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Primary intestinal T-cell lymphoma (PITL) is highly aggressive and includes celiac disease-related enteropathy-associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), and primary intestinal peripheral T-cell lymphoma, not otherwise specified (ITCL-NOS). MEITL is the most common PITL in Asia, comprising of monomorphic medium-sized cells typically expressing CD8, CD56, and cytotoxic granules. Occasional cases with intermediate features between MEITL and ITCL-NOS are difficult to be classified and warrant further investigation. We collected 54 surgically resected PITLs from Taiwan, with 80% presenting with bowel perforation. The overall outcome was poor with a median survival of 7 months. Based on histopathology (monomorphic vs. pleomorphic) and immunophenotype, we classified these cases into 4 groups: MEITL with typical immunophenotype (n=34), MEITL with atypical immunophenotype (n=5), pleomorphic PITL with MEITL-like immunophenotype (n=6), and ITCL-NOS (n=9). There was no EATL in our cohort. Targeted next-generation sequencing of the first 3 groups showed highly prevalent loss-of-function mutations for SETD2 (85%, 80%, and 83%, respectively) and frequent activating mutations for STAT5B (64%, 60%, and 50%, respectively) and JAK3 (38%, 20%, and 50%, respectively). In contrast, ITCL-NOS cases had less frequent mutations of SETD2 (56%) and STAT5B (11%) and rare JAK3 mutations (11%). Our results suggest that there is a wider morphologic and immunophenotypic spectrum of MEITL as currently defined in the 2017 WHO classification. MEITL with atypical immunophenotype and PITL with MEITL-like immunophenotype shared clinicopathologic and molecular features similar to MEITL but distinct from ITCL-NOS, indicating that such cases may be considered as immunophenotypic or histopathologic variants of MEITL.

Pleomorphic mantle cell lymphoma (PMCL) can closely mimic diffuse large B-cell lymphoma (DLBCL) morphologically, and expression of CD5 and cyclin D1 is helpful for differential diagnosis. To date, no cases of CD5/cyclin D1 double-negative PMCL have been reported. Four cases of B-cell lymphoma with an immunophenotype of CD5(-) cyclin D1(-) SOX11(+) and morphologic features compatible with DLBCL were included. Two were previously identified, and the other 2 were screened from 500 cases of B-cell lymphoma. We analyzed their clinicopathologic, immunophenotypic, genetic, and gene expression features. Cases of cyclin D1-positive PMCL, cyclin D1-negative PMCL, germinal center B-cell (GCB) DLBCL, and activated B cell (ABC) DLBCL were also studied for comparison. Similar to other PMCL cases, these 4 patients were mainly elderly male individuals with an aggressive clinical course. None of these tumors had detectable translocations involving CCND1, CCND2, CCND3, CCNE1, CCNE2, MYC, BCL2, or BCL6. The genome-wide copy number profile of these 4 cases was similar to that of cyclin D1-negative PMCL. None of these tumors had high expression of cyclin D1, cyclin D2, or cyclin D3. Similar to cyclin D1-negative PMCL, these cases had higher expression of cyclin E1 and cyclin E2 compared with cyclin D1-positive PMCL. The gene expression pattern of these tumors was also similar to that of cyclin D1-negative PMCL. Here we report for the first time 4 cases of CD5/cyclin D1 double-negative PMCL. SOX11 positivity is useful to identify these rare tumors, and further genetic and gene expression analysis can be used to confirm the diagnosis.

Dengue is one of the most prevalent arthropod-borne viral diseases in humans. There is still no effective vaccine or treatment to date. Previous studies showed that mosquito-derived factors present in saliva or salivary gland extract (SGE) contribute to the pathogenesis of dengue. In this study, we aimed to investigate the interplay between mosquito vector and DENV and to address the question of whether the mosquito vector alters the virus that leads to consequential disease manifestations in the mammalian host. DENV2 cultured in C6/36 cell line (culture-DENV2) was injected to Aedes aegypti intrathoracically. Saliva was collected from infected mosquitoes 7 days later. Exploiting the sensitivity of Stat1-/- mice to low dose of DENV2 delivered intradermally, we showed that DENV2 collected in infected mosquito saliva (msq-DENV2) induced more severe hemorrhage in mice than their culture counterpart. Msq-DENV2 was characterized by smaller particle size, larger plaque size and more rapid growth in mosquito as well as mammalian cell lines compared to culture-DENV2. In addition, msq-DENV2 was more efficient than culture-DENV2 in inducing Tnf mRNA production by mouse macrophage. Together, our results point to the possibility that the mosquito vector provides an environment that alters DENV2 by changing its growth characteristics as well as its potential to cause disease., Author summary The transmission cycle of dengue virus involves a complex interaction of the virus with the mosquito vector and the human host. DENV enters the mosquito through an infectious blood meal. The virus first infects and replicates in the mosquito midgut before it is translocated to the hemolymph and ultimately reaches the salivary gland. The virus is then released to the saliva and transmitted to the human host through a mosquito blood meal. Previous studies showed that mosquito saliva, salivary gland proteins or mosquito bite modulates arbovirus infection in the mammalian host. Here, we investigate the interplay between the mosquito vector and DENV and address whether the virus is altered in the mosquito vector that consequentially influences disease manifestations in the mammalian host. By excluding the effect of saliva, we demonstrated that after infecting Aedes aegypti, DENV2 acquired the potential to induce more severe hemorrhage in Stat1-/- mice. Msq-DENV2 exhibited smaller particle size, larger plaque size and more rapid growth rate, and was also more efficient in inducing macrophage Tnf production compared to culture-DENV2. Taken together, our data support the notion that mosquito A. aegypti alters DENV2 by changing its growth characteristics as well as its potential to cause disease.

Radiotherapy plays a major role in the curative treatment of head and neck cancer, either as a single modality therapy, or in combination with surgery or chemotherapy, or both. Despite advances to limit radiation-induced side-effects, the major salivary glands are often affected. This frequently leads to hyposalivation which causes an increased risk for xerostomia, dental caries, mucositis, and malnutrition culminating in a significant impact on patients’ quality of life. Previous research demonstrated that loss of salivary function is associated with a decrease in polarity regulators and an increase in nuclear Yap localization in a putative stem and progenitor cell (SPC) population. Yap activation has been shown to be essential for regeneration in intestinal injury models; however, the highest levels of nuclear Yap are observed in irradiated salivary SPCs that do not regenerate the gland. Thus, elucidating the inputs that regulate nuclear Yap localization and determining the role that Yap plays within the entire tissue following radiation damage and during regeneration is critical. In this study, we demonstrate that radiation treatment increases nuclear Yap localization in acinar cells and Yap-regulated genes in parotid salivary tissues. Conversely, administration of insulin-like growth factor 1 (IGF1), known to restore salivary function in mouse models, reduces nuclear Yap localization and Yap transcriptional targets to levels similar to untreated tissues. Activation of Rho-associated protein kinase (ROCK) using calpeptin results in increased Yap-regulated genes in primary acinar cells while inhibition of ROCK activity (Y-27632) leads to decreased Yap transcriptional targets. These results suggest that Yap activity is dependent on ROCK activity and provides new mechanistic insights into the regulation of radiation-induced hyposalivation.

Background/Purpose: Bioaggregates such as Portland cement (PC) can be an economical alternative for mineral trioxide aggregate (MTA) with additional benefit of less discoloration. MTA has been known to induce differentiations of several dental cells. MicroRNAs are important regulators of biological processes, including differentiation, physiologic homeostasis, and disease progression. This study is to explore how PC enhances the differentiation of periodontal ligament (PDL) cells in microRNAs level. Methods: PDL cells were cultured in a regular PC- or MTA-conditioned medium or an osteoinduction medium (OIM). Alizarin red staining was used to evaluate the extent of mineralization. Transfection of microRNA mimics induced exogenous miR-31 and miR-146a expression. The expression of microRNAs and differentiation markers was assayed using reverse-transcriptase polymerase chain reaction. Results: PC enhanced the mineralization of PDL cells in a dose-dependent manner in the OIM. Exogenous miR-31 and miR-146a expression upregulated alkaline phosphatase (ALP), bone morphogenic protein (BMP), and dentin matrix protein 1 (DMP1) expression. However, miR-31 and miR-146a modulates cementum protein 1 (CEMP1) expression in different ways. PC also enhanced ALP and BMP but attenuated CEMP1 in the OIM. Although the OIM or PC treatment upregulated miR-21, miR-29b, and miR-146a, only miR-146a was able to be induced by PC in combination with OIM. Conclusion: This study demonstrated that PC enhances the differentiation of PDL cells, especially osteogenic through miR-146a upregulation. In order to control the ankylosis after regenerative endodontics with the usage of bioaggregates, further investigations to explore these differentiation mechanisms in the miRNA level may be needed. Keywords: Portland cement, Bioaggregate, miR-146a, Osteogenic differentiation, Periodontal ligament (PDL)

Background The incidence of hair loss among Chinese male has increased to 21.3 per hundred. Hair restoration has been an effective technique. Detailed hair distribution has a tremendous impact on the surgery design. Objective To investigate the pattern of hair distribution in Chinese young adult males. Methods A total of 1000 males without hair disease were enrolled. We evaluated the locations of the main anatomical marks at different sites on the scalp and analyzed the hair density and follicular unit structure using the standard photographs and trichoscope. Results The hairline shapes were classified as: linear (48.7%), linear with central protrusion (27.9%), round (9.8%), round with central protrusion (13.7%). The average height of the median line was 6.78 ± 0.75 cm, the ratio of the median line and the forehead height was 0.333. The average distance from the parietal whorl to the vertical bimeatal line was 7.05 ± 3.32 cm, and most of the PWs were on the right (51.4%) and had a clockwise pattern (73.3%). The hair density was 171.12 ± 18.32 hairs/cm in the vertex. 1-hair follicular units were (75.90% and 56.39%) in anterior hairline and temporal area. Conclusion Our study clearly assisted understanding of scalp anatomy and hair distribution in Chinese young adult males.

Gelsolin (GSN) protein, expressed in circulating monocytes, was previously reported to be associated with osteoporosis in both Chinese and Caucasian women. This study aims to test if plasma GSN protein level is associated with hip bone mineral density (BMD) in Chinese population. Based on two study Groups containing 6,308 old Chinese, we adopted extreme sampling scheme and selected 3 independent samples (Subgroups 1-3) for discovery, replication, and validation purposes. We tested plasma GSN concentration, and analyzed whether plasma GSN level differs between subjects with extremely low vs. high hip BMD. In Group 1 (N = 1,860), the plasma GSN level increased in the female with low BMD, which was discovered in the Subgroup 1 (N = 42, p = 0.093) and replicated in the Subgroup 2 (N = 39, p = 0.095). With more extreme sampling for the Subgroup 3 from the Group 2 (N = 4,448), the difference of plasma GSN level in the female with low BMD vs. high BMD is more significant (N = 45, p = 0.037). After the subjects were pooled from Subgroups 2 and 3, the difference in plasma GSN between low and high BMD subjects became even more significant (p = 0.016). The plasma GSN level was negatively correlated with total hip BMD (r = -0.26, p = 0.033). We concluded that plasma GSN was associated with hip BMD in Chinese postmenopausal women and plasma GSN might be a potential risk biomarker for osteoporosis.

Low bone mineral density (BMD) is a risk factor of osteoporotic fracture (OF). Peripheral blood monocytes (PBM) can differentiate into osteoclasts to resorb bone. It was known that PBM-expressed Anxa2 protein is associated with BMD, and extracellular Anxa2 protein promotes osteoclastogenesis. This study aimed to test 1) whether Anxa2 protein level in PBM differs significantly between subjects with OF and without fracture history (NF); 2) whether Anxa2 level in plasma is associated with BMD; 3) how Anxa2 protein at various concentrations would affect osteoblastic activity in vitro. All the study subjects were Chinese Han elderly. Firstly, Anxa2 protein in PBM was identified and quantitated by LC-MS/MS and compared between 45 OF cases and 42 healthy controls. Secondly, plasma Anxa2 protein level was quantitated by ELISA and compared between unrelated subjects with extremely low vs. high hip BMD (0.63±0.10 vs. 1.05±0.10 g/cm2, n = 75). Furthermore, in vitro functional assay was utilized to test the effects of extracellular Anxa2 protein on osteoblastic growth. We found that Anxa2 protein expression in PBM was significantly up-regulated in OF vs. NF subjects (fold change [FC)] = 1.16, P

Growth hormone (GH) is an important hormone released by the pituitary gland that plays a key role in the growth and development of organisms. In our study, TargetScan analysis and the dual luciferase reporter assays were used to predict and screen for miRNAs that might act on the rat Gh1 gene, and we identified miR-543-5p. Then, the GH3 cell line and the primary rat pituitary cells were transfected with miRNA mimic, inhibitor, and siRNA. We detected the Gh1 gene expression and the GH secretion by real-time PCR and ELISAs, respectively, to verify the regulatory effect of miR-543-5p on GH secretion. The results showed that miR-543-5p can inhibit Gh1 mRNA expression and reduce GH secretion. MiR-543-5p inhibitor upregulated Gh1 mRNA expression and increased GH secretion compared with the negative control. In summary, miR-543-5p downregulates Gh1 expression, resulting in a decrease in GH synthesis and secretion, which demonstrates the important role of miRNAs in regulating GH and animal growth and development.

Radiotherapy is a common treatment option for head and neck cancer patients; however, the surrounding healthy salivary glands are often incidentally irradiated during the process. As a result, patients often experience persistent xerostomia and hyposalivation, which deceases their quality of life. Clinically, there is currently no standard of care available to restore salivary function. Repair of epithelial wounds involves cellular proliferation and establishment of polarity in order to regenerate the tissue. This process is partially mediated by protein kinase C zeta (PKCζ), an apical polarity regulator; however, its role following radiation damage is not completely understood. Using an in vivo radiation model, we show a significant decrease in active PKCζ in irradiated murine parotid glands, which correlates with increased proliferation that is sustained through 30 days post-irradiation. Additionally, salivary glands in PKCζ null mice show increased basal proliferation which radiation treatment did not further potentiate. Radiation damage also activates Jun N-terminal kinase (JNK), a proliferation-inducing mitogen-activated protein kinase normally inhibited by PKCζ. In both a PKCζ null mouse model and in primary salivary gland cell cultures treated with a PKCζ inhibitor, there was increased JNK activity and production of downstream proliferative transcripts. Collectively, these findings provide a potential molecular link by which PKCζ suppression following radiation damage promotes JNK activation and radiation-induced compensatory proliferation in the salivary gland.

To develop an effective ocular drug delivery carrier, we prepared two different charged gelatin nanoparticles (GPs) and evaluated particle size, surface charge, and morphology. Thein vitrobiocompatibility of GPs was assessed using human corneal epithelium (HCE) cells andin vivosafety by administering them as eye drops to New Zealand rabbits. The GPs prepared using type A gelatin were positively charged (GP(+), +33 mV; size,180.6±45.7 nm). Water-soluble tetrazolium salt (WST)-1 assay showed that both GPs were nontoxic to HCE cells. The fluorescence intensity of HCE cells cultured with cationic GPs conjugated with a fluorescent dye was higher than that of the anionic GP-treated HCE cells.In vivoexamination showed no serious irritation to the rabbit eyes. Furthermore, corneal thickness and ocular pressure in the eyes of the treated rabbits were similar to those in the eyes of normal rabbits. Microscopic examination of corneal cryosections showed widely distributed fluorescent nanocarriers, from the anterior to the posterior part of the cornea of the GP(+) group, and higher fluorescence intensity in the GP(+) group was also observed. In conclusion, GPs as cationic colloidal carriers were efficiently adsorbed on the negatively charged cornea without irritating the eyes of the rabbits and can be retained in the cornea for a longer time. Thus, GPs(+) have a great potential as vehicles for ocular drug delivery.

Despite increasing application of the pre-grafting expansion during autologous fat transplantation in breast reconstruction, little is known about its mechanism of action. To address that, ventral skins of miniature pigs were treated over a 10-day or 21-day period, with continuous suction at −50 mm Hg via a 7-cm diameter rubber-lined suction-cup device. Soft tissue thickness increased immediately after this external volume expansion (EVE) treatment, such increase completely disappeared by the next day. In the dermis and subcutaneous fat, the EVE treated groups showed significant increases in blood vessel density evident by CD31 staining as well as in vascular networks layered with smooth muscle cells when compared with the control group. This finding was corroborated by the increased percentage of endothelial cells present in the treatment groups. There was no significant difference in the percentages of proliferating basal keratinocytes or adipocytes, nor in epidermal thickness. Moreover, the EVE had no effect on proliferation or differentiation potential of adipose stem cells. Taken together, the major effects of EVE appeared to be vascular remodeling and maturation of functional blood vessels. This understanding may help clinicians optimize the vascularity of the recipient bed to further improve fat graft survival.

Background Effects of vitamin D deficiency in pregnancy have been associated with some adverse pregnancy outcomes. The 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1) is integral to the vitamin D metabolic pathway. The enzyme catalyzes localized conversion of pro-hormone 25-hydroxyvitamin D3 to active 1,25-dihydroxyvitamin D3. Our aim was to investigate the expression of CYP27B1 at the fetal-maternal interface in the first trimester pregnancy and to determine whether CYP27B1 was associated with recurrent miscarriage (RM). Methods Expressions of CYP27B1 mRNA and protein in villi and decidua from 20 women undergoing primary miscarriage, 20 women with RM and 20 women with normal pregnancy were evaluated by western blot, and quantitative real-time PCR. The co-localization of CYP27B1 and certain cytokines including IL-10, IFN-γ, TNF-α, and IL-2 expression were examined using immunohistochemistry and confocal microscopy. Results Women with RM had a significantly lower expression of CYP27B1 mRNA and protein in villous and decidual tissues compared with the normal pregnant women (P = 0.000 in villus, P = 0.002 in decidua for mRNA; P = 0.036 in villus, P = 0.007 in decidua for protein.). Compared with the normal pregnancy, immunostaining for CYP27B1 was significantly decreased in villous trophoblasts and decidual glandular epithelial cells in RM women. No significant differences in the localization of CYP27B1, IL-10, IFN-γ, TNF-α, and IL-2 expression were identified between the normal pregnant and RM women. Conclusions Women with RM have a lower level of CYP27B1 expression in chorionic villi and decidua compared with normal pregnant women, suggesting that reduced CYP27B1 expression may be associated with RM. The consistent localization of CYP27B1 and IL-10, IFN-γ, TNF-α, and IL-2 expression in villous and decidual tissues suggests the importance of the local production of 1,25(OH)2D3 at the fetal-maternal interface to regulate cytokine responses.

Amplification of 11q13.3 is a frequent event in human cancers, including head and neck squamous cell carcinoma. This chromosome region contains several genes that are potentially cancer drivers, including FADD (Fas associated via death domain), an apoptotic effector that was previously identified as a novel oncogene in laryngeal/pharyngeal cancer. This study was designed to explore the role of FADD in oral squamous cell carcinomas (OSCCs) samples from Taiwanese patients, by assessing copy number variations (CNVs) and protein expression and the clinical implications of these factors in 339 male OSCCs. The intensity of FADD protein expression, as determined by immunohistochemistry, was strongly correlated with gene copy number amplification, as analyzed using a TaqMan CNV assay. Both FADD gene copy number amplification and high protein expression were significantly associated with lymph node metastasis (P < 0.001). Patients with both FADD copy number amplification and high protein expression had the shortest disease-free survival (DFS; P = 0.074 and P = 0.002) and overall survival (OS; P = 0.011 and P = 0.027). After adjusting for primary tumor status, tumor differentiation, lymph node metastasis and age at diagnosis, DFS was still significantly lower in patients with either copy number amplification or high protein expression (hazard ratio [H.R.] = 1.483; 95% confidence interval [C.I.], 1.044–2.106). In conclusion, our data reveal that FADD gene copy number and protein expression can be considered potential prognostic markers and are closely associated with lymph node metastasis in patients with OSCC in Taiwan.

Summary 1. The aim of the present study was to investigate the effects of simulated microgravity on the arterial dilatory responsiveness and l-arginine (l-Arg)–nitric oxide (NO)–cGMP pathway in the abdominal aorta of rats. 2. Twenty healthy male Sprague-Dawley were randomly divided into control and simulated microgravity groups. Rats in the simulated microgravity group were subjected to hindlimb unweighting (HU). After 4 weeks, arterial dilatory responsiveness was examined in vitro in isolated abdominal aortic rings. Western blotting was used to measure endothelial (e) and inducible (i) NO synthase (NOS) protein content. Total concentrations of nitrate and nitrite (NOx), the stable metabolites of NO, were determined by the chemiluminescence method. Nitric oxide synthase activity in the abdominal aorta was determined through the conversion of [3H]-l-Arg to [3H]-l-citrulline. 3. The data showed that the dilatory responses of the arterial rings to l-Arg and acetylcholine decreased in rats exposed to simulated microgravity, but the dilatory responses to sodium nitroprusside and 8-bromo-cGMP were similar in both simulated microgravity and control rats. The expression of eNOS and iNOS did not differ significantly between the two groups. The NOx concentration in the abdominal aorta of HU rats was significantly less than that in control rats. Nitric oxide synthase activity in the aorta decreased after 4 weeks of HU. 4. The data indicate that endothelium-dependent vasorelaxation in the abdominal aorta decreased due to 4 weeks of simulated microgravity in rats and that this impaired dilatory responsiveness may result from decreased NOS activity.

Most primary intestinal natural killer (NK)-cell and T-cell lymphomas (PINKTL) in the Northern Europe are enteropathy-associated T-cell lymphomas, a complication of celiac disease, which is rare in the East. Primary intestinal NK-cell lymphoma is extremely rare and is poorly characterized. We investigated 30 cases of PINKTL from Taiwan with male: female at 2:1, median age at 55.5, 80% with jejunal/ileal involvement, 77% with perforation, 27% with multicentric tumors, and 67% at stage IE. All 7 cases tested for serum IgA anti-tissue transglutaminase were negative. Only 3 (10%) tumors showed enteropathy. Six (20%) were NK-cell lymphoma and 24 (80%) were T-cell lymphoma. The tumor cells in 21/30 (70%) cases were small to medium sized, which correlated with the coexpression of both CD8 and CD56. All tumors expressed at least 1 cytotoxic marker. All 6 NK-cell lymphomas were negative for betaF1, diffusely positive for Epstein-Barr virus-encoded mRNA (EBER), and polyclonal for T-cell receptor gene rearrangement. Five (22%) of the 24 T-cell tumors expressed betaF1, 8 (35%) of the 23 tumors were positive for EBER, and 20 (95%) of the 21 tumors were clonal for T-cell receptor. The overall 1-year survival was 36%. Univariate regression analysis showed that NK-cell lineage, multicentricity, and perforation were associated with poor prognosis. NK-cell lineage (P=0.037) was a poor prognostic factor by multivariate Cox proportional hazard regression analysis. PINKTL in Taiwan is predominantly not enteropathic with a high frequency of perforation, small to medium tumor cell size and cytotoxic phenotype. Primary intestinal NK-cell lymphoma carries a very poor prognosis, and is probably a distinct entity.

Cell transplantation via direct intramyocardial injection is a promising therapy for patients with myocardial infarction; however, retention of the transplanted cells at the injection sites remains a central issue following injection of dissociated cells. Using a thermoresponsive hydrogel system with a multiwell structure, we successfully developed an efficient technique to generate spherically symmetric bodies of mesenchymal stromal cells (MSCs) inherent with endogenous extracellular matrices (ECMs) for direct intramyocardial injection. After injection through a needle and upon transferring to another growth surface, the time required to attach, migrate, and proliferate was significantly shorter for the MSC bodies than the dissociated MSCs. Employing a syngeneic rat model with experimental myocardial infarction, an intramyocardial injection was conducted with a needle directly into the peri-infarct areas. There were four treatment groups (n = 10): sham, phosphate-buffered saline, dissociated MSCs, and MSC bodies. The results obtained in the echocardiography and catheterization measurements demonstrated that the MSC body group had a superior heart function to the dissociated MSC group. Histologically, it was found that MSC bodies could provide an adequate physical size to entrap into the interstices of muscular tissues and offer a favorable ECM environment to retain the transplanted cells intramuscularly. Additionally, transplantation of MSC bodies stimulated a significant increase in vascular density, thus improving the cardiac function. These results indicated that the spherically symmetric bodies of MSCs developed in the study may serve as a cell-delivery vehicle and improve the efficacy of therapeutic cell transplantation.

Aims To provide the basis for uniform cardiac tissue regeneration, a spatially uniform distribution of adhered cells within a scaffold is a prerequisite. To achieve this goal, a bioengineered tissue graft consisting of a porous tissue scaffold sandwiched with multilayered sheets of mesenchymal stromal cells was developed. Methods and results This tissue graft (sandwiched patch) was used to replace the infarcted wall in a syngeneic Lewis rat model with an experimentally chronic myocardial infarction (MI). There were four treatment groups ( n ≥ 10): sham, MI, empty patch, and sandwiched patch. After a 7 day culture of the sandwiched patch, a tissue graft with relatively uniform cell concentrations was obtained. The cells were viable and tightly adhered to the tissue scaffold, as the endogenous extracellular matrix inherent with multilayered cell sheets can act as an adhesive agent for cell attachment and retention. At retrieval, the area of the empty patch was relatively enlarged, suggesting reduced structural support, while that of the sandwiched patch remained about the same ( P = 0.56). In the immunofluorescent staining, host cells together with neo-microvessels were clearly observed in the empty patch; however, there were still a large number of unfilled pores within the patch. In the sandwiched patch, besides host cells, originally seeded cells were populated within the entire patch. No apparent evidence of apoptotic cell death was found in both studied patches. Thus, the sandwiched-patch-treated hearts demonstrated a better heart function to the empty-patch-treated hearts ( P < 0.05). Conclusion The results demonstrated that this novel bioengineered tissue graft can serve as a useful cardiac patch to restore the dilated left ventricle and stabilize heart functions after MI.

The purposes of this study were to investigate the facial changes by two-jaw surgery for mandibular prognathism accompanying maxillary hypoplasia and skeletal open bite, and to design a regression model that predicts the soft tissue profile changes after two-jaw surgery. Fourteen cases diagnosed as mandibular prognathism accompanying maxillary hypoplasia and skeletal open bite at the Nihon University Hospital, School of Dentistry at Matsudo were studied. The surgical methods used were Le Fort type I osteotomy for the maxilla and sagittal split ramus osteotomy for the mandible. Angle measurements showed significant differences in SNA, ANB, FA, FD and MPA (p

Heterotopic salivary gland tissue (HSGT) in the lower neck is an unusual developmental anomaly with characteristic clinical and microscopic findings. The exact embryogenesis remains unclear. This rare entity must be considered in the differential diagnosis of neck mass with fistula. We present a typical HSGT totally removed using the stepladder excision technique and showing an internal fistula. Interpretation of this case from the anatomical and pathological points of view, we support the argument that the embryogenesis of HSGT is more probably related to ectodermal heteroplasia of the precervical sinus of His and further conclude that an association with branchial cleft sinus may exist and cannot be seen as an exclusion criteria for diagnosis of HSGT. Due to possible but infrequent neoplastic transformation, it is important to check HSGT in every encountered cervical anomaly related to any branchial apparatus derived lesion.

Objective: User data and information about anatomy education were used to guide development of a learning environment that is efficient and effective. The research question focused on how to design instructional software suitable for the educational goals of different groups of users of the Visible Human data set. The ultimate goal of the study was to provide options for students and teachers to use different anatomy learning modules corresponding to key topics, for course work and professional training. Design: The research used both qualitative and quantitative methods. It was driven by the belief that good instructional design must address learning context information and pedagogic content information. The data collection emphasized measurement of users' perspectives, experience, and demands in anatomy learning. Measurement: Users' requirements elicited from 12 focus groups were combined and rated by 11 researchers. Collective data were sorted and analyzed by use of multidimensional scaling and cluster analysis. Results: A set of functions and features in high demand across all groups of users was suggested by the results. However, several subgroups of users shared distinct demands. The design of the learning modules will encompass both unified core components and user-specific applications. The design templates will allow sufficient flexibility for dynamic insertion of different learning applications for different users. Conclusion: This study describes how users' requirements, associated with users' learning experiences, were systematically collected and analyzed and then transformed into guidelines informing the iterative design of multiple learning modules. Information about learning challenges and processes was gathered to define essential anatomy teaching strategies. A prototype instrument to design and polish the Visible Human user interface system is currently being developed using ideas and feedback from users.

Post-spaceflight orthostatic intolerance is one of the most important adverse effects after exposure to space microgravity, and there are still no effective countermeasures. It has been considered that arterial remodeling may play an important role in the occurrence of post-spaceflight orthostatic intolerance, but the cellular mechanisms remain unknown. In this study, we investigated whether an inflammatory response exists in the common carotid artery of rats exposed to simulated microgravity. For this, Sprague–Dawley rats were subjected to 4 weeks of hindlimb unweighting to simulate microgravity. The expression levels of the adhesion molecules E-selectin and vascular cell adhesion molecule-1 (VCAM-1), and the cytokine monocyte chemoattractant protein-1 (MCP-1) in the common carotid artery of simulated microgravity rats were evaluated by immunohistochemical staining, quantitative RT–PCR, and Western blot analyses. The recruitment of monocytes in the common carotid artery of rats exposed to simulated microgravity was investigated by en face immunofluorescence staining and monocyte binding assays. Our results provided convincing evidence that there is an inflammatory response in the common carotid artery of rats exposed to simulated microgravity. Our work suggests that the inflammatory response may be a novel cellular mechanism that is responsible for the arterial remodeling that occurs during exposure to microgravity.

Localized peripheral primitive neuroectodermal tumor of the conjunctiva: a rare presentation

Previous studies have demonstrated inconsistent roles of Rho kinase (ROCK) in the decreased vasoconstriction of rat hindquarter vessels induced by hindlimb unweighting (HU). The present study was designed to determine the unclear role of ROCK in the mediation of HU-induced decreased femoral arterial vasoconstriction. 28-day HU rat was adopted as the animal model. With or without Y-27632, a ROCK inhibitor, isometric force of femoral artery was measured. The expression of ROCK and its effects on downstream targets were also examined. Results showed that (1) HU caused a significant decrease of the phenylephrine (PE)-evoked and potassium chloride (KCl)-evoked femoral arterial vasoconstriction (P

This study aims to use 936 females’ 3D foot anthropometric data to cluster foot shapes and to develop a new sizing system. Twelve-foot dimensions including foot length, ball of foot length, outside ball of foot length, foot breadth, heel breadth, ball circumference, instep circumference, toe height, arch height, instep height, toe 1 angle and toe 5 angle were collected. The PCA results indicated that foot breadth, foot length and arch height were selected as the three principal components. The percentage of total variance explained by the 3 principal components was 76.65 %. Using K-means clustering can classify female subjects’ foot into 3 foot types. The new sizing system had less number of sizes, high coverage rate and provided updated foot dimensions as comparing with the current sizing system (CNS 4800-S1093). The manufacturer can apply these results for shoe last design and footwear production with better fitness and less production cost.

3D foot anthropometric data was collected and classified into several foot shapes. A 3D foot anthropometric database which contains 1835 male right foot scanning images was used. The subjects aged from 18 to 60 years old. A 3D foot scanner was used to collect 12 foot dimensions including foot length, ball of foot length, outside ball of foot length, foot breadth, heel breadth, ball circumference, instep circumference, toe height, navicular height, instep height, toe 1 angle and toe 5 angle. The principle component analysis (PCA) and K-means cluster analysis was applied to classify male subjects' foot shapes. The PCA results indicated that foot breadth, foot length and navicular height were selected as three principle components. The percentage of total variance explained by the 3 principle components was 72.96%. The use of K-means clustering can classify male subjects' foot into 6 foot types. In addition, a new foot sizing system was developed for Taiwanese males. Comparing the new sizing system with the current CNS 4800-S1093 sizing system, the new sizing system can reduce the size numbers, and provide updated foot dimensions. Thus, the manufacturer can apply these results for shoe last design and footwear production with better fitness and lower cost.

Observations and analytical experiments were conducted on the key factors that stimulated males of Paraglenea fortunei Saunders to approach females and attempt copulation. It is suggested that vision, stridulation, and palpi do not play a primary role in stimulating male sexual activity. The key stimulus that triggers male response is a female sex pheromone. This is air-borne and effective only within a range of about 3 cm. The main olfactory receptors for the female sex pheromone are situated in the male's antennae; a few receptors were found in other undetermined parts of the body.

TWIST is an important transcription factor during embryonic development and has recently been found to promote the epithelial-mesenchymal transition (EMT) phenomenon seen during the initial steps of tumor metastasis. To further investigate the potential targets and interacting genes of TWIST in human gastric cancer, we performed microarray analysis to compare the gene expression profiles in HGC-27 cells, with or without small interfering RNA (siRNA)-mediated depletion of TWIST. Our results showed that NF1, RAP1A, SRPX, RBL2, PFDN4, ILK, F2R, ERBB3, and MYB were up-regulated, whereas AKR1C2, FOS, GDF15, NR2F1, ATM, and CTPS were down-regulated after TWIST depletion. Moreover, TWIST-depleted HGC-27 cells showed a reversal of the morphologic and molecular changes associated with EMT. These results provide evidence that TWIST regulates the expression of several genes involved in the differentiation, adhesion, and proliferation of gastric cancer cells. The role of TWIST in the development of certain types of gastric cancer is discussed.

Autologous vein grafts is still commonly used for arterial reconstructive procedures. Their success is limited by the development of neointimal hyperplasia. Clinical and experimental evidence suggest that the bone marrow derived mesenchymal stem cells (MSCs) participate in the neovascularization. The current study used a direct approach to test the hypothesis that, after vein grafting in a rat model, MSCs have potential effects on reendothelialization and neointimal formation. MSCs were isolated by bone marrow cell adherence. Autologously interpositioning left external jugular vein (LEJV) to left common carotid artery-induced vein grafting model of r at w as utilized. Vascular lesion formation after transplantation of MSCs labeled with 4',6-diamidino-2-phenylindole (DAPI) was investigated. Two weeks after implantation, immunofluorescence studies revealed that engrafted cells acquired an endothelial phenotype, and some expressed endothelial nitric oxide synthase (eNOS). Furthermore, proliferation of cells and neointimal formation decreased significantly after MSC implantation. Real-time reverse transcription-PCR and western blotting analysis showed a rise of eNOS expression in the MSC group compared with the vein grafting group. Therefore, engrafted MSCs appeared to differentiate into endothelial cells, diminish the neointima formation and contribute to the improvement on endothelial function, which indicates that MSCs may exert an important function as repair mechanism in vascular injury after vein grafting.

Ganglion cysts of the spine are uncommon. They occur mostly in the dorsolateral trunk and arise with the greatest frequency in the lumbar spine. However, they are rarely symptomatic. We report a rare case of a patient with a ganglion cyst of the lower cervical spine presenting with acute Brown-Sequard syndrome. The patient had no history of trauma. Magnetic resonance imaging of the cervical spine showed a cystic lesion connecting to the synovial joint C6-7 and compressing the posterior aspect of the spinal cord. The patient underwent emergent C6-7 laminectomy with total removal of the cyst. Neurological function recovered completely 4 months after operation. Ganglion cysts should be considered in the differential diagnosis of an extradural mass of the cervical spine. Magnetic resonance imaging provides a rapid and correct diagnosis, and laminectomy with removal of the cyst results in good neurological recovery.

An 83-year-old man presented with a 1-month history of multiple flesh-colored waxy papules over his bilateral waist, and bilateral inguinal and suprapubic areas. He had also noted multiple blister-like nodules over his buccal mucosa and various-sized purpuric tumors on his tongue for over a year. Both types of lesions were asymptomatic. His medical history included hypertension, chronic renal insufficiency, and previous cerebrovascular accident, and he was regu-larly followed up at our hospital. There was no relevant family history and no constitutional symptoms, except for a 1-month history of right hip and right shoulder pain.Two skin biopsy specimens were obtained from the ab-domen and lip. Histopathologic examination of the ab-dominal papule revealed a large amount of pink amorphous deposits in the superficial dermis. Histopathologic exami-nation of the lip showed similar deposits in the submucosa and small vessel walls. Congo red staining of both speci-mens revealed green birefringence under polarized light.Protein electrophoresis revealed a pattern indicative of monoclonal gammopathy, with a spike in the beta region. Immunofixation electrophoresis of blood and urine disclosed IgA-lambda paraprotein and lambda light chain parapro-tein, respectively. Biopsy results from the bone marrow re-vealed sheets of plasma cells, including some immature forms, and occasional Dutcher bodies. The plasma cells accounted for up to 70% of all nucleated cells focally. No evidence of bone or renal involvement was found in skull X-ray or renal echo examinations. However, magnetic reso-nance imaging of the heart revealed abnormal thickening and akinesia of the septal wall of the left ventricle.

Sir,Local recurrence of giant cell tumour of bone is observed frequently in the sacrum, despite tumour excision.1 We report another case, presenting as an intra-abdominal mass 7 years after the ini...

Only three cases of clitoral schwannoma have been reported in the English language literature, with none of them being a plexiform schwannoma. Here we report the first plexiform schwannoma of the clitoris. A 41-year-old woman without neurofibromatosis presented with a 2 x 2 cm, slowly growing, painless tumor of the clitoris. Simple excision of the tumor was performed, and pathological examination revealed a plexiform schwannoma. No evidence of recurrence was noted after 2 years of follow-up. Despite its rarity, a schwannoma should be included in the differential diagnosis of a clitoral enlargement or mass. Our case, despite its unique plexiform growth pattern, has clinical features similar to those of other reported cases of clitoral schwannoma.

A case of vaginal and cervical endodermal sinus (yolk sac) tumor in a 6-month-old female infant is reported. The patient presented with an intermittent bloody discharge on her diapers. Pelvic CT showed an irregular soft tissue density mass with heterogeneous enhancement within the vagina and extending to the cervix. The histopathologic features were identical to those of endodermal sinus tumors.

1. The distributions of gastrin- and cholecystokinin-like immunoreactivities in the dog and cat vagus nerves have been studied after nerve section and ligation. 2. In dogs, there was an increase in cholecystokinin-octapeptide-like immunoreactive material on the cranial side of ligatures on the thoracic or cervical vagi. When pairs of ligatures were tied on the cervical vagi there was accumulation proximal, and a slight decrease distal to, the upper ligature. There was also a modest increase distal to the lower ligature. 3. In cats, section of the vagus above the nodose ganglion, and hence degeneration of the efferent fibres, did not prevent increases in cholecystokinin-octapeptide-like immunoreactivity on the cranial side of ligatures which were later tied below the ganglion. Removal of the superior cervical ganglion had no effect on the accumulation of immunoreactive material above the ligatures. Section of the vagus below the nodose ganglion, and hence degeneration of both afferent and efferent fibres, abolished the accumulation on the cranial side of ligatures which were later tied below the section. Cholecystokinin-octapeptide-like material is therefore localized to afferent fibres with cell bodies in the nodose ganglion. 4. Immunoreactive forms were characterized by gel filtration and ion exchange chromatography, and the use of region-specific antisera. In all cats, and all but one dog, a molecule with the properties of sulphated cholecystokinin octapeptide was found to predominate. In some cats (30%) and dogs (26%) a molecule with the properties of heptadecapeptide gastrin (G17) was identified; concentrations of G17 were generally low compared with cholecystokinin octapeptide. In three dogs (20%) there was an accumulation of heptadecapeptide gastrin above the ligatures. 5. Axonal transport of cholecystokinin octapeptide in the vagus is consistent with a neuro-regulatory role for this peptide. However, the functional significance of its localization in afferent fibres, and transport towards the periphery, remains to be determined.

The mechanism of the perforation in the epithelial root sheath of the lower first molar tooth germ of the mouse was studied by light and electron microscopy. The findings obtained were as follows : (1) By frontal serial sections and reconstructed models of the epithelial root sheath, the first perforation area appeared at the buccal and slightly mesial region of the root bifurcation. (2) In the prospective perforation area, the epithelial cells of the root sheath and undifferentiated follicular cells had many small cytoplasmic processes which were in intimate contact with or penetrated through the basal lamina. (3) In the perforating region, the basal lamina was absent, and the epithelial intercellular space was enlarged, then a close approximation or the direct cell-to-cell contact between the mesenchymal cells of the dental sac and the outer epithelial layer of the root sheath was observed. (4) The cytoplasmic process of the mesenchymal cells penetrated through the intercellular space of the root sheath and became attached to the dentine. By the contact with the dentinal matrix, the mesenchymal cells differentiated into the highly active functional cells. These results suggest that during the early root formation, the epitheliomesen-chymal interaction between the epithelial root sheath and the dental sac may exist and play an inductive role in the perforation of the epithelial root sheath.