Microvasculature of the feline stomach

The feline gastric microvasculature was studied by corrosion of the injected vascular bed, which allowed evaluation of the vascular pattern of the different tunics. The serosal pattern consisted of numerous interconnected capillary vessels, forming a delicate network. Submucosal arteries supplied the muscular tunic through numerous anastomosing vessels that followed the direction of the smooth muscle fibers. The entire mucosal tunic was supplied by arterioles derived from the submucosal plexus; these gave rise to capillaries that surrounded the gastric glands and terminated in a diffuse, anastomosing subepithelial capillary network. Venules coursed through the mucosa in a perpendicular manner, forming submucosal veins.     

Status of the circulatory bed of the vascular membrane of the eyeball and retrobulbar structures during experimental venous stasis

In 43 test animals the state of the blood bed in the retrobulbar formations and the eyeball vasular tunic has been studied under venous congestion produced by ligation of the anterior vena cava (in dogs) and both external jugular veins (in rabbits). A complex of histological, histotopographic, morphometric and variation-statistical techniques has been used. The results obtained demonstrate that disturbances in the venous outflow in the anterior vena cava system produce certain responses in all parts of the retrotubular adipose tissue, of the eyeball muscles, of the optic nerve tunics, of the vascular tunic. Certain stageness is noted in the course of venous congestion. Places of the greatest morphological changes in the eyeball vascular tunic are determined. They are zones of vorticose veins formation and the area corresponding to the posterior pole of the eyeball. The analysis of the specific areas of the intermuscular arteries and veins cross sections demonstrates that in the reaction of these vessels to the different venous outflow in the anterior vena cava system these is certain unevenness in different ofthalmic muscles.     

鼠兔子宫血管铸型的光镜和扫描电镜观察

用光镜和扫描电镜观察了ＡＢＳ丁酮溶液灌注的达乌尔鼠兔子宫血管与微血管构筑情况。子宫大部分血液来自子宫动脉,小部分来自生殖动脉。各弓状动脉进入宫壁后,即在宫壁内分支形成３个血管层：浆膜层、大血管层和粘肌层。研究发现鼠兔子宫内膜血管呈树杆状或有轻度弯曲向腔面垂直穿行,直至浅层分支形成毛细血管网和较大的窦状毛细血管;其内膜血管形态与有月经的人子宫内膜螺旋动脉明显差异。文中还对子宫微血管构筑与月经产生机制     

A new method for cannulation of the common bile duct in an experiment]

The proposed method of common biliary duct cannulation is simple, easily performed and permits studying bile hydrodynamics biligenesis for a necessary time. Tightness of the system is completely preserved after removal a choledochostomical tube. Walls of the invaginated stump of the cystic duct are swiftly abated as a result of hydrostatic pressure and cover its gap. The presence of purse string kapron suture in a stump orifice creates an obstacle to deinvagination. Good reparation properties of serous and subserous membranes, covering the biliary duct, promote rapid closing of stoma. Effectiveness of the proposed method of common biliary duct cannulation by means of the invaginated stump of the cystic duct is confirmed by the smooth postoperative course and absence of a biliary fistula after the tube removal.     

The neural tube patterns vessels developmentally using the VEGF signaling pathway

Embryonic blood vessels form in a reproducible pattern that interfaces with other embryonic structures and tissues, but the sources and identities of signals that pattern vessels are not well characterized. We hypothesized that the neural tube provides vascular patterning signal(s) that direct formation of the perineural vascular plexus (PNVP) that encompasses the neural tube at mid-gestation. Both surgically placed ectopic neural tubes and ectopic neural tubes engineered genetically were able to recruit a vascular plexus, showing that the neural tube is the source of a vascular patterning signal. In mouse-quail chimeras with the graft separated from the neural tube by a buffer of host cells, graft-derived vascular cells contributed to the PNVP, indicating that the neural tube signal(s) can act at a distance. Murine neural tube vascular endothelial growth factor A (VEGFA) expression was temporally and spatially correlated with PNVP formation, suggesting it is a component of the neural tube signal. A collagen explant model was developed in which presomitic mesoderm explants formed a vascular plexus in the presence of added VEGFA. Co-cultures between presomitic mesoderm and neural tube also supported vascular plexus formation, indicating that the neural tube could replace the requirement for VEGFA. Moreover, a combination of pharmacological and genetic perturbations showed that VEGFA signaling through FLK1 is a required component of the neural tube vascular patterning signal. Thus, the neural tube is the first structure identified as a midline signaling center for embryonic vascular pattern formation in higher vertebrates, and VEGFA is a necessary component of the neural tube vascular patterning signal. These data suggest a model whereby embryonic structures with little or no capacity for angioblast generation act as a nexus for vessel patterning.     

Leaf structure in relation to solute transport and phloem loading in Zea mays L.

Small and intermediate (longitudinal) vascular bundles of the Zea mays leaf are surrounded by chlorenchymatous bundle sheaths and consist of one or two vessels, variable numbers of vascular parenchyma cells, and two or more sieve tubes some of which are associated with companion cells. Sieve tubes not associated with companion cells have relatively thick walls and commonly are in direct contact with the vessels. The thick-walled sieve tubes have abundant cytoplasmic connections with contiguous vascular parenchyma cells; in contrast, connections between vascular parenchyma cells and thin-walled sieve tubes are rare. Connections are abundant, however, between the thin-walled sieve tubes and their companion cells; the latter have few connections with the vascular parenchyma cells. Plasmolytic studies on leaves of plants taken directly from lighted growth chambers gave osmotic potential values of about-18 bars for the companion cells and thin-walled sieve tubes (the companion cell-sieve tube complexes) and about-11 bars for the vascular parenchyma cells. Judging from the distribution of connections between various cell types of the vascular bundles and from the osmotic potential values of those cell types, it appears that sugar is actively accumulated from the apoplast by the companion cell-sieve tube complex, probably across the plasmalemma of the companion cell. The thick-walled sieve tubes, with their close spatial association with the vessels and possession of plasmalemma tubules, may play a role in retrieval of solutes entering the leaf apoplast in the transpiration stream. The transverse veins have chlorenchymatous bundle sheaths and commonly contain a single vessel and sieve tube. Parenchymatic elements may or may not be present. Like the thick-walled sieve tubes of the longitudinal bundles, the sieve tubes of the transverse veins have plasmalemma tubules, indicating that they too may play a role in retrieval of solutes entering the leaf apoplast in the transpiration stream.     

The Vascular Effects of Sodium Tanshinone IIA Sulphonate in Rodent and Human Pregnancy

Danshen, in particular its derivative tanshinone IIA (TS), is a promising compound in the treatment of cardiovascular diseases and has been used for many years in traditional Chinese medicine. Although many actions of TS have been researched, its vasodilator effects in pregnancy remain unknown. There have been a few studies that have shown the ability of TS to reduce blood pressure in women with hypertensive pregnancies; however, there are no studies which have examined the vascular effects of TS in the pregnant state in either normal or complicated pregnancies. Our aim was to determine the vasoactive role of TS in multiple arteries during pregnancy including: rat resistance (mesenteric and uterine) and conduit (carotid) arteries. Further, we aimed to assess the ability of TS to improve uterine blood flow in a rodent model of intrauterine growth restriction. Wire myography was used to assess vascular responses to the water-soluble derivative, sodium tanshinone IIA sulphonate (STS) or to the endothelium-dependent vasodilator, methylcholine. At mid-pregnancy, STS caused direct vasodilation of rat resistance (pEC₅₀ mesenteric: 4.47±0.05 and uterine: 3.65±0.10) but not conduit (carotid) arteries. In late pregnancy, human myometrial arteries responded with a similar sensitivity to STS (pEC₅₀ myometrial: 3.26±0.13). STS treatment for the last third of pregnancy in eNOS^-/- mice increased uterine artery responses to methylcholine (E_max eNOS^-/-: 55.2±9.2% vs. eNOS^-/- treated: 75.7±8.9%, p<0.0001). The promising vascular effects, however, did not lead to improved uterine or umbilical blood flow in vivo, nor to improved fetal biometrics; body weight and crown-rump length. Further, STS treatment increased the uterine artery resistance index and decreased offspring body weight in control mice. Further research would be required to determine the safety and efficacy of use of STS in pregnancy.     

Placental growth factor is a potent vasodilator of rat and human resistance arteries

The objectives of this study were to determine whether placental growth factor (PlGF) exerts a vasodilatory effect on rat uterine vessels (arcuate arteries and veins) and to examine regional differences in reactivity by comparing these responses to those of comparably sized mesenteric vessels. We also sought to examine and compare its effects on human uterine and subcutaneous vessels. All vessels were studied in vitro, under pressurized (rat) or isometric wire-mounted (human) conditions, and exposed to a range of PlGF concentrations. Inhibitors of nitric oxide and prostaglandin synthesis were included in an effort to understand the causal mechanism(s). In rat uterine arteries, the effects of receptor inhibition and activation using selective ligands for VEGFR-1 (PlGF) vs. VEGFR-2 (VEGF-E) were determined, and real-time RT-PCR was performed to evaluate the effect of pregnancy on relative abundance of VEGFR-1 and VEGFR-2 message in the vascular wall. PlGF was a potent vasodilator of all vessels studied, with greatest sensitivity observed in rat uterine arteries. Pregnancy significantly augmented dilator sensitivity to PlGF, and this effect was associated with selective upregulation of VEGFR-1 message in the pregnant state. The contribution of nitric oxide was appreciable in rat and human uterine arteries, with lesser effects in rat uterine veins and mesenteric arteries, and with no observable effect in human subcutaneous vessels. Based on these results, we conclude that PlGF is a potent vasodilator of several vessel types in both humans and rats. Its potency and mechanism vary with physiological state and vessel location and are mediated solely by the VEGFR-1 receptor subtype. Gestational changes in the uterine circulation suggest that this factor may play a role in modulating uterine vascular remodeling and blood flow during the pregnant state.     

Pregnancy-induced alterations of vascular function in mouse mesenteric and uterine arteries

Normal pregnancy involves dramatic changes to maternal vascular function, while abnormal vascular adaptations may contribute to pregnancy-associated diseases such as preeclampsia. Many genetic mouse models have recently emerged to study vascular pathologies of pregnancy. However, vascular adaptations to pregnancy in normal mice are not fully understood. Thus, we studied changes in vascular reactivity during normal mouse pregnancy. We hypothesized that pregnant mice will have enhanced endothelial-dependent vasodilation compared with nonpregnant mice, via an enhancement of the nitric oxide synthase (NOS) prostaglandin H synthase (PGHS), and other endothelial-derived hyperpolarizing pathways. Late pregnant (Day 17-18) C57BL/6J mice (n = 10) were compared with nonpregnant mice (n = 7). Uterine and mesenteric arteries were mounted on a wire myograph system and assessed for endothelium-dependent (methacholine) and -independent (sodium nitroprusside; SNP) relaxation responses. Endothelial-dependent relaxation was enhanced in pregnant uterine and mesenteric arteries, which was blunted after the addition of inhibitors of the PGHS or NOS pathways. In nonpregnant mice, these pathways had no effect in modulating relaxation in uterine arteries, whereas vasodilation in mesenteric arteries was reduced only by NOS inhibition. Both uterine and mesenteric vessels had nonnitric oxide- and nonprostaglandin-mediated relaxation, but this relaxation was not enhanced during pregnancy. Endothelial-independent relaxation was also enhanced in pregnant uterine but not mesenteric arteries. Our data indicate that uterine and mesenteric arteries from pregnant mice have enhanced vasodilation. Understanding vascular adaptations to normal mouse pregnancy is crucial for interpreting changes that may occur in genetic mouse models.     

Mechanisms involved in calcitonin gene-related Peptide-induced relaxation in pregnant rat uterine artery

Human and rodent studies have demonstrated that calcitonin gene-related peptide (CGRP), a potent vasodilator, relaxes uterine tissue during pregnancy but not during labor. The vascular sensitivity to CGRP is enhanced during pregnancy, compared to nonpregnant human uterine arteries. In the present study, we hypothesized that uterine artery relaxation effects of CGRP are enhanced in pregnant rats compared to nonpregnant diestrus rats (NP-DE) and that several secondary messenger systems are involved in this process. We also hypothesized that the expression of CGRP-A receptor components, calcitonin receptor-like receptor (CRLR), receptor activity-modifying protein (RAMP1), and CGRP-B receptors are greater in pregnant rats. For vascular relaxation studies, uterine arteries from either NP-DE or Day 18 pregnant rats were isolated, and responsiveness of the vessels to CGRP was examined with a small vessel myograph. CGRP-A and CGRP-B receptor expressions were assessed by RT-PCR and Western immunoblotting, respectively. CGRP (10(-10)--10(-7) M) produced a concentration-dependent relaxation of norepinephrine-induced contractions in both NP-DE and Day 18 pregnant rat uterine arteries. Pregnancy increased the vasodilator sensitivity to CGRP significantly (P < 0.05) compared to NP-DE rats. CGRP receptor antagonist, CGRP8-37, inhibited CGRP-induced relaxation of pregnant uterine arteries. The CGRP-induced relaxation was not affected by NG-nitro-l-arginine methyl ester (L-NAME) (nitric oxide inhibitor, 10(-4) M) but was significantly (P < 0.05) attenuated by inhibitors of guanylate cyclase (ODQ, 10(-5) M) and adenylate cyclase (SQ 22536, 10(-5) M). CGRP-induced vasorelaxation was significantly (P < 0.05) attenuated by potassium channel blockers KATP (glybenclamide, 10(-5) M) and K(CA) (tetraethylammonium, 10(-3) M). The expression of CRLR and RAMP1 was significantly (P < 0.05) elevated during pregnancy compared to nonpregnant diestrus state (NP-DE). However, CGRP-B receptor proteins in uterine arteries were not altered with pregnancy compared to those of NP-DE. These studies suggest that CGRP-induced increases in uterine artery relaxation may play a role in regulating blood flow to the uterus during pregnancy and, therefore, in fetal growth and survival.     

Uterine vascular degeneration is present throughout the uterine wall of multiparous mares. Colinearity between elastosis, endometrial grade, age and parity

Vascular degeneration is present in endometrial vessels of multiparous aged mares. The lesions associated with vascular degeneration consist of enlargement, duplication and splitting of the membrana elastica interna and perivascular deposits of elastin. However, there are no similar data available for deep myometrial vessels and the vascular layer. The objectives of the present study were to characterize the status of vasculature in full-thickness uterine necropsy samples and to correlate these findings to endometrial grade, age, and parity. Elastosis was present in myometrial vessels, as well as in large arteries and veins located between the circular and longitudinal myometrial layers. Vascular degeneration was associated with number of foals (P < 0.001) and endometrial grade (P < 0.05), but not with mare age (P > 0.05). Endometrial grade was associated with age (P < 0.001) and vascular grade (P < 0.05), but not with number of foals (P > 0.05). The presence of elastosis in the myometrial vessels was related to problems associated with chronic uterine infection (CUI) and delayed uterine clearance (DUC) of infertile mares. Uterine contractility was impaired in mares affected by CUI and/or DUC and could be related to a lack of myometrial blood flow. Additionally, degeneration of large vessels in the vascular layer may indicate a general compromise in uterine blood flow and fertility. The main conclusions were the presence of vascular elastosis in large deep myometrial vessels as well as in endometrial vessels, and that the factor with the strongest association with vascular degeneration was number of foals (P < 0.001), followed by endometrial grade (P < 0.05), but no association with mare age.     

Increases of calcium and magnesium and decreases of phosphorus and iron with aging in human uterine tubes

To elucidate compositional changes of the uterine tube by aging, the authors studied age-related changes of elements in human uterine tubes by inductively coupled plasma-atomic emission spectrometry. The uterine tubes were resected postmortem or surgically removed from patients with uterine myoma. It was found that the contents of calcium and magnesium increased progressively with aging in uterine tubes, whereas the contents of phosphorus and iron decreased gradually with aging. The sulfur content of uterine tubes remained constant and independent of aging. Regarding relationships between elements, significant relationships were found between calcium and magnesium contents, between phosphorus and iron contents, between phosphorus and sulfur contents, and between phosphorus and sodium contents in human uterine tubes.     

Hemodynamic changes evaluated by Doppler ultrasonographic technology in the ovaries and uterus of dairy cattle after the puerperium

The present detailed study aimed to establish for the first time the ovarian and uterine hemodynamic change in dairy cows after the end of the puerperal period to investigate a possible association between Doppler indices and volume of blood flow. Twenty cows weighing 500–600 kg (mean 400 ± 50 kg) and 4–5 years of age (mean 3.2 ± 0.5 years) categorized into two main groups (true anestrum, with corpus luteum, n = 10) and (normal cyclic, n = 10), The period of examination started from day 39 till day 70 after calving with day after day routinely examination by b-mode and Doppler performed on both ovaries with ovarian arteries (OA) and uterus with uterine arteries (MUA) in the ipsilateral (ipsi) and contralateral (contra) side to ovulation, in addition to a thickness in horns and body was measured. Estradiol and progesterone were also measured. Results showed that both Doppler indices in the OA and MUA ipsi and contra had a positive (P ≤ 0.001) correlation with contra Doppler indices, but revealed a negative (P ≤ 0.05) correlation with ipsi and contra Doppler velocities, blood flow rate and volume in anestrum cows. Both ovarian and uterine ipsi indices showed an increase (P ≤ 0.05) in the anestrum cows, and both PSV and EDV of both arteries ipsilateral showed (P ≤ 0.05) a decrease in the anestrum cows, the ipsi and contra ovarian and uterine colored % were lower in anestrum group than the normal group. Estradiol (P ≤ 0.05) decreased in anestrum cows than the normal, while progesterone increased in the anestrum group. Conclusion, although uterine and ovarian morphology were changed in anestrum cows, the vascular system of the ovary as well as uterus underwent much more marked vascular changes, the most significant being that of blood flow velocities and volume.     

Cortisol-mediated regulation of uterine artery contractility: effect of chronic hypoxia

We previously demonstrated that cortisol regulated alpha(1)-adrenoceptor-mediated contractions differentially in nonpregnant and pregnant uterine arteries. Given that chronic hypoxia during pregnancy has profound effects on maternal uterine artery reactivity, the present study investigated the effects of chronic hypoxia on cortisol-mediated regulation of uterine artery contractions. Pregnant (day 30) and nonpregnant ewes were divided between normoxic control and chronically hypoxic [maintained at high altitude (3,820 m), arterial Po(2): 60 mmHg for 110 days] groups. Uterine arteries were isolated and contractions measured. In hypoxic animals, cortisol (10 ng/ml for 24 h) increased norepinephrine-induced contractions in pregnant, but not in nonpregnant, uterine arteries. The 11beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone did not change cortisol effects in nonpregnant uterine arteries, but abolished it in pregnant uterine arteries by increasing norepinephrine pD(2) (-log EC(50)) in control tissues. The dissociation constant of norepinephrine-alpha(1)-adrenoceptors was not changed by cortisol in nonpregnant, but decreased in pregnant uterine arteries. There were no differences in the density of glucocorticoid receptors between normoxic and hypoxic tissues. Cortisol inhibited the norepinephrine-induced increase in Ca(2+) concentrations in nonpregnant arteries, but potentiated it in pregnant arteries. In addition, cortisol attenuated phorbol 12,13-dibutyrate-induced contractions in normoxic nonpregnant and pregnant uterine arteries, but had no effect on the contractions in hypoxic arteries. The results suggest that cortisol differentially regulates alpha(1)-adrenoceptor- and PKC-mediated contractions in uterine arteries. Chronic hypoxia suppresses uterine artery sensitivity to cortisol, which may play an important role in the adaptation of uterine vascular tone and blood flow in response to chronic stress of hypoxia during pregnancy.     

Counter current transfer and back transport of 3H-PGF2 alpha in the cow's broad ligament vasculature ipsilateral and contralateral to the corpus luteum

Eight cows of similar age (5-7 years) were chosen for the experiment. Isolated reproductive tract was supplied with autologous oxygenated and heated (40 degrees C) blood through the uterine artery and ovarian artery. 3H-PGF2 alpha in total dose of 2 MBq (10(7) cpm) was injected into each of the uterine lumen of isolated organ. Blood samples were collected at 5 min intervals during 120 min of experiment using cannulae inserted into the branches of uterine arteries about 1 cm below the horns and from ovarian arteries inserted 0.5 cm below the ovaries. The concentration of 3H-PGF2 alpha found in blood plasma taken from uterine artery or from ovarian artery on the side with active corpus luteum (CL) was significantly lower (p less than 0.001) compare with contralateral side to active CL. Radioactive PGF2 alpha found in branches of uterine arteries on both ipsilateral and contralateral side to CL was significantly higher (p less than 0.001) compare to ovarian artery of the same side. It is concluded that absorption of 3H-PGF2 alpha from uterine lumen into venous blood as well as its counter current transfer in area of broad ligament vasculature were reduced on the side of uterine horn with active CL probably as an effect of estrogen:progesterone ratio on vascular constriction in area of uterine vasculature.     

Features of the structure of arteries of the lower extremities in man

A comparative investigation has been performed on structural peculiarities of muscle arteries having various caliber in the lower extremities and in the anterior thoracic wall (section material, 40 observations). An essential predominance of the muscle tunic thickness and deterioration of blood supply has been stated in the arterial wall and in the distal parts of the lower extremities. The structural peculiarities revealed in the arteries of the extremities are connected with functional conditions of blood supply in the zone at the vertical position of the human body (orthostatic arterial hypertension).     

Pregnancy Augments G Protein Estrogen Receptor (GPER) Induced Vasodilation in Rat Uterine Arteries via the Nitric Oxide - cGMP Signaling Pathway

Background

The regulation of vascular tone in the uterine circulation is a key determinant of appropriate uteroplacental blood perfusion and successful pregnancy outcome. Estrogens, which increase in the maternal circulation throughout pregnancy, can exert acute vasodilatory actions. Recently a third estrogen receptor named GPER (G protein-coupled estrogen receptor) was identified and, although several studies have shown vasodilatory effects in several vascular beds, nothing is known about its role in the uterine vasculature.

Aim

The aim of this study was to determine the function of GPER in uterine arteries mainly during pregnancy. Uterine arteries were isolated from nonpregnant and pregnant rats.

Methods

Vessels were contracted with phenylephrine and then incubated with incremental doses (10⁻¹²–10⁻⁵ M) of the selective GPER agonist G1.

Results

G1 induced a dose-dependent vasodilation which was: 1) significantly increased in pregnancy, 2) endothelium-dependent, 3) primarily mediated by NO/cGMP pathway and 4) unaffected by BK_ca channel inhibition.

Conclusion

This is the first study to show the potential importance of GPER signaling in reducing uterine vascular tone during pregnancy. GPER may therefore play a previously unrecognized role in the regulation of uteroplacental blood flow and normal fetus growth.     

Endothelial vasodilator production by uterine and systemic arteries. V. Effects of ovariectomy, the ovarian cycle, and pregnancy on prostacyclin synthase expression

Prostacyclin (PGI(2)) is a potent vasodilator, the level of which is increased during pregnancy, and is the main eicosanoid of which production is elevated in the endothelium and vascular smooth muscle (VSM) of both uterine and omental (systemic) arteries. We tested the hypothesis that during physiologic states that have high uterine blood flow, such as pregnancy and the follicular phase of the ovarian cycle (versus luteal phase and ovariectomized ewes), there is an increased level of prostacyclin synthase (PGIS) expression in ovine uterine and omental artery endothelium and VSM. To investigate this, the cellular localization and PGIS protein expression level in uterine and systemic arteries was examined by immunohistochemistry as well as by Western immunoblot analysis of endothelial-isolated protein and denuded vessels (VSM). Whole uterine, but not omental (systemic), arteries from the pregnant ewes showed an increase (P < 0.001) in PGIS expression. Further localization of PGIS protein by immunohistochemistry and quantification by Western analysis showed PGIS to be somewhat higher in the uterine artery VSM (69 +/- 7%) than endothelium (31 +/- 7%). PGIS protein levels in uterine and omental artery endothelial isolated protein were not altered by ovariectomy or the ovarian cycle, although they were both significantly elevated by pregnancy. Uterine and omental artery VSM PGIS expression levels also were not altered by ovariectomy or the ovarian cycle, whereas PGIS expression, in uterine but not omental artery VSM showed a significant elevation during pregnancy. Thus, the rise in PGI(2) production by uterine arteries observed in ovine pregnancy is paralleled by an elevation in PGIS expression in both endothelium and VSM, whereas those seen in omental arteries is associated with increases in endothelial PGIS.     

The morphology of allograft rejection in Styela plicata (Urochordata: Ascidiacea)

Summary This study identifies three discrete processes responsible for the rejection of tunic tissue transplanted between individuals of the solitary ascidian Styela plicata. The first stage of rejection is characterized by the destruction of blood vascular components within incompatible allografts. In the second phase, dense boundaries of extracellular material are deposited between grafts and the surrounding host tunic, effectively amputating the transplanted tissues. Finally, detached transplants undergo a gradual necrosis which results in the total degeneration of extracellular graft matrices. Of these three phases, the initial cellular depletion of allografts is responsible for the immunological specificity that is characteristic of histocompatibility in S. plicata. The subsequent amputation and necrosis of extracellular graft matrices are taken to be non-specific consequences of the initial cellular reactivity.     

Differential analysis of ovarian and endometrial cancers identifies a methylator phenotype

Despite improved outcomes in the past 30 years, less than half of all women diagnosed with epithelial ovarian cancer live five years beyond their diagnosis. Although typically treated as a single disease, epithelial ovarian cancer includes several distinct histological subtypes, such as papillary serous and endometrioid carcinomas. To address whether the morphological differences seen in these carcinomas represent distinct characteristics at the molecular level we analyzed DNA methylation patterns in 11 papillary serous tumors, 9 endometrioid ovarian tumors, 4 normal fallopian tube samples and 6 normal endometrial tissues, plus 8 normal fallopian tube and 4 serous samples from TCGA. For comparison within the endometrioid subtype we added 6 primary uterine endometrioid tumors and 5 endometrioid metastases from uterus to ovary. Data was obtained from 27,578 CpG dinucleotides occurring in or near promoter regions of 14,495 genes. We identified 36 locations with significant increases or decreases in methylation in comparisons of serous tumors and normal fallopian tube samples. Moreover, unsupervised clustering techniques applied to all samples showed three major profiles comprising mostly normal samples, serous tumors, and endometrioid tumors including ovarian, uterine and metastatic origins. The clustering analysis identified 60 differentially methylated sites between the serous group and the normal group. An unrelated set of 25 serous tumors validated the reproducibility of the methylation patterns. In contrast, >1,000 genes were differentially methylated between endometrioid tumors and normal samples. This finding is consistent with a generalized regulatory disruption caused by a methylator phenotype. Through DNA methylation analyses we have identified genes with known roles in ovarian carcinoma etiology, whereas pathway analyses provided biological insight to the role of novel genes. Our finding of differences between serous and endometrioid ovarian tumors indicates that intervention strategies could be developed to specifically address subtypes of epithelial ovarian cancer.