Aims-To determine the incidence, natural course, and severity of dry eye occurring or worsening after haematopoietic stem cell transplantation (SCT). Methods-At a tertiary care hospital, 53 patients undergoing allogeneic or autologous SCT followed by at least 180 days of follow up were studied prospectively. Examination included grading of symptoms of dry eye, evaluation of ocular surface, tear break up time, and Schirmer tests with and without nasal stimulation. Meibomian gland secretion was also examined using a slit lamp while applying steady digital pressure. Results-Of the 53 patients, 44 received allografts. Half of these patients (22) developed dry eye or their pre-existing dry eye worsened after SCT, while none of nine autograft recipients did. Onset of dry eye was 171 (SD 59) days after SCT. Two types of dry eye occurred. One (n=10) was severe with ocular surface findings resembling Sjögren's syndrome and reduction of reflex tearing soon after onset. A mild type (n=12) had unimpaired reflex tearing. Meibomian gland dysfunction (MGD) was more frequent and severe in patients with dry eye and chronic graft versus host disease (GVHD), and overall severity of dry eye was greater in patients with MGD and chronic GVHD. Conclusions-Dry eye after SCT occurred only in allograft recipients, and was not evident in autograft recipients. The severe form of dry eye had a tendency to develop rapidly. Further study on the prediction and treatment of severe dry eye after SCT is necessary.
We report a novel protein family consisting of three members, each of which contains RUN and TBC motifs and appears to be associated with small G protein-mediated signal transduction pathway. We named these proteins as small G protein signaling modulators (SGSM1/2/3). Northern blot analysis revealed that human SGSM2/3 are expressed ubiquitously in various tissues, whereas SGSM1 is expressed mainly in brain, heart, and testis. Mouse possessed the same protein family genes, and the in situ hybridization and immunohistochemical staining of tissue sections revealed that mouse Sgsm1/2/3 are expressed in the neurons of central nervous system, indicating the strong association of Sgsm family with neuronal function. Furthermore, endogenous Sgsm1 protein was localized in the trans-Golgi network of mouse Neuro2a cells by immunofluorescence microscopy. Expression of various cDNA constructs followed by immunoprecipitation assay revealed that human SGSM1/2/3 proteins are coprecipitated with RAP and RAB subfamily members of the small G protein superfamily. Based on these results, we postulated that the SGSM family members function as modulators of the small G protein RAP and RAB-mediated neuronal signal transduction and vesicular transportation pathways.
Chemical sensing in living systems demands optical sensors that are bright, stable, and sensitive to the rapid dynamics of chemical signaling. Lanthanide-doped upconverting nanoparticles (UCNPs) efficiently convert near infrared (NIR) light to higher energy emission and allow biological systems to be imaged with no measurable background or photobleaching, and with reduced scatter for subsurface experiments. Despite their advantages as imaging probes, UCNPs have little innate chemical sensing ability and require pairing with organic fluorophores to act as biosensors, although the design of stable UCNP-fluorophore hybrids with efficient upconverted energy transfer (UET) has remained a challenge. Here, we report Yb3+- and Er3+-doped UCNP-fluorophore conjugates with UET efficiencies up to 88%, and photostabilities 100-fold greater by UET excitation than those of the free fluorophores under direct excitation. Despite adding distance between Er3+ donors and organic acceptors, thin inert shells significantly enhance overall emission without compromising UET efficiency. This can be explained by the large increase in quantum yield of Er3+ donors at the core/shell interface and the large number of fluorophore acceptors at the surface. Sensors excited by UET show increases in photostability well beyond those reported for other methods for increasing the longevity of organic fluorophores, and those covalently attached to UCNP surface polymers show greater chemical stability than those directly coordinated to the nanocrystal surface. By conjugating other fluorescent chemosensors to UCNPs, these hybrids may be extended to a series of NIR-responsive biosensors for quantifying the dynamic chemical populations critical for cell signaling.
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