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Biomedical subjects

C Marshall

Publications and source records attributed to C Marshall.

At least 73 records · Page 4Linked to original sources

A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 5. Design and implementation of the trial.

A large-scale malaria intervention programme using insecticide-treated bed nets and chemoprophylaxis administered to children was introduced into a rural area of The Gambia. The operation was carried out using the existing primary health care (PHC) service in the region. Training of the village health workers, sensitization of the communities, and implementation of net impregnation and the drug delivery programme are described. This delivery system resulted in over 90% of nets being treated with insecticide and 80% of children receiving over 90% of their tablets during the rainy season. There was considerable variation in the distribution of permethrin on a bed net and between individual nets, which is likely to facilitate the spread of insecticide resistance in the local mosquito populations. Bed nets made from heavier fabrics tended to absorb more insecticide than those made from lighter materials. Four months after dipping, 89% of the insecticide had been lost from treated nets. This was probably due mainly to women washing their nets, an activity carried out on average once every 2 months during the rainy season. The high number of insecticide-treated bed nets in the study area demonstrated that a malaria control programme operated through a PHC system can be implemented successfully.

Antimalarials↗

Suppression of pregnancy-induced nausea and vomiting with sensory afferent stimulation.

This study examined the effect of sensory affect stimulation (SAS) delivered through the volar surface of the wrist on pregnancy-induced nausea and vomiting. Twenty-three women with significant nausea and vomiting in the first 14 weeks of pregnancy were enrolled in a randomized, crossover study comparing an active SAS unit and an inactive placebo unit. Twenty-one women experienced improvement in symptoms, 20 (87%) with the SAS unit and 10 (43%) with the placebo device. Nine women had an improvement with both devices. Eleven women reported an improvement with SAS only, while one woman had placebo improvement only. SAS applied to the wrist can effectively improve pregnancy-induced nausea and vomiting as compared to a placebo device.

Adult↗

Specific association of activated MAP kinase kinase kinase (Raf) with the plasma membranes of ras-transformed retinal cells.

Plasma membrane-enriched fractions were prepared from human embryonic retinal cells transformed with either adenovirus E1A and oncogenic ras DNA, or E1A and E1B DNA. Ras comprised 5-10% of the membrane protein from the E1A/ras transformed cells, whereas the membranes from E1A/E1B transformed cells did not overexpress Ras. The membranes from E1A/ras cells contained MAP kinase kinase kinase (MAPKKK) activity, even after washing in 0.5 M NaCl, whereas the membranes from E1A/E1B cells did not. Neither membrane fraction contained MAP kinase kinase or MAP kinase activity after washing with 0.5M NaCl. Immunoblotting experiments revealed about 10-fold more c-Raf in the membranes from E1A/ras cells than from E1A/E1B cells, and 50-60% of the MAPKKK activity in Triton X100-solubilised membranes from E1A/ras cells was immunoprecipitated with anti-Raf antibodies. A striking enrichment of c-Raf in the plasma membranes of E1A/ras cells was also demonstrated by immunocytochemistry, where it was co-localized with Ras. The MAPKKK activity in E1A/ras membranes was unaffected by incubation with protein phosphatases or by inclusion of protein phosphatase inhibitors during isolation, nor was it activated by GTP-Ras or inhibited by GDP-Ras. The results support the view that Ras and c-Raf interact with one another, but that neither c-Raf phosphorylation nor its interaction with GTP-Ras are alone sufficient for activation. The identification of MAPKKK activity in the membranes of ras-transformed cells may prove useful in elucidating the mechanism by which Raf is activated by Ras.

Amino Acid Sequence↗

Mentorship in critical care.

In line with Project 2000, the development of core-curriculum based training in post-basic education has led to changes in assessment strategies. The Critical Care core-curriculum with its reduced time span of only six months has meant that specialist input is reduced. The time span for each branch has almost halved that of the traditional ENB 176 course. The students spend eight weeks in the classroom leaving only 16 weeks for practice. As a result, it becomes very important to have an effective mentoring programme. This article looks at the mentoring dimension in post registration common core courses. It defines the term as used, and outlines factors which influence an effective mentoring programme as well as suggesting some ways which may help mentors maintain this role.

Critical Care↗

Sustained activation of the mitogen-activated protein (MAP) kinase cascade may be required for differentiation of PC12 cells. Comparison of the effects of nerve growth factor and epidermal growth factor.

Stimulation of PC12 cells with nerve growth factor (NGF) increased mitogen-activated protein kinase kinase (MAPKK) activity > 20-fold after 5 min to a level that was largely sustained for at least 90 min. MAPKK activity was stimulated to a similar level by epidermal growth factor (EGF), but peaked at 2 min, declining thereafter and returning to basal levels after 60-90 min. Activation of MAPKK by either growth factor occurred prior to the activation of MAP kinase, consistent with MAPKK being the physiological activator of MAP kinase. The results demonstrate that the transient activation of MAPKK by EGF and its sustained activation by NGF underlies the transient and sustained activation of MAP kinase induced by EGF and NGF respectively. NGF or EGF induced the same two forms of MAPKK that were resolved on a Mono Q column. The Peak-1 MAPKK was activated initially and partially converted into the more acidic peak-2 MAPKK after prolonged growth-factor stimulation. The Peak-2 MAPKK was 20-fold more sensitive to inactivation by the catalytic subunit of protein phosphatase 2A. Stimulation with NGF caused a striking translocation of MAP kinase from the cytosol to the nucleus after 30 min, but not nuclear translocation of MAP kinase occurred after stimulation with EGF. The results suggest that sustained activation of the MAP kinase cascade may be required for MAP kinase to enter the nucleus, where it may initiate the gene transcription events required for neuronal differentiation of PC12 cells.

Animals↗

Evolution of the primate lentiviruses: evidence from vpx and vpr.

The genomes of the four primate lentiviral groups are complex and contain several regulatory or accessory genes. Two of these genes, vpr and vpx, are found in various combinations within the four groups and encode proteins whose functions have yet to be elucidated. Comparison of the encoded protein sequences suggests that the vpx gene within the HIV-2 group arose by the duplication of an ancestral vpr gene within this group. Evolutionary distance analysis showed that both genes were well conserved when compared with viral regulatory genes, and indicated that the duplication occurred at approximately the same time as the HIV-2 group and the other primate lentivirus groups diverged from a common ancestor. Furthermore, although the SIVagm vpx proteins are homologous to the HIV-2 group vpx proteins, there are insufficient grounds from sequence analysis for classifying them as vpx proteins. Because of their similarity to the vpr proteins of other groups, we suggest reclassifying the SIVagm vpx gene as a vpr gene. This creates a simpler and more uniform picture of the genomic organization of the primate lentiviruses and allows the genomic organization of their common precursor to be defined; it probably contained five accessory genes: tat, rev, vif, nef and vpr.

Amino Acid Sequence↗

MAPKAP kinase-2; a novel protein kinase activated by mitogen-activated protein kinase.

A novel protein kinase, which was only active when phosphorylated by the mitogen-activated protein kinase (MAP kinase), has been purified 85,000-fold to homogeneity from rabbit skeletal muscle. This MAP kinase activated protein kinase, termed MAPKAP kinase-2, was distinguished from S6 kinase-II (MAPKAP kinase-1) by its response to inhibitors, lack of phosphorylation of S6 peptides and amino acid sequence. MAPKAP kinase-2 phosphorylated glycogen synthase at Ser7 and the equivalent serine (*) in the peptide KKPLNRTLS*VASLPGLamide whose sequence is similar to the N terminus of glycogen synthase. MAPKAP kinase-2 was resolved into two monomeric species of apparent molecular mass 60 and 53 kDa that had similar specific activities and substrate specificities. Peptide sequences of the 60 and 53 kDa species were identical, indicating that they are either closely related isoforms or derived from the same gene. MAP kinase activated the 60 and 53 kDa forms of MAPKAP kinase-2 by phosphorylating the first threonine residue in the sequence VPQTPLHTSR. Furthermore, Mono Q chromatography of extracts from rat phaeochromocytoma and skeletal muscle demonstrated that two MAP kinase isoforms (p42mapk and p44mapk) were the only enzymes in these cells that were capable of reactivating MAPKAP kinase-2. These results indicate that MAP kinase activates at least two distinct protein kinases, suggesting that it represents a point at which the growth factor-stimulated protein kinase cascade bifurcates.

3T3 Cells↗

Relative importance of molecular, neontological, and paleontological data in understanding the biology of the vertebrate invasion of land.

Meyer and Wilson's (1990) 12S rRNA phylogeny unites lungfish and tetrapods to the exclusion of the coelacanth. These workers also provide a list of morphological features shared in common between modern lungfish and tetrapods, and they conclude that these traits were probably present in their last common ancestor. However, the exquisite fossil records of the abundant extinct lungfishes and rhipidistians show that at least 13 out of Meyer and Wilson's 14 supposed ancestral traits were not present in the last common ancestor of lungfishes and tetrapods. Using extant taxa to infer ancestral morphologies is fraught with difficulties; just like molecular sequences, ancestral character states of morphological traits may be severely overprinted by subsequent modifications. Modern lungfish are air-breathing nonmarine forms, yet their Devonian forebears were marine fish that did not breathe air. Fossils dating from the time of origin of tetrapods in the Devonian offer the only hope of understanding the morphological innovations that led to tetrapods; morphological analysis of the "living fossils," the coelacanth and lungfish, only lends confusion.

Animals↗

Hypoxic pulmonary vasoconstriction is not endothelium dependent.

Feline intrapulmonary arteries (mean diameter, 0.9 mm) were equilibrated in Earle's solution at constant tension in a chamber bubbled with an hyperoxic gas mixture (30% oxygen, 5% carbon dioxide, balance nitrogen). The endothelium was removed from half the vessels by gentle rubbing. The isometric response to the addition of acetylcholine (1*10(-6) M) was dilator in the vessels with endothelium and constrictor in those without endothelium. Intermittent exposure to a hypoxic gas mixture (0% oxygen, 5% carbon dioxide, balance nitrogen) for 20 min with five repetitions demonstrated sustained constrictor responses in the presence or absence of endothelium. Endothelial cells are, therefore, not required for the mediation of hypoxic pulmonary vasoconstriction.

Animals↗

The amino acid sequence of a mammalian MAP kinase kinase.

The amino acid sequence of the dual specificity mitogen-activated protein kinase kinase (MAPKK) has been determined by cDNA cloning and amino acid sequencing. MAPKK (393 residues, Mr 43,330) is a new member of the protein kinase subclass that comprises byr1 and STE7 that are involved in pheromone dependent signal transduction in yeast, wis1 a mitotic regulator in S. pombe and PBS2, which confers antibiotic resistance in S. cerevisiae.

Amino Acid Sequence↗

Cyclosporine's effect on functional reserve in the renal allograft.

Thirteen renal allograft recipients (6 patients on cyclosporine/7 patients on azathioprine) participated in a short-term oral protein-loading study to determine the effect of cyclosporine on an allograft's functional reserve. The baseline glomerular filtration rate of the two groups were similar (52 +/- 18 ml/min/1.73 m2 for the azathioprine/conventional therapy (CT) group and 47 +/- 12 ml/min/1.73 m2 for the cyclosporine (CsA) group), as were the baseline effective renal plasma flows (218 +/- 78 ml/min/1.73 m2 and 222 +/- 75 ml/min/1.73 m2, respectively). At 3 hr following the protein load there was an increase in GFR to 66 +/- 28 ml/min/1.73 m2 in the CT group. The GFR (39 +/- 8 ml/min/1.73 m2) of the CsA group at this time was unchanged. The responses in ERPF were similar. No significant difference was found between the two groups baseline RAA profiles (4.7 +/- 3.3 ng/ml/hr (CT) and 4.7 +/- 1.7 ng/ml/hr [CsA]), or those at the third hour (8.1 +/- 8.3 ng/ml/hr (CT) and 3.5 +/- 1.9 ng/ml/hr [CsA]). The data in this study indicate that CsA alters the renal allograft's response to a protein meal. This difference may be related to an altered vasodilatory response. This altered vascular reactivity may be mediated through renin activation and/or other hemodynamic regulators such as prostaglandins.

Adult↗

Influence of bronchial arterial PO2 on pulmonary vascular resistance.

In six anesthetized and mechanically ventilated adult sheep, the bronchial artery was perfused with blood from an oxygenator-pump circuit. When the lungs were ventilated with 100% O2 and the bronchial O2 tension (PbrO2) was approximately 600 Torr, the mean of the pulmonary vascular resistances (PVR) measured at the beginning (3.32 +/- 0.29 units) and end (3.17 +/- 0.13 units) of the experiment was 3.24 +/- 0.20 units. When the PbrO2 was changed to 58 +/- 1 Torr, the PVR (2.99 +/- 0.14 units) did not change significantly. However, when the lungs were ventilated with air as PbrO2 was decreased to 91 +/- 4, 77 +/- 3, 56 +/- 2, and 42 +/- 1 Torr, the PVR increased to 3.67 +/- 0.18, 4.03 +/- 0.16, 4.79 +/- 0.19, and 4.71 +/- 0.35 units, respectively. However, when the PbrO2 was decreased further to 26 +/- 1 and 13 +/- 1 Torr, the PVR decreased to 3.77 +/- 0.28 and 3.91 +/- 0.30 units, respectively. In contrast, the bronchial vascular resistance decreased monotonically as PbrO2 decreased. The bronchial circulation supplies vasa vasorum to the walls of all but the smallest pulmonary arteries, and it is therefore suggested that the PO2 of the bronchial circulation is responsible for the bimodal response of the pulmonary vasculature, with stimulation of hypoxic pulmonary vasoconstriction at moderate hypoxemia and of hypoxic pulmonary vasodilation at profound hypoxemia. The physiological and pathophysiological significance of the influence of systemic PO2 on pulmonary vascular tone is discussed.

Animals↗

Elder abuse.

Elder abuse encompasses physical, psychological, and financial abuse and also includes the violation of an individual's rights, or social abuse. Detection of elder abuse is often obstructed by the denial or shame of the abused older adult and the denial or improper assessment by health care professionals. The ethical struggle professionals face when they suspect abuse may also impede assessment or intervention. Preliminary data on etiologic factors related to elder abuse suggest that misinformation, the caregiver's lack of understanding of the needs of older adults, social isolation, a history of dysfunctional family relationships, and the psychopathologic factors of the caregiver are salient factors for understanding elder abuse. In addition, caregiver burden related to the care of the impaired elder and other external life events is a risk factor for elder abuse. Self-neglect is the type of elder abuse most often reported and the most difficult to handle, because older adults have a right to refuse services. Home care providers often face practical and ethical dilemmas in cases of self-neglect. When making an assessment for elder abuse, it is best to use a multidisciplinary approach. In addition to physical indicators (bruises, malnutrition, fractures), attention must be paid to the social, family, and sexual history of the patient. The psychological history of the patient and caregiver is also important. Reporting laws exist in all states, and health care practitioners must become familiar with the laws in their states. Awareness of elder abuse by professionals working in home care is essential, because the failure to detect abuse can interfere with interventions and in some cases lead to death.

Aged↗

Erythema multiforme in two horses.

Erythema multiforme is reported for the first time in 2 South African horses. Both horses displayed a sudden, fulminant outbreak of raised, non-alopecic and non-pruritic plaques over the dorsolateral aspects of the neck and trunk. In both cases the distribution of the lesions was bilaterally symmetrical. Histopathological findings included hydropic degeneration of basal epidermal cells, eosinophilic necrosis of individual or groups of keratinocytes, intra-epidermal and sub-epidermal cleft formation and mixed, dermal, perivascular infiltrates. An initiating cause could not be identified in either case. Both horses underwent gradual spontaneous remission within 3 months.

Animals↗

Endothelium-derived relaxing factor is not responsible for inhibition of hypoxic pulmonary vasoconstriction by inhalational anesthetics.

Inhalational anesthetics inhibit hypoxic pulmonary vasoconstriction (HPV). One mechanism suggested for this action is stimulation of release of endothelium-derived relaxing factor. The present study has tested this hypothesis. These studies were performed in 66 ventilated and perfused isolated rat lungs. There were three study protocols. Study 1 examined the effect of HPV of the inhibition of soluble guanylate cyclase by methylene blue (MB). In the presence or absence of MB, the lungs constricted to hypoxia with pulmonary artery pressure increases of 8.6 +/- 0.2 cmH2O and 11.5 +/- 0.4 cmH2O, respectively, and halothane, enflurane, and isoflurane caused a reversible 50% decrease in the pulmonary pressor response, but acetylcholine (ACh) was vasodilatory in the saline group and vasoconstrictor in the MB group. In Study II a dose-response curve was established for the potent stimulator (Sin 1) of the enzyme guanylate cyclase. In the presence of MB the dose-response curve for Sin 1 was shifted to the right with an increase in the ED50 for Sin 1 from 44 microM for the control to 85 microM for the MB group. In Study III, baseline pulmonary artery pressure was increased with U46619, and the hypoxic pressor response was increased (28.9 +/- 2.5 cmH2O), but halothane again caused a 50% decrease (11.0 +/- 1.8 cmH2O) in the response to hypoxia. In summary, when soluble guanylate cyclase activity is inhibited by MB, the inhibition of hypoxic pulmonary vasoconstriction by halothane, isoflurane, or enflurane was unaltered, and release of endothelium-derived relaxing factor (EDRF) is therefore not an essential mechanism underlying this action.

Animals↗