bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucocerebrosidase Mutations alter the endoplasmic reticulum and lysosomes in Lewy body disease
Authors: Kurzawa‐Akanbi Marzena , Hanson Peter S , Blain Peter G , Lett Debra J , McKeith Ian G , Chinnery Patrick F , Morris Christopher M 
Published: July 2012

J. Neurochem. (2012) 123, 298–309.AbstractLewy body disease (LBD) development is enhanced by mutations in the GBA gene coding for glucocerebrosidase (GCase). The mechanism of this association is thought to involve an abnormal lysosomal system and we therefore sought to evaluate if lysosomal changes contribute to the pathogenesis of idiopathic LBD. Analysis of post‐mortem frontal cortex tissue from 7 GBA mutation carriers with LBD, 5 GBA mutation carriers with no signs of neurological disease and human neural stem cells exposed to a GCase inhibitor was used to determine how GBA mutation contributes to LBD. GBA mutation carriers demonstrated a significantly reduced level of GCase protein and enzyme activity and retention of glucocerebrosidase isoforms within the endoplasmic reticulum (ER). This was associated with enhanced expression of the lysosomal markers LAMP1 and LAMP2, though the expression of ATP13A2 and Cathepsin D was reduced, along with the decreased activity of Cathepsin D. The ER unfolded protein response (UPR) regulator BiP/GRP78 was reduced by GBA mutation and this was a general phenomenon in LBD. Despite elevation of GRP94 in LBD, individuals with GBA mutations showed reduced GRP94 expression, suggesting an inadequate UPR. Finally, human neural stem cell cultures showed that inhibition of GCase causes acute reduction of BiP, indicating that the UPR is affected by reduced glucocerebrosidase activity. The results indicate that mutation in GBA leads to additional lysosomal abnormalities, enhanced by an impaired UPR, potentially causing α‐synuclein accumulation.
Reduced repression of cytokine signaling ameliorates age‐induced decline in hematopoietic stem cell function
Authors: Norddahl Gudmundur L. , Wahlestedt Martin , Gisler Santiago , Sigvardsson Mikael , Bryder David 
Published: July 2012

SummaryAging causes profound effects on the hematopoietic stem cell (HSC) pool, including an altered output of mature progeny and enhanced self‐propagation of repopulating‐defective HSCs. An important outstanding question is whether HSCs can be protected from aging. The signal adaptor protein LNK negatively regulates hematopoiesis at several cellular stages. It has remained unclear how the enhanced sensitivity to cytokine signaling caused by LNK deficiency affects hematopoiesis upon aging. Our findings demonstrate that aged LNK−/− HSCs displayed a robust overall reconstitution potential and gave rise to a hematopoietic system with a balanced lineage distribution. Although aged LNK−/− HSCs displayed a distinct molecular profile in which reduced proliferation was central, little or no difference in the proliferation of aged LNK−/− HSCs was observed after transplantation when compared to aged WT HSCs. This coincided with equal telomere maintenance in WT and LNK−/− HSCs. Collectively, our studies suggest that enhanced cytokine signaling can counteract functional age‐related HSC decline.
Management of a cohesive tropical soil to enhance rootability and increase the efficiency of nitrogen and potassium use
Authors: MOURA E. G. , OLIVEIRA A. K. C. , COUTINHO G. , PINHEIRO K. M. , AGUIAR A. C. F. 
Published: July 2012

AbstractThe efficiency in the use of nitrogen (N) and potassium (K) may be severely limited in soils with high rates of nutrient loss and that also tend to harden and restrict root growth. The choice of legume residues should take into account the nutrient supply and the need for soil improvement. We assessed the capacity of alley cropping systems to enhance root development, increase nutrient uptake and improve the use of N and K in maize. The experiment included six treatments with residues of four perennial Fabaceae: Clitoria + Gliricidia (C + G); Acacia + Gliricidia (A + G); Leucaena +Gliricidia (L + G); Leucaena + Clitoria (L + C); Leucaena + Acacia (L + A) and a control without legumes. We determined chemical and physical indicators, root length density (RLD) and an efficiency index. The results demonstrate the effects of amending soils with N and K with root growth constrained by hard‐setting. The application of combined residues improved the physical properties of hard‐setting soils and increased basic cations in the topsoil. A combination of residues with N and K fertilizer increased the maize yield. The relative efficiency and RLD in the L + A treatments were highest as a result of increased application through the residues containing N and K. The choice of residues for hard‐setting soils should take into account the supply of nutrients as well as the improvement of soil properties.
Evidence for muscarinic receptors in the adrenal medulla of the dog
Authors: KAYAALP S. O. , TÜRKER R. K. 
Published: July 2012

The release of catecholamines from the adrenal medulla by the cholinergic drugs was monitored by the perfusion pressure rise in autoperfused and sympathetically denervated hindlimbs of the dog.
Acetylcholine, dimethylphenylpiperazinium (DMPP) and methacholine, given in relatively small doses into the aorta proximal to the blood supply to the adrenal glands, caused a marked rise in perfusion pressure which was due to the release of catecholamines from the adrenal medulla.
Atropine (1 mg/kg intravenously) blocked the pressor response to methacholine only. The ganglion‐blocking agents (mecamylamine 4–5 mg/kg or hexamethonium 10 mg/kg) given subsequently blocked the pressor responses to the other two cholinergic drugs. The ganglion‐blocking agents, when given before atropine, blocked the pressor action only of DMPP. These agents partly depressed, rather than potentiated, the pressor response to methacholine.
The results suggest that muscarinic as well as nicotinic receptors are present in the adrenal medulla of the dog.
Neither atropine nor ganglion‐blocking drugs alone reduced the pressor response to acetylcholine. It is postulated that the blockade of one set of receptors makes more acetylcholine available for the other set of receptors and so inactivation of the former receptors are compensated by the increased release through the activation of the latter's.
Histamine release by sodium chloroplatinate
Authors: SAINDELLE A. , RUFF F. 
Published: July 2012

The chloroplatinate ion can release histamine from the tissues in various species of animals.
This property is not shared by other complex ions with co‐ordination number 6, or other complex platinum ions.
The release of histamine may form the basis of the known disease platinosis which affects people who work in platinum refineries, and which is characterized by symptoms of an allergic nature.
The mechanism of the liberation of histamine by chloroplatinate resembles that which occurs during anaphylactic shock.
Chemotherapeutic reactions of Chandlerella hawkingi, the filarial parasite of the Indian jungle crow, Corvus macrorhynchos (Wagler)
Authors: CHATTERJEE R. K. , SEN A. B. 
Published: July 2012

A high percentage of Indian jungle crows (Corvus macrorhynchos Wagler), found in and around Lucknow, harbour a natural filarial infection Chandlerella hawkingi. The microfilariae of this species are sheathed and show nocturnal periodicity.
Fourteen compounds active against other kinds of filariae, especially against Litomosoides carinii, were tested against Ch. hawkingi in jungle crows to find whether this infection would be suitable for routine filarial chemotherapy. This is apparently the first report of systematic screening of antifilarial compounds against an avian filariasis.
Tartar emetic (10 mg/kg intravenously, daily for 6 days) and arsenamide (5 mg/kg intraperitoneally, daily for 6 days) proved to be effective in killing adult worms. Trivalent tryparsamide, though effective, was toxic in the doses tried. Diethylcarbamazine and other compounds tested were ineffective.
The chemotherapeutic susceptibilities of Ch. hawkingi differ considerably from those of L. carinii and Wuchereria bancrofti.
Differences between the effects of saxitoxin (paralytic shellfish poison) and tetrodotoxin on the frog neuromuscular junction
Authors: EVANS M. H. 
Published: July 2012

End‐plate potentials (e.p.p.) have been recorded from the neuromuscular junctions of frog sartorius and extensor longus dig. IV muscles, using intracellular micropipettes. Either curare or MgCl2 were present in the Ringer solution, to keep the e.p.p. amplitude below the threshold for a muscle action potential and contraction.
It has been shown that saxitoxin (paralytic shellfish poison) usually caused a progressive reduction in the amplitude of the e.p.p. Occasionally, when it was applied in the presence of MgCl2, the e.p.p. disappeared abruptly.
Tetrodotoxin usually caused the e.p.p. to disappear abruptly. Occasionally, when applied in the presence of curare, the e.p.p. declined progressively for a short time before disappearing abruptly.
It is concluded that at the frog neuromuscular junction the preferential site of action of saxitoxin is at the nerve terminals, but tetrodotoxin preferentially blocks nerve conduction at a site proximal to the junction.
It is suggested that this preparation would be a convenient and reliable test object for distinguishing saxitoxin from tetrodotoxin.
Hypothalamo‐pituitary‐adrenal function in the rat after prolonged treatment with Cortisol
Authors: HODGES J. R. , SADOW JANET 
Published: July 2012

Cortisol, administered subcutaneously every day for long periods, caused growth retardation, adrenal atrophy and impaired hypothalamo‐pituitary‐adrenal (HPA) function in the rat.
The growth rate and the functional activity of the HPA system gradually returned to normal after steroid withdrawal.
Normal adrenal sensitivity to corticotrophin returned more rapidly than normal pituitary corticotrophic function, suggesting that the initial impairment of HPA function was due both to reduced responsiveness of the adrenal gland to corticotrophin and failure of the pituitary gland to secrete the hormone.
Modification of the vasoconstrictor action of sympathomimetic agents by bretylium tosylate and tranylcypromine in man
Authors: FREWIN D. B. , JELLETT L. B. , WHELAN R. F. 
Published: July 2012

The vasoconstrictor actions of tyramine, methylamphetamine and ephedrine on the blood vessels of the human hand have been found to be potentiated by administration intra‐arterially of the adrenergic neurone blocking agent, bretylium tosylate.
One mechanism suggested for the enhancement of vasoconstriction is that bretylium possesses monoamine oxidase inhibitilng activity, which, in the case of tyramine, is protective both to the sympathomimetic agent and the intraneuronal transmitter which it releases. In the case of methylamphetamine and ephedrine, which are not substrates for the enzyme, protection of the intraneuronal transmitter alone might occur, accounting for the lesser degree of potentiation of the effect of these amines by bretylium.
Comparison of the influences of bretylium and the monoamine oxidase inhibitor, tranylcypromine, on the vasoconstrictor action of the sympathomimetic agents shows a similar pattern of enhancement in the presence of both these drugs.
Tranylcypromine caused enhancement of the response of the hand vessels to noradrenaline, and this action could contribute to its potentiation of the effect of the sympathomimetic amines.
For a monoamine oxidase inhibiting action of bretylium to be effective in potentiating the constrictor actions of the sympathomimetic agents on the hand blood vessels at a time when reflex sympathetic activity is blocked it is necessary to postulate that these drugs and reflex nerve activity act either on different compartments of the transmitter store or by different release mechanisms.
The effects of prostaglandins on the intraocular pressure of the rabbit
Authors: BEITCH BARBARA R. , EAKINS K. E. 
Published: July 2012

. The effects of intracameral injections of prostaglandins E1, E2, F1α, F2α, and A1 were studied on the intraocular pressure (IOP) of rabbits anaesthetized with urethane.
. With the exception of prostaglandin F1α, all the prostaglandins studied were found to be capable of producing a large, sustained rise in IOP, accompanied in many cases by miosis.
. A marked decrease in response to repeated injections was found with all the prostaglandins studied; this effect was more pronounced following a large initial response to the prostaglandin.
. The descending order of potency in their ability to raise IOP was as follows: prostaglandin E1∼E2>F2α>A1>F1α.
. Intracameral injections of prostaglandins E1 and E2 resulted in an increase in the protein content of the aqueous humour, which was related to the magnitude of the sustained increase in IOP.
. Stabilization of the blood‐aqueous barrier with polyphloretin phosphate markedly reduced both the IOP response and the effect of prostaglandin E2 on the protein content of the aqueous humour.
. It is concluded that the production of local vasodilatation and increased permeability of the blood‐aqueous barrier play an important part in the effect of prostaglandins on the IOP. The involvement of prostaglandins in the response of the rabbit eye to irritation is discussed.
Structure and pharmacological actions of phyllocaerulein, a caerulein‐like nonapeptide: its occurrence in extracts of the skin of Phyllomedusa sauvagei and related Phyllomedusa species
Authors: ANASTASI A. , BERTACCINI G. , CEI J. M. , DE CARO G. , ERSPAMER V. , IMPICCIATORE M. 
Published: July 2012

. The South American amphibian Phyllomedusa sauvagei contains in its skin large amounts of a polypeptide closely resembling caerulein in its pharmacological actions. This polypeptide, called phyllocaerulein, was obtained in a pure form, and upon acid hydrolysis, enzymic digestion and end‐group determination experiments it proved to be a nonapeptide of the following compositionPyr‐Glu‐Tyr(SO3H)‐Thr‐Gly‐Trp‐Met‐Asp‐Phe‐NH2It may be seen that caerulein and phyllocaerulein have in common the C‐terminal heptapeptide and the N‐terminal pyroglutamyl residue.
. Phyllocaerulein is indistinguishable from caerulein even in parallel bio‐assay. However, the former polypeptide seems to be somewhat more potent than the latter on all the preparations tested.
. In different batches of Phyllomedusa sauvagei skin the phyllocaerulein content ranged between 150 and 600 μg/g of fresh tissue.Phyllocaerulein or similar polypeptides occur also in the skin of several other Phyllomedusa species, among which are Phyll. burmeisteri, Phyll. dachnicolor, Phyll, helenae, Phyll. annae, Phyll. callidryas and Phyll. bicolor.
. The qualitative identification and quantitative estimation of caerulein‐like polypeptides in crude skin extracts may be complicated by the concomitant occurrence of other active polypeptides. These, however, are poorly effective on some test preparations which seem to respond selectively to caerulein.
. Like that of caerulein, the biological significance of phyllocaerulein is completely obscure.
The effects of pronethalol and propranolol on the coronary circulation of the dog
Authors: DAVIS W. G. , MacDONALD D. C. , MASON D. F. J. 
Published: July 2012

. The actions of pronethalol and propranolol have been studied to see if there was any relationship between the reduction in coronary flow and any other cardiovascular action they have.
. The experiments were carried out in anaesthetized open chest dogs. Measurements included central arterial, left and right venous or atrial pressures, heart rate, ventricular size and stroke volume, intra‐ventricular pressures, total left coronary flow, arterial and coronary sinus blood pO2. The pressure‐time index (PTI) and maximum rate of isovolumetric contraction (dp/dt) were obtained from these records.
. It was concluded that, in these experiments, the reduction in coronary flow produced by pronethalol and propranolol was not directly related to a decrease in perfusion pressure, a raised venous pressure, the increase in ventricular volume and hence wall tension, the decrease in heart rate, or to the increased duration of systole.
. The PTI and dp/dt were always reduced at the same time as the coronary flow. These findings are discussed.
. Studies of the effects of sympathetic stimulation, of phentolamine, of reduced arterial oxygen tension and electrical pacing of the heart, all after β‐blockade, did not support the suggestion that the reduction in coronary flow after β‐blockade was due to the unmasking of an active vasoconstriction.
Antagonism of some smooth muscle actions of prostaglandins by polyphloretin phosphate
Authors: EAKINS K. E. , KARIM S. M. M. , MILLER J. D. 
Published: July 2012

The antagonism of the smooth muscle stimulating actions of PGF2α and PGE2 by polyphloretin phosphate (PPP) was studied on several isolated smooth muscle preparations and on the blood pressure of the anaesthetized rabbit.
PPP (2·5–20 μg/ml) reversibly inhibited contractions of the jird colon produced by PGE2 or PGF2α; PGF2α was more readily antagonized than PGE2.
PPP (2·5–30 μg/ml) reversibly antagonized contractions produced by PGE2 and PGF2α on the isolated rabbit jejunum and uterus. In these preparations PPP antagonized PGE2 as readily as PGF2α.
It is concluded that PPP is a selective antagonist to the prostaglandins on these tissues, for contractions produced by other agonists, such as acetylcholine, angiotensin, 5‐hydroxytryptamine and bradykinin were not reduced by concentrations of PPP which markedly antagonized responses to the prostaglandins.
Intravenous injections of PPP (25–200 mg/kg) resulted in a variable antagonism to the fall in blood pressure produced by intravenous injections of PGF2α in the anaesthetized rabbit; vasodepressor responses produced by PGE2 and acetylcholine were not antagonized.
The mechanism of this antagonism by PPP is not clear and must await further investigation.
Prostaglandin uptake and metabolism by the perfused rat liver
Authors: DAWSON W. , JESSUP SHEILA J. , McDONALD‐GIBSON WENDY , RAMWELL P. W. , SHAW JANE E. 
Published: July 2012

The prostaglandins are C20 unsaturated fatty acids which exhibit diverse physiological effects of short duration. We have investigated the speed of removal of PGE1 and PGF1α from the circulating blood and their subsequent metabolism by the isolated perfused rat liver.
Following either a single injection of radiolabeled PGE1 or PGF1α into the hepatic artery or portal vein, or recirculation of prostaglandins through the liver for 2·5 h, the distribution of radioactivity within extracts of bile, blood and liver was determined. The nature of the radioactive products of metabolism was inferred by comparison of the distribution of radioactivity after injecting carbon and tritium labelled standards, and by thin‐layer chromatography, gas‐liquid chromatography, ultraviolet and bioassay analysis.
A single injection of 1–14C PGE1 indicated that the liver could efficiently remove 89–95% of circulating PGE1 on a single passage. Biliary excretion was excluded as a major route for elimination of unchanged PGE1, because only 0·3–0·8% of the injected radioactivity was detected in the bile. During recirculation of 1–14C PGE1, 11–19% of the injected radioactivity was detected as exchanged 14CO2. The radioactivity detected within liver was identified with further fragments resulting from decarboxylation of PGE1, which were incorporated into fatty acids and then phospholipids.
Studies with 5,6–3H PGE1, and comparison with the results obtained using 1–14C PGE1, revealed a 30‐fold increase in the percentage of radioactivity excreted into the bile, suggesting that biliary excretion may be a major route for elimination of compounds smaller than C20 prostaglandin. Evidence that the cyclopentane ring was intact was inferred by formation of a PGB compound on treatment with alkali; similar biliary excretion of 9–3H PGF1α also occurred. In addition, the increased radioactivity detected within the liver (37%) and blood (43%) after a single injection of 5,6–3H PGE1 had the solvent partition and thin‐layer chromatography properties of PGE1, but were associated with a less polar compound smaller than the C20 parent structure.
These results indicate rapid uptake of circulating prostaglandins by the rat liver. Decarboxylation of prostaglandins results in pharmacological inactivation. The products are excreted into the bile and venous effluent. These processes would curtail the duration of effects following prostaglandin injection.
Carbon tetrachloride metabolism in sheep and in Fasciola hepatica
Authors: FOWLER J. S. L. 
Published: July 2012

The excretion of carbon tetrachloride and its metabolites in bile and urine were studied.
Liver flukes in vitro metabolized carbon tetrachloride and hexachloroethane by dechlorination.
Carbon tetrachloride, liver lipid from rabbits which received carbon tetrachloride and a carbon tetrachloride methyl oleate complex were toxic to liver flukes in vitro, in the presence of sheep bile.
A direct fasciocidal action of carbon tetrachloride may contribute to the therapeutic effect of the drug.
The effects of papaverine on the electrical and mechanical activity of the guinea‐pig taenia coli
Authors: TASHIRO N. , TOMITA T. 
Published: July 2012

Effects of papaverine (5 × 10−6–5 × 10−5m) were studied on the spontaneous and evoked electrical and mechanical activity of the guinea‐pig taenia coli. In normal Locke solution, papaverine slowed and finally stopped the spontaneous spike discharge, usually with a small hyperpolarization of a few mV.
Papaverine did not change the membrane resistance in normal Locke solution. It abolished the repetitive firing of spikes during the depolarization in response to a current pulse, but a single spike of normal amplitude could always be evoked.
The mechanical response elicited by a single spike was reduced by papaverine in normal Locke solution. During the maintained depolarization produced by a long current pulse the tonic component of the contraction was more reduced than the phasic component related to the initial spike activity.
The effects of papaverine were essentially the same as in normal Locke solution when NaCl was replaced with LiCl, or in excess K (24 mm), except that the membrane resistance was increased by papaverine in the presence of excess K.
Excess Ca (6 mm) antagonized the effect of papaverine on the mechanical response, but not on the electrical response. When the muscle was depolarized in Ca‐free solution, papaverine caused repolarization of the membrane and electrical activity reappeared. This effect was similar to that of Mg (4 mm).
The mechanism by which papaverine suppresses the spontaneous spike activity is discussed and is compared with that of isoprenaline, from which it appears to differ. The observations indicate that papaverine, like Mg, may bind with a site at the membrane with which Ca normally binds, thereby modifying the electrical and mechanical activity controlled by Ca.