Passive cutaneous anaphylaxis induced in guinea pigs by insulins and their component chains.
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Animals↗
Biomedical subjects
S Wilson
Publications and source records attributed to S Wilson.
Use of linkage data obtained in single families: prenatal diagnosis of a new X-linked mental retardation syndrome.
Prenatal diagnosis was requested by an obligate carrier of a new syndrome of X-linked mental retardation. There was close linkage between the disease gene and the hypervariable VNTR marker DXS255 with a lod score of 4.82 at o = 0 (90% support interval 0.00-0.12). When the request for prenatal diagnosis was made, additional family members were examined, resulting in an amended lod score of 6.71 at o = 0.0 (90% support interval 0.00-0.09). There were no informative flanking markers at the time of the request for prenatal diagnosis; hence it proceeded by 2 point linkage analysis. The fetus was female with a carrier risk in the interval of 91-100%. Given the limitations of the mapping data available for this disorder at the time of the request, the options of accepting or rejecting this as a case for prenatal diagnosis were carefully considered. Whilst prenatal diagnosis based on fetal sexing would be sufficient to prevent the birth of an affected child, the magnitude of the known two-point lod score between DXS255 and the disease gene provided a means for diagnosis with an accuracy between 91 and 100%.
Female↗
Delayed cardioprotection is associated with the sub-cellular relocalisation of ventricular protein kinase C epsilon, but not p42/44MAPK.
Both noradrenaline administration to rats and rapid cardiac pacing in dogs induces delayed protection of the heart against ischaemia-induced ventricular arrhythmias. In an attempt to establish molecular mechanisms underlying the delayed cardioprotection, we have examined the potential role of two kinases, PKC epsilon and p42/44MAPK. These protein kinases are expressed in the ventricles of the heart and are characterised by their ability to regulate ion-flux and gene transcription. In the rat p42MAPK is predominantly localised in the high-speed supernatant fraction of the ventricle homogenate, whereas p44MAPK is enriched in the nuclear low speed pellet. A small proportion of the p42MAPK is activated even in hearts from control animals. However, neither kinase is relocalised or activated by noradrenaline administration and this provides preliminary evidence the p42/44MAPK may not play a significant role in delayed protection in this species. In contrast, noradrenaline does induce the translocation of PKC epsilon to cell membranes, a response that is sustained for up to 4 h. However, PKC epsilon is down-regulated from the cytoplasm after 24 h post noradrenaline treatment. PKC epsilon is also translocated to the membrane in dogs that have been classically pre-conditioned and cardiac paced. In the latter case, translocation of PKC epsilon from the cytoplasm to the cell membrane is evident 24 h after pacing. These results indicate that the release of endogenous mediators may either inhibit down-regulation or elicit an increase in PKC epsilon mRNA expression. Therefore, in dog heart the subcellular relocalisation of PKC epsilon persists into the 'second window' and may play a central role in the molecular mechanism governing delayed cardioprotection. It is important in the future to identify either the gene products that are induced or the target protein(s) that are phosphorylated by PKC epsilon.
Animals↗
Use of NeoR B16F1 murine melanoma cells to assess clonality of experimental metastases in the immune-deficient chick embryo.
Recent work on molecular and genetic aspects of metastasis has emphasized the need for assays in immune-deficient animal hosts. The commonly used assays in athymic nude mice may not always be appropriate, and assays in other hosts are required. We have developed a metastasis assay in the naturally immune-deficient chicken embryo. As part of our characterization of this assay we have examined the clonality of individual experimental (i.v.-derived) metastases in this host. For these studies we developed a cell line, B16-Neo, from parental B16F1 murine melanoma cells. B16-Neo cells carry a stable drug-resistance marker, the bacterial neo gene, which confers resistance to the drug G418, but are unaltered in experimental metastatic properties in the chick embryo relative to parental B16F1 cells. We observe that the majority of individual liver tumors that arise following i.v. injection of mixtures of these cells contain cells of a single marker phenotype and are likely to be clonal in origin. These results are similar to those obtained by others for metastases in immune-competent mice, suggesting similar mechanisms of metastasis formation in these two systems. In both hosts it should be noted, however, that a small but significant proportion of metastases appear not to be clonal in origin.
Animals↗
Alpha-2-adrenoceptor control of cortisol and ACTH in normal volunteers: preliminary open trial of the effects of acute and chronic idazoxan.
To examine the role of alpha 2-adrenoceptors in the control of cortisol and ACTH, hormone responses to the selective alpha 2-antagonist idazoxan were studied in 12 normal volunteers. Plasma cortisol and ACTH were measured from 0930h-1230h on three occasions: before, on the 1st day, and on the 22nd day of an open treatment trial with idazoxan 40 mg administered three times per day. Compared with pretreatment cortisol levels, acute but not chronic idazoxan treatment attenuated the normal diurnal fall in plasma cortisol. Plasma ACTH concentrations were not altered by either dose of idazoxan. The attenuation of the diurnal fall in cortisol after acute idazoxan may be mediated through increased central availability of norepinephrine, and is similar to responses after high doses of the less selective alpha 2-antagonist yohimbine. Activity of central noradrenergic neurons appears to be reduced or normalized by chronic idazoxan, indicated by restoration of the normal diurnal fall in cortisol.
Adrenergic alpha-Antagonists↗
Investigation of pion-treated human skin nodules for therapeutic gain.
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Elementary Particles↗
Bisphosphonates: a potential role in the prevention of osteoporosis in laying hens.
Osteoporosis in layers is associated with the modelling and remodelling of medullary bone. Cancellous bone volume (CBV) decreases initially during medullary bone modelling and continues to decrease during subsequent remodelling. In an attempt to maintain peak structural bone mass, the bisphosphonate, alendronate, was administered to pullets before medullary bone modelling. At point of lay CBV was significantly greater (P<0.01) in the alendronate group (17.59 per cent) than in controls (13.79 per cent), while medullary bone volume (MBV) was not significantly affected. After 20 weeks, CBV remained significantly higher (P<0.02) in the alendronate group (12.72 per cent) than in controls (9.80 per cent) and MBV was lower in the alendronate group than the control group. CBV was however reduced and MBV increased in both groups compared with values at point of lay. Alendronate therefore appeared to prevent the bone loss associated with medullary bone modelling but not that which occurs during remodelling.
Alendronate↗
Retrospective study of the use of a plantar transverse incision versus a dorsal incision for excision of neuroma.
The authors present a retrospective study comparing the results and complications of dorsal incision versus plantar transverse incision for excision of neuroma. The authors found several advantages using the plantar transverse incision. These included improved exposure and access to the neuroma, and no incidence of amputation neuromas postoperatively.
Foot Diseases↗
Pilot-scale purification of zeamatin, an antifungal protein from maize.
Zeamatin is an antifungal protein isolated from the seeds of Zea mays. A practical process for isolation and purification was developed to increase recovery yields for future testing of zeamatin as a novel therapeutic drug. Zeamatin was extracted with buffer from corn meal milled to flour. Solids were removed from the extract using pressure filtration, and zeamatin was purified using two separate reverse-phase chromatography steps. Determination of the amino-terminal amino acid sequence, Western blotting using anti-zeamatin antibody, and activity against Candida albicans were used to confirm that the purified protein was zeamatin. From 5 kg of corn meal, approximately 110 mg of zeamatin was purified to apparent homogeneity.
Amino Acid Sequence↗
Atypical beta-adrenoceptor on brown adipocytes as target for anti-obesity drugs.
Recent studies suggest that thermogenesis in brown adipose tissue has an important role in the regulation of energy balance. Thermogenesis is effected by noradrenaline released from sympathetic nerve endings; the noradrenaline stimulates beta-adrenoceptors, causing lipolysis, and the released fatty acids then promote the uncoupling of oxidative phosphorylation from electron transport. It has been widely accepted that mammalian beta-adrenoceptors exist as two subtypes, beta 1 and beta 2, and rat brown adipocyte beta-adrenoceptors have been classed as beta 1 or as a mixed beta 1/beta 2 population. The beta 1 subtype predominates in atria, whereas the beta 2 subtype predominates in trachea. However, we have now found a novel group of beta-adrenoceptor agonists that selectively stimulate lipolysis in brown adipocytes. In contrast, isoprenaline, fenoterol and salbutamol are less potent as stimulants of lipolysis than as stimulants of atrial rate or tracheal relaxation. Therefore, beta-adrenoceptors in rat brown adipocytes are of neither the beta 1 nor beta 2 subtypes. Compounds that selectively stimulate brown adipocyte beta-adrenoceptors should have potential as thermogenic anti-obesity agents and this has been demonstrated with BRL 26830A , BRL 33725A and BRL 35135A .
Adipose Tissue, Brown↗
Differential regulation of collagen gene expression in granulation tissue and non-repair connective tissues in vitamin C-deficient guinea pigs.
Poor wound healing during vitamin C deficiency is thought to be due to decreased hydroxylation of proline residues in collagen. In non-repair connective tissues of guinea pigs, however, procollagen gene expression is not decreased until weight loss occurs during the third and fourth weeks of scurvy (phase II) with only a moderate decrease in proline hydroxylation. Decreased procollagen gene expression is related to the induction of insulin-like growth factor binding proteins 1 and 2 that inhibit insulin-like growth factor-I action. We examined wound healing and granulation tissue formation during phase I of vitamin C deficiency. Synthetic sponges were implanted on day 7 of vitamin C deficiency and analyzed at 6 and 10 days after surgery, when there was no weight loss or induction of insulin-like growth factor binding proteins. Healing of incisions was almost complete at 10 days after surgery in normal controls but not in scorbutic animals. The area around the incision and implant exhibited excessive angiogenesis and hemorrhaging of vessels in the scorbutic animals at 6 and 10 days after surgery. At 10 days after surgery, collagen synthesis in the implants of scorbutic guinea pigs was 36% lower than control values, with a normal extent of proline hydroxylation. Concentrations of messenger RNAs for types I and III procollagens were slightly increased by scurvy at 6 days after surgery but were decreased by 26% and 40%, respectively, at 10 days. Fibronectin mRNA levels were unaffected by scurvy at both time points. Our results suggest that poor wound healing in phase I of scurvy may be related to defective interstitial procollagen gene expression and defective blood vessel formation, but it does not involve inhibition of proline hydroxylation or induction of insulin-like growth factor binding proteins. mRNA for insulin-like growth factor-II, transforming growth factor-beta(1), and transforming growth factor-beta(2) were significantly expressed in implants, but their patterns of expression did not correlate with changes in procollagen gene expression.
Journal Article↗
Simple manual method for harvesting granulocytes.
The method described requires no special equipment and permits the harvesting of granulocytes from collections of fresh concentrated erythrocytes with buffy coat. In contrast to the use of a cell separator, it requires little time of technologists and none of medical staff to recover an equivalent number of granulocytes. This method makes granulocyte transfusion practicable for the support of neutropenic patients even in centers with no leukopheresis program.
Cell Separation↗
Flumazenil in alcohol withdrawal: a double-blind placebo-controlled study.
The purpose of the present study was to study gamma-aminobutyric acid (GABA)-A receptor function in alcohol-dependent subjects during withdrawal, using the benzodiazepine antagonist flumazenil. In particular, we wanted to examine the hypotheses that an endogenous inverse agonist ligand at the GABA-A benzodiazepine receptor (GBzR) is active during withdrawal (in which case flumazenil should be anxiolytic), or whether chronic alcohol intake results in a shift in sensitivity of the receptor in the inverse agonist direction (in which case flumazenil should be anxiogenic). Results from 15 alcohol-dependent subjects in a double-blind placebo-controlled cross-over study showed that flumazenil was neither anxiolytic nor anxiogenic, although withdrawal scores were reduced during the course of the study. The fact that flumazenil was not anxiogenic, as it is in panic disorder, suggests that the GBzR is functioning differently in these two clinically similar conditions.
Adult↗
Canine muscular dystrophy: confirmation of X-linked inheritance.
The genetic basis of muscular dystrophy in golden retriever dogs was investigated by means of experimental matings and cytogenetic studies. An affected male golden retriever was mated to three normal females, producing an F1 generation of six males and 14 females, all of which were clinically normal. Of six F1 females retained for breeding, all were shown to be carriers of muscular dystrophy in outcrosses to unrelated normal male dogs or in backcrosses to the affected male golden retriever. In outcrosses of carrier females, three of seven male and none of nine female offspring were affected, as expected under the X-linked recessive hypothesis. Backcrosses of F1 females to their affected sire also yielded results that are consistent with this hypothesis: 15 of 32 males and 5 of 17 females had muscular dystrophy. Cytogenetic studies of a carrier female, an affected male offspring, and a normal male sibling revealed no detectable abnormalities of the X chromosome.
Animals↗
The personal problem-solving side of the nursing process.
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Adaptation, Psychological↗
The effects of thioctic acid on motor nerve terminals in acrylamide-poisoned rats.
Acrylamide causes a distal neuropathy by combining with and depleting glutathione and other sulphydryl-containing compounds in axons and nerve terminals. This results in damage to the axon membrane and impaired efficiency of synaptic vesicle recycling. The changes may be assessed by staining nerve terminals in muscle with zinc iodide and osmium, a technique which depends upon the presence of sulphydryl compounds for the development of the stain. The present experiments were designed to test whether thioctic acid, itself a sulphydryl-containing compound, could protect against acrylamide-induced damage of motor nerve terminals. In vitro and in vivo experiments on acrylamide-poisoned rats showed that thioctic acid was able to maintain the integrity of the nerve terminal membrane, as shown by the ability of the terminals to develop 'spontaneous' sprouts and to stain with the zinc iodide osmium technique. Thioctic acid treatment also enhanced recovery after partial denervation of muscles in both normal and acrylamide-poisoned animals. The results suggest that thioctic acid is itself able to react with the acrylamide before the latter has a chance to bind and deplete axonal and nerve terminal glutathione.
Acrylamide↗
Design characteristics of floss-holding devices for persons with upper extremity disabilities.
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Adult↗