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Biomedical subjects

M Spencer

Publications and source records attributed to M Spencer.

At least 55 records · Page 3Linked to original sources
PubMed1995

An Ets site in the whey acidic protein gene promoter mediates transcriptional activation in the mammary gland of pregnant mice but is dispensable during lactation.

The whey acidic protein (WAP) gene is specifically expressed in mammary tissue, and its transcription is induced several thousand-fold during pregnancy and remains high throughout lactation. A purine-rich sequence (PRS) located around -110 of the WAP gene promoter is conserved between mice, rats, and rabbits, suggesting that it features a regulatory element. This PRS contains an invariant GGAA/T core motif characteristic of the binding site for Ets transcription factors. Electromobility shift assays demonstrate that Ets1 binds specifically to the PRS. Experiments in transgenic mice further demonstrate that this PRS/Ets site plays a critical role in the activation of WAP transgenes during pregnancy, but that its presence is not required for high expression throughout lactation. Transgenes with an intact PRS/Ets site are expressed at high levels at day 13 of pregnancy, with little further increase during late pregnancy and lactation. In contrast, WAP transgenes with a mutation in the PRS/Ets site, which abrogates the binding of Ets1, are not expressed at midpregnancy, but their transcriptional activity is not affected during lactation. These results demonstrate that Ets-signaling pathways can function as stage-specific transcriptional activators of milk protein genes in the developing mammary gland. In addition, this work extends earlier findings that gene activation during pregnancy and lactation is mediated, in part, by different mechanisms.

Animals↗
PubMed1995

Consumer product-related ocular trauma.

Leading causes of consumer product-related ocular trauma have not been well described. To delineate these causes in a nationally representative sample, data collected by the US Consumer Product Safety Commission (USCPSC) were reviewed. Data were obtained from the National Electronic Injury Surveillance System (NEISS), a national probability sample survey conducted by USCPSC that continuously monitors consumer product-related injuries treated in hospital emergency rooms across the United States. These data formulated the product summary report for the calendar year 1991. The sampling frame for the NEISS consisted of hospitals listed on the Center for Health Statistics Master Inventory File stratified geographically by size of hospital and number of emergency-room visits. During the calendar year 1991, there were a nationally estimated 298,852 consumer product-related eye injuries treated in hospital emergency rooms. Appoximately 500 different products were implicated in these injuries, with the leading cause being contact lenses (hard and soft), accounting for an estimated 26,490 emergency-room visits. This is followed by welding equipment (12,771 visits), hair curlers/curling irons (5946 visits), and workshop power grinders (5476 visits). Consumer products account for a sizable number of ocular injuries requiring treatment in hospital emergency rooms. Research on outcomes and prevention strategies of the injuries is warranted.

Adolescent↗
PubMed1995

Device-related, nonintravascular infections.

The intensive care environment is conducive to the transmission of microorganisms because of the array of medical equipment and the frequent contamination of the hands of health care workers. This article reviews recommended nursing interventions for the following nonintravascular devices: automatic implantable cardioverter defibrillators, chest tubes, peritoneal dialysis, enteral nutrition, electronic thermometers, oximeter sensors, and urinary drainage devices.

Catheters, Indwelling↗
PubMed1994

An eye-specific G beta subunit essential for termination of the phototransduction cascade.

Heterotrimeric G proteins couple various receptors to intracellular effector molecules. Although the role of the G alpha subunit in effector activation, guanine nucleotide exchange and GTP hydrolysis has been well studied, the cellular functions of the G beta subunits are less well understood. G beta gamma dimers bind G alpha subunits and anchor them to the membrane for presentation to the receptor. In specific systems, the G beta subunits have also been implicated in direct coupling to ion channels and to effector molecules. We have isolated Drosophila melanogaster mutants defective in an eye-specific G-protein beta-subunit (G beta e), and show here that the beta-subunit is essential for G-protein-receptor coupling in vivo. Remarkably, G beta mutants are also severely defective in the deactivation of the light response, demonstrating an essential role for the G beta subunit in terminating the active state of this signalling cascade.

Animals↗
PubMed1993

Pertussis toxin expression in Drosophila alters the visual response and blocks eating behaviour.

Pertussis toxin inactivates certain G-proteins by introducing an ADP-ribose group near the carboxyl-terminus of the alpha-subunit. The major pertussis toxin substrate in Drosophila tissues is Go alpha. We introduced a pertussis toxin gene under control of the hsp70 heat-shock promoter into the Drosophila genome. When heat-shocked, transformed flies produce active pertussis toxin which ADP-ribosylates endogenous Go alpha. Pertussis toxin is expressed in photoreceptors, in the lamina of the eye and in epithelial cells lining the gut. As expected from the absence of Go alpha in photoreceptors, pertussis toxin does not affect the photoreceptor component of the Drosophila visual response. However, it abolishes light on- and off-transients in the electroretinogram. These transients normally arise from the lamina, a tissue where Go alpha transcripts have been detected. Pertussis toxin expression also blocks embryonic development and shortens the lifetime of adult Drosophila. Following heat-shock, transformed adults are active, but they fail to take up nutrients because they stop eating. High energy metabolites are significantly depleted shortly after pertussis toxin expression is induced and the flies die within 48 h.

Adenosine Diphosphate Ribose↗
PubMed1993

Blood glutathione status during exercise: effect of carbohydrate supplementation.

Blood glutathione status and activities of antioxidant enzymes have been investigated during prolonged exercise with or without carbohydrate (CHO) supplementation. Eight subjects cycled at approximately 70% of maximal oxygen uptake to fatigue [134 +/- 19 (SE) min] on the first occasion (control, CON) and at the same work load and duration on the second occasion but with CHO ingestion during exercise. Blood reduced glutathione (GSH) concentration increased from 0.55 +/- 0.05 mM at rest to 0.77 +/- 0.09 mM after 120 min of exercise during CON (P < 0.01) but remained constant during CHO exercise. Blood glutathione disulfide (GSSG) levels were unchanged during CON and CHO exercise. Blood GSH + GSSG content and GSH/GSSG ratio were also significantly (P < 0.05) elevated during CON but not during CHO exercise. The increases in GSH and GSH + GSSG in CON were associated with decreases in plasma glucose and insulin levels. Activities of blood GSH peroxidase, GSSG reductase, and glucose-6-phosphate dehydrogenase were significantly increased during the CHO exercise, whereas only GSSG reductase activity was elevated during the CON ride. It is concluded that blood GSH increases during prolonged exercise and that CHO supplementation may prevent blood GSH increase possibly because of its inhibitory effects on hepatic hormonal releases, which stimulate GSH output.

Adult↗
PubMed1993

Detection of microemboli in patients with artificial heart valves using transcranial Doppler: preliminary observations.

Embolic events, particularly involving the central nervous system, represent one of the important hazards associated with the implantation of mechanical valves. The use of the transcranial Doppler to insonate the middle cerebral artery has allowed us to detect microembolic events in some of these patients. Patients with long term implantation and frequent microemboli appear to be more prone to transient ischemic attacks or stroke. Evaluation of 26 patients with mechanical valves revealed 14 with detectable microemboli, four of whom experienced central nervous system symptoms. Modifications in the medical or anticoagulant regimes have not been successful in decreasing or eliminating these microemboli. As the transcranial Doppler is a non-invasive means of quantifying these microemboli, it may become a useful tool in identifying those patients in need of a new type of antithrombotic regimen, or even a valve replacement. Transcranial Doppler could thus provide advance warning before a catastrophic cerebral embolism occurs.

Aortic Valve↗
PubMed1993

Case study: stoma relocation.

Stoma site relocation presented management problems in a 78 year old female. The old stoma site, located close to the new site, deteriorated due to the patient's debilitated condition. A wound care program was needed that incorporated simplicity and debridement for yellow slough.

Aged↗
PubMed1992

The history of malaria control in the southwest Pacific region, with particular reference to Papua New Guinea and the Solomon Islands.

A number of phases in the history of malaria control in the Southwest Pacific Region can be recognized. During the first phase (1898-1923) it was known that anopheline mosquitoes carried malaria, but as yet the identity of the local vectors had not been established. The incrimination of the vectors in 1923 gave a sound basis for control, which remained largely urban in location except for the distribution of the larvivorous fish Gambusia affinis. The exigencies of the Pacific War and the presence of large numbers of combat troops in malarious areas resulted in the establishment of Mobile Entomological Sections and Malaria Control Units, and the collection and collation of large amounts of entomological, epidemiological and parasitological information. Larval control measures, carried out with very large labour lines and with military precision, were effective. The availability of dichlorodiphenyltrichloroethane (DDT) in 1943 made attack on adult vector mosquitoes also possible; DDT was applied widely in Papua New Guinea and the Solomon Islands by spraying and misting with adulticidal devices in tents and buildings, and by release from aircraft. Atebrin and dimethylphthalate also became available in quantity, for the suppression and treatment of malaria and for personal protection against mosquitoes, respectively. The wartime successes gave hope for peacetime anti-malaria activities carried out within village communities, which to this stage had not been seriously attempted. By three years after the end of the war the World Health Organization, the South Pacific Commission, and local administrative structures had been set up. Extensive investigations into the nature and severity of malaria endemicity were undertaken and recorded. Initially malaria control remained localized and largely urban, and was carried out by conventional antilarval measures, but at the same time new anti-malaria compounds became available for prophylaxis and treatment. Uncertainty still remained as to the usefulness of indoor spraying with DDT against anophelines of the punctulatus group. By 1953 the results of detailed studies in test huts set up for the purpose were known to been couraging, and the decision was made in 1954 to begin in Netherlands New Guinea (West Irian) a pilot project of routine residual spraying with DDT in village houses.(ABSTRACT TRUNCATED AT 400 WORDS)

History, 19th Century↗
PubMed1991

Dose-dependent responses to nerve growth factor by adult rat cholinergic medial septum and neostriatum neurons.

This study describes the relationship between the concentration of intraventricularly infused nerve growth factor (NGF) and several responses by axotomized cholinergic medial septum neurons and normal cholinergic neostriatal neurons of the adult rat. NGF infused for 14 days starting either immediately after a unilateral fimbria-fornix transection or after a 2-week delay period elicited similar dose-response relationships for the maintenance or restoration of ChAT and NGF receptor positivity and cell body size and for intraseptal 'sprouting' of the axotomized medial septum neurons. Thus, in the medial septum it appears that the expression of 'marker' molecules, cell body size and the induction of 'sprouting' are regulated by virtually the same concentrations of NGF in the two treatment strategies. This suggests that NGF has a general regulatory role and injured but untreated neurons remain fully susceptible to NGF at least up to 2 weeks after the lesion. A 14-day infusion with NGF also induced an above-normal cell body size (hypertrophy) both in axotomized medial septum and in intact striatal cholinergic neurons. The hypertrophic response of normal striatal neurons required less NGF than did that of medial septum neurons. Since the striatal response began to be detectable at a similar concentration as that required for the full maintenance or restoration of ChAT and NGF receptor positivity it could be seen as an unwanted side-effect. The definition of a sub-optimal dose with which a significant, but not maximal response can be elicited will allow future evaluations of potentially additive or synergistic actions by other agents.

Animals↗
PubMed1991

Expression of a whey acidic protein transgene during mammary development. Evidence for different mechanisms of regulation during pregnancy and lactation.

Expression of the mouse whey acidic protein (WAP) gene is specific to the mammary gland, is induced several thousand-fold during pregnancy, and is under the control of steroid and peptide hormones. To study developmental regulation of the mouse WAP gene, a 7.2-kilobase (kb) WAP transgene, including 2.6 kb of 5'- and 1.6 kb of 3'-flanking sequences, was introduced into mice. Of the 13 lines of mice examined, 6 expressed the transgenes during lactation at levels between 3 and 54% of the endogenous gene. Although expression was dependent on the site of integration, the transgenes within a given locus were expressed in a copy number-dependent manner and were coordinately regulated. The WAP transgenes were expressed specifically in the mammary gland, but showed a deregulated pattern of expression during mammary development. In all six lines of mice, induction of the WAP transgenes during pregnancy preceded that of the endogenous gene. During lactation, expression in two lines increased coordinately with the endogenous gene, and in three other lines of mice, transgene expression decreased to a basal level. These data indicate that the 7.2-kb gene contains some but not all of the elements necessary for correct developmental regulation. At a functional level it appears as if a repressor element, which inactivates the endogenous gene until late pregnancy, and an element necessary for induction during lactation are absent from the transgene. Complementary results from developmental and hormone induction studies suggest that WAP gene expression during pregnancy and lactation is mediated by different mechanisms.

Animals↗
PubMed1991

Recoverin: a calcium sensitive activator of retinal rod guanylate cyclase.

Vertebrate retinal photoreceptors recover from photoexcitation-induced hydrolysis of guanosine 3', 5'-monophosphate (cyclic GMP) by resynthesizing cyclic GMP, which reopens cation channels that have been closed by light. Activation of guanylate cyclase by light-induced depletion of cytosolic calcium is a key event in this recovery process. This cyclase has now been shown to be regulated by a 23-kilodalton calcium binding protein. The protein is present in both rod and cone photoreceptors and was named recoverin because it promotes recovery of the dark state. The amino acid sequence of recoverin exhibits three potential calcium binding sites (EF hands). That recoverin binds calcium was confirmed with calcium-45 and by observing calcium-induced changes in its tryptophan fluorescence. Recoverin activated guanylate cyclase when free calcium was lowered from 450 to 40 nM, an effect that was blocked by an antibody to recoverin. Thus, guanylate cyclase in retinal rods is stimulated during recovery by the calcium-free form of recoverin. A comparison of recoverin with other calcium binding proteins reveals that it may represent, along with the protein visinin, a family of proteins that are regulated by submicromolar calcium concentrations.

Amino Acid Sequence↗
PubMed1991

Peripheral visual changes and spatial attention.

Three experiments are reported investigating the attentional effects of peripheral visual changes. In agreement with previous work, experiment 1 demonstrated facilitatory and inhibitory effects of a peripheral visual change on the latency of peripheral target detection. However, after a few minutes practice the facilitatory effect disappeared entirely. The inhibitory effect, though slightly reduced in later blocks, remained significant. Hence, the two effects are dissociable and not inter-dependent as argued by Maylor (1985). In experiments 2 and 3 the perceptual salience of the peripheral cue was manipulated. With a low energy, barely noticeable cue there was no reduction in either facilitation or inhibition as a function of practice. In contrast, the attentional effects of cues higher in energy tended to diminish with practice. Theoretical implications of these data are discussed.

Adult↗
PubMed1991

A randomised placebo-controlled trial of topical cysteamine therapy in patients with nephropathic cystinosis.

Five patients with nephropathic cystinosis were evaluated to assess the ability of topical cysteamine to clear corneal cystine crystals. All patients were randomised to receive topical cysteamine 0.2% six times a day in one eye with normal saline in the other eye as a control. All five patients showed some improvement in visual symptoms (photophobia, blepharospasm and visual acuity) together with an improvement in corneal crystal density. Three of these also had an improvement in Snellen visual acuity and contrast sensitivity.

Adolescent↗