maximum three-point LOD score of 3.19 between D4S408 and D4S2924. Nonparametric analyses further supported the presence of a locus on chromosome 4q35. A maximum score of 2.62 (P=.01) was obtained between D4S1652 and D4S171 by use of the GENEHUNTER program, and a maximum score of 3.57 (P=.0002) was obtained at D4S2924 using the affected pedigree member method. Analysis of a further 10 pedigrees suggests the presence of this locus in at least one additional family, indicating a possible predisposing locus and not a pedigree-specific mutation. Our results suggest the presence of a novel BAD susceptibility locus on chromosome 4q35.

Bipolar Disorder↗
PubMed1997

Exclusion of linkage between bipolar affective disorder and chromosome 16 in 12 Australian pedigrees.

Several recent reports of possible susceptibility loci for bipolar affective disorder (BAD) have identified sites on a number of chromosomes. Specifically, two Danish studies have suggested the presence of a susceptibility locus for BAD on chromosome 16p13. As the first step of a whole genome scan, we screened 12 Australian families with markers at 16p13 and also a number of markers spanning the entirety of chromosome 16. Linkage analysis was undertaken using both the parametric lod score method (two- and multipoint) with different models and diagnostic thresholds, and the nonparametric affected pedigree member (APM) method. Results of lod score analysis convincingly excluded the 16p13 region from linkage to BAD in these families, while APM provided no support for linkage. Furthermore, using the broad definition of BAD, with individuals affected by bipolar I and II and recurrent unipolar disorders included, the entire chromosome was excluded from linkage to BAD with autosomal-dominant transmission at a maximum age-specific penetrance of 60%, and with autosomal-dominant and recessive modes of transmission at a maximum age-specific penetrance level of 90%. Diagnostic thresholds which did not include unipolar affected individuals were somewhat less informative. However, a majority (between 63-96%, depending upon the model) of the chromosome was clearly excluded using narrow diagnostic thresholds. Moreover, no positive lod scores were obtained at theta = 0.00 for any tested model or diagnostic threshold. Our results indicate that no linkage exists between BAD and chromosome 16 markers in this group of Australian families.

Australia↗
PubMed1997

Parental sex effects in bipolar affective disorder pedigrees.

A combined linkage analysis was performed on chromosome 18 data and produced modest evidence in three of four data sets for linkage of a susceptibility locus for bipolar disorder to markers on chromosome 18p. All data sets showed a preponderance of females among affected individuals. When this was taken into account, no convincing evidence was obtained for excess transmission from mothers compared to fathers. In addition, there was no evidence for differences in the proportions of affected offspring from affected fathers and mothers. We conclude that these combined data do not support previous suggestions of a maternal effect on transmission of bipolar affective disorder.

Adolescent↗
PubMed1997

Distribution and characterization of natriuretic peptide receptors in the gills of the spiny dogfish, Squalus acanthias.

The distribution and nature of natriuretic peptide receptors (NPR) in the gills of dogfish, Squalus acanthias, were examined by tissue section autoradiography, competition analysis, protein electrophoresis, guanylate cyclase (GC) assays, and molecular cloning. Specific NP binding occurred on the gill filaments, but not on the interbranchial septum or gill arch. The binding was densest on the efferent edge of the gills. Higher resolution light-microscopic examination of emulsion-coated sections showed that specific binding occurred mainly on the secondary lamellae and filament body and not on the arterial circulation. At least two types of NPR were revealed. One is linked to GC since NP binding stimulates the production of cGMP. The GC receptor may be similar to the NPR-B mammalian receptor since only pCNP stimulated cGMP production. The second receptor is not linked to GC and binds the specific ligand C-ANF [rat des(Gln18, Ser19, Gly20, Leu21, Gly22)]. The sequence of a cDNA generated using primers based on conserved regions of vertebrate NPR-C had considerable homology with mammalian and eel NPR-C and eel NPR-D. The presence of GC-linked NPR and NPR-C/ NPR-D suggests that the gills are an important target organ for NP action.

Amino Acid Sequence↗
PubMed1997

Lack of evidence for functional natriuretic peptide receptors in the heart of the cane toad, Bufo marinus.

Several studies have shown that the heart of species from each vertebrate class contains natriuretic peptide binding sites which suggests that ANP released from the heart may act in a paracrine/autocrine fashion. The present study used a set of techniques to study cell surface receptors in order to investigate the presence and nature of NPRs in the heart of the cane toad, Bufo marinus. Autoradiographical studies of both atria and ventricle showed no variation between total and non-specific binding, indicating a lack of NP binding sites in these tissues. This was confirmed with in vitro binding studies in which increasing concentrations of ANP did not compete for any specific binding. Increasing concentrations of ANP did not increase cGMP generation and physiological experiments showed that both ANP and CNP had no effect on the force or rate of contraction of a sino-atrial preparation. Molecular expression studies, however, showed that mRNA for NPRs was expressed in the heart, in spite of the lack of evidence for NPR on the cell surface. Overall, this study showed that no functional NPRs are present in the heart, and provided evidence that the heart is not a target organ for NP action in B. marinus.

Animals↗
PubMed1996

Rat natriuretic peptide binds specifically to plant membranes and induces stomatal opening.

Stomatal aperture changes modulate the rate of transpiration and gas exchange in plants. High cellular turgor of the guard cell pair due to water and solute influx leads to stomatal opening, whereas closing is caused by turgor reduction due to water and solute efflux. This process is controlled by plant hormones. We demonstrate that a vertebrate peptide hormone, the rat atrial natriuretic peptide (rANP), induces stomatal opening in Tradescantia sp. in a concentration dependent manner and provide evidence that rANP affects the amiloride sensitive Na+/H- channel. Furthermore, rANP was found to bind specifically to plant membranes isolated from leaf tissue. We propose that a plant natriuretic peptide (NP) analogue is part of a multifactorial control system that regulates transpiration and solute movements in plants.

Amiloride↗
PubMed1996

Nonlinkage of D6S260, a putative schizophrenia locus, to bipolar affective disorder.

To examine whether genes that predispose to schizophrenia also confer a predisposition to other psychiatric disorders such as bipolar affective disorder (BAD), we tested for linkage between the recently identified schizophrenia susceptibility locus D6S260 and the inheritance of BAD in 12 large Australian pedigrees. We found no evidence for linkage over a region of 12-27 cM from the D6S260 locus, depending on the model used. Our results therefore do not provide support for the continuum theory of psychosis.

Australia↗
PubMed1995

Localisation and characteristics of natriuretic peptide receptors in the gills of the Atlantic hagfish Myxine glutinosa (Agnatha).

Specific binding of iodinated natriuretic peptides 125I-ANP and 125I-CNP was examined in the gill of the Atlantic hagfish Myxine glutinosa by tissue section autoradiography, saturation and competition analysis of binding to membrane preparations, affinity cross-linking, followed by SDS-PAGE and guanylate cyclase assays. Autoradiographs showed specific, saturable binding on the respiratory lamellar epithelium. In vitro analysis of the binding sites demonstrated that 125I-ANP bound to two receptor sites with the same affinity (Kd = 15.4 +/- 1.6 pmol l-1; Bmax = 45.9 +/- 3.0 fmol mg-1 protein). 125I-CNP bound to high- and low-affinity receptor sites; variables for the high-affinity site (Kd = 12.9 +/- 4.7 pmol l-1; Bmax = 23.4 +/- 6.5 fmol mg-1 protein) did not differ from those for the 125I-ANP sites. The low-affinity site had an apparent Kd and Bmax of 380 +/- 80 pmol l-1 and 120 +/- 21 fmol mg-1 protein, respectively. All receptors had an apparent molecular mass of approximately 150 kDa, with no indication of a mammalian type NPR-C at a lower apparent molecular mass. 1 nmol l-1 unlabelled rANP and 20 and 30 nmol l-1 unlabelled pCNP and C-ANF, respectively, competed for 50% of 125I-ANP sites. 0.1 nmol l-1 rANP and pCNP and 8 nmol l-1 C-ANF competitively inhibited 50% of 125I-CNP binding. Both rANP and pCNP stimulated cyclic GMP production, although rANP was a more potent stimulator than was pCNP. C-ANF did not stimulate cyclic GMP production. These data suggest the existence of an ANP guanylate-cyclase-linked receptor similar to the mammalian NPR-A and an ANP/CNP receptor that may be similar to, although not structurally homologous with, the mammalian NPR-C clearance receptor.

Animals↗
PubMed1995

Natriuretic peptide receptors in the kidney and the ventral and dorsal aortae of the Atlantic hagfish Myxine glutinosa (Agnatha).

The character of natriuretic peptide receptors (NPRs) in the kidney and aortae of the Atlantic hagfish Myxine glutinosa was determined and compared with that of NPRs in hagfish gills. The relationship of hagfish kidney and aortic NPRs with NPRs from higher vertebrates was also examined. Iodinated atrial and C-type natriuretic peptides (NPs) (125I-ANP, 125I-CNP) were used in tissue section autoradiography, competition studies and guanylate cyclase (GC) assays. Rat atrial and porcine C-type NPs (rANP, pCNP) and rat des[Gln18, Ser19, Gly20, Leu21 Gly22]ANP-(4-23)-NH2 (C-ANF, which binds to the mammalian and teleost 'clearance' receptor, NPR-C), were used as competing ligands. 125I-ANP binding sites were observed on both aortae and on the glomeruli, neck segments and archinephric ducts of the kidney. 4.0 nmol l-1 rANP competed for 50% of 125I-ANP glomerular sites. 125I-CNP did not visibly bind to any of the tissues, but 300 nmol l-1 pCNP competed for 50% of 125I-ANP glomerular sites. C-ANF failed to compete for 125I-ANP sites. rANP and pCNP stimulated cyclic GMP production in kidney membrane preparations, but C-ANF did not, demonstrating that the hagfish kidney NPR is GC-linked. This study suggests that a predominant population of ANP-like receptors, similar to the mammalian NPR-A, exists in the myxinoid aortae and kidney tissue. However, no detectable population of a receptor that binds all NPs, such as is present in the hagfish gill, nor an NPR similar to the NPR-C of higher vertebrates was discovered.

Animals↗
PubMed1994

Phosphoglycerate kinase pseudogenes in the tammar wallaby and other macropodid marsupials.

Phosphoglycerate kinase (EC 2.7.2.3; PGK) exists in two forms in marsupials. PGK1 is an X-linked house-keeping enzyme, and PGK2 is a mainly testis-specific enzyme under autosomal control. We have used PGK1 probes derived from two closely related species of macropodid marsupials (kangaroos and wallabies) to demonstrate the existence of a large family of pseudogenes in the tammar wallaby (Macropus eugenii). Over 30 fragments are detectable after Taq digestion. We estimate that there are 25-30 copies per genome. Most are autosomally inherited and are apparently not closely linked. Only two restriction fragments that appeared to be sex linked could be detected. Varying degrees of hybridization of fragments to the probes suggest different levels of homology, and hence different ages of origin. The existence of two PGK1 homologous restriction fragments from the X and a large number from the autosomes was also demonstrated by somatic cell hybridization for two other macropodid species, the wallaroo (M. robustus) and the red kangaroo (M. rufus). These results are compared with those from human and mouse, and it is suggested that the propensity of PGK1 to form pseudogenes is an ancient (approximately 130 MYR BP) characteristic of mammals. The high level of polymorphism detected in the tammar makes these PGK1 probes potentially useful for measuring genetic variability in this species and other macropodids.

Animals↗
PubMed1994

The distribution and colocalization of neuropeptides in fish cardiac neurons.

Most if not all intracardiac nerve cell bodies in four species of teleost fish and a primitive air breathing fish contained immunoreactivity (IR) to vasoactive intestinal peptide (VIP). Intracardiac nerve cell bodies contained no other neuropeptide although galanin (GAL)-, substance P (SP)- and calcitonin gene-related peptide (CGRP)-IR were detected in cardiac axons. Varicose VIP-IR axons were observed in close association to the cardiac muscle in the sinus venosus and atrium, but not in the ventricle. Slightly less than half the total number of VIP-IR axons also contained colocalised GAL-IR. A smaller number of varicose axons containing colocalised SP- and CGRP-IR were also present in the sinus venous and atrium. In addition, a subpopulation of CGRP-IR axons present in the sinus venosus and atrium did not contain SP-IR. SP-IR axons lacking CGRP-IR formed boutons around the axon hillock and soma of the majority of VIP-IR nerve cell bodies. Associated with a small number of VIP/-ganglion cells were VIP/- boutons. No neuropeptides were observed in the ventricle of any species of fish studied here. These results suggest that a VIP-like peptide is localised in the cholinergic postganglionic parasympathetic neurons. Associated with some of these neurons are nerve boutons containing either SP alone or VIP alone. In addition, the fish heart is innervated by extrinsic nerve fibres containing: GAL/VIP; CGRP alone; and CGRP/SP.

Animals↗
PubMed1994

Localization and analysis of natriuretic peptide receptors in the gills of the toadfish, Opsanus beta (teleostei).

The distribution and nature of natriuretic peptide binding sites was determined in the gills of the toadfish, Opsanus beta. Specific 125I-labeled rat atrial natriuretic peptide (rANP) and 125I-labeled porcine C-type natriuretic peptide (pCNP) binding sites were observed on the afferent and efferent filamental arteries and lamellar arterioles, and on the marginal channels of the secondary lamellae. In both section autoradiography and competition assays, the binding of both ligands was completely displaced by 1 microM rANP and 1 microM pCNP, but residual binding was observed with 1 microM of the type C natriuretic peptide receptor (NPR-C)-specific ligand C-ANF. Electrophoresis of gill membranes cross-linked with 125I-rANP showed a major band at 75 kDa and a fainter band at 140 kDa. Both rANP and pCNP significantly stimulated the production of cGMP above basal levels; C-ANF had no stimulatory effect. These data show that the intrafilamental gill vasculature of toadfish contains a major population of natriuretic peptide receptors very similar to mammalian clearance receptors and a smaller population of receptors that are linked to a membrane-bound guanylate cyclase.

Animals↗
PubMed1993

The effect of Ca2+, Cd2+ and Ni2+ on detergent-permeabilized vascular smooth muscle from the shark, Squalus acanthias.

We examined the effect of Ca2+, Cd2+, or Ni2+ on vascular smooth muscle intracellular proteins involved in contraction, using rings of detergent-permeabilized aortae from the spiny dogfish, Squalus acanthias. Addition of Ca2+ stimulated contraction of the vascular smooth muscle, and permeabilization by treatment with Triton X-100 increased the sensitivity to Ca2+ nearly 5 log units, demonstrating that this protocol left contractile and regulatory proteins intact. Addition of 1 microM calmodulin did not increase the sensitivity of the rings to Ca2+, suggesting that this preparation is not leaky to this regulatory protein. Neither Cd2+ nor Ni2+ stimulated contraction of permeabilized rings demonstrating that the previously-described contractile action of these heavy metals is not mediated by direct stimulation of intracellular proteins, rather by interaction with sarcolemmal proteins.

Animals↗
PubMed1993

Linkage analysis of the hemoglobin F determinant(s) in an Australian hemoglobin Lepore (Boston) kindred.

Genetic determinants that influence the levels of fetal hemoglobin (Hb F) in a single Australian kindred with heterozygous Hb Lepore (Boston) were sought. There were 22 affected individuals, some of whom had high Hb F and others with Hb F levels within the normal range. Family members were typed for restriction fragment length polymorphisms (RFLPs) associated with the beta-globin gene complex and the nearby genetic markers D11S12, INS, HRAS, and PTH. Prior to linkage analysis, a cohort of 54 unrelated Hb Lepore heterozygotes was analyzed to establish the distribution of Hb F levels measured by alkaline denaturation (Hb FAD). An Hb F level of > 2.0% was used as the cutoff point for linkage analysis of the putative hereditary persistence of fetal hemoglobin (HPFH) determinant(s) in this kindred. Positive peak lod scores were obtained for the entire pedigree between the HPFH determinant and Hb Lepore (Zm+f = 2.35 at theta = 0.15) and beta-globin cluster (HBBC) (Zm+f = 2.38 at theta = 0.20) marker loci, indicating the possibility of an independent HPFH gene at some distance from the beta-globin gene cluster. However, most of these lod scores result from the non-Hb Lepore members of the family who, with one exception, do not have high Hb F, and when only those affected with Hb Lepore were analyzed the lod score values at these loci fell to small positive values (< 1.0). These data do not support an independent cosegregating HPFH determinant separate from the Hb Lepore locus in this pedigree. The results favor a pleiotropic effect of the Hb Lepore lesion itself influencing Hb F levels by genetic or environmental factors not yet elucidated.

Adolescent↗
PubMed1993

Confirmation of chromosome 9p linkage in familial melanoma.

Malignant melanoma occurs as a familial cancer in 5%-10% of cases where it segregates in a manner consistent with autosomal dominant inheritance. Evidence from cytogenetics, fine-mapping studies of deletions in melanomas, and recent linkage studies supports the location of a human melanoma predisposition gene on the short arm of chromosome 9. We have carried out linkage analysis using the 9p markers IFNA and D9S126 in 26 Australian melanoma kindreds. Multipoint analysis gave a peak lod score of 4.43, 15 cM centromeric to D9S126, although a lod score of 4.13 was also found 15 cM telomeric of IFNA. These data confirm the existence of a melanoma susceptibility gene on 9p and indicate that this locus most probably lies outside of the IFNA-D9S126 interval. No significant heterogeneity was found between families, when either pairwise or multipoint data were analyzed using HOMOG.

Adult↗
PubMed1992

The distribution and colocalization of neuropeptides in perivascular nerves innervating the large arteries and veins of the snake, Elaphe obsoleta.

Single- and dual-labelling immunohistochemistry were used to determine the distribution and coexistence of neuropeptides in perivascular nerves of the large arteries and veins of the snake, Elaphe obsoleta, using antibodies for vasoactive intestinal polypeptide, substance P, calcitonin gene-related peptide, neuropeptide Y, galanin, somatostatin, and leu-enkephalin. Blood vessels were sampled from four regions along the body of the snake: region 1, arteries and veins anterior to the heart; region 2, central vasculature 5 cm anterior and 10 cm posterior to the heart; region 3, arteries and veins in a 30-cm region posterior to the liver; and region 4, dorsal aorta and renal arteries, renal and intestinal veins, 5-30 cm cephalad of the vent. A moderate to dense distribution of vasoactive intestinal polypeptide-like immunoreactive fibres was found in most arteries and veins of regions 1-3, but fibres were absent from the vessels of region 4. The majority of vasoactive intestinal polypeptide-like immunoreactive fibres contained colocalized substance P-like immunoreactivity, and these fibres were unaffected by either capsaicin or 6-hydroxydopamine (6-OHDA) pretreatment. In the anterior section of the snake, the vagal trunks contained many cell bodies with colocalized vasoactive intestinal polypeptide and substance P-like immunoreactivity. It is suggested that the vasoactive intestinal polypeptide/substance P-like immunoreactive cell bodies and fibres are parasympathetic postganglionic nerves. Neuropeptide Y-like immunoreactive fibres were observed in all arteries and veins, being most dense in regions 3 and 4. The majority of these fibres also contained colocalized galanin-like immunoreactivity, and were absent in tissues from 6-OHDA pretreated snakes, suggesting that neuropeptide Y and galanin are colocalized in adrenergic nerves. A small number of neuropeptide Y-like immunoreactive fibres contained vasoactive intestinal polypeptide but not galanin, and were unaffected by 6-OHDA treatment. All calcitonin gene-related peptide-like immunoreactive fibres contained colocalized substance P-like immunoreactivity, and these fibres were observed in all vessels, being particularly dense in the carotid artery and jugular veins. All calcitonin gene-related peptide/substance P-like immunoreactive fibres appeared damaged after capsaicin treatment suggesting they represent fibres from afferent sensory neurons. A sparse plexus of somatostatin-like immunoreactive fibres was observed in the vessels only from region 4. No enkephalin-like immunoreactive fibres were found in any blood vessels from any region. This study provides morphological evidence to suggest that there is considerable functional specialization within the components of the rat snake peripheral autonomic system controlling the circulation, in particular the regulation of venous capacitance.

Adrenergic Fibers↗
PubMed1992

Immunohistochemical localisation of natriuretic peptides in the heart and brain of the gulf toadfish Opsanus beta.

The distribution of natriuretic peptide immunoreactivity was determined in the heart and brain of the gulf toadfish Opsanus beta using the avidin-biotin peroxidase technique. Four antisera were used: the first raised against porcine brain natriuretic peptide which cross-reacts with atrial natriuretic and C-type natriuretic peptides (termed natriuretic peptide-like immunoreactivity); the second raised against porcine brain natriuretic peptide which cross-reacts with C-type natriuretic peptide but not with atrial natriuretic peptide (termed porcine brain natriuretic peptide-like immunoreactivity); the third raised against rat atrial natriuretic peptide; and the fourth raised against eel atrial natriuretic peptide. Natriuretic peptide- and porcine brain natriuretic peptide-like immunoreactivity was observed in all cardiac muscle cells of the atrium. In the ventricle, natriuretic peptide-like immunoreactivity was found in all cardiac muscle cells, however, porcine brain natriuretic peptide-like immunoreactivity was confined to muscle cells adjacent to the epicardium. There was no discernible difference in the distribution of natriuretic peptide-like immunoreactivity and porcine brain natriuretic peptide-like immunoreactivity in the brain. Immunoreactive perikarya were observed only in the preoptic region of the diencephalon, and many immunoreactive fibres were found in the telencephalon, preoptic area, and rostral hypothalamus, lateral to the thalamic region. There was no immunoreactivity in any region of the hypophysis. A pair of distinct immunoreactive fibre tracts ran caudally from the preoptic area to the thalamic region, from which fibres extended to the posterior commissure, area praetectalis, dorsolateral regions of the midbrain tegmentum, and tectum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗