Omentum Research Articles

Comparison of Omentum and Subcutis as Implant Sites for Device-Encapsulated Human iPSC-Derived Pancreatic Endoderm in Nude Rats

Subcutaneous implants of device-encapsulated stem cell–derived pancreatic endoderm (PE) can establish a functional beta cell mass (FBM) with metabolic control in immune-compromised mice. In a study with human-induced pluripotent stem cell-PE, this outcome was favored by a preformed pouch which allowed lesion-free insertion of devices in a pre-vascularized site. This was not reproduced in nude rats, known to exhibit a higher innate reactivity than mice and therefore relevant as preclinical model: a dense fibrotic capsule formed around subcutis (SC) implants with virtually no FBM formation. Placement in omentum (OM) of nude rats provided a less fibrous, better vascularized environment than SC. It resulted in less donor cell loss (56% recovery at post-transplant-PT week 3 versus 16% in SC) allowing FBM-formation. At PT week 30, 6/13 OM-recipients exhibited glucose-induced plasma hu-C-peptide to 0.1–0.4 ng/ml, versus 0/8 in SC-recipients. These levels are more than 10-fold lower than in a state of metabolic control. This shortcoming is not caused by inadequate glucose responsiveness of the beta cells but by their insufficient number. The size of the formed beta cell mass (0.4 ± 0.2 µl) was lower than that reported in mice receiving the same cell product subcutaneously; the difference is attributed to a lower expansion of pancreatic progenitor cells and to their lower degree of differentiation to beta cells. This study in the nude rat model demonstrates that OM provides a better environment for formation of beta cells in device-encapsulated PE-implants than SC. It also identified targets for increasing their dose-efficacy.

Cytokine status in the omentum and peritoneum in metastatic gastric cancer.

e16557 Background: Gastric cancer (GC) is one of the most common malignant tumors and the second most common cause of cancer deaths in Russia. Many researchers note the ambiguous role of cytokines in the pathogenesis of tumor processes. The purpose of the study was to determine characteristics of the cytokine status in the omentum and peritoneum of patients with metastatic GC. Methods: The main group (Mgr) included 23 patients with T2-4N0-3M1 GC with metastases to the peritoneum and greater omentum, the mean age 58.9±9.7 years. The comparison group (Cgr) included 20 non-cancer patients, the mean age 55.9±9.7 years. Tissues of the omentum (OT) and peritoneum (PT) were obtained from all patients during cytoreductive and diagnostic surgeries. Ex tempore tissues were disintegrated using BD Medimachine (USA) with 0.9% NaCl; the cell suspension was centrifuged, and the supernatant was collected and aliquoted. Levels of cytokines IL-1β, IL-2, IL-6, IL-8, IL-18, TNF-α, IL-10 (Vektor-Best, Russia) and IL-1RA (eBioscience, Austria) were determined by ELISA. The results were expressed as the specific content per 1 g of protein evaluated by the biuret method (pg/mL/g of protein). Statisical analysis of the results was performed with the Statistica 10 program (StatSoft Inc., USA). Significance of differences was evaluated using the Mann-Whitney and Wilkinson tests; differences were considered significant at p < 0.05. Results: In Cgr, levels of IL-6, IL-8, IL-18 and IL-1β in OT were 4.1±1.1, 3.4±0.7, 21.2±5.5 and 10.8±2.1, while in Mgr – 55.3±24.4, 32.5±13.8, 144.9±48.4 and 21.01±5.4 pg/mL/g of protein, i.e. 13.7, 9.5, 6.9 and 1.9 times (p≤0.05) higher than in Cgr, respectively. The specific content of IL-1RA in OT was 12.6 times higher, p≤0.05 (215.7±69.8 vs. 2723.1±730.1), and the IL-10 concentration did not differ significantly. In PT of Cgr, levels of IL-8, IL-18 and IL-6 were 9.8±7.3, 35.2±21.7, 7.5±3.7, and in Mgr – 250.7±21.4, 322.9±16.9, 61.1±27.6 pg/mL/g, i.e. 25.7, 9.2 and 8.2 times (p≤0.05) higher than in Cgr. IL-1RA in PT of Mgr was 24.4 times higher than in Cgr, p≤0.05 (7656.2±3160.3 vs. 357.69±180.86). Conclusions: A certain microenvironment is formed in OT and PT affected by metastases, with specific features in the ratio and concentrations of various cytokines, which undoubtedly contribute to the formation of a secondary tumor.

Breast Lipofilling Does Not Pose Evidence of Chronic Inflammation in Rats.

Laboratory reports on adipose tissue suggest that fat grafting to the breast may pose an oncologic risk. One possible reason for this is the theoretic chronic inflammation due to adipokynes released by grafted white adipose tissue (WAT). The aim of this study was to analyze inflammatory activity in lipofilled breast through the use of proinflammatory markers. Fifty-four paired-breasts of female rats were divided into 4 groups: control, sham, and breasts grafted with either autologous subcutaneous (SC) WAT or autologous omentum (OM). The WAT was prepared through centrifugation, and the grafting was performed with the use of 0.9-mm blunt-tip cannula. The rats were killed 8 weeks postoperatively, and their breasts were harvested for immunohistochemical staining for CD68-expressing macrophages, gene expression (real-time PCR) for monocyte chemoattractant protein 1 (MCP-1), F4/80, Cox-2, and IL-6. The weights of the rats that underwent a procedure differed from those of the unmanipulated control group (P < 0.01). The macrophage counts of CD68 differed only between breasts lipofilled with OM and control (P < 0.01). MCP-1, F4/80, and Cox-2 were similarly expressed among the groups (P = 0.422, P = 0.143, and P = 0.209, respectively). The expression of IL-6 differed between breast samples grafted with SC and OM WAT (P = 0.015), but not between samples of control and OM (P = 0.752), and control and SC (P = 0.056). No inflammation activity was identified in the microenvironment of lipofilled breasts, indicating that chronic inflammation does not seem to be triggered by the breast lipofilling procedure.

Abstract AP17: OVARIAN TUMOR STIMULATION CONVERTS NORMAL OVARY AND OMENTAL MESENCHYMAL STEM CELLS INTO TUMOR–PROMOTING CARCINOMA–ASSOCIATED MESENCHYMAL STEM CELLS

Abstract BACKGROUND: Ovarian carcinoma-associated mesenchymal stem cells (CA-MSCs) are multipotent cells which influence the creation of the ovarian tumor microenvironment. CA-MSCs strongly promote ovarian cancer growth, cancer stem cell-like cells and chemotherapy resistance. CA-MSCs lack tumor associated somatic mutations, however compared to normal MSCs, CA-MSCs have a unique expression profile which mediates their pro-tumorigenic properties. The origin of CA-MSCs is unknown. We hypothesized that CA-MSCs are derived from local tissue MSCs reprogrammed by the ovarian tumor to become pro-tumorigenic CA-MSCs. METHODS: We define a “CA-MSC-like expression profile” of 6 genes significantly and reproducibly differentially expressed between normal human MSCs (from bone marrow (BM), omentum (OM) or ovary (OV)) and patient-derived CA-MSCs. Three normal MSC populations were grown with human ovarian cancer cells and analyzed to determine if tumor stimulation can induce a CA-MSC-like expression profile. Tumor stimulated MSCs were functionally analyzed to determine if acquisition of a CA-MSC-like expression profile correlates with development of pro-tumorigenic functions. Methylation array analysis of normal MSCs versus CA-MSCs was performed to explore the role of epigenetic regulation in the formation a CA-MSC. RESULTS: Tumor stimulation of normal OV and OM MSCs but not BM MSCs yield expression changes which approximate the CA-MSC-like expression profile. In vivo tumor stimulation of normal OM MSCs most effectively induces a CA-MSC-like expression profile. The development of a CA-MSC-like expression profile correlates with gain of pro-tumorigenic functions including induction of cancer cell chemotherapy resistance, enrichment of the ovarian cancer stem cell-like pool and enhancement of tumor growth. In contrast, tumor stimulated BM MSCs--which do not develop a CA-MSC-like expression profile--fail to gain pro-tumorigenic functions. Further, methylation array analysis demonstrates significant global differences in methylation patterns of CA-MSCs versus normal MSCs, indicating that epigenetic alterations may drive the development of the CA-MSC phenotype. CONCLUSIONS: Collectively we demonstrate that normal OV and OM MSCs are capable of becoming CA-MSCs through in vivo tumor stimulation with development of a distinct CA-MSC-like expression profile with corresponding pro-tumorigenic functions. These findings highlight the critical influence of the tumor on the normal host environment, manipulating normal cells to become cancer-supporting cells. The differential capacity of OV and OM MSCs but not BM MSCs to become CA-MSCs also highlights the heterogeneity of MSCs and may factor into the intraperitoneal tropism of ovarian cancer spread. Ultimately, understanding how tumor stimulation drives the development of CA-MSCs may identify powerful targets to disrupt the formation and function of the ovarian tumor microenvironment. Citation Format: Coffman, LG and Buckanovich, RJ. OVARIAN TUMOR STIMULATION CONVERTS NORMAL OVARY AND OMENTAL MESENCHYMAL STEM CELLS INTO TUMOR–PROMOTING CARCINOMA–ASSOCIATED MESENCHYMAL STEM CELLS [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr AP17.

Obesity-associated insulin resistance is correlated to adipose tissue vascular endothelial growth factors and metalloproteinase levels

BackgroundThe expansion of adipose tissue is linked to the development of its vasculature, which appears to have the potential to regulate the onset of obesity. However, at present, there are no studies highlighting the relationship between human adipose tissue angiogenesis and obesity-associated insulin resistance (IR).ResultsOur aim was to analyze and compare angiogenic factor expression levels in both subcutaneous (SC) and omentum (OM) adipose tissues from morbidly obese patients (n = 26) with low (OB/L-IR) (healthy obese) and high (OB/H-IR) degrees of IR, and lean controls (n = 17). Another objective was to examine angiogenic factor correlations with obesity and IR.Here we found that VEGF-A was the isoform with higher expression in both OM and SC adipose tissues, and was up-regulated 3-fold, together with MMP9 in OB/L-IR as compared to leans. This up-regulation decreased by 23% in OB/-H-IR compared to OB/L-IR. On the contrary, VEGF-B, VEGF-C and VEGF-D, together with MMP15 was down-regulated in both OB/H-IR and OB/L-IR compared to lean patients. Moreover, MMP9 correlated positively and VEGF-C, VEGF-D and MMP15 correlated negatively with HOMA-IR, in both SC and OM.ConclusionWe hereby propose that the alteration in MMP15, VEGF-B, VEGF-C and VEGF-D gene expression may be caused by one of the relevant adipose tissue processes related to the development of IR, and the up-regulation of VEGF-A in adipose tissue could have a relationship with the prevention of this pathology.

Functional development of a transplanted embryonic kidney: effect of transplantation site

A xenotransplanted metanephros may undergo complete nephrogenesis in the host animal, forming a functional kidney. This suggests that, in future, xenometanephroi could become an unlimited source of material for renal transplantation. Although the omentum (OM) is the primary site for transplantation, we speculated that the growth of the transplant could differ depending on the site of transplantation. Thus, we determined the optimal transplantation site for the metanephros in terms of retaining its ability to produce renin and erythropoietin (EPO). Rat metanephroi were transplanted into the OM, paraaortic area (PA), or both (OM+PA) of unilaterally nephrectomized host rats. After 2-3 weeks, blood was rapidly withdrawn in order to induce production of renin and EPO in the transplants. Histological analysis indicated that transplants in both the PA and OM were well differentiated, demonstrating polarity of the medulla through to the cortex. Plasma renin activity (PRA) increased in response to the induction procedure, but transplants in the PA expressed PRA more effectively than did those in the OM. Real-time polymerase chain reaction (PCR) revealed higher levels of renin mRNA expression in transplants in the PA than in those in the OM. Although EPO production increased 24 hours after the induction procedure, the levels did not differ significantly between OM- and PA-transplanted rats. Compared with transplantation to the OM, transplantation of rat metanephroi to the PA results in better renin production, whereas the transplantation site does not affect EPO production.

Adipose tissue lamin A/C messenger RNA expression in women

Mutations in the lamin A/C gene ( LMNA) cause lipodystrophy. However, little data are available on lamin A/C expression in various fat depots in women. We recruited 34 women scheduled for gynecologic surgery. Blood samples were collected on the morning of surgery to obtain a detailed lipid profile. Radiological examinations were performed to measure total body fat mass and abdominal fat accumulation. Fat samples were taken from the subcutaneous (SC) fat depot and from the greater omentum (OM) during the surgical procedure. Whole adipose tissue samples were used for total messenger RNA (mRNA) extraction and real-time polymerase chain reaction quantification of the LMNA transcript. No association was observed between lamin A/C mRNA expression, either in SC or OM fat tissue, and adiposity measures. Women with low SC lamin A/C expression, identified on the basis of the median value of SC lamin A/C mRNA expression, had a significantly altered lipid profile including lower levels of high-density lipoprotein (HDL) cholesterol and HDL 2 cholesterol and reduced HDL 2 cholesterol to HDL 3 cholesterol ratio ( P < .05 for all). These women were also characterized by higher cholesterol to HDL cholesterol, low-density lipoprotein–triglycerides, very low-density lipoprotein–apolipoprotein B, and low-density lipoprotein cholesterol to HDL cholesterol ( P < .05 for all). Low SC lamin A/C mRNA expression levels were also associated with significantly increased lipolysis in isolated fat cells from this fat depot. Specifically, the response to lipolytic agent isoproterenol was significantly increased at doses ranging from 10 −5 to 10 −10 mol/L ( P < .05). A similar trend was observed in OM fat cells but did not reach significance. In conclusion, low lamin A/C expression in SC adipose tissue is associated with significant alterations in the lipid profile and increased fat cell lipolysis, independent of the level of total or abdominal adiposity.

Scaling of the giant dipole resonance widths in hot rotating nuclei from the ground state values

The system atics ofthe giant dipole resonance (GDR) widths in hot and rotating nucleiare studied in term softem peratureT,angularm om entum J and m assA.Thedierentexperim ental datain thetem peraturerangeof1-2M eV havebeen com pared with thetherm alshapeuctuation m odel(TSFM ) in the liquid drop form alism using a m odied approach to estim ate the average values ofT,J and A in the decay ofthe com pound nucleus. The values ofthe ground state GDR widthshave been extracted from theTSFM param etrization in theliquid drop lim itforthe corrected T,Jand A foragiven system and com pared with thecorrespondingavailablesystem atics ofthe experim entally m easured ground state GDR widthsfor a range ofnucleifrom A = 45 to 194. Am azingly, the nature of the theoretically extracted ground state GDR widths m atches rem arkably well,though 1.5 tim essm aller,with the experim entally m easured ground state GDR widthsconsistently overa widerangeofnuclei.

Constructive Criticism: The Human Sciences in the Age of Theory ed. by Martin Kreiswirth, Thomas Carmichael

Màrtiri Kreiswirth ànd Thomas Carmichael, eds. Constructive Criticism: The Human Sciences in theAge o f Theory. Toronto: U ofToronto P, 1995". Pp. 223 + viii. $43.00 paper, $17.93 paper. The turns and returns o f th eory seem to teach that criticism should be con ­ structive and (thus) that destruction is not enough. D econstruction, w hich D errida brought to N orth A m erica and w hich de M an m ade the dom inant m ode o f th eory there for about a decade, suggests som ething m ore than H eidegger’s d estru ction w h ile indicating that con struction cannot occu r w ith ou t a certain am ount o f d estruction. Paradoxically, the skepticism o f the pre-Socratics and the rh etorical turn o f the Sophists found a kind o f ricorso in deconstruction. The return to skepticism and rhetoric represents, in the 1960s, a blatant, and perhaps necessary, challenge to Plato’s essential, ideal and logocentric view o f philosophy. D econstruction, philosophy that aspired to the condition o f literature in D errid a’s case and criticism that aspired to philosophy in de M an ’s, questioned the received w isdom o f a W estern philosoph ical tradition, w hich, in an anecdote, had been called a footn ote to Plato. That A ristotle had challenged his teacher, that Sidn ey reshaped A ristotle to give p oetics a higher place, that Shelley rew orked n eo-Platon ism , is som etim es forgotten, but the challenge o f d eco n stru c­ tion, although rooted in antiquity, happens in a new context— the up h eav­ als o f the 1960s. A n o th er crisis in m im esis o r rep resen tatio n is upon us. E ach crisis respon d s to new historical circu m stan ces. H ow texts relate to a changing w orld, w here w riters and readers face each oth er across a m utable rh eto ri­ cal abyss, becom es dram atic in each age becau se even if that period denies its ow n im portance, it reads and lives everyth in g from the present. Even in the nam e o f h isto ry a certain p resentism represen ts itself as if to erase the traces o f history that efface h om ologies in the guise o f difference. It is possible to be skeptical abou t a skepticism that calls itself new as a m eans o f effacin g its ow n gen ealogy in order to cou n ter a tradition it w ishes to oppose. A s present th eory declares its m om ent, as an avant-garde, it has little regard for history, o r any h istorical cu rren ts that do not su pp ort its prem ise, or any utopian p review that does not provide for the m om ent from w hich it rejects and projects. This m oving rhetorical now is skeptical o f all things except itself even as it speaks abou t its skepticism o f itself. In this b rief response, I can on ly hint at the issues that these essays raise, especially in the em phasis on the op p osition betw een rhetoric and p hilosoph ical truth that resides in the rebarbative notion o f represen ta270 IHart tion. Constructive Criticism is a collection o f essays that tries to com e to term s w ith recent changes in critical theory. The title echoes and addresses deconstru ction, but the b o ok also calls attention to cultural, postcolonial, fem inist, gay and lesbian critiques, theoretical m ovem ents that have gath ­ ered m om entum since the late sixties. The editors structure the collection along the lines o f several p ro b lem atics— th eorists, theory, representation and situation. The essays on theorists exam ine the follow ing specific issues: D oes the later Foucault stay w ith a rad ical skeptical view o f truth or is...

2216 Endoscopic gastric perforation repair with omental patch, using endoscopic clips.

INTRODUCTION - Perforation of the digestive tract wall is a complication of some therapeutic procedures. In such an event, the endoscopic repair is less invasive and its performance has been reported in several cases. On the other hand, the idea of using an omental patch for such repairs has been applied for a long time to the surgical treatment of gastroduodenal ulcer perforation. This study shows the results of combining both techniques and allows to establish a guideline for this kind of repair. METHOD -Ten threecross Large White, Landrace and Pietan pigs were submitted to a standardized gastric perforation procedure by aspiration and cutting, for which a polypectomy snare and an end adapter for endoscopic esophageal varices ligation were used. The omentum (OM) was pulled to the gastric cavity in most cases by aspiration with the endoscope) and then caught with the metallic snare and fixed to the muscular layer of the stomach by endoscopic metallic clips. By changing the position of the snare it was possible to place the clips in any convenient position. This procedure was carried out under general anesthesia. The animals received food on the first day after the operation. They were sacrificed on the 15th postoperative day. RESULTS - Nine animals had a normal postoperative course. In all of them, an ulcer could be seen at the repaired site. On the external side of the wall, the OM was adherent. No other alterations were observed in the peritoneal cavity. The gastric wall histology showed a moderate inflammatory process in these pigs. In one animal whose muscular layer could not be seen during the procedure, the clips attached the OM to the mucosa. This animal died on the 11th postoperative day. Examination of the peritoneal cavity at sacrifice revealed intense peritonitis. The perforation was not repaired in this animal. CONCLUSION - This seems to be a simple and easy technique for EGPR, as safe as the conventional surgery.With the use of antibiotics, the risk of infection could be considered acceptable, especially in view of the advantages offered by a less invasive procedure. It seems to be important to attach the omentum to the muscular layer. The EGPR with a patch of OM seems to be an interesting option to be confirmed by further studies.

Dynamical models of the middle atmosphere for tracer studies

The distribution of ozone and other tracers depends on chemical factors and on the atmospheric circulations, which themselves depend, through heat sources and sinks, on the ozone amount. Examples of the sensitivity of ozone to variations in the dynamics are given from a two dimensional model. The total ozone depends greatly on the heating rate in the equatorial low er stratosphere; changes of tens of milli atmosphere centimetres f arise from alteration of only a few tens of kelvins per day in heating. The effects of variations in m om entum flux and mixing-surface slope are also discussed. T he current ability to model dynamics for tracer studies is reviewed. Only three dimensional models provide a consistent formulation; they simulate many observed atmospheric phenomena broadly b u t not in detail. However, the amount of computing needed precludes all but the simplest treatment of chem istry. Two dimensional models offer a valuable com promise. Although these are rather empirical and not adequately based on sound physical principles, good agreement can be found in practice between observed and modelled ozone, winds and temperatures. The calculation of model-dependent meridional circulations in two dimensional models is shown to be important, for which a parametrization of the momentum flux is an essential prerequisite. Some observations are given tha t suggest that a parametrization based on potential vorticity fluxes may be possible. This would be consistent with the usual formulation of tracer transport.

A simplified technique for performing the ventriculo-peritoneal shunt. Technical note.

W E HAVE found tha t the use of the Pudenz -Heye r valve with a ventr iculo-peri toneal shunt provides the mos t favorable me thod of t r e a t m e n t for congenital and acquired hydrocephalus. The simple ventr iculo-peri toneal shunt was prone to early malfunct ion because of the insinuation of omen tum into the distal end of the tubing. For this reason, ventr iculo-caval and ventriculo-atrial shunts have been generally adopted. The Pudenz -Heye r shunt ing device has a leaf valve a t the distal end of the tubular system. This va lve remains closed a t all t imes except when fluid is passing outward, thus prevent ing o m e n t u m f rom gaining access to the tubula r system. Consequently, we chose to per form ventriculo-peri toneal shunts when confronted with the problem of a child who a l ready had one internal and two external jugular veins thrombosed from previous ventr iculo-venous shunts. Our resuits in these cases p roved so favorable tha t we ul t imately made it our practice to use this method as a m a t t e r of routine. Although the technique of establishing a ventI iculo-peri toneal shunt is relatively simple in an adult , the appl ica t ion to a newborn or premature child is more complicated. The problems of general anesthesia in the newborn add to the difficulties. We are report ing our simplified technique for performing the ventriculo-peri toneal shunt under local anesthesia. Our experience includes 67 procedures performed on 6~ newborn children and 5 adults , for either congenital or acquired hydrocephalus of either the communica t ing or the obstruct ive varieties.

Adiabatic coupling between nuclear and electronic motion in molecules. II

The adiabatic coupling between nuclear and electronic motion is investigated for diatomic molecules which at infinite separation consist of two atoms at least one of which has non- zero orbital angular momentum, and as an example quantitative results at all nuclear separations R are given for the 2 pn u state of H 2 + . Several other systems are considered, but attention is restricted to configurations in which R is sufficiently large that the adiabatic coupling effect may be represented by an expansion in powers of R -1 with leading term proportional to R -2 . Some consequences of an R -2 interaction are briefly discussed and finally the generalization to include spin angular m om entum is indicated.