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Sharon Key

Publications and source records attributed to Sharon Key.

6 recordsLinked to original sources
PubMed2006

Reversal of Sjogren's-like syndrome in non-obese diabetic mice.

BACKGROUND: Non-obese diabetic (NOD) mice exhibit autoimmune diabetes and Sjögren's-like syndrome. OBJECTIVE: To test whether a treatment that reverses end-stage diabetes in the NOD mouse would affect their Sjögren's-like syndrome. METHODS: NOD mice have a proteasome defect. Improperly selected naive T cells escape, but can be killed by reintroducing major histocompatibility complex class I self-peptides on matched normal splenocytes. The proteasome defect also impairs nuclear factor kB, a transcription factor in pathogenic memory T cells, increasing their susceptibility to tumour necrosis factor-induced apoptosis stimulated through complete Freund's adjuvant (CFA). The impact of this two-limb therapy (injections of matched normal splenocytes and CFA) on the autoimmune salivary gland disease of the NOD mice was studied. RESULTS: All NOD mice receiving the above treatment had a complete recovery of salivary flow and were protected from diabetes. Restoration of salivary flow could be the result of a combination of rescue and regeneration of the gland, as confirmed by immunohistochemical analysis. All untreated NOD mice showed a continuous decline in salivary flow, followed by hyperglycaemia and death. CONCLUSION: This study establishes that a brief intervention in NOD mice with Sjögren's-like syndrome can reverse salivary gland dysfunction.

Animals↗
PubMed2006

Comment on papers by Chong et al., Nishio et al., and Suri et al. on diabetes reversal in NOD mice.

Chong et al., Nishio et al., and Suri et al. (Reports, 24 March 2006, pp. 1774, 1775, and 1778) confirmed that treating nonobese diabetic (NOD) mice with an immune adjuvant and semisyngenic spleen cells can reverse the disease but found that spleen cells did not contribute to the observed recovery of pancreatic islets. We show that islet regeneration predominately originates from endogenous cells but that introduced spleen cells can also contribute to islet recovery.

Animals↗
PubMed2004

Using DSP, a reversible cross-linker, to fix tissue sections for immunostaining, microdissection and expression profiling.

Mammalian organs are typically comprised of several cell populations. Some (e.g. brain) are very heterogeneous, and this cellular complexity makes it difficult, if not impossible, to interpret expression profiles obtained with microarrays. Instruments, such as those manufactured by Leica or Arcturus, that permit laser capture microdissection of specific cells or cell groups from tissues were developed to solve this problem. To take full advantage of these instruments, however, one must be able to recognize cell populations of interest and, after they are harvested, to extract intact, unmodified RNA from them. Here we describe a novel, fast and simple method to fix and immunostain tissue sections that permits this to be done.

Animals↗
PubMed2003

Differentiation of human bone marrow-derived cells into buccal epithelial cells in vivo: a molecular analytical study.

BACKGROUND: Adult bone marrow-derived (BMD) cells could be used to repair damaged organs and tissues, but the intrinsic plasticity of these cells has been questioned by results of in-vitro studies suggesting that such cells might fuse with other cells giving the appearance of differentiation. We aimed to determine whether fusion events are important in vivo. METHODS: To test whether BMD cells can colonise an epithelial tissue and differentiate there without fusion, we did in-situ hybridisation with Y and X chromosome probes labelled with 35-sulphur or digoxigenin, or labelled fluorescently. We did immunohistochemistry with anticytokeratin 13 along with fluorescence in-situ hybridisation to identify Y-chromosome positive buccal epithelial cells in cheek scrapings obtained from five females who had received either a bone-marrow transplant or an allogeneic mobilised peripheral-blood progenitor-cell transplant (enriched in CD34+ cells) from male donors. FINDINGS: When examined 4-6 years after male-to-female marrow-cell transplantation, all female recipients had Y-chromosome-positive buccal cells (0.8-12.7%). In more than 9700 cells studied, we detected only one XXXY-positive cell (0.01%) and one XXY cell (0.01%), both of which could have arisen when an XY cell fused with an XX cell. INTERPRETATION: Male BMD cells migrate into the cheek and differentiate into epithelial cells, an occurrence that does not depend on fusion of BMD cells to recipient cells. This finding might be an example of transdifferentiation of haemopoietic or stromal progenitor cells. Plasticity of BMD cells could be useful in regenerative medicine.

Adult↗
PubMed2003

Transplanted bone marrow generates new neurons in human brains.

Adult bone marrow stem cells seem to differentiate into muscle, skin, liver, lung, and neuronal cells in rodents and have been shown to regenerate myocardium, hepatocytes, and skin and gastrointestinal epithelium in humans. Because we have demonstrated previously that transplanted bone marrow cells can enter the brain of mice and differentiate into neurons there, we decided to examine postmortem brain samples from females who had received bone marrow transplants from male donors. The underlying diseases of the patients were lymphocytic leukemia and genetic deficiency of the immune system, and they survived between 1 and 9 months after transplant. We used a combination of immunocytochemistry (utilizing neuron-specific antibodies) and fluorescent in situ hybridization histochemistry to search for Y chromosome-positive cells. In all four patients studied we found cells containing Y chromosomes in several brain regions. Most of them were nonneuronal (endothelial cells and cells in the white matter), but neurons were certainly labeled, especially in the hippocampus and cerebral cortex. The youngest patient (2 years old), who also lived the longest time after transplantation, had the greatest number of donor-derived neurons (7 in 10,000). The distribution of the labeled cells was not homogeneous. There were clusters of Y-positive cells, suggesting that single progenitor cells underwent clonal expansion and differentiation. We conclude that adult human bone marrow cells can enter the brain and generate neurons just as rodent cells do. Perhaps this phenomenon could be exploited to prevent the development or progression of neurodegenerative diseases or to repair tissue damaged by infarction or trauma.

Adult↗