Differential expression of basement membrane collagen-IV alpha l to alpha 6 chains during oral carcinogenes

This study aimed to resolve if basement membrane (BM) collagen alpha chains undergo remodeling during oral. carcinogenesis. Using immunohistochemistry and transmission electron microscopy, we found that BMs in oral epithelial dysplasias (OED: mild, n=10; moderate, n=10; severe, n=10) and carcinoma in situ (CIS) (n=10) differed from normal mucosa (n=6) and oral epithelial hyperplasia (n=5) in showing: (1) excessive lamina densa-like material ultrastructurally, and (2) stronger immunoexpression for alpha 5(IV) than for alpha 1(IV), alpha 2(IV), and alpha 6(IV) chains-findings that implicate these molecules' role as an adhesive template for the attachment and persistence of basal dysplastic cells. Incipient loss of BM integrity in CIS, where alpha 5(IV)/alpha 6(IV) chains were more frequently absent than alpha 1(IV)/alpha 2(IV) chains, suggests that alpha(IV) network disruption is crucial for progression of dysplastic cells into the extracellular compartment, marking transition into the invasive phase. In carcinomatous BM, the disappearance of alpha(IV) chains was more severe in poorly differentiated oral squamous cell carcinoma (OSCC) (n=10) than in well-differentiated OSCC (n=10). In all samples examined, alpha 3(IV) and alpha 4(IV) chains were absent. These findings taken together suggest that BM collagen-IV alpha chains undergo remodeling where selective increase and loss of these molecules are probably early and late events, respectively, during progression of oral dysplasia to cancer. This record was migrated from the OpenDepot repository service in June, 2017 before shutting down

The relationship between health-related quality of life and social networks among Japanese family caregivers for people with disabilities

<p>Abstract</p> <p>Aims</p> <p>The purpose of this study was to examine HRQOL depending on whether the participants have family members with disabilities or not. In addition, we examined the relationship between HRQOL and social networks among family caregivers in Japan.</p> <p>Methods</p> <p>The study has a cross-sectional design. Survey forms were distributed to 9205 people aged 30 and older who visited a dispensing pharmacy within fifteen areas of Japan. We collected data on gender, age, job status, and care giving status for persons with disabilities. Moreover, we assessed support size, social support, and HRQOL. Out of the 2029 questionnaires returned, 1763 (male: 663, female: 1100, mean age = 63.06 ± 13.34) were valid for statistical analyses (the available response rate was 19.15%).</p> <p>Results</p> <p>A significant difference in HRQOL was identified between family caregivers and non-family caregivers. Further, in males (N = 101), the results confirmed that only social support predicted the PCS and MCS scores, while other variables did not predict either score. On the other hand, in females (N = 144), it was found from the second step of hierarchical multiple regression analysis that only age explained the PCS score, while job status and support size explained the MCS score.</p> <p>Conclusion</p> <p>It is reasonable to conclude that the HRQOL of family caregivers was lower than that of non-family caregivers, and that the HRQOL of family caregivers was estimated by their social networks.</p

Glucocerebrosidases catalyze a transgalactosylation reaction that yields a newly-identified brain sterol metabolite, galactosylated cholesterol

?-Glucocerebrosidase (GBA) hydrolyzes glucosylceramide (GlcCer) to generate ceramide. Previously, we demonstrated that lysosomal GBA1 and nonlysosomal GBA2 possess not only GlcCer hydrolase activity, but also transglucosylation activity to transfer the glucose residue from GlcCer to cholesterol to form ?-cholesterylglucoside (?-GlcChol) in vitro. ?-GlcChol is a member of sterylglycosides present in diverse species. How GBA1 and GBA2 mediate ?-GlcChol metabolism in the brain is unknown. Here, we purified and characterized sterylglycosides from rodent and fish brains. Although glucose is thought to be the sole carbohydrate component of sterylglycosides in vertebrates, structural analysis of rat brain sterylglycosides revealed the presence of galactosylated cholesterol (?-GalChol), in addition to ?-GlcChol. Analyses of brain tissues from GBA2-deficient mice and GBA1- and/or GBA2-deficient Japanese rice fish (Oryzias latipes) revealed that GBA1 and GBA2 are responsible for ?-GlcChol degradation and formation, respectively, and that both GBA1 and GBA2 are responsible for ?-GalChol formation. Liquid chromatography?tandem MS revealed that ?-GlcChol and ?-GalChol are present throughout development from embryo to adult in the mouse brain. We found that ?-GalChol expression depends on galactosylceramide (GalCer), and developmental onset of ?-GalChol biosynthesis appeared to be during myelination. We also found that ?-GlcChol and ?-GalChol are secreted from neurons and glial cells in association with exosomes. In vitro enzyme assays confirmed that GBA1 and GBA2 have transgalactosylation activity to transfer the galactose residue from GalCer to cholesterol to form ?-GalChol. This is the first report of the existence of ?-GalChol in vertebrates and how ?-GlcChol and ?-GalChol are formed in the brain.Medical Biochemistr

A pigmented calcifying cystic odontogenic tumor associated with compound odontoma: a case report and review of literature

<p>Abstract</p> <p>Background</p> <p>Pigmented intraosseous odontogenic lesions are rare with only 47 reported cases in the English literature. Among them, pigmented calcifying cystic odontogenic tumor, formerly known as calcifying odontogenic cyst, is the most common lesion with 20 reported cases.</p> <p>Methods</p> <p>A case of pigmented calcifying cystic odontogenic tumor associated with odontoma occurring at the mandibular canine-premolar region of a young Japanese boy is presented with radiographic, and histological findings. Special staining, electron microscopic study and immunohistochemical staining were also done to characterize the pigmentation.</p> <p>Results</p> <p>The pigments in the lesion were confirmed to be melanin by Masson-Fontana staining and by transmission electron microscopy. The presence of dendritic melanocytes within the lesion was also demonstrated by S-100 immunostaining.</p> <p>Conclusion</p> <p>The present case report of pigmented calcifying cystic odontogenic tumor associated with odontoma features a comprehensive study on melanin and melanocytes, including histochemical, immunohistochemical and transmission electron microscopic findings.</p

Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications

© The Author(s) 2018The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that results from coronary or cerebrovascular thrombosis. There is ample evidence from both laboratory and clinical studies to suggest that in addition to inhibiting platelet aggregation, antithrombotic medications have shear-dependent effects, potentiating thrombus fragility and/or enhancing endogenous fibrinolysis. Such shear-dependent effects, potentiating the fragility of the growing thrombus and/or enhancing endogenous thrombolytic activity, likely contribute to the clinical effectiveness of such medications. It is not clear how much these effects relate to the measured inhibition of platelet aggregation in response to specific agonists. These effects are observable only with techniques that subject the growing thrombus to arterial flow and shear conditions. The effects of antithrombotic medications on thrombus stability and ways of assessing this are reviewed herein, and it is proposed that thrombus stability could become a new target for pharmacological intervention.Peer reviewedFinal Published versio

Short-Term Visual Deprivation Does Not Enhance Passive Tactile Spatial Acuity

An important unresolved question in sensory neuroscience is whether, and if so with what time course, tactile perception is enhanced by visual deprivation. In three experiments involving 158 normally sighted human participants, we assessed whether tactile spatial acuity improves with short-term visual deprivation over periods ranging from under 10 to over 110 minutes. We used an automated, precisely controlled two-interval forced-choice grating orientation task to assess each participant's ability to discern the orientation of square-wave gratings pressed against the stationary index finger pad of the dominant hand. A two-down one-up staircase (Experiment 1) or a Bayesian adaptive procedure (Experiments 2 and 3) was used to determine the groove width of the grating whose orientation each participant could reliably discriminate. The experiments consistently showed that tactile grating orientation discrimination does not improve with short-term visual deprivation. In fact, we found that tactile performance degraded slightly but significantly upon a brief period of visual deprivation (Experiment 1) and did not improve over periods of up to 110 minutes of deprivation (Experiments 2 and 3). The results additionally showed that grating orientation discrimination tends to improve upon repeated testing, and confirmed that women significantly outperform men on the grating orientation task. We conclude that, contrary to two recent reports but consistent with an earlier literature, passive tactile spatial acuity is not enhanced by short-term visual deprivation. Our findings have important theoretical and practical implications. On the theoretical side, the findings set limits on the time course over which neural mechanisms such as crossmodal plasticity may operate to drive sensory changes; on the practical side, the findings suggest that researchers who compare tactile acuity of blind and sighted participants should not blindfold the sighted participants

Variations in mineralogy of dust in an ice core obtained from northwestern Greenland over the past 100 years

Our study is the first to demonstrate a high-temporal-resolution record of mineral composition in a Greenland ice core over the past 100 years. To reconstruct past variations in the sources and transportation processes of mineral dust in northwestern Greenland, we analysed the morphology and mineralogical composition of dust in the SIGMA-D ice core from 1915 to 2013 using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). The results revealed that the ice core dust consisted mainly of silicate minerals and that the composition varied substantially on multi-decadal and inter-decadal scales, suggesting that the ice core minerals originated from different geological sources in different periods during the past 100 years. The multi-decadal variation trend differed among mineral types. Kaolinite, which generally formed in warm and humid climatic zones, was abundant in colder periods (1950–2004), whereas mica, chlorite, feldspars, mafic minerals, and quartz, which formed in arid, high-latitude, and local areas, were abundant in warmer periods (1915–1949 and 2005–2013). Comparison to Greenland surface temperature records indicates that multi-decadal variation in the relative abundance of these minerals was likely affected by local temperature changes in Greenland. Trajectory analysis shows that the minerals were transported mainly from the western coast of Greenland in the two warming periods, which was likely due to an increase in dust sourced from local ice-free areas as a result of shorter snow/ice cover duration in the Greenland coastal region during the melt season caused by recent warming. Meanwhile, ancient deposits in northern Canada, which were formed in past warmer climates, seem to be the best candidate during the colder period (1950–2004). Our results suggest that SEM–EDS analysis can detect variations in ice core dust sources during recent periods of low dust concentration.</p

A spindle cell carcinoma presenting with osseous metaplasia in the gingiva: a case report with immunohistochemical analysis

<p>Abstract</p> <p>Background</p> <p>Spindle cell carcinoma (SpCC) is a rare, high malignant variant of squamous cell carcinoma (SCC), which shows biphasic proliferation of conventional SCC component and malignant spindle shape cells with sarcomatous appearance.</p> <p>Methods</p> <p>A case of Spindle cell carcinoma with bone-like calcified materials, occurring at the mandibular molar region of 71-years-old Japanese male patient was presented with gross finding, histological findings and MRI image. To identify the characteristics of the bone-like materials, immunohistochemistry were performed.</p> <p>Results</p> <p>Histologically, the cancer cells were composed of spindle cells and epithelial cells which form nests with prominent keratinization. Histological findings showed typical histology of the SpCC, however, as an uncommon finding, spatters of calcified, bone-like materials were observed in between the cancer cells. Immunohistochemistry revealed that cancer cells were positive for cytokeratins and vimentin to a varying degree and negative for Desmin, S-100, Osteopontin, BMP-2 or BMP-4. These findings implied that the calcified materials were formed by metaplasia of the stromal cells.</p> <p>Discussion</p> <p>Bone-like materials formation by osseous and/or cartilaginous metaplasia of the stroma in the carcinoma has been reported. However, the detailed mechanism of these metaplasia and affection on the clinical feature, prognosis and therapies are not well established. In summary, we presented an unique case of SpCC, which has not been described in the literature.</p