Cyclic Changes of Nerve Fibers in Human Endometrium

Objective: The presence of nerve fibers in human endometrium remains unsettled but recent immunocytochemical studies have shown that there was increased innervation in the endometrium from women with endometriosis and some nerve fibers in the normally cycling human endometrium. In the current study, we used uterine tissue cryosections from normal cycling women, which previously provided better immunocytochemical staining for lymphatic vessels than in paraffin sections. Materials and Methods: A total of 16 cases from normally cycling women were included representing menstrual, early proliferative, early to late secretary phase. Neurofilament and CD 56 were used as immunocytochemical markers for nerve fibers with cryosections. Results: There were consistent presence of nerve fibers in myometrium and basalis. Few small nerve fibers were identified in early proliferative endometrium and more nerve fibers were present in lower-half functionalis from mid-secretary phase. Late-secretary functionalis showed less nerve fibers in the upper-half than the lower-half functionalis, implying growing nerve fibers from lower functionalis to upper functionalis in late-secretary phase. Conclusion: Nerve fibers appeared to cyclically grow from basalis to lower functionalis and then from lower functionalis to upper functionalis concomitantly with blood vessels in normally cycling human endometrium. These cycling endometrial nerve fibers consisted mostly of nonmyelinated small nerve fibers, which may transmit pelvic pain in the normally cycling women.

Cyclic Changes of Lymphatic Vessels in Human Endometrium

Objective: The presence of lymphatic vessels in endometrium has been controversial and recent immunocytochemical studies with routinely paraffin embedded sections revealed lymphatic vessels in basalis and occasionally in functionalis. We aimed to investigate endometrial lymphatic vessels by immunocytochemical staining using cryosections, which provided better and consistent immunostaining for lymphatic vessels with a lymphatic marker, D2-40. We aimed further to explore the structure-function relationship of lymphatic vessels in the menstrual cycle. Materials and Methods: Sixteen cases of endometrium from menstrual, early-proliferative to latesecretary phase were immunostained for D2-40 and lymphatic vessels were morphometrically analyzed for functionalis, basalis and myometrium, respectively. Results: Lymphatic vessels were consistently most numerous in myometrium, followed by basalis in all phases whereas menstrual endometrium showed small, fragmented aggregates of lymphatic vessels in thin basalis. Earlyto mid-secretary endometrium revealed many lymphatic vessels in basalis and lower-functionalis with few lymphatic vessels in upper-functionalis. Late-secretary endometrium revealed more lymphatic vessels in upper-functionalis with dilated walls, which then burst at the surface of functionalis. Conclusions: These degenerating lymphatic vessels with markedly dilated lumen in upper-functionalis may contribute to lymphatic leakage in late-secretary phase. These immunostained lymphatic vessels in functionalis support proliferating and degenerating lymphatic vessel cycle synchronized with the menstrual cycle of endometrial arteries to maintain adequate fluid leakage.

Cyclic Changes of Lymphatic and Venous Vessels in Human Endometrium

Context: Cyclic changes of endometrial arteries are well established but possible cyclic changes of lymphatic and venous vessels have not been fully documented. There are no published morphological reports to support cyclic changes of endometrial lymphatic and venous vessels. Objective: Using cryosections of human endometrium, this study aimed to unveil possible cyclic changes of lymphatic and venous vessels. We previously reported cyclic changes of lymphatic vessels in human endometrium using D2-40. Design: A total of 16 cases representing menstrual, proliferative and mid and late secretary phase were studied. For Immunocytochemical staining, lymphatic vessel endothelial hyaluronan receptor 1 and von Willebr and factor were used for lymphatic and venous vessels, respectively. We used polyclonal LYVE-1 in this study, which revealed more lymphatic vessels than using D2-40. Results: Residual lymphatic and venous vessels were present in menstrual basalis. In Day 5 - 9 endometrium, there were sparse lymphatic vessels but were numerous growing venous vessels in thin proliferating functionalis. In Day 14 - 22 endometrium, there were scattered lymphatic vessels and numerous venous vessels in functionalis. In Day 25 - 26 endometrium, there were many dilated lymphatic vessels and numerous dilated, disintegrating venous vessels in upper functionalis than lower functionalis. Conclusion: The above findings support that lymphatic vessels are sparse but venous vessels are numerous in early proliferative functionalis. Lymphatic vessels grow from basalis to thin functionalis. In premenstrual phase, lymphatic vessels proliferate from lower to upper functionalis, and both lymphatic and venous vessels disintegrate for shedding by this immunocytochemical study using lymphatic and venous markers. Thus, all lymphatic, venous and arterial vessels undergo menstrual cyclic changes and shed for menstruation.

Tumor-Associated Lymphatic and Venous Vessels in Medullary Thyroid Carcinomas

Objective: Medullary thyroid carcinomas (MTCs) invade local lymph node through lymphatic vessels and metastasize to distant organs hematogenously and account for a significant mortality. There are possibly increased lymphatic and venous vessels, through which the tumor spreads to lymph nodes and distant organs. Materials and Methods: By immunocytochemical staining for lymphatic and venous vessels, MTC lesions with adjacent normal thyroid and both normal and metastatic lymph nodes were studied for the peritumoral lymphatic and venous vessels, which were morphometrically compared with those of normal thyroid and lymph nodes. Sixteen cases of MTC cases with adjacent thyroid tissues and attached lymph nodes were immunocytochemically stained for lymphatic vessels using lymphatic vessel hyaluronan receptor (LYVE-1) and venous vessels for factor VIII (F-8). The immunostained sections of MTC lesions and metastatic lymph nodes were morphometrically compared for the number and sizes of the vessels with those of normal thyroid tissues and lymph nodes. Results: Significantly increased lymphatic vessels and markedly increased blood vessels were identified in many MTC cases at the peritumoral tissues and metastatic lymph nodes whereas a few lymphatic vessels and no venous vessels were identified in midst of MTCs. The irregular peritumoral lymphatic vessels resembled that of immature lymphatic vessels observed in papillary thyroid carcinomas and increased irregularly, entrapped venous vessels in peritumoral tissues resembled those observed in follicular thyroid carcinomas. Conclusion: The significantly increased lymphatic vessels and markedly increased venous vessels in the peritumoral thyroid tissue support a propensity of MTCs for providing an easy access of tumor cells to both lymphatic spread to the regional lymph nodes and venous spread to distant organs with further tumor spread through metastatic lymph nodes by moderately increased lymphatic and venous vessels.

Cancer-Associated Lymphatic and Venous Vessels in Colonic Carcinomas

Objective: Colonic carcinomas spread to regional lymph nodes and liver. There are cancer-associated lymphatic and venous vessels at the margin of colonic carcinomas, which facilitate spreading carcinoma through lymphatic and venous vessels. This study aimed to examine cancer-associated lymphatic and venous vessels in TNM T1 to T3 carcinomas using lymphatic vessel hyaluronan receptor for lymphatic vessels and von Willebrand factor for venous vessels by immunocytochemical staining. Materials and Methods: A total of 40 cases of moderately differentiated colonic carcinoma were studied using routinely formalin-fixed and paraffin-embedded sections. The cases consisted of 10 cases of TNM T1, 15 cases each of T2 and T3 cases. Immunocytochemical staining was performed using goat antihuman LYVE-1for lymphatic vessels and rabbit antihuman von Willebrand factor for venous vessels. Results: In TNM T1 carcinoma, increased, irregular and narrow lymphatic and venous vessels were present in the adjacent normal mucosa to the carcinoma, some of which penetrated cancerous lesion. There were no tumor emboli in lymphatic and venous vessels. In TNM T2 carcinoma, there were few lymphatic and venous vessels in midst of the carcinoma whereas numerous small lymphatic and venous vessels were present within muscle layers adjacent to the invading carcinoma. Extramural tumor embolus was present in submucosa in one case. In TNM T3 carcinoma, cancer has invaded through the muscle layers where dilated lymphatic and venous vessels were present adjacent to cancerous nests. Tumor emboli were identified in two cases by immunocytochemical staining. Conclusion: The current study showed cancer-associated lymphatic and venous vessels at the interface in TNM T1 carcinoma to dilated intramuscular lymphatic and venous vessels adjacent to invading cancerous nests in TNM T3 carcinoma, and supports cancerous cells spread via lymphatic and venous vessels through muscle layers to subserosa as supported by tumor emboli in the lymphovascular system.

Integration of body-mounted ultrasoft organic solar cell on cyborg insects with intact mobility

Cyborg insects have been proposed for applications such as urban search and rescue.Body-mounted energy-harvesting devices are critical for expanding the range of activity and functionality of cyborg insects.However,their power outputs are limited to less than 1 mW,which is considerably lower than those required for wireless locomotion control.The area and load of the energy harvesting device considerably impair the mobility of tiny robots.Here,we describe the integration of an ultrasoft organic solar cell module on cyborg insects that preserves their motion abilities.Our quantified system design strategy,developed using a combination of ultrathin film electronics and an adhesive-nonadhesive interleaving structure to perform basic insect motion,successfully achieved the fundamental locomotion of traversing and self-righting.The body-mounted ultrathin organic solar cell module achieves a power output of 17.2 mW.We demonstrate its feasibility by displaying the recharging wireless locomotion control of cyborg insects.

Cell-Based Microfluidic Device Utilizing Cell Sheet Technology

The developmentof microelectromechanical systems hasresulted in the rapid development of polydimethylpolysiloxane(PDMS)microfluidic devices for drug screening models.Various cell functions,such as the response of endothelial cells to fluids,have beenelucdated using microuidic devices.Additionlly,organon-achip systems that includeorgans that are importantfor biologicalcirculation,such as the heart,liver,pancreas,kidneys,and brain,have been developed.These organs realize the biologicalcirculation system in a manner that cannot be reproduced by artificial organs;however,the flow channels between the organsare often artifically created by PDMS.In this study,we developeda microfluidic device consisting only of cels,by combiningcell sheet technology with microtitanium wires.Microwires were placed between stacked fibroblast cellsheets,and the celisheets adhered to each other,afer which the microwires were removed leaving a luminal structure with a size approximatelyequal to the arteriolar size.The lumen structure was constructed using wires with diameters of 50,100,150,and 200μm,which were approximations of the arteriole diameters.Furthermore using a perfusion device,we successfully perfused theluminal structure created inside the celsheets.The results revealed that a aulture solution can be supplied toa cellsheet witha very high cell density.The biofabrication technology proposed in this study can contribute to the development of organ-on-a-chip systems.

Titanium Culture Vessel Presenting Temperature Gradation for the Thermotolerance Estimation of Cells

Hyperthermia can be induced to exploit the thermal intolerance of cancer cells,which is worse than that of normal cells,as a potential noninvasive cancer treatment.To develop an effective hyperthermia treatment,thermal cytotoxicity of cells should be comprehensively investigated.However,to conduct such investigations,the culture temperature must be accurately regulated.We previously reported a culture system in which the culture temperature could be accurately regulated by employing metallic culture vessels.However,appropriate temperature conditions for hyperthermia depend on the cell species.Consequently,several experiments need to be conducted,which is a bottleneck of inducing hyperthermia.Hence,we developed a cell culture system with temperature gradation on a metallic culture surface.Michigan Cancer Foundation-7 cells and normal human dermal fibroblasts were used as cancer and normal cell models,respectively.Normal cells showed stronger thermal tolerance;this was because the novel system immediately exhibited a temperature gradation.Thus,the developed culture system can be used to investigate the optimum thermal conditions for effective hyperthermia treatment.Furthermore,as the reactions of cultured cells can be effectively assessed with the present results,further research involving the thermal stimulation of cells is possible.