144,912 research outputs found
7Li NMR of Normal Human Erythrocytes
Lithium has been known to be an effective medication for people with bipolar disorder. The mechanisms of action of lithium in the brain is not very well understood. NMR spectroscopy and imaging are effective both in determining lithium levels in tissue and brain. We have monitored lithium levels in red blood cells. We have been able to separate intra- and extracellular compartments of lithium using shift reagents, thereby obtaining T^1 \u27s of both the compartments. Lithium uptake as a function of hematocrit was monitored weekly over a 3 week period. The time constant of 50 mM lithium uptake at 25°C and 85% hematocrit was found to be 16.5 hrs. The time constant of 1.8 mM lithium uptake at 37 °C and 45% hematocrit was found to be 11.6 hrs. Experiments on the visibility of the quadrupolar nuclei indicate that it is only 74-90% visible and the visibility decreased with decreasing concentrations
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Expression of proliferation-dependent antigens during cellular ageing of normal and progeroid human fibroblasts
Normal human fibroblasts display a limited lifespan in
culture, which is due to a steadily decreasing fraction of
cells that are able to proliferate. Using antibodies that react
with antigens present in proliferating cells only, in an
indirect immunofluorescence assay, we have estimated the
fraction of proliferating cells in cultures of normal human
fibroblasts. Furthermore, we have estimated the rate of
decline in the fraction of proliferating cells during the
process of cellular ageing by application of the assay to
normal human fibroblasts throughout their lifespan in
culture. Werner’s Syndrome is an autosomal recessive
disease in which individuals display symptoms of ageing
prematurely. Werner’s Syndrome fibroblasts display a
reduced lifespan in culture compared with normal human
fibroblasts. Like normal human fibroblasts, the growth of
Werner’s Syndrome fibroblasts is characterised by a
decreasing fraction of cells reacting with the proliferationassociated
antibodies throughout their lifespan in culture.
However, the rate of loss of proliferating cells in Werner’s
Syndrome fibroblasts during the process of cellular ageing
is accelerated 5- to 6-fold compared with the rate determined
for normal human fibroblasts
Motion Sickness Symptomatology of Labyrinthine Defective and Normal Subjects During Zero Gravity Maneuvers
Motion sickness symptomology of labyrinthine defective and normal human subjects during zero gravity maneuver
Expression of the CD6 T lymphocyte differentiation antigen in normal human brain
Antigens shared by the immune and central nervous systems (CNS) have been described repeatedly.
The present study reports the expression of the CD6 lymphocyte differentiation antigen in normal human
brain evidenced by immunohistochemistry and Northern blot analysis. A panel of various anti-CD6
monoclonal antibodies (mabs) tested on serial cryostat sections identified CD6-positive cells randomly
scattered in parenchyma of all examined brain areas. Northern blot analysis with a highly sensitive cRNA
probe revealed a 3.1 kb CD6-specific mRNA in various brain regions, especially in basalganglia and cortex
cerebellum. Staining with mabs raised against different hematopoietic cell types, as well as hybridization
with probes specific for the ß- and y-T cell receptor (TCR) chains support the notion that CD6 is
expressed by original brain cells. The nature of the CD6-positive cell type and possible functions of shared
antigens in immune and nervous systems are discusse
The epigenomic landscape of transposable elements across normal human development and anatomy
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E-cigarette aerosols induce unfolded protein response in normal human oral keratinocytes.
Objective: Since the introduction in 2004, global usage of e-cigarettes (ECs) has risen exponentially. However, the risks of ECs on oral health are uncertain. The purpose of this study is to understand if EC aerosol exposure impacts the gene pathways of normal human oral keratinocytes (NHOKs), particularly the unfolded protein response (UPR) pathway. Materials and methods: EC aerosols were generated reproducibly with a home-made puffing device and impinged into the culture medium for NHOKs. DNA microarrays were used to profile the gene expression changes in NHOKs treated with EC aerosols, and the Ingenuity Pathway Analysis (IPA) was used to reveal signaling pathways altered by the EC aerosols. Quantitative PCR was used to validate the expression changes of significantly altered genes. Results: DNA microarray profiling followed by IPA revealed a number of signaling pathways, such as UPR, cell cycle regulation, TGF-β signaling, NRF2-mediated oxidative stress response, PI3K/AKT signaling, NF-κB signaling, and HGF signaling, activated by EC aerosols in NHOKs. The UPR pathway genes, C/EBP homologous protein (CHOP), activating transcription factor 4 (ATF4), X box binding protein 1 (XBP1), and inositol-requiring enzyme 1 alpha (IRE1α) were all significantly up-regulated in EC aerosol-treated NHOKs whereas immunoglobulin heavy-chain binding protein (BIP) and PRKR-like ER kinase (PERK) were slightly up-regulated. qPCR analysis results were found to be well correlated with those from the DNA microarray analysis. The most significantly changed genes in EC aerosol-treated NHOKs versus untreated NHOKs were CHOP, ATF4, XBP1, IRE1α and BIP. Meanwhile, Western blot analysis confirmed that CHOP, GRP78 (BIP), ATF4, IRE1α and XBP1s (spliced XBP1) were significantly up-regulated in NHOKs treated with EC aerosols. Conclusion: Our results indicate that EC aerosols up-regulate the UPR pathway genes in NHOKs, and the induction of UPR response is mediated by the PERK - EIF2α - ATF4 and IRE1α - XBP1 pathways
Versican splice variant messenger RNA expression in normal human Achilles tendon and tendinopathies
Versican is the principal large proteoglycan expressed in mid-tendon, but its role in tendon pathology is unknown. Our objective was to define the expression of versican isoform splice variant messenger ribonucleic acid (mRNA) in normal Achilles tendons, in chronic painful tendinopathy and in ruptured tendons. Total RNA isolated from frozen tendon samples (normal n = 14; chronic painful tendinopathy n = 10; ruptured n = 8) was assayed by relative quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for total versican, versican variants V0, V1, V2, V3 and type I collagen a1 mRNA, normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Differences between sample groups were tested by Wilcoxon statistics. Painful and ruptured tendons showed a significant decrease (median 2-fold) in the expression of versican mRNA, in contrast to an increased expression (median 8-fold) of type I collagen a1 mRNA in painful tendons. Versican splice variants V0 and V1 mRNA were readily detected in normal samples, V3 levels were substantially lower, and V2 levels were more variable. Each of V1, V2 and V3 mRNA showed significant decreases in expression in painful and ruptured tendons, but V0 was not significantly changed. Changes in versican expression relative to that of collagen, and alterations in the balance of versican splice variants, may contribute to changes in matrix structure and function in tendinopathies
Modeling the variability of shapes of a human placenta
While it is well-understood what a normal human placenta should look like, a
deviation from the norm can take many possible shapes. In this paper we propose
a mechanism for this variability based on the change in the structure of the
vascular tree
Distinct expression patterns of ER alpha and ER beta in normal human mammary gland
AIM: Two oestrogen receptors (ERs) have been identified to date—the “classic” ERa and the more
recently described ERb. Although much is known about ERa at the mRNA and protein levels, our
knowledge of the expression and distribution of ERb protein is much more limited. The aim of this study
was to compare the cellular distribution of ERa and ERb in normal human mammary gland.
METHODS: Formalin fixed, paraffin wax embedded material was obtained from reduction
mammoplasty specimens, normal tissue adjacent to breast tumour, or fibroadenoma. Sections were
immunohistochemically stained for ERa, ERb, and the progesterone receptor. The staining pattern for
each antibody was evaluated and compared.
RESULTS: ERa was restricted to the cell nuclei of epithelial cells lining ducts and lobules. Although ERb
was also seen in these cells, additional strong staining was detected specifically in the cell nuclei of
myoepithelial cells. Occasional staining was seen in surrounding stromal and endothelial cell nuclei
and in lymphocytes.
CONCLUSIONS: ER subtypes have distinct distribution patterns in the normal mammary gland. The widespread
distribution of ERb suggests that it may be the dominant ER in the mammary gland where it may
be acting as a natural suppressor
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