Biomedical subjects

P A Janssens

Publications and source records attributed to P A Janssens.

At least 19 recordsLinked to original sources

PubMed2006

Virulence and pathogenesis of the MSW and MSD strains of Californian myxoma virus in European rabbits with genetic resistance to myxomatosis compared to rabbits with no genetic resistance.

The pathogenesis of two Californian strains of myxoma virus (MSW and MSD) was examined in European rabbits (Oryctolagus cuniculus) that were either susceptible to myxomatosis (laboratory rabbits) or had undergone natural selection for genetic resistance to myxomatosis (Australian wild rabbits). MSW was highly lethal for both types of rabbits with average survival times of 7.3 and 9.4 days, respectively, and 100% mortality. Classical clinical signs of myxomatosis were not present except in one rabbit that survived for 13 days following infection. Previously described clinical signs of trembling and shaking were observed in laboratory but not wild rabbits. Despite the high resistance of wild rabbits to myxomatosis caused by South American strains of myxoma virus, the MSW strain was of such high virulence that it was able to overcome resistance. The acute nature of the infection, relatively low viral titers in the tissues and destruction of lymphoid tissues, suggested that death was probably due to an acute and overwhelming immunopathological response to the virus. No virus was found in the brain. The MSD strain was attenuated compared to previously published descriptions and therefore was only characterized in laboratory rabbits. It is concluded that Californian MSW strain of myxoma virus is at the extreme end of a continuum of myxoma virus virulence but that the basic pathophysiology of the disease induced is not broadly different to other strains of myxoma virus.

Animals↗

PubMed2001

The evolution of nuclear receptors: evidence from the coral Acropora.

We have amplified and sequenced PCR products derived from 10 nuclear receptor (NR) genes from the anthozoan cnidarian Acropora millepora, including five products corresponding to genes not previously reported from the phylum Cnidaria. cDNAs corresponding to seven of these products were sequenced and at least three encode full-length proteins, increasing the number of complete cnidarian NR coding sequences from one to four. All clear orthologs of Acropora NRs either lack an activation domain or lack a known ligand, consistent with the idea that the ancestral nuclear receptor was without a ligand. Phylogenetic analyses indicate that most, and possibly all, presently identified cnidarian NRs are members of NR subfamily 2, suggesting that the common ancestor of all known nuclear receptors most resembled members of this subfamily.

Amino Acid Sequence↗

PubMed2001

Secretion of whey acidic protein and cystatin is down regulated at mid-lactation in the red kangaroo (Macropus rufus).

Milk collected from the red kangaroo (Macropus rufus) between day 100 and 260 of lactation showed major changes in milk composition at around day 200 of lactation, the time at which the pouch young begins to temporarily exit the pouch and eat herbage. The carbohydrate content of milk declined abruptly at this time and although there was only a small increase in total protein content, SDS PAGE analysis of milk revealed asynchrony in the secretory pattern of individual proteins. The levels of alpha-lactalbumin, beta-lactoglobulin, serum albumin and transferrin remain unchanged during lactation. In contrast, the protease inhibitor cystatin, and the putative protease inhibitor whey acidic protein (WAP) first appeared in milk at elevated concentrations after approximately 150 days of lactation and then ceased to be secreted at approximately 200 days. In addition, a major whey protein, late lactation protein, was first detected in milk around the time whey acidic protein and cystatin cease to be secreted and was present at least until day 260 of lactation. The co-ordinated, but asynchronous secretion of putative protease inhibitors in milk may have several roles during lactation including tissue remodelling in the mammary gland and protecting specific proteins in milk required for physiological development of the dependent young.

Amino Acid Sequence↗

PubMed2000

The gene for a novel member of the whey acidic protein family encodes three four-disulfide core domains and is asynchronously expressed during lactation.

Secretion of whey acidic protein (WAP) in milk throughout lactation has previously been reported for a limited number of species, including the mouse, rat, rabbit, camel, and pig. We report here the isolation of WAP from the milk of a marsupial, the tammar wallaby (Macropus eugenii). Tammar WAP (tWAP) was isolated by reverse-phase HPLC and migrates in SDS-polyacrylamide gel electrophoresis at 29.9 kDa. tWAP is the major whey protein, but in contrast to eutherians, secretion is asynchronous and occurs only from approximately days 130 through 240 of lactation. The full-length cDNA codes for a mature protein of 191 amino acids, which is comprised of three four-disulfide core domains, contrasting with the two four-disulfide core domain arrangement in all other known WAPs. A three-dimensional model for tWAP has been constructed and suggests that the three domains have little interaction and could function independently. Analysis of the amino acid sequence suggests the protein belongs to a family of protease inhibitors; however, the predicted active site of these domains is dissimilar to the confirmed active site for known protease inhibitors. This suggests that any putative protease ligand may be unique to either the mammary gland, milk, or gut of the pouch young. Examination of the endocrine regulation of the tWAP gene showed consistently that the gene is prolactin-responsive but that the endocrine requirements for induction and maintenance of tWAP gene expression are different during lactation.

Amino Acid Sequence↗

PubMed1997

Interstitial orchitis with impaired steroidogenesis and spermatogenesis in the testes of rabbits infected with an attenuated strain of myxoma virus.

The pathogenesis of infertility associated with acute viral orchitis was investigated in a rabbit model. Infection of postpubertal male European rabbits with an attenuated strain of myxoma virus caused systemic disease with viral replication to high titres in the testes. Infected rabbits developed an interstitial orchitis and epididymitis. This was associated with degeneration of the seminiferous epithelium, decreased serum testosterone concentrations and increased serum LH concentrations. Virus was localized within the interstitial cells. Clearance of infectious virus from the testis occurred between day 20 and day 30 after infection, although viral DNA could still be detected by polymerase chain reaction at 120 days. Viral clearance was associated with a return to normal serum testosterone and LH concentrations. Anti-sperm antibodies were present in the serum as early as 5 days after infection and declined during the recovery phase. Rabbits were infertile at 60 days but returned to normal fertility 60-90 days after infection.

Animals↗

PubMed1993

Insulin counters the glycogenolytic effect of arginine vasotocin in liver pieces from the axolotl, Ambystoma mexicanum, cultured in vitro.

In organ cultures of liver tissue from the axolotl, Ambystoma mexicanum, 1 nmol/l arginine vasotocin (AVT) increased tissue cyclic AMP (cAMP) concentration, activated glycogen phosphorylase, and caused glycogen breakdown and glucose release. Addition of 10 nmol/l insulin had no effect on any of these parameters. Addition of glucagon together with AVT caused a further increase in tissue cAMP but not in glucose release. Ten nanomoles per liter of insulin added to the cultures 5 min before 1 nmol/liter AVT inhibited all the above actions of AVT. This inhibitory action of insulin was not apparent in the presence of the cAMP phosphodiesterase inhibitor isobutylmethylxanthine (IBMX), which indicates that insulin activates cAMP phosphodiesterase and so reduces the concentration of cAMP in the tissue. This cannot occur in the presence of IBMX. These findings confirm previous reports that AVT causes hepatic glycogenolysis in the axolotl via an increase in tissue cAMP level.

1-Methyl-3-isobutylxanthine↗

PubMed1993

Hormone-induced rise in cytosolic Ca2+ in axolotl hepatocytes: extracellular origin and control by cAMP.

In amphibian liver, signal transduction of [Arg8]vasotocin (AVT), a "classical" Ca(2+)-dependent hormone in rat liver, is mediated via the generation of adenosine 3',5'-cyclic monophosphate (cAMP) and not via inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. In isolated hepatocytes from axolotl, hormones that stimulated cAMP formation (the order of efficacy was glucagon > isoprenaline > epinephrine > or = AVT) also provoked a pronounced increase in cytosolic Ca2+, as indicated from changes in fura 2 fluorescence. 8-Bromoadenosine 3',5'-cyclic monophosphate at 100 microM was as potent as maximally effective concentrations of glucagon. Ins(1,4,5)P3 mobilized Ca2+ from the endoplasmic reticulum of saponin-permeabilized axolotl hepatocytes with a half-maximal effect at 0.65 microM, as did GTP (20 microM), even in the absence of polyethylene glycol. However, the hormonally induced increase in cytosolic Ca2+ was not due to a mobilization of the cation from internal stores by Ins(1,4,5)P3, but to an increased inflow from the extracellular medium. We conclude that in axolotl liver, in contrast to rat liver, hormones stimulate the production of cAMP that, in addition to stimulating processes such as glycogenolysis, also regulates the opening of an ion gate in the plasma membrane, which allows the inflow of Ca2+. To our knowledge this is the first demonstration of a second messenger-operated Ca2+ channel in a splanchnic tissue.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1992

Hormones regulating hepatic glycogenolysis in two chelonians use cyclic AMP, and not Ca2+, as intracellular messenger.

In teleosts, lungfish, amphibians, and a reptile, Amphibolurus nuchalis, hormonal stimulation of hepatic glycogenolysis is mediated by a rise in intracellular cyclic AMP concentration. In mammals, by contrast, the inositol trisphosphate/Ca2+/diacylglycerol signal transduction pathways are also involved. The present study describes the hormonal regulation of hepatic glycogenolysis in adult long-necked turtles, Chelodina longicollis, and hatchlings of the loggerhead turtle, Caretta caretta. Adrenaline and glucagon, but not neurohypophysial peptides, stimulated glycogenolysis, glycogen phosphorylase activity, and accumulation of cAMP in cultured liver pieces from either C. longicollis or C. caretta. The actions of adrenaline were blocked by a beta-adrenergic antagonist, propranolol, but were unaffected by an alpha-adrenergic antagonist, phentolamine. The effects of adrenaline were maintained in Ca(2+)-free medium containing EGTA, and were not mimicked by the Ca2+ ionophore, A23187. The beta-adrenergic ligand, [125I]iodocyanopindolol (ICP), specifically bound to membranes prepared from C. longicollis liver, with a calculated KD of 59 pM and a Bmax of 171 fmol/mg protein. The adrenergic ligands, propranolol, isoprenaline, adrenaline, phenylephrine, phenoxybenzamine, noradrenaline, and phentolamine displaced ICP with KD's of 50 nM, 5 microM, 22 microM, 140 microM, 180 microM, 250 microM, and 1 mM, respectively. The alpha-adrenergic ligands, prazosin and yohimbine, did not bind specifically to the membranes, although prazosin did bind to membranes prepared similarly from rat liver. Thus the glycogenolytic actions of adrenaline are mediated via beta-adrenergic receptors in liver from C. longicollis and C. caretta and alpha-adrenergic receptors may play no role in the control of hepatic metabolism in these chelonians.

1-Methyl-3-isobutylxanthine↗

PubMed1991

Development of mammalian endothermic metabolism: quantitative changes in tissue mitochondria.

The development of energy metabolism of mammalian tissues was assessed in the tammar wallaby Macropus eugenii by the measurement of mitochondrial parameters in the liver, heart, kidney, and brain. Tissues taken from wallabies (n = 27) ranging from 10-day-old pouch young (weighing approximately 4 g) to adults (averaging 6.2 kg) were weighed and fixed, and mitochondrial volume and mitochondrial membrane surface area (MMSA) were determined by quantitative electron microscopy techniques. Developmental changes in these parameters were analyzed chronologically and allometrically. Relative growth rates of all four tissues decreased during development. Liver and heart showed constant allometric growth throughout development, whereas kidney and brain showed biphasic allometric growth. Tissue metabolic intensity assessed by MMSA (m2/cm3 tissue) was constant in liver, showed a threefold increase in brain during pouch life, showed a fourfold increase in the heart between 100 and 200 days of age, and showed a twofold increase in the kidney at the end of pouch life. In all tissues, adult levels of tissue metabolic capacity were present at pouch exit. In all four tissues, total MMSAs were at "reptilian" levels at birth and gradually increased to "mammalian" levels. Each tissue exhibited a different developmental timetable. When the total MMSAs for all four tissues were summed there was a similar pattern of allometric development between summed MMSA and whole animal metabolic rate.

Aging↗

PubMed1990

Gonadal hormones inhibit the induction of metamorphosis by thyroid hormones in Xenopus laevis tadpoles in vivo, but not in vitro.

Although the major hormones controlling amphibian metamorphosis are those of the thyroid, other hormones, notably prolactin and the adrenal steroids, modulate the effects of thyroid hormones (TH). Some authors report that the gonadal steroids stimulate the metamorphic actions of TH whereas others report inhibition. The aims of the present study were to determine the effects of gonadal steroids on TH-induced metamorphosis in Xenopus laevis and to determine the site of action of these steroids. In all cases, hormones were added to the water in which the tadpoles were swimming. The gonadal steroids, testosterone and 17 beta-estradiol, inhibited triiodothyronine (T3)-induced metamorphosis in living, premetamorphic tadpoles of X. laevis. Both steroids, at 3.4 microM, prevented the reduction in body weight and the shrinkage of head and alimentary canal brought about by 1 nM T3. In contrast, 3.4 microM corticosterone stimulated T3-induced metamorphosis. Addition of 100 nM T3 to the medium induced a large reduction in size of X. laevis tails cultured in vitro. The antagonistic effects of testosterone were not reproduced in such cultures, whereas the synergistic action of corticosterone was maintained. Testosterone had no effect upon the specific binding of T3 to X. laevis tail tissue, whereas corticosterone increased such binding. These findings indicate that, while corticosterone stimulates the metamorphic actions of T3 by acting directly in the peripheral tissues, the gonadal steroids, particularly testosterone, inhibit T3 by acting at a more central site. Prolactin is known to antagonize the metamorphic actions of T3 and one such central action could be the stimulation of prolactin synthesis. However, testosterone inhibited the prometamorphic actions of bromocriptine, which stimulates metamorphosis by inhibiting production of prolactin. Thus the central action of testosterone is unlikely to be a stimulation of prolactin production.

Animals↗

PubMed1990

Thyroid hormones during development of a marsupial, the tammar wallaby, Macropus eugenii.

The levels of thyroid hormones in the plasma and the activities of 5'-deiodinase activity in liver and kidney were determined in the tammar wallaby, Macropus eugenii, from early pouch life to adulthood. The total concentration of plasma thyroxine (T4) was below 15 nmol/l before day 75 of pouch life, rose to about 75 nmol/l at day 160, and then decreased to about 12 nmol/l in the adult. The total concentration of plasma tri-iodothyronine (T3) was below 0.4 nmol/l before day 120, increased to 3 nmol/l by about day 220 and then decreased to 1.0 nmol/l in adults. Concentrations of free T4 and free T3 followed a similar pattern but peaked at 45 and 160 pmol/l respectively. Concentrations of reverse T3 (rT3) were extremely variable, ranging from 0 to 1 nmol/l at day 100, and from 0 to greater than 2 nmol/l at day 180. After about day 230, rT3 levels fell rapidly and were below 0.3 nmol/l in adults. Liver and kidney 5'-deiodinase activities, which were undetectable before day 80, reached adult levels by day 220. Half-maximal activity of both these enzymes occurred at about day 205, mid-way between the peaks of T4 and T3. These findings suggest that the systems supporting synthesis and release of hormones from the thyroid gland are probably mature by about day 160 of pouch life in the tammar, while peripheral deiodinase activity, which is a major factor in the production of T3 in the plasma, matures by about day 220. These events thus precede the development of physiological independence of the young tammar from its mother.

Animals↗

PubMed1990

[Not Available].

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Belgium↗

PubMed1988

Binding of adrenergic ligands to liver plasma membrane preparations from the axolotl, Ambystoma mexicanum; the toad, Xenopus laevis; and the Australian lungfish, Neoceratodus forsteri.

The beta-adrenergic ligand iodocyanopindolol (ICP) bound specifically to hepatic plasma membrane preparations from the axolotl, Ambystoma mexicanum (Bmax, 40 fmol/mg protein (P) at free concentration above 140 pM; KD, 42 pM); the toad, Xenopus laevis (Bmax, 200 fmol/mg P at 1 nM; KD, 300 pM); and the Australian lungfish, Neoceratodus forsteri (Bmax, 100 fmol/mg P at 5 nM). For the lungfish, the Scatchard plot was curved showing two classes of binding site with KD's of 20 and 500 pM. Neither the alpha 1-adrenergic ligand prazosin nor the alpha 2-adrenergic ligand yohimbine bound specifically to hepatic membrane preparations from any of the three species. Several adrenergic ligands displaced ICP from hepatic membrane preparations of all three species with KD's of Axolotl--propranolol, 50 nM; isoprenaline, 600 nM; adrenaline, 10 microM; phenylephrine, 20 microM; noradrenaline, 40 microM; and phentolamine, greater than 100 microM; X. laevis--propranolol, 30 nM; isoprenaline, 100 microM; adrenaline, 200 microM; noradrenaline, 300 microM; phenylephrine, 1 mM; and phentolamine, greater than 1 mM; N. forsteri,--propranolol, 25 nM; isoprenaline, 1 microM; adrenaline, 20 microM; phenylephrine, 35 microM; noradrenaline, 600 microM; and phentolamine, 400 microM. These findings suggest that alpha-adrenergic receptors are not present in hepatic plasma membrane preparations from these three species and that the hepatic actions of catecholamines are mediated via beta-adrenergic receptors. The order of binding of the beta-adrenergic ligands suggests that the receptors are of the beta 2 type.

Ambystoma↗

PubMed1987

Hormonal regulation of hepatic glycogenolysis in the toad, Xenopus laevis, is mediated by cyclic AMP and not Ca2+.

Hepatic glycogenolysis and glycogen phosphorylase a activity were stimulated by arginine vasotocin (AVT) in liver pieces from Xenopus laevis cultured in vitro. In each case, the EC50 was about l nM. The increased rate of glycogenolysis brought about by either AVT or adrenaline was maintained for at least 6 hr and was unchanged when Ca2+ salts were omitted from the medium or when 2.5 mM EGTA was added. Neither the Ca2+ ionophore, A23187, nor the Ca2+ channel blocker, verapamil, had any effect on the rate of glycogenolysis in the presence or the absence of either hormone. Tissue cyclic AMP levels were unchanged by addition of AVT alone but were doubled in the presence of AVT plus either of the phosphodiesterase inhibitors, isobutylmethylxanthine or RO20-1724. These findings suggest that hormones regulating hepatic glycogenolysis in X. laevis use cyclic AMP, and not Ca2+, as an intracellular messenger. We would argue that cytosolic Ca2+ may not have become involved in regulation of hepatic glycogenolysis until after the ancestors of present day amphibians separated from those of present day mammals.

Animals↗

PubMed1987

Hormonal regulation of hepatic glycogenolysis in the carp, Cyprinus carpio.

Carp (Cyprinus carpio) liver maintained normal glycogen content and enzyme complement for several days in organ culture. Epinephrine-stimulated glycogenolysis, phosphorylase activation, and cyclic AMP (cAMP) accumulation in a concentration-dependent manner with EC50s of 100, 100, and 500 nM, respectively. These actions were blocked by the beta-adrenergic antagonist, propranolol, but not by the alpha-adrenergic antagonist phentolamine. Glycogenolysis and tissue cAMP were uninfluenced by 10(-6) M arginine vasotocin, arginine vasopressin, lysine vasotocin, lysine vasopressin, mesotocin, or oxytocin, but were slightly increased by 10(-5) M isotocin and slightly decreased by 10(-6) M angiotensin II. [125I]-iodocyanopindolol (ICP), a beta-adrenergic ligand, bound to isolated carp liver membranes with a KD of 83 pM. Maximum binding of 45 fmol/mg protein was at 600 pM. Propranolol, isoprenaline, epinephrine, phenylephrine, norepinephrine, and phenoxybenzamine displaced ICP with KDs of 100 nM, 2, 20, 20, 60, and 200 microM, respectively. The alpha-adrenergic antagonists, yohimbine and prazosin, showed no specific binding. These data provide evidence that catecholamines act via beta-adrenergic receptors in carp liver and that alpha-adrenergic receptors are not present. Vasoactive peptides play no significant role in regulation of carp liver glycogenolysis.

Alanine Transaminase↗

PubMed1986

Physiological and metabolic changes associated with weaning in the tammar wallaby, Macropus eugenii.

The tammar wallaby (Macropus eugenii) is a small macropodid marsupial in which the major part of weaning occupies the period between 28 and 36 weeks of pouch life. Before weaning the diet of the tammar is high in carbohydrate and low in lipid/volatile fatty acid whereas the reverse applies after weaning. The adult tammar is a forestomach fermenter. The aim of this study was to elucidate some of the physiological and metabolic changes associated with this major change in the diet. Hepatic glycogen content increased gradually early in development to a maximum of 7% of liver weight at 28-30 weeks of pouch life. It then fell precipitously to less than 1% of liver weight at 36 weeks before recovering to the adult level of about 3% liver weight. Plasma glucose levels were maintained at about 10 mM until 36 weeks, after which they fell gradually to adult values of about 4 mM. Hepatic hexokinase activity increased several-fold between 18 and 30 weeks of pouch life, remained high until 42 weeks, and then fell to the adult level. The hepatic activities of fructose-bisphosphatase and particulate phosphoenolpyruvate carboxykinase (PEPCK) were unchanged during development but soluble hepatic PEPCK activity, which was low until 28 weeks of pouch life, increased 3-4 fold between 30 and 36 weeks and then fell slightly to the adult level. Hepatic pyruvate kinase increased in activity up to 28 weeks and then fell to about half peak values at 36 weeks and 20% of peak activity in the adult.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonia↗

PubMed1986

Glucagon and insulin regulate in vitro hepatic glycogenolysis in the axolotl Ambystoma mexicanum via changes in tissue cyclic AMP concentration.

Glucagon increases the rate of glycogenolysis in in vitro cultures of hepatic tissue from the axolotl Ambystoma mexicanum. The hormone causes an increase in the concentration of cyclic AMP in the tissue which is followed by activation of glycogen phosphorylase and subsequent breakdown of glycogen and release of glucose from the tissue. Insulin counteracts the glycogenolytic effect of glucagon by inhibiting the increase in tissue cyclic AMP concentration brought about by glucagon. This inhibitory effect of insulin is not seen in the presence of the phosphodiesterase inhibitor IBMX and so it appears that the initial action of insulin is a stimulation of cyclic AMP phosphodiesterase activity which lowers the tissue concentration of cyclic AMP and so counters the actions of hormones that act by raising the tissue concentration of cyclic AMP. This model for the mode of action of insulin is supported by the finding that insulin also interferes with the glycogenolytic actions of adrenaline, a second hormone which acts by raising tissue cyclic AMP concentrations.

1-Methyl-3-isobutylxanthine↗

PubMed1986

Changes in prolactin in peripheral plasma during lactation in the brushtail possum Trichosurus vulpecula.

A heterologous double-antibody radioimmunoassay has been validated for prolactin in plasma and pituitary preparations of T. vulpecula. Serial dilutions of crude pituitary homogenates and plasmas from several marsupials and purified prolactin from the tammar, Macropus eugenii, showed parallel dose response curves. In both male and female possums plasma prolactin concentrations increased in response to a single intravenous injection of thyrotrophin releasing hormone. Plasma prolactin concentrations were measured in six lactating females (June-November) and in four non-lactating females (July-October). In the following year prolactin levels were also measured in 11 possums with young less than 50 days old and in 24 possums with young aged between 100 and 145 days. In early lactation prolactin concentrations were low (less than 8 ng/ml) but increased to high levels (greater than 30 ng/ml) by 120 days and remained high until about 160 days of lactation. Thereafter concentrations declined although the young continued to take milk from the mother for a further 30-50 days. The changes in plasma prolactin concentrations throughout lactation are very similar to those described for the tammar, and this unusual pattern appears to be common to marsupials. Non-lactating possums showed no consistent changes in plasma prolactin concentrations between July and October.

Animals↗