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Biomedical subjects

M S Johnson

Publications and source records attributed to M S Johnson.

At least 19 recordsLinked to original sources
PubMed2007

Cryptic speciation in two widespread subterranean amphipod genera reflects historical drainage patterns in an ancient landscape.

The landscape of the Pilbara region of Western Australia has been relatively unchanged for 100 million years. The ancient river systems of this region might be expected to be sources of isolation and divergence for aquatic species. Hence, the occurrence of widespread groundwater taxa in this landscape offers the opportunity to examine associations between genetic diversity and drainage patterns. Pilbarus and Chydaekata are two widespread genera of subterranean amphipods endemic to the Pilbara, each occupying multiple tributaries. We used molecular data to examine the roles of drainage patterns in structuring genetic diversity. Gene flow within a tributary may be facilitated by the occasional occurrence of these amphipods in springs, which results in their downstream dispersal during episodic flooding. However, tributary boundaries may form hydrological barriers to gene flow, resulting in localised isolation of populations and divergence. Samples of both genera, collected throughout three river basins, were examined for sequence divergence in the cytochrome c oxidase I mitochondrial gene. There was no evidence of contemporary gene flow among populations of either genus, and each tributary contained highly divergent lineages, which were not associated with similar morphological differentiation. This suggests cryptic speciation has occurred, and similar phylogenetic signals in both taxa imply similar evolutionary histories. Surface populations may have been driven into subterranean refugia by the cessation of flow in the rivers, associated with Tertiary climate change, while morphological evolution may have been constrained by stabilising selection. The lack of congruence between molecular diversity and morphology raises important practical issues for conservation.

Amphipoda↗
PubMed2007

Results of pacemaker implantation in 104 dogs.

OBJECTIVES: To document the outcome, survival and complications involved in pacemaker implantation in dogs in a retrospective study. METHODS: Case records for all dogs in which pacemaker implantation was performed were reviewed. RESULTS: A total of 104 dogs underwent pacemaker implantation. Dogs were presented with atrioventricular (AV) block (71), sick sinus syndrome (25) or vasovagal syncope (eight). Age at presentation varied from six months to 13 years with a median age of seven years and two months. The Labrador was the most commonly represented breed (17 cases). All but one dog survived pacemaker implantation, with 93 showing resolution of their clinical signs while 10 dogs showed intermittent residual signs. One-, three- and five-year survival estimates were 86, 65 and 39 per cent, respectively. Major complications after implantation were documented in 15 dogs and three of these led to fatalities. Minor complications were noted in 23 dogs. Sudden death occurred in six dogs three to 55 months following successful pacemaker implantation. CLINICAL SIGNIFICANCE: Transvenous pacemaker implantation was successful in reducing or eliminating clinical signs in over 90 per cent of dogs with third-degree atrioventricular (AV) block or sick sinus syndrome. In dogs with vasovagal syncope, six of eight dogs had greatly reduced frequency of collapse and two became asymptomatic. Although the procedure was associated with complications, these were rarely life threatening and good survival was documented in the majority of cases.

Animals↗
PubMed2007

Successful medical treatment of 15 dogs with pyothorax.

OBJECTIVES: To review the success of non-surgical management, which included antibiotics and a single thoracocentesis, in 15 dogs presenting with pyothorax. METHODS: Sixteen dogs were selected retrospectively from case files at the Veterinary Cardiorespiratory Centre. RESULTS: One dog was diagnosed with a mass suspected to be a pulmonary abscess on ultrasound examination and was referred for surgery. Fifteen dogs were treated medically. Springer spaniels were the most commonly presented breed (six cases) followed by Labrador retrievers (three cases). Under sedation or general anaesthesia, thoracocentesis was performed unilaterally and as much purulent effusion as possible was removed. Lavage of the thorax was not undertaken. In most dogs, antibiotic treatment was ampicillin at a mean dose of 33 mg/kg administered three times daily and 25 mg/kg metronidazole administered twice daily. Antibiotics were provided for a minimum of six weeks. All dogs recovered completely and did not show relapse on prolonged follow-up. This included one dog, which had very widespread pleural adhesions and minimal effusion. CLINICAL SIGNIFICANCE: In dogs that do not have evidence of pulmonary masses or consolidations and no evidence of granular pleural effusion, medical therapy may be curative even in chronic cases of pyothorax with pleural adhesions.

Ampicillin↗
PubMed2006

Neurotrophic modulation of myelinated cutaneous innervation and mechanical sensory loss in diabetic mice.

Human diabetic patients often lose touch and vibratory sensations, but to date, most studies on diabetes-induced sensory nerve degeneration have focused on epidermal C-fibers. Here, we explored the effects of diabetes on cutaneous myelinated fibers in relation to the behavioral responses to tactile stimuli from diabetic mice. Weekly behavioral testing began prior to streptozotocin (STZ) administration and continued until 8 weeks, at which time myelinated fiber innervation was examined in the footpad by immunohistochemistry using antiserum to neurofilament heavy chain (NF-H) and myelin basic protein (MBP). Diabetic mice developed reduced behavioral responses to non-noxious (monofilaments) and noxious (pinprick) stimuli. In addition, diabetic mice displayed a 50% reduction in NF-H-positive myelinated innervation of the dermal footpad compared with non-diabetic mice. To test whether two neurotrophins nerve growth factor (NGF) and/or neurotrophin-3 (NT-3) known to support myelinated cutaneous fibers could influence myelinated innervation, diabetic mice were treated intrathecally for 2 weeks with NGF, NT-3, NGF and NT-3. Neurotrophin-treated mice were then compared with diabetic mice treated with insulin for 2 weeks. NGF and insulin treatment both increased paw withdrawal to mechanical stimulation in diabetic mice, whereas NT-3 or a combination of NGF and NT-3 failed to alter paw withdrawal responses. Surprisingly, all treatments significantly increased myelinated innervation compared with control-treated diabetic mice, demonstrating that myelinated cutaneous fibers damaged by hyperglycemia respond to intrathecal administration of neurotrophins. Moreover, NT-3 treatment increased epidermal Merkel cell numbers associated with nerve fibers, consistent with increased numbers of NT-3-responsive slowly adapting A-fibers. These studies suggest that myelinated fiber loss may contribute as significantly as unmyelinated epidermal loss in diabetic neuropathy, and the contradiction between neurotrophin-induced increases in dermal innervation and behavior emphasizes the need for multiple approaches to accurately assess sensory improvements in diabetic neuropathy.

Animals↗
PubMed2005

Characterization of novel splice variants of the PAC1 receptor in human neuroblastoma cells: consequences for signaling by VIP and PACAP.

Expression of VPAC and PAC1 receptor isoforms was determined in six neuroblastoma cell lines as well as in human embryonic and adult brain using reverse transcriptase PCR and quantitative PCR. PAC1 receptor splice variants missing a 21 amino acid sequence in the amino terminal domain were found to be the major receptor variants in the neuroblastoma cell lines and also were highly expressed in embryonic brain compared to adult brain. In four of the neuroblastoma cell lines, VIP and PACAP stimulated cyclic AMP production with different potencies and levels of maximal stimulation. High potency and greatest maximal stimulation of cyclic AMP for each peptide were recorded in SH-SY5Y cells, indicating the presence of high affinity VIP and PACAP receptors. Further characterization of specific VPAC and PAC1 receptor isoforms was carried out in the SH-SY5Y cell line, where along with known PAC1 receptor splice variants and the VPAC2 receptor, a number of novel PAC1 receptor splice variants were identified. The comparatively low level expression of the VPAC2 receptor along with the poor responsiveness of SH-SY5Y cells to the VPAC2 receptor-specific agonist Ro 25-1553 indicated that this receptor did not contribute significantly to the observed VIP responses. When the individual PAC1 receptor isoforms were expressed in COS 7 cells, the ability of VIP to activate cyclic AMP production was increased more than 50-fold at the majority of the PAC1 receptor variants lacking the 21 amino acid amino terminal domain sequence compared to those with the complete domain. Smaller changes were seen in the potency of PACAP-38. Similar trends were seen with inositol phosphate responses, where in each case agonist potencies were lower than for cyclic AMP production. The results of this study show that the combination of different amino terminal and intracellular loop 3 splicing variants in the PAC1 receptor dictates the ability of agonists, particularly VIP, to activate signaling pathways. VIP has considerably greater potency at most PAC1 receptors with the short amino terminal domain, and these therefore may mediate physiological effects of both VIP and PACAP. Furthermore, there may be a phenotypic switch in the expression of different PAC1 receptor amino terminal splice variants between embryonic and mature nervous system, indicating that regulation of this event may have an important role in VIP/PACAP function, particularly in the developing nervous system.

Adult↗
PubMed2005

Estrogen increases sensory nociceptor neuritogenesis in vitro by a direct, nerve growth factor-independent mechanism.

Estrogen affects many aspects of the nervous system, including pain sensitivity and neural regulation of vascular function. We have shown that estrogen elevation increases sensory nociceptor innervation of arterioles in Sprague-Dawley rat mammary gland, external ear and mesentery, suggesting widespread effects on sensory vasodilatory innervation. However, it is unclear whether estrogen elicits nociceptor hyperinnervation by promoting target release of neurotrophic factors, or by direct effects on sensory neurons. To determine if estrogen may promote axon sprouting by increasing release of target-derived diffusible factors, dorsal root ganglia explants were co-cultured with mesenteric arterioles for 36 h in the absence or presence of 17beta-estradiol (E2). Mesenteric arteriolar target substantially increased neurite outgrowth from explanted ganglia, but estrogen had no effect on outgrowth, suggesting that estrogen does not increase the availability of trophic proteins responsible for target-induced neurite outgrowth. To assess the direct effects of estrogen, dissociated neonatal dorsal root ganglion neurons were cultured for 3 days in the absence or presence of E2 and nerve growth factor (NGF; 1-10 ng/mL), and immunostained for the nociceptor markers peripherin or calcitonin gene-related peptide. NGF increased neuron size, survival and numbers of neurons with neurites, but did not affect neurite area per neuron. Estrogen did not affect neuron survival, size or numbers of neurons with neurites, but did increase neurite area per neuron. The effects of these agents were not synergistic. We conclude that estrogen exerts direct effects on nociceptor neurons to promote axon outgrowth, and this occurs through an NGF-independent mechanism.

Animals↗
PubMed2004

Toxicologic and histopathologic response of the terrestrial salamander Plethodon cinereus to soil exposures of 1,3,5-trinitrohexahydro-1,3,5-triazine.

Red-backed salamanders (Plethodon cinereus) were exposed to four different concentrations of 1,3,5-trinitrohexahydro-1,3,5-triazine (RDX) in soil under controlled laboratory conditions for 28 days. Wild-caught P. cinereus (N = 20/treatment) were exposed to target concentrations of 5,000, 1000, 100, 10, and 0 mg RDX/kg soil (dry wt) using a microcosm design. Animals were fed 5 to 10 uncontaminated mutant Drosophila flies every 3 days and monitored daily. Animals were weighed 1 day before being placed in treatment and weekly thereafter. RDX concentrations in soil were analytically determined after the compound was added and mixed at the beginning, the midpoint, and the end of exposure. RDX soil concentrations were relatively stable throughout the exposure period. Signs of overt toxicity were observed primarily in the highest exposure group. Salamanders exposed to 5,000 mg RDX/kg soil exhibited signs of neuromuscular effects (lethargy, gaping, hypersensitivity, tremors) and exhibited significant weight loss. A single moribund animal from this group lost >20% of its original body weight and was killed. Animals in this exposure group also lost weight relative to animals in other treatments. Histopathologic evaluations, including an evaluation of melanomacrophage parameters, indicated no strong treatment-related findings. This study provided information regarding the effects from subchronic dermal exposure of a terrestrial amphibian species to RDX in soil and provides a microcosm approach to the evaluation of toxicity of contaminants in soil to a terrestrial vertebrate.

Administration, Cutaneous↗
PubMed2004

Seasonal variations in activity concentrations of 99Tc and 137Cs in the edible meat fraction of crabs and lobsters from the central Irish Sea.

Discharges of most radionuclides into the Irish Sea from the BNFL site at Sellafield have decreased over the past 20 years or so. For a few radionuclides, however, discharges have peaked more recently. Notably, operation of the Enhanced Actinide Removal Plant (EARP) since 1994 has led to an increase in discharges of (99)Tc, as a result of the treatment of previously stored waste, with consequent increases in (99)Tc activity concentrations in a number of marine species, particularly in crustaceans such as lobsters. Previous research has considered the significance of factors such as sex and body weight on radionuclide concentrations. The current project set out to investigate whether seasonal variations in radionuclide concentrations in crabs and lobsters occur, with particular emphasis on the dynamics of (99)Tc and (137)Cs. Organisms were obtained from a site off the Isle of Man, where radionuclide concentrations were measurable but the site was sufficiently distant from Sellafield that the radionuclides were well mixed in the water column and not likely to be influenced by the pulsed nature of discharges of (99)Tc. Crab and lobster samples were collected monthly, between February 2000 and February 2001. Fifteen or 16 individuals (evenly split as male and female) of each species were collected on each occasion. Seawater samples were also collected over the 12-month period. Activity concentrations of (99)Tc in the edible meat fraction (both brown and white meat) ranged from 0.23 to 2.46 Bq kg(-1) (fresh weight (fw)) in crabs and 124 to 216 Bq kg(-1) (fw) in lobsters, with no observed seasonal variations. Activity concentrations of (137)Cs in both crab and lobster were lower, ranging from <0.16 to 0.85 Bq kg(-1) for crab meat (fw) and <0.3 to 3.3 Bq kg(-1) for lobster meat (fw). A statistically significant increase in activity concentrations of (137)Cs in the meat was observed in the summer months for both crab and lobster. The cause has not been investigated but may be related to the laying down of energy reserves during the active feeding period over the summer. At all times, uptake of (99)Tc is higher in the brown meat fraction of both crabs and lobsters, whilst (137)Cs is more uniformly distributed. These results are used to discuss the implications for sampling and monitoring programmes.

Animals↗
PubMed2004

Identification and characterization of a novel luciferase-like protein in the human female reproductive tract.

A novel cDNA was cloned from human endometrium, matching a human gene with the interim name KIAA1463. An mRNA identified by 5'-rapid amplification of cDNA ends was found to be 3349 nt in length. PCR analysis also identified another transcript of 6626 nt, with an open reading frame encoding a 900 amino acid protein. A fold recognition program identified similarity to firefly luciferase containing an AMP-binding motif; hence, we refer to the predicted protein as the AMP binding/luciferase-like protein (ALLP). ALLP mRNA and protein were expressed throughout the female reproductive tract with the highest levels found in the ovary and uterus. In situ hybridization and immunohistochemistry showed predominant localization of the ALLP mRNA/protein in endometrial glandular epithelium and within the theca and granulosa cells in the ovary. In the endometrium expression of ALLP, mRNA and protein were higher during d 16-21 of the secretory phase of the cycle. Western blot analysis showed decreased expression of ALLP in the postmenopausal endometrium, and hormone replacement therapy increased the expression of ALLP. Endometrial adenocarcinoma cell lines expressed more ALLP, compared with cultured primary endometrial cells or normal endometrial tissue. The ubiquitous expression of ALLP in reproductive and nonreproductive tissues suggests that this protein, which is probably regulated by ovarian steroids, plays an important metabolic role and may be involved in such processes as implantation and tumorigenesis.

Adenosine Monophosphate↗
PubMed2003

Accumulation of lead, zinc, and cadmium in a wild population of Clethrionomys glareolus from an abandoned lead mine.

Lead, zinc, and cadmium were determined in a range of tissues from wild populations of bank voles (Clethrionomys glareolus) trapped on an abandoned metalliferous mine site and a reference site. Estimated dietary intakes indicated that animals were exposed to elevated levels of all three metals at the mine site, and this was generally reflected in metal residues in body tissues. Lead concentrations were significantly higher in all tissues of animals from the mine compared to the reference site, while Cd was higher only in the kidney. There was evidence of age-accumulation (using total body weight as an index of age) of Cd in both the liver and kidney of mine site animals but no evidence of such accumulation of lead in bone. In contrast to Cd and Pb, Zn was lower in the tissues of mine site animals compared to the reference site. Based on critical tissue concentrations, the ecotoxicological risk to a wild population of bank voles (Clethrionomys glareolus), associated with total substrate levels of 1 microg g(-1) dry weight Cd and 700 microg g(-1) dry weight Zn at this mine site is negligible, but that associated with 4000 microg g(-1) dry weight Pb may be considered significant.

Aging↗
PubMed2003

Limits to sustained energy intake. VIII. Resting metabolic rate and organ morphology of laboratory mice lactating at thermoneutrality.

We have previously shown that the food intake and milk production of MF1 laboratory mice lactating at 30 degrees C, 21 degrees C and 8 degrees C increase as temperature declines. These data suggest that mice are not limited peripherally by the capacity of the mammary glands to produce milk but are limited by the capacity of the animal to dissipate body heat generated as a by-product of food processing and milk production. Here, we measure resting metabolic rate (RMR; prior to breeding and at peak lactation) and organ morphology (at peak lactation) in MF1 mice exposed to 30 degrees C (thermoneutrality) and compare these traits with the same parameters measured previously in mice at 21 degrees C and 8 degrees C. The masses of visceral organs primarily responsible for energy flux (heart, lungs, stomach, small intestine, large intestine, liver, pancreas, spleen and kidneys) increased as temperature declined. The masses of all these organs differed between mice exposed to 8 degrees C and 21 degrees C, whereas only the masses of heart, liver and kidneys differed between mice at 21 degrees C and 30 degrees C. The increases in organ masses were paralleled by increases in RMR at peak lactation above the levels measured prior to breeding, with mice at 8 degrees C and 21 degrees C having significantly higher increases in RMR than mice at 30 degrees C (29.6 kJ day(-1), 25.5 kJ day(-1) and 8.1 kJ day(-1), respectively). The observed changes in visceral organs and RMR are consistent with both the heat dissipation and peripheral limit hypotheses. However, mice exposed to 8 degrees C had substantially larger mammary glands than mice at 21 degrees C or 30 degrees C (2.450 g, 1.115 g and 0.956 g dry mass, respectively), which argues against the peripheral limitation hypothesis and is consistent with the heat dissipation limit hypothesis. In addition, cold exposure resulted in greater masses of brown adipose tissue, white adipose tissue, pelage and tail. We discuss these changes in the context of the potential thermoregulatory benefits from use of the heat generated as a by-product of milk synthesis.

Analysis of Variance↗
PubMed2002

Specific interaction between the hop1 intracellular loop 3 domain of the human PAC(1) receptor and ARF.

The PAC(1), VPAC(1) and VPAC(2) receptors are members of the secretin (Group II) family of G protein-coupled receptors. All members of this family activate adenylate cyclase and several have also been shown to activate phospholipase C. We have recently reported that the rat VPAC(1), VPAC(2) and PAC(1) receptors activate phospholipase D and that distinct pathways are utilised by two intracellular loop 3 splice variants of PAC(1), one of which is ARF-dependent. Phospholipase D activation by the hop1, but not the null (short), form of the PAC(1) receptor is sensitive to brefeldin A, an inhibitor of GTP exchange at ARF. We have expressed the null and hop1 intracellular loop 3 domains of the human PAC(1) receptor in bacteria as GST-fusion proteins and used them as peptide affinity matrices to determine whether a functional interaction exists between these domains and ARF. Using this GST pull-down assay, we have shown binding of the small G protein ARF6 to the hop1 but not the null domain of this receptor.

ADP-Ribosylation Factors↗
PubMed2002

Quantifying 137Cs aggregated transfer coefficients in a semi-natural woodland ecosystem adjacent to a nuclear reprocessing facility.

Radiocaesium (137Cs) activity concentrations and aggregated transfer factors (Tag values) were calculated for vascular plants, fungal fruiting bodies and invertebrates in a semi-natural Picea sitchensis woodland (Lady Wood) adjacent to the British Nuclear Fuels plc. reprocessing facility at Sellafield, Cumbria, UK. The Tag values for vascular plants ranged from 7.1 x 10(-4) - 1.9 x 10(-2) m2 kg(-1), the maximum value being for Pteridium aquilinum. Fungal fruiting bodies had higher Tag values (1.9 x 10(-3) - 1.8 x 10(-1) m2 kg(-1)) than vascular plants, with a maximum value for Mycena galericulata. None of the activity concentrations for edible foodstuffs collected within this study (fungi and berries) exceeded the EC recommended limits of 137Cs in foodstuffs grown within the UK. The invertebrate community sampled during the study had Tag values ranging from 3.4 x 10(-4) to 1.3 x 10(-2) m2 kg(-1). There were no systematic differences in 137Cs activity concentration between invertebrate guilds, or between seasonal cohorts within guilds. The invertebrates in Lady Wood were exposed to a dose from 137Cs (internal gamma + beta and external gamma) ranging between 4.37 x 10(-4) and 6.40 x 10(-4) mGy day(-1). Including dose from radionuclides other than 137Cs and accounting for uncertainties due to the relative biological effectiveness of differing radionuclides could increase total dose by approximately an order of magnitude. These dose rates are at least three orders of magnitude lower than the 1 mGy d(-1) level at which harm may be caused to terrestrial biota, hence the risk to the invertebrate community from the effects of ionising radiation in Lady Wood is low.

Cesium Radioisotopes↗
PubMed2002

Isotopic processes in atmospheric chemistry.

Trace gases are responsible for the atmospheric processes underlying air pollution and global change. Analysis of the distribution of stable isotopes in these gases is a way of gaining additional knowledge that may not otherwise be available. This approach requires knowledge of the isotopic signature of emissions sources and chemical reactions. This review focuses on the chemical physics of the processes underlying the distribution of stable isotopes in atmospheric gases.

Air Pollutants↗
PubMed2002

Additional signals from VPAC/PAC family receptors.

The receptors for the neuropeptides vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide are strong activators of adenylate cyclase, but recent evidence suggests that they can elicit a number of additional intracellular signals. Some of these are likely to be downstream of the conventional adenylate cyclase pathway, but it is now clear that others reflect novel primary coupling events of the receptors.

Animals↗
PubMed2002

Food chain transfer of zinc within the ecosystems of old and modern metalliferous mine wastes.

Concentrations of zinc in mine waste, vegetation, invertebrate and small mammals from abandoned mines and a modern mine site have been determined in order to assess and compare environmental risk. Very high concentrations of zinc in mine waste from all sites were reflected in vegetation zinc levels but not in invertebrates and mammals. Physiological regulatory control mechanisms operate to optimise zinc retention, and maintain homeostasis in animals by enhancing absorption of zinc from diets low in the trace element, and by buffering the potential accumulative effects of high dietary levels of the metal. Zinc is not considered to be an acute toxicity factor precluding colonisation of these mine sites by invertebrates and mammals though it maybe a selective force influencing the species composition and relative abundance in animal communities.

Animals↗
PubMed2001

A fragment library based on Gaussian mixtures predicting favorable molecular interactions.

Here, a protein atom-ligand fragment interaction library is described. The library is based on experimentally solved structures of protein-ligand and protein-protein complexes deposited in the Protein Data Bank (PDB) and it is able to characterize binding sites given a ligand structure suitable for a protein. A set of 30 ligand fragment types were defined to include three or more atoms in order to unambiguously define a frame of reference for interactions of ligand atoms with their receptor proteins. Interactions between ligand fragments and 24 classes of protein target atoms plus a water oxygen atom were collected and segregated according to type. The spatial distributions of individual fragment - target atom pairs were visually inspected in order to obtain rough-grained constraints on the interaction volumes. Data fulfilling these constraints were given as input to an iterative expectation-maximization algorithm that produces as output maximum likelihood estimates of the parameters of the finite Gaussian mixture models. Concepts of statistical pattern recognition and the resulting mixture model densities are used (i) to predict the detailed interactions between Chlorella virus DNA ligase and the adenine ring of its ligand and (ii) to evaluate the "error" in prediction for both the training and validation sets of protein-ligand interaction found in the PDB. These analyses demonstrate that this approach can successfully narrow down the possibilities for both the interacting protein atom type and its location relative to a ligand fragment.

Algorithms↗