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81.
82.
An introduction to stem cells 总被引:20,自引:0,他引:20
1998 saw the publication of two papers describing the growth in vitro of human embryonic stem (ES) cells derived either from the inner cell mass (ICM) of the early blastocyst or the primitive gonadal regions of early aborted fetuses. Work on murine ES cells over many years had already established the amazing flexibility of ES cells, essentially able to differentiate into almost all cells that arise from the three germ layers. The realization of such pluripotentiality (see below) has, of course, resulted in the field of stem cell research going into overdrive, the establishment of many new biotechnology companies (http://www.stemcellresearchnew.com/catalog1677.html), and a genuine belief that stem cell research will deliver a revolution in terms of how we treat cardiovascular disease, neurodegenerative disease, cancer, diabetes, and the like. However, many people believe that early human embryos should be accorded the same status as any sentient being and thus their 'harvesting' for stem cells is morally unjustifiable. With this in mind, other sources of malleable stem cells have been sought. In the adult, organ formation and regeneration was thought to occur through the action of organ- or tissue-restricted stem cells (i.e. haematopoietic stem cells giving rise to all the cells of the blood, neural stem cells making neurons, astrocytes, and oligodendrocytes). However, it is now believed that stem cells from one organ system, for example the haematopoietic compartment can develop into the differentiated cells within another organ system, such as the liver, brain or kidney. Thus, certain adult stem cells may turn out be as malleable as ES cells and so also be useful in regenerative medicine. This brief overview summarizes the important attributes of tissue-based stem cells and clarifies the terms used. 相似文献
83.
84.
Mark A. Micale J. Marie Haren Jeffrey M. Conroy Carol A. Crowe Stuart Schwartz 《American journal of medical genetics. Part A》1995,57(1):79-81
Parental origin of de novo deletions in the short arm of chromosome 9 in patients with a clinical diagnosis of del(9p) syndrome was assessed in 13 patients using polymerase chain reaction (PCR) analysis of highly polymorphic dinucleotide repeat micro-satellite markers located in the putative deleted region. The deletion was found to be of paternal origin in 9 cases and of maternal origin in the remaining 4 cases, suggesting that the molecular event resulting in the deletion occurs in both male and female gametogenesis and that genomic imprinting does not appear to play a role in the patho-genesis of del(9p) syndrome. © 1995 Wiley-Liss, Inc. 相似文献
85.
Meg Stuart Jane E. Butler David F. Collins Janet L. Taylor Simon C. Gandevia 《The Journal of physiology》2002,545(3):731-737
Many freshwater turtles in temperate climates may experience winter periods trapped under ice unable to breathe, in anoxic mud, or in water depleted of O2 . To survive, these animals must not only retain function while anoxic, but they must do so for extended periods of time. Two general physiological adaptive responses appear to underlie this capacity for long-term survival. The first is a coordinated depression of metabolic processes within the cells, both the glycolytic pathway that produces ATP and the cellular processes, such as ion pumping, that consume ATP. As a result, both the rate of substrate depletion and the rate of lactic acid production are slowed greatly. The second is an exploitation of the extensive buffering capacity of the turtle's shell and skeleton to neutralize the large amount of lactic acid that eventually accumulates. Two separate shell mechanisms are involved: release of carbonate buffers from the shell and uptake of lactic acid into the shell where it is buffered and sequestered. Together, the metabolic and buffering mechanisms permit animals to survive for 3–4 months at 3 °C with no O2 and with circulating lactate levels of 150 mmol l−1 or more. 相似文献
86.
In the event of smallpox bioterrorism, widespread vaccination may be required. Vaccinia immune globulin (VIG) has been used to treat complications from the smallpox vaccine. While the potency of VIG was defined by its ability to neutralize intracellular mature virus, a second form of vaccinia called the extracellular enveloped virus (EEV) is critical for virus spread in the host. The B5R-protein is one of many EEV-specific proteins. Immunoprecipitation and ELISA revealed that VIG recognizes the B5R-protein. An EEV plaque-reduction assay using a recombinant vaccinia that lacks the majority of the extracellular domain of B5R showed that the ability of VIG to neutralize EEV is principally directed at B5R. In addition, absorbing out the anti-B5R antibody present in VIG through the addition of recombinant B5R protein abrogated VIG's ability to significantly neutralize wild-type EEV. This work demonstrates the prominent role of B5R as a target of EEV-neutralizing activity of human antibodies. 相似文献
87.
Physiological and morphological properties of motoneurones in the central nervous system of the leech 总被引:5,自引:2,他引:5 下载免费PDF全文
A E Stuart 《The Journal of physiology》1970,209(3):627-646
1. A number of motor cell bodies have been identified in the segmental ganglia of the ventral nerve cord of the medicinal leech. These motoneurones supply either excitatory or inhibitory innervation to the muscles in the body wall.2. Several tests were made to establish that each of the identified motoneurones directly innervates muscle fibres. (a) By injecting a fluorescent dye into the cell bodies of motoneurones, their axons were traced through one or both contralateral roots. (b) Electrical stimulation of a motoneurone by an intracellular electrode caused a single nerve impulse to travel through the roots to the muscles where it set up an excitatory or an inhibitory junctional potential. (c) Impulses set up in the roots were conducted antidromically to the cell body. (d) If the preparation was bathed in 20 mM-Mg(2+), which blocks chemical synapses, conduction from the cell body to the muscles was not interrupted. Thus it is unlikely that an interneurone was interposed in the pathway within the ganglion.3. Fourteen pairs of excitatory cells and three pairs of inhibitory cells can be identified in each of the twenty-one segmental ganglia. These neurones together supply the five different muscle layers in each segment which execute the movements of the leech. Each neurone innervates a territory of muscle fibres which has a consistent size and location from segment to segment. Several lines of evidence suggest that the identified cells form a major fraction of the total number of excitatory motoneurones in the ganglion.4. The territories of the motoneurones are arranged in a quilt-like pattern closely resembling that already found for the receptive fields of sensory cells on the skin. Within the longitudinal muscle sheet, individual cells supply narrow or wide strips. The firing of each cell thus could produce bending of the segment in various directions or symmetrical shortening of it, depending on which of the motoneurones were active.5. It is possible to deduce which motoneurones are firing to produce a particular movement of the animal. Thus these experiments provide a basis for studying reflex integration between motoneurones and the identified mechanosensory cells in the ganglion. 相似文献
88.
R. Shafiq Geoffrey W. Stuart Jennifer Sandbach Paul Maruff Jon Currie 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1998,118(2):221-229
Latencies of eye movements to peripheral targets are reduced when there is a short delay (typically 200 ms) between the offset
of a central visual fixation point and the target onset. This has been termed the gap effect. In addition, some subjects, usually with practice, exhibit a separate population of very short latency saccades, called express saccades. Both these phenomena have been attributed to disengagement of visual attention when the fixation point is extinguished. A
competing theory of the gap effect attributes it to disengagement of oculomotor fixation during the temporal gap. It is known
that auditory targets are effective in eliciting saccadic eye movements, and also that covert attention operates in the auditory
modality. If the gap effect and express saccades are due to disengagement of spatial attention, both should persist in the
auditory modality. However, fixation of gaze is largely under visual control. If the gap effect results from disengagement
of fixation, then at least a reduced effect should be seen in the auditory modality. Human subjects performed the gap task
and a control task in the dark, using auditory fixation points and saccadic targets, on five successive days. Despite this
practice, express saccades were not observed. There was a reliable gap effect, but the reduction in saccadic latency was only
17 ms, compared with 32 ms for the same subjects in the visual modality. This suggests that about half the gap effect is due
to disengagement of visual fixation. The remainder was not due to non-specific warning effects and could be attributed to
offset of the auditory fixation stimulus.
Received: 1 March 1996 / Accepted: 11 July 1997 相似文献
89.
BAG1 over-expression in brain protects against stroke 总被引:3,自引:0,他引:3
Kermer P Digicaylioglu MH Kaul M Zapata JM Krajewska M Stenner-Liewen F Takayama S Krajewski S Lipton SA Reed JC 《Brain pathology (Zurich, Switzerland)》2003,13(4):495-506
The co-chaperone BAG1 binds and regulates 70 kDa heat shock proteins (Hsp70/Hsc70) and exhibits cytoprotective activity in cell culture models. Recently, we observed that BAG1 expression is induced during neuronal differentiation in the developing brain. However, the in vivo effects of BAG1 during development and after maturation of the central nervous system have never been examined. We generated transgenic mice over-expressing BAG1 in neurons. While brain development was essentially normal, cultured cortical neurons from transgenic animals exhibited resistance to glutamate-induced, apoptotic neuronal death. Moreover, in an in vivo stroke model involving transient middle cerebral artery occlusion, BAG1 transgenic mice demonstrated decreased mortality and substantially reduced infarct volumes compared to wild-type littermates. Interestingly, brain tissue from BAG1 transgenic mice contained higher levels of neuroprotective Hsp70/Hsc70 protein but not mRNA, suggesting a potential mechanism whereby BAG1 exerts its anti-apoptotic effects. In summary, BAG1 displays potent neuroprotective activity in vivo against stroke, and therefore represents an interesting target for developing new therapeutic strategies including gene therapy and small-molecule drugs for reducing brain injury during cerebral ischemia and neurodegenerative diseases. 相似文献
90.
Bi-directional modulation of T cell-dependent antibody production by prostaglandin E(2). 总被引:1,自引:0,他引:1
Xiaowen He Cornelia M Weyand J?rg J Goronzy Wanyun Zhong John M Stuart 《International immunology》2002,14(1):69-77
T cell-dependent Ig production involves interaction between T cells and B cells. This study evaluated the effects of prostaglandin (PG) E(2) on Ig production in a system in which B cells were co-cultured with autologous CD4(+) T cell clones non-specifically activated by anti-CD3. The effects of PGE(2) on T cell-dependent Ig production differed substantially, depending on the T cells employed. We selected six T cell clones that were able to enhance Ig production (resistant T cell clones) and six T cell clones that inhibited Ig production in the presence of PGE(2) (sensitive T cell clones) for comparison. The resistant T cells produced high levels (>1000 pg/ml) of IL-2 and/or IL-4, and expressed high CD40L, OX40 and CD45RA, and low CD45RO. In contrast, sensitive T cells secreted low IL-2 (<500 pg/ml) and IL-4 (<200 pg/ml), and expressed low CD40, OX40 and CD45RA, and high CD45RO. Adding supernatant derived from resistant T cell clones restored Ig production inhibited by PGE(2), while removing IL-2, IL-4 or IL-10 using specific antibodies inhibited Ig production. In addition, we demonstrated a direct effect of PGE(2) on B cells to enhance Ig production. Consistently, in the presence of resistant T cells, PGE(2) increased B cell proliferation and differentiation. In conclusion, the effects of PGE(2) on Ig production consist of its indirect effects through T cells and its direct effects on B cells. The outcome of the effects can be up-regulatory or down-regulatory, depending whether resistant or sensitive T cells are involved. 相似文献