This report describes light and electron microscopic observations in 11 patients with intraepithelial carcinomas concomitant with invasive squamous cell carcinomas of the esophagus. The junctions ...between the intraepithelial carcinomas and non-neoplastic tissues were examined using an electron microscope. Vertical sections through the basal laminae revealed intraepithelial carcinomas with bulky outgrowths and simple replacement histological patterns. The bulky outgrowths contained many pseudopodial cytoplasmic projections from the tumor cells through the basal laminae, while the simple replacement patterns included rare small breaks in the basal laminae. Horizontal sections parallel to the basal laminae showed that the cells of the poorly differentiated squamous cell carcinoma were readily distinguishable from the non-neoplastic cells in the surface layer of the esophageal epithelia and distinctly smaller and darker than the normal prickle cells. At most of the junctions, mesenchymal cells, degenerated cells, and amorphous material separated the tumor cells from the non-neoplastic epithelial cells. However, tumor cells were occasionally attached directly to normal epithelial cells with well-developed desmosomes. Ductal involvement of the carcinomas was found in the submucosal esophageal gland proper. The tumor cells invaded between the ductal cells and basal laminae, and neoplastic cells were also directly attached to the benign ductal cells by poorly-developed desmosomes. The host-tumor junctions in the intraepithelial carcinomas of the human esophagus consisted of basal laminae with hemidesmosomes and pseudopodial projections, mesenchymal cell accumulations and direct attachments with desmosomes.
The development of a chopstick-like two-fingered micromanipulator based on a hybrid mechanism is presented. The microhand consists of two 3-prismatic-revolute-spherical (PRS) parallel modules ...connected serially in a mirror image style. Each module has a long glass pipette as an end effector. The development process consists of three phases. In the first phase, analysis and mathematical modeling, a novel solution of the inverse kinematics problem (IKP) of a 3-revolute-prismatic-spherical (RPS) parallel module, is derived and applied with proper modification to the case of 3-PRS of the proposed mechanism. The solution is extended to the two-fingered hybrid mechanism of the microhand. In the optimization and design phase, the optimization of the chosen design parameters of a theoretical 3-PRS parallel module is carried out using two approaches: discretization method and genetic algorithms. Based on the optimal design parameters, a CAD model of the 3-PRS finger module is built, and a complementary optimization step using the ANSYS Workbench program is carried out to determine suitable characteristics of the pin flexure hinge. Finally, the total CAD model of the two-fingered hand is built. In the realization and implementation phase, the description of the hardware system of the two-fingered microhand prototype is presented. The program description, calibration method, practical Jacobian matrices, practical workspace, and error analysis of the prototype are discussed.
Thymic dendritic cells (DCs) promote immune tolerance by regulating negative selection of autoreactive T cells in the thymus. How DC homing to the thymus is transcriptionally regulated is still ...unclear. Microphthalmia-associated transcription factor (Mitf) is broadly expressed and plays essential roles in the hematopoietic system. Here, we used Mitf-mutated mice (Mitfvit/vit) and found enlargement of the thymus and expansion of CD4/CD8 double-positive T cells. Mitf was highly expressed in a subset of thymic DCs among the hematopoietic system. Genetic mutation or pharmacological inhibition of Mitf in DCs decreased the expression levels of Itga4, which are critical molecules for the homing of DCs to the thymus. Further, inhibition of Mitf decreased thymic DC number. These results suggest a pivotal role of Mitf in the maintenance of T cell differentiation by regulating the homing of DC subsets within the thymus.
•Mitfvit/vi mice show expansion of double-positive T cells in the thymus.•Mitf is highly expressed in a subset of thymic dendritic cells.•Suppression of Mitf decreases dendritic cell homing to the thymus.
Abstract
Context
Although numerous theories are reported on sex differences in longevity, the underlying biological mechanisms remain unknown. We previously reported that telomere length in the zona ...reticularis cells of the human adrenal cortex was significantly longer in older than that in younger subjects. However, we could not evaluate sex differences in the telomere lengths.
Objective
To compare the telomere lengths of adrenocortical and adrenal medullar cells between men and women from infancy through older adulthood.
Methods
Adrenal glands of 30 male (aged 0 to 100 years) and 25 female (aged 0 to 104 years) autopsied subjects were retrieved from autopsy files. Using quantitative fluorescence in situ hybridization, relative telomere lengths were determined in the parenchymal cells of the 3 adrenocortical zones and medulla. Age-related changes in the weight of adrenal glands were also investigated.
Main results
Older male subjects (aged 65 years or older) had significantly shorter telomere lengths in zona fasciculata (ZF) cells compared to the corresponding female subjects. In men, older subjects exhibited a significant age-related reduction in adrenal weight; however, no age-related changes in adrenal weight were detected in women.
Conclusion
Telomere attrition of ZF cells was correlated with adrenal weight reduction in older men but not in older women, suggesting a decreased number of ZF cells in older men. This may help us understand the possible biological mechanisms of sex difference in longevity of humans.
Hematopoietic stem cells (HSCs) maintain quiescence by activating specific metabolic pathways, including glycolysis. We do not yet have a clear understanding of how this metabolic activity changes ...during stress hematopoiesis, such as bone marrow transplantation. Here, we report a critical role for the p38MAPK family isoform p38α in initiating hematopoietic stem and progenitor cell (HSPC) proliferation during stress hematopoiesis in mice. We found that p38MAPK is immediately phosphorylated in HSPCs after a hematological stress, preceding increased HSPC cycling. Conditional deletion of p38α led to defective recovery from hematological stress and a delay in initiation of HSPC proliferation. Mechanistically, p38α signaling increases expression of inosine-5′-monophosphate dehydrogenase 2 in HSPCs, leading to altered levels of amino acids and purine-related metabolites and changes in cell-cycle progression in vitro and in vivo. Our studies have therefore uncovered a p38α-mediated pathway that alters HSPC metabolism to respond to stress and promote recovery.
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•Conditional deletion of p38α disrupts the hematopoietic stem cell stress response•Induction of p38α after stress promotes hematopoietic stem cell cycling•p38α promotes proliferation by activating purine metabolism•Mitf acts downstream of p38α to regulate the purine metabolism pathway gene
Karigane et al. characterize a regulatory pathway involved in hematopoietic stem cell stress responses. They show that p38α, which is activated by hematopoietic stress, promotes purine metabolism through Mitf-mediated Impdh2 upregulation. Activated purine metabolism promotes hematopoietic stem/progenitor cell cycling and maintains repopulation capacity after transplantation.
Electromagnetic navigation bronchoscopy (ENB) is a minimally invasive technology that guides endoscopic tools to pulmonary lesions. ENB has been evaluated primarily in small, single-center studies; ...thus, the diagnostic yield in a generalizable setting is unknown.
NAVIGATE is a prospective, multicenter, cohort study that evaluated ENB using the superDimension navigation system (Medtronic, Minneapolis, Minnesota). In this United States cohort analysis, 1215 consecutive subjects were enrolled at 29 academic and community sites from April 2015 to August 2016.
The median lesion size was 20.0 mm. Fluoroscopy was used in 91% of cases (lesions visible in 60%) and radial endobronchial ultrasound in 57%. The median ENB planning time was 5 minutes; the ENB-specific procedure time was 25 minutes. Among 1157 subjects undergoing ENB-guided biopsy, 94% (1092 of 1157) had navigation completed and tissue obtained. Follow-up was completed in 99% of subjects at 1 month and 80% at 12 months. The 12-month diagnostic yield was 73%. Pathology results of the ENB-aided tissue samples showed malignancy in 44% (484 of 1092). Sensitivity, specificity, positive predictive value, and negative predictive value for malignancy were 69%, 100%, 100%, and 56%, respectively. ENB-related Common Terminology Criteria for Adverse Events grade 2 or higher pneumothoraces (requiring admission or chest tube placement) occurred in 2.9%. The ENB-related Common Terminology Criteria for Adverse Events grade 2 or higher bronchopulmonary hemorrhage and grade 4 or higher respiratory failure rates were 1.5% and 0.7%, respectively.
NAVIGATE shows that an ENB-aided diagnosis can be obtained in approximately three-quarters of evaluable patients across a generalizable cohort based on prospective 12-month follow-up in a pragmatic setting with a low procedural complication rate.
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