Dilated cardiomyopathy in dystrophic epidermolysis bullosa: a lethal complication of epidermolysis bullosa.
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Anesthesia, General↗
Biomedical subjects
R Addison
Publications and source records attributed to R Addison.
How to administer enemas and suppositories.
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Administration, Rectal↗
Spatial and temporal trends and effects of contaminants in the Canadian Arctic marine ecosystem: a review.
Recent studies have added substantially to our knowledge of spatial and temporal trends of persistent organic pollutants and heavy metals in the Canadian Arctic marine ecosystem. This paper reviews the current state of knowledge of contaminants in marine biota in the Canadian Arctic and where possible, discusses biological effects. The geographic coverage of information on contaminants such as persistent organochlorines (OCs) (PCBs, DDT- and chlordane-related compounds, hexachlorocyclohexanes, toxaphene) and heavy metals (mercury, selenium, cadmium, lead) in tissues of marine mammal and sea birds is relatively complete. All major beluga, ringed seal and polar bear stocks along with several major sea bird colonies have been sampled and analysed for OC and heavy metal contaminants. Studies on contaminants in walrus are limited to Foxe Basin and northern Québec stocks, while migratory harp seals have only been studied recently at one location. Contaminant measurements in bearded seal, harbour seal, bowhead whale and killer whale tissues from the Canadian Arctic are very limited or non-existent. Many of the temporal trend data for contaminants in Canadian Arctic biota are confounded by changes in analytical methodology, as well as by variability due to age/size, or to dietary and population shifts. Despite this, studies of OCs in ringed seal blubber at Holman Island and in sea birds at Prince Leopold Island in Lancaster Sound show declining concentrations of PCBs and DDT-related compounds from the 1970s to 1980s then a levelling off during the 1980s and early 1990s. For other OCs, such as chlordane, HCH and toxaphene, limited data for the 1980s to early 1990s suggests few significant declines in concentrations in marine mammals or sea birds. Temporal trend studies of heavy metals in ringed seals and beluga found higher mean concentrations of mercury in more recent (1993/1994) samples than in earlier collections (1981-1984 in eastern Arctic, 1972-1973 in western Arctic) for both species. Rates of accumulation of mercury are also higher in present day animals than 10-20 years ago. Cadmium concentrations in the same animals (eastern Arctic only) showed no change over a 10-year period. No temporal trend data are available for metals in sea birds or polar bears. There have been major advances in knowledge of specific biomarkers in Canadian Arctic biota over the past few years. The species with the most significant risk of exposure to PCBs and OC pesticides may be the polar bear which, based on comparison with EROD activity in other marine mammals (beluga, ringed seal), appears to have elevated CYP1A-mediated activity. The MFO enzyme data for polar bear, beluga and seals suggest that even the relatively low levels of contaminants present in Arctic animals may not be without biological effects, especially during years of poor feeding.
Animals↗
Long term use of desmopressin for urinary symptoms in multiple sclerosis.
The benefit of desmopressin (DDAVP) in the treatment of the urinary symptoms of multiple sclerosis has until now only been shown in short crossover studies of up to 6 weeks. We report 19 patients who have used the drug for an average of 2 years and 4 months, 18 of whom confirmed continued dramatic benefit without any obvious change in dosage used or efficacy and with few side effects. Ten of the 19 patients had also used DDAVP during daytime for special occasions with notable success. This is the first study to suggest that DDAVP is safe and effective in long term use in MS.
Adult↗
A cell-free translation-translocation system reconstituted with subcellular fractions from the wall-less variant fz;sg;os-1V of Neurospora crassa.
A translation-translocation system reconstituted with subcellular fractions from the wall-less variant fz;sg;os-1V of Neurospora crassa reproduces in vitro translocation and processing of a secretory protein. The translation extract was isolated from the wall-less variant by gently lysing cells by a freeze-thaw procedure. This method yielded more extract then the method developed previously (R. Addison, J. Biol. Chem. 262: 17031, 1987) as well as reducing microsomal contamination. The microsomal fraction was isolated from lysed cells using a series of discontinuous sucrose gradients. The resultant microsomes were less inhibitory to translation of various transcripts and consisted of a more homogenous mixture of vesicles then microsomes prepared previously. Polyclonal antibodies directed against a polypeptide of approximately 75 kDa from the microsomes were used in indirect-immunofluorescence microscopy. The resultant fluorescent pattern shows a network of tubulo-reticular structures in a juxtanuclear region, which is the pattern expected of the rough endoplasmic reticulum.
Cell Wall↗
Contaminant-induced immunotoxicity in harbour seals: wildlife at risk?
Persistent, lipophilic polyhalogenated aromatic hydrocarbons (PHAHs) accumulate readily in the aquatic food chain and are found in high concentrations in seals and other marine mammals. Recent mass mortalities among several marine mammal populations have been attributed to infection by morbilliviruses, but a contributing role for immunotoxic PHAHs, including the polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) was not ruled out. We addressed this issue by carrying out a semi-field study in which captive harbour seals were fed herring from either the relatively uncontaminated Atlantic Ocean or the contaminated Baltic Sea for 2 years. We present here an overview of results obtained during this study. An impairment of natural killer (NK) cell activity, in vitro T-lymphocyte function, antigen-specific in vitro lymphocyte proliferative responses, and in vivo delayed-type hypersensitivity and antibody responses to ovalbumin was observed in the seals fed the contaminated Baltic herring. Additional feeding studies in PVG rats using the same herring batches suggested that an effect at the level of the thymus may be responsible for changes in cellular immunity, that virus-specific immune responses may be impaired, and that perinatal exposure to environmental contaminants represents a greater immunotoxic threat than exposure as a juvenile or adult. Together with the pattern of TCDD toxic equivalents of different PHAHs in the herring, these data indicate that present levels of PCBs in the aquatic food chain are immunotoxic to mammals. A review of contaminant levels in free-ranging harbour seals inhabiting polluted areas of Europe and North America suggests that many populations may be at risk to immunotoxicity. This could result in diminished host resistance and an increased incidence and severity of infectious disease.
Animals↗
Translocation of Neurospora crassa transcription factor NUC-1 into the nucleus is induced by phosphorus limitation.
NUC-1, a basic helix-loop-helix zipper protein, activates the expression of several genes involved in phosphorus acquisition in Neurospora crassa. In the present study we investigated whether posttranscriptional mechanisms control the activity of NUC-1. The NUC-1 level was higher (up to fivefold) in wild-type cells grown at low external phosphate concentration and in mutant strains expressing the phosphorus acquisition genes constitutively than in a wild-type strain grown at high external phosphate concentration. Using indirect immunofluorescence we demonstrated that NUC-1 is localized at least predominantly in the cytosol when wild-type N. crassa is grown with an adequate supply of phosphate, whereas NUC-1 is largely concentrated in the nucleus upon limitation of external phosphate. In mutant strains expressing the phosphorus acquisition genes constitutively, NUC-1 localization was also primarily in the nucleus. Thus, subcellular compartmentation of regulatory proteins is an important mechanism in regulating gene expression in filamentous fungi.
Biological Transport↗
Asm-1+, a Neurospora crassa gene related to transcriptional regulators of fungal development.
This report describes the identification, cloning, and molecular analysis of Asm-1+ (Ascospore maturation 1), the Neurospora crassa homologue of the Aspergillus nidulans stuA (stunted A) gene. The Asm-1+ gene is constitutively transcribed and encodes an abundant, nucleus-localized 68.5-kD protein. The protein product of Asm-1+ (ASM-1), contains a potential DNA-binding motif present in related proteins from A. nidulans (StuA), Candida albicans (EFGTF-1), and Saccharomyces cerevisiae (Phd1 and Sok2). This motif is related to the DNA binding motif of the Swi4/Mbp1/Res family of transcription factors that control the cell cycle. Deletion of Asm-1+ destroys the ability to make protoperithecia (female organs), but does not affect male-specific functions. We propose that the APSES domain (ASM-1, Phd1, StuA, EFGTF-1, and Sok2) defines a group of proteins that constitute a family of related transcription factors involved in the control of fungal development.
Amino Acid Sequence↗
Faecal incontinence.
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Fecal Incontinence↗
A novel integration signal that is composed of two transmembrane segments is required to integrate the Neurospora plasma membrane H(+)-ATPase into microsomes.
The Neurospora plasma membrane H(+)-ATPase belongs to a family of cation-motive porters called P-type ATPases. Putative transmembrane segments of these enzymes contain one or more charged residues. Conditions were determined by which a transmembrane segment with charged residues is integrated into its cognate membrane. We constructed fusion proteins flanked by the hydrophilic domains of the amino and carboxyl termini of the H(+)-ATPase that contained either one or two transmembrane segments. Neurospora in vitro translation system supplemented with homologous microsomes was programmed with RNA transcripts of these constructs. When transmembrane segment number one (M1) or number two (M2) of the H(+)-ATPase was engineered into the construct, the resultant protein did not integrate into microsomes. When M1 and M2 were placed in tandem, the resultant protein integrated into microsomes as judged by the criteria of resistance to extraction at pH 11.5 and protection from protease digestion. The integration event depended on ATP and GTP and on microsomal protein(s). We posited that membrane topology of the amino-terminal third of the H(+)-ATPase, and perhaps of other P-type ATPases is achieved by inserting transmembrane segments into membrane in pairs.
Amino Acid Sequence↗
The membrane topology of the carboxyl-terminal third of the Neurospora plasma membrane H(+)-ATPase.
To localize transmembrane segments in the carboxyl-terminal third of the Neurospora plasma membrane H(+)-ATPase, we constructed fusion proteins on the cDNA level. These contained DNA fragments encoding hydrophilic residues of the amino and carboxyl termini of the H(+)-ATPase with a DNA fragment encoding the putative transmembrane segment. To report translocation into microsomes, a DNA fragment encoding three consensus N-linked glycosylation sites was engineered carboxyl-terminal to the putative transmembrane segment. Fusion proteins were synthesized in a Neurospora in vitro translation system supplemented with homologous microsomes. By the criteria of glycosylation of fusion proteins by microsomes, sedimentation of products with microsomes after alkaline extraction, and analysis of protected fragments generated from proteinase K digestion of integrated products, we localized six transmembrane segments in the carboxyl-terminal third of the H(+)-ATPase. These results support a 10-segment model of the Neurospora H(+)-ATPase.
Amino Acid Sequence↗
Topology of the Neurospora plasma membrane H(+)-ATPase. Localization of a transmembrane segment.
The Neurospora plasma membrane H(+)-ATPase is a polytopic integral membrane protein. To localize transmembrane segments, mutants were constructed that contained the amino and carboxyl termini of the H(+)-ATPase with putative transmembrane segment. A stretch of amino acid residues from yeast invertase that has three consensus N-linked glycosylation sites was placed carboxyl terminal of the putative transmembrane segment. RNA transcripts of these mutants were translated in a Neurospora in vitro system that was supplemented with microsomes from Neurospora. By the criteria of glycosylation of the polypeptide chain, resistance to extraction at pH 11.5, and protection from proteinase K digestion, only one transmembrane segment could be identified within the amino acid residues 272-314 of the primary sequence of the H(+)-ATPase.
Amino Acid Sequence↗
The initial association of a truncated form of the Neurospora plasma membrane H(+)-ATPase and of the precursor of yeast invertase with microsomes are distinct processes.
Translocation and integration activities were assessed in Neurospora microsomes (nRM) after modification either by a sulfhydryl alkylating reagent or by a proteinase. A Neurospora in vitro system was programmed with RNA transcripts that encode the amino-terminal 194 amino-acid residues of the Neurospora plasma membrane H(+)-ATPase (pma194+) or the 262 amino-acid residues of the precursor of yeast invertase (preinv262). The processing of preinv262 was blocked in N-phenylmaleimide- and in trypsin-pretreated nRM. In contrast, the binding of preinv262 to microsomes was unaffected in the chemically alkylated nRM, but was affected in the trypsin-pretreated nRM. In the chemically alkylated vesicles, the integration of the pma194+ was not affected, but was partially blocked in the trypsin-pretreated vesicles. These data imply that trypsin-sensitive components are required for these activities in nRM, and that binding, translocation and integration can be differentiated by their sensitivity to chemical alkylation of sulfhydryl groups in nRM. Evaluated also were the effects of temperature on translocation and integration activities in the nRM. These were maximal at 20 degrees C, whereas the binding of preinv262 was maximal at 0 degree C. Taken together, these data demonstrate that the processing of preinv262 by nRM can be resolved into two steps: binding of the precursor protein to nRM and subsequent translocation into the lumen of the vesicles. Whereas, the integration of the pma194+ into nRM could not be resolved into separable steps. Taken together, these results are interpreted to imply that the initial association of truncated forms of the pma+ and the precursor of invertase to the surface of the nRM are distinct processes.
Alkylation↗
GTP is required for the integration of a fragment of the Neurospora crassa H(+)-ATPase into homologous microsomal vesicles.
The integration of a fragment of the Neurospora crassa plasma membrane H(+)-ATPase was examined to determine if insertion of the fragment into homologous microsomal vesicles is obligatorily dependent on a nucleoside triphosphate. RNA transcripts that encoded the amino terminal 344 amino acids of the Neurospora crassa plasma membrane H(+)-ATPase(pma(344)+) were translated in a N. crassa in vitro system. The pma(344)+ integrated post-translationally into homologous microsomal vesicles independent of the associated ribosomes and dependent on the presence of GTP or guanylyl imidodiphosphate, a nonhydrolyzable analogue of GTP. ATP or analogues thereof did not support the integration of pma(344)+ into nRM post-translationally. These results were interpreted to suggest that a GTPase plays an essential role in the integration of the amino terminal portion of the pma+ into the endoplasmic reticulum.
Adenosine Triphosphate↗
Studies on the sedimentation behavior of the Neurospora crassa plasma membrane H(+)-ATPase synthesized in vitro and integrated into homologous microsomal membranes.
RNA transcripts that encoded the Neurospora crassa plasma membrane H(+)-ATPase (pma+), a polytopic integral membrane protein, and the pma+344, a truncated pma+ with the amino terminal 344 amino acids, were translated in a N. crassa in vitro system. The microsomal membranes integrated products were insensitive to extraction by Na2CO3 (pH 11.5). The velocity sedimentation behavior of the in vitro synthesized pma+ were examined under various conditions. The pma+ migrated on linear sucrose gradients as aggregates which were heterogeneous in size, in the regions of 9-13 S; whereas, these values were reduced when Triton X-100 was presence in the gradients. The formation of these aggregates is interpreted to suggest a mechanism that maintains this polytopic integral membrane protein in a soluble form until it is targeted to the membranes. The sedimentation coefficient of the Triton X-100 solubilized microsomal membranes integrated pma+ corresponded roughly to a monomer of the pma+. Furthermore, a comparison of the trypsin cleavage patterns of the in vitro synthesized pma+ and of the microsomal membranes integrated pma+ suggest that they have different tertiary, or quaternary, structures. The latter did not give the characteristic trypsin cleavage patterns that have been observed for the native pma+ in the presence of its ligands MgATP and vanadate (Addison, R. and Scarborough, G.A. (1982) J. Biol. Chem. 257, 10421-10426). This was interpreted to suggest that the microsomal membranes integrated pma+ cannot interact with its substrate, suggesting that it is catalytically inactive.
Cell Membrane↗
Translocation of a fragment of invertase across microsomal vesicles isolated from Neurospora crassa requires the hydrolysis of a nucleoside triphosphate.
The step which requires the hydrolysis of a nucleoside triphosphate for translocation of a protein across microsome was investigated by studying translocation uncoupled from translation using two truncated products of invertase: one product contains the first 262 amino acids of the secreted invertase (Inv262); the other, the first 104 amino acids (Inv104). The truncated products were translated from RNA transcripts without a stop codon. It is demonstrated that the translated products contain an associated ribosome, and the associated ribosome is essential for the posttranslational translocation phenomenon. Also, it is demonstrated that binding of Inv262 to microsomal vesicles made from the cell wall-less mutant of Neurospora crassa does not require the hydrolysis, or the presence, of a nucleoside triphosphate. However, the posttranslational translocation across the membrane, as monitored by glycosylation of the translocated polypeptide chain, does. The data suggest that a nucleoside triphosphatase activity is associated with the translocation of invertase across the membrane. Furthermore, it is demonstrated that binding, and subsequent translocation across the membrane, is dependent on trypsin-sensitive membrane component(s).
Glycoside Hydrolases↗
Limited relapse in Guillain-Barré syndrome after plasma exchange.
Ten of 94 consecutive patients with acute Guillain-Barré syndrome treated with plasma exchange relapsed after initial improvement. Deterioration occurred five to 42 days after the first series of exchanges, was usually mild, and in eight re-treated patients, responded to a second series of plasma exchanges. None developed chronic inflammatory demyelinating polyneuropathy. The initial exchanges began three to 22 days (mean, 11 days and ended 14 to 27 days (mean, 19 days after the onset of illness. The biphasic course on these patients with limited relapses suggests that plasma exchange removes a circulating factor that continues to be active if treatment is stopped too early. Re-treatment with a second, and sometimes a third, series of plasma exchanges may be affective.
Adolescent↗
Secretory protein translocation in a neurospora crassa in vitro system. Hydrolysis of a nucleoside triphosphate is required for posttranslational translocation.
An in vitro translocation system has been reconstituted with subcellular fractions from the cell wall-less mutant of Neurospora crassa (fz;sg;os-1). Prepro alpha factor and invertase, secretory proteins from yeast, were faithfully translocated and glycosylated by Neurospora microsomes when presence cotranslationally in the Neurospora translation system. When presence cotranslationally in the Neurospora translation system, microsomes from canine pancreas(cRM) could also translocate and glycosylate the secretory proteins. However, salt-extracted cRM, which is depleted of canine signal recognition particle, could not. Furthermore, prepro alpha factor and a truncated form of invertase, containing the first 262-amino acid residues of the secretory invertase, were glycosylated by Neurospora microsomes posttranslationally, whereas only the truncated form of invertase was glycosylated by cRM when added posttranslationally. The full length invertase was not glycosylated posttranslationally. Posttranslational glycosylation of prepro alpha factor and of the truncated form of invertase is dependent on the hydrolysis of a nucleoside triphosphate. These data suggest that posttranslational glycosylation of prepro alpha factor occurs via a novel type of recognition mechanism which is either absent or ineffective in cRM.
Animals↗