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排序方式: 共有267条查询结果,搜索用时 15 毫秒
1.
Irene Jao Vicki Marsh Primus Che Chi Melissa Kapulu Mainga Hamaluba Sassy Molyneux Philip Bejon Dorcas Kamuya 《Bioethics》2020,34(8):819-832
Controlled human malaria infection (CHMI) studies involve the deliberate infection of healthy volunteers with malaria parasites under controlled conditions to study immune responses and/or test drug or vaccine efficacy. An empirical ethics study was embedded in a CHMI study at a Kenyan research programme to explore stakeholders’ perceptions and experiences of deliberate infection and moral implications of these. Data for this qualitative study were collected through focus group discussions, in-depth interviews and non-participant observation. Sixty-nine participants were involved, including CHMI study volunteers, community representatives and research staff. Data were managed using QSR Nvivo 10 and analysed using an inductive-deductive approach, guided by ethics literature. CHMI volunteers had reasonable understanding of the study procedures. Decisions to join were influenced by study incentives, trust in the research institution, their assessment of associated burdens and motivation to support malaria vaccine development. However, deliberate malaria infection was a highly unusual research strategy for volunteers, community representatives and some study staff. Volunteers’ experiences of physical, emotional and social burdens or harms were often greater than anticipated initially, and fluctuated over time, related to specific procedures and events. Although unlikely to deter volunteers' participation in similar studies in furture, we argue that the dissonance between level of understanding of the burdens involved and actual experiences are morally relevant in relation to community engagement, informed consent processes, and ongoing support for volunteers and research staff. We further argue that ethics oversight of CHMI studies should take account of these issues in deciding whether consent, engagement and the balance of benefits and harms are reasonable in a given context. 相似文献
2.
J E Tropea R J Molyneux G P Kaushal Y T Pan M Mitchell A D Elbein 《Biochemistry》1989,28(5):2027-2034
Australine [(1R,2R,3R,7S,7aR)-3-(hydroxymethyl)-1,2,7-trihydroxypyrrolizid ine] is a polyhydroxylated pyrrolizidine alkaloid that was isolated from the seeds of the Australian tree Castanospermum australe and characterized by NMR and X-ray diffraction analysis [Molyneux et al. (1988) J. Nat. Prod. (in press)]. Since swainsonine and catanospermine are polyhydroxylated indolizidine alkaloids that inhibit specific glycosidases, we tested australine against a variety of exoglycosidases to determine whether it would inhibit any of these enzymes. This alkaloid proved to be a good inhibitor of the alpha-glucosidase amyloglucosidase (50% inhibition at 5.8 microM), but it did not inhibit beta-glucosidase, alpha- or beta-mannosidase, or alpha- or beta-galactosidase. The inhibition of amyloglucosidase was of a competitive nature. Australine also inhibited the glycoprotein processing enzyme glucosidase I, but had only slight activity toward glucosidase II. When incubated with cultured cells, this alkaloid inhibited glycoprotein processing at the glucosidase I step and caused the accumulation of glycoproteins with Glc3Man7-9(GlcNAc)2-oligosaccharides. 相似文献
3.
Trimethyloxonium modification of single batrachotoxin-activated sodium channels in planar bilayers. Changes in unit conductance and in block by saxitoxin and calcium 总被引:13,自引:9,他引:4 下载免费PDF全文
Single batrachotoxin-activated sodium channels from rat brain were modified by trimethyloxonium (TMO) after incorporation in planar lipid bilayers. TMO modification eliminated saxitoxin (STX) sensitivity, reduced the single channel conductance by 37%, and reduced calcium block of inward sodium currents. These effects always occurred concomitantly, in an all-or-none fashion. Calcium and STX protected sodium channels from TMO modification with potencies similar to their affinities for block. Calcium inhibited STX binding to rat brain membrane vesicles and relieved toxin block of channels in bilayers, apparently by competing with STX for the toxin binding site. These results suggest that toxins, permeant cations, and blocking cations can interact with a common site on the sodium channel near the extracellular surface. It is likely that permeant cations transiently bind to this superficial site, as the first of several steps in passing inward through the channel. 相似文献
4.
The usefulness of computed tomography (CT) was assessed in 325 consecutive patients with a "clinically definite first stroke" from a community stroke register. CT detected five "non-stroke" lesions (two cerebral gliomas, one cerebral metastasis, and two subdural haematomas), a frequency of 1.5%. Five patients were identified with cerebellar haemorrhage, but only one survived long enough to have a CT scan. CT was useful in excluding intracranial haemorrhage as the cause of the stroke in four patients receiving anticoagulants and seven receiving antiplatelet treatment; it showed intracranial haemorrhage in one patient taking aspirin. Forty six patients were in atrial fibrillation at the time of their stroke; four had intracranial haemorrhages and three had haemorrhagic cerebral infarcts. Nineteen patients with presumed ischaemic minor stroke were considered suitable for carotid endarterectomy; CT showed small haemorrhages in two. The CT scan provides very useful information in a minority (up to 28%) of patients with first stroke, who can be selected on quite simple criteria: (a) doubt (usually because of an inadequate history) whether the patient has stroke or a treatable intracranial lesion; (b) the possibility of cerebellar haemorrhage or infarction; (c) the exclusion of intracranial haemorrhage in patients who either are already taking or likely to need antihaemostatic drugs or are being considered for carotid endarterectomy; (d) if the patient deteriorates in a fashion atypical of stroke. 相似文献
5.
Relative apparent synapomorphy analysis (RASA). I: The statistical measurement of phylogenetic signal 总被引:10,自引:9,他引:1
We have developed a new approach to the measurement of phylogenetic signal
in character state matrices called relative apparent synapomorphy analysis
(RASA). RASA provides a deterministic, statistical measure of natural
cladistic hierarchy (phylogenetic signal) in character state matrices. The
method works by determining whether a measure of the rate of increase of
cladistic similarity among pairs of taxa as a function of phenetic
similarity is greater than a null equiprobable rate of increase. Our
investigation of the utility and limitations of RASA using simulated and
bacteriophage T7 data sets indicates that the method has numerous
advantages over existing measures of signal. A first advantage is
computational efficiency. A second advantage is that RASA employs known
methods of statistical inference, providing measurable sensitivity and
power. The performance of RASA is examined under various conditions of
branching evolution as the number of characters, character states per
character, and mutations per branch length are varied. RASA appears to
provide an unbiased and reliable measure of phylogenetic signal, and the
general approach promises to be useful in the development of new techniques
that should increase the rigor and reliability of phylogenetic estimates.
相似文献
6.
7.
Variation in heat-shock proteins among species of desert fishes (Poeciliidae, Poeciliopsis) 总被引:4,自引:0,他引:4
Analysis of the heat-shock proteins (hsps) of six closely related species
of Poeciliopsis demonstrated the existence of biochemical diversity in the
hsp100, hsp70, hsp60, and hsp30 protein families among species. Each
species expressed five to seven hsp70-related isoforms. Constitutive 70-kD
isoforms were identical among species, but four different patterns of
heat-inducible isoforms were seen in these six species. Members of the
hsp70 family of molecular chaperones are included among the most highly
conserved proteins known, and the possibility of variation in hsp70 among
closely related species has rarely been addressed. The hsp30 family is
known to be less conserved than the hsp70 family, and, as expected, the
Poeciliopsis hsp30 patterns showed more variation. Most of the hsp30
isoforms characteristic of a particular species were unique to that
species. Hsp100 and hsp60 were identical in five of the species, but
alternate isoforms were found in P. monacha. The small size and limited
geographical distribution of the P. monacha population have probably
contributed to the uniqueness of the monacha pattern. Two of the species
were shown to acquire thermotolerance, the ability to withstand normally
lethal temperatures when subjected to a gradual temperature increase.
Rapid-heating protocols commonly used to establish critical thermal maxima
of organisms do not include this inducible component of thermoresistance
and therefore do not adequately assess an organism's capacity to withstand
thermal stress.
相似文献
8.
Karen Molyneux Barbra J. Starman Peter H. Byers Raymond Dalgleish 《Human genetics》1993,90(6):621-628
RNase A protection analysis was used in the search for the cause of a non-lethal osteogenesis imperfecta (OI) phenotype (Sillence type III). Cleavage of the hybrid formed between a normal 2(I) sequence and RNA isolated from the patient indicated the presence of a mismatch. The position of the mismatch was determined and the corresponding area of COL1A2 was amplified using the polymerase chain reaction. Sequencing of cloned amplified DNA revealed the deletion, which was not present in either parent, of the final three bases of exon 19 in one of the patient's two COL1A2 alleles. The deletion results in the loss of amino acid 255 (a valine encoded by the last codon of exon 19) of the triple helical region of half of the 2(I) collagen chains but does not disrupt the splicing of the heterogeneous nuclear RNA (hnRNA). This provides further evidence that OI type III may result from autosomal dominant mutations rather than only from autosomal recessive mutations as had previously been believed. 相似文献
9.
The effects of calystegines isolated from edible fruits and vegetables on mammalian liver glycosidases 总被引:1,自引:0,他引:1
Asano Naoki; Kato Atsushi; Matsui Katsuhiko; Watson Alison A.; Nash Robert J.; Molyneux Russell J.; Hackett Lucy; Topping Joanna; Winchester Bryan 《Glycobiology》1997,7(8):1085-1088
The polyhydroxylated nortropane alkaloids called calyste-ginesoccur in many plants of the Convolvulaceae, Solanaceae, andMoraceae families. Certain of these alkaloids exhibit potentinhibitory activities against glycosidases and the recentlydemonstrated occurrence of calystegines in the leaves, skins,and sprouts of potatoes (Solatium tuberosum), and in the leavesof the eggplant (S.melongena), has raised concerns regardingthe safety of these vegetables in the human diet. We have surveyedthe occurrence of calystegines in edible fruits and vegetablesof the families Convolvulaceae, Solanaceae, and Moraceae byGC-MS. Calystegines A3, B1, B2, and C1 were detected in allthe edible fruits and vegetables tested; sweet and chili peppers,potatoes, eggplants, tomatoes, Physalis fruits, sweet potatoes,and mulberries. Calystegines B1 and C1 were potent competitiveinhibitors of the bovine, human, and rat β-glucosidaseactivities, with K1 values of 150, 10, and 1.9 µM, respectivelyfor B1 and 15,1.5, and 1 µM, respectively, for C1. CalystegineB2 was a strong competitive inhibitor of the -galactosidaseactivity in all the livers. Human β-xylosidase was inhibitedby all four nortropanes, with calystegine C1 having a K1 of0.13 µM. Calystegines A3 and B2 selectively inhibitedthe rat liver β-glucosidase activity. The potent inhibitionof mammalian β-glucosidase and -galactosidase activitiesin vitro raises the possibility of toxicity in humans consuminglarge amounts of plants that contain these compounds. edible plants calystegines glycosidase inhibitors bovine, human, and rat liver 相似文献
10.
Variation in heat shock proteins within tropical and desert species of poeciliid fishes 总被引:8,自引:0,他引:8
Norris CE; diIorio PJ; Schultz RJ; Hightower LE 《Molecular biology and evolution》1995,12(6):1048-1062
The 70-kilodalton heat shock protein (hsp70) family of molecular
chaperones, which contains both stress-inducible and normally abundant
constitutive members, is highly conserved across distantly related taxa.
Analysis of this protein family in individuals from an outbred population
of tropical topminnows, Poeciliopsis gracilis, showed that while
constitutive hsp70 family members showed no variation in protein isoforms,
inducibly synthesized hsp70 was polymorphic. Several species of
Poeciliopsis adapted to desert environments exhibited lower levels of
inducible hsp70 polymorphism than the tropical species, but constitutive
forms were identical to those in P. gracilis, as they were in the
confamilial species Gambusia affinis. These differences suggest that
inducible and constitutive members of this family are under different
evolutionary constraints and may indicate differences in their function
within the cell. Also, northern desert species of Poeciliopsis synthesize a
subset of the inducible hsp70 isoforms seen in tropical species. This
distribution supports the theory that ancestral tropical fish migrated
northward and colonized desert streams; the subsequent decrease in
variation of inducible hsp70 may have been due to genetic drift or a
consequence of adaptation to the desert environment. Higher levels of
variability were found when the 30- kilodalton heat shock protein (hsp30)
family was analyzed within different strains of two desert species of
Poeciliopsis and also in wild-caught individuals of Gambusia affinis. In
both cases the distribution of hsp30 isoform diversity was similar to that
seen previously with allozyme polymorphisms.
相似文献