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Objective: To assess the diagnostic efficiency of positron emission tomography with 18-fluorine fluorodeoxyglucose in detecting breast cancer in augmented breasts. Design: Retrospective study. Setting: University hospital, Korea. Subject: 9 cases or 8 patients with breasts augmented with paraffin or silicone. Intervention: FDG-PET, mammography, and ultrasonography Results: The mammogram detected the breast cancer in only 1 of 3 patients, and ultrasonography gave a false positive result in 1 patient with an augmented breast. In contrast, PET predicted all the cancers and 5/6 benign lesions. 2/3 breast cancers had axillary FDG uptake interpreted as showing metastatic involvement, and in 1 case with cancer with no axillary lymph node involvement there was no FDG uptake in the axilla, which correlated with the pathological finding. Conclusions: Although the high cost of PET makes its use as a screening test for all patients with augmented breasts unrealistic, it would be the best diagnostic choice if other methods failed. [ABSTRACT FROM AUTHOR]

• Minimal immunosuppression pig-to-monkey corneal xenotransplantation was studied. • We compared graft survival rate of full-thickness and lamellar xenotransplantation. • Partial corneal grafts had superior survival to full-thickness grafts. • Full-thickness graft tissue presented a higher immunological response. The graft survival rate of full-thickness corneal xenotransplantation (XTP) with minimal immunosuppression in genetically engineered pigs is unknown, whereas lamellar corneal XTP shows satisfactory results. We compared graft survival between full-thickness and lamellar transplantations in the same genetically engineered pig. Six pig-to-monkey corneal transplantations were performed on 3 transgenic pigs. Two corneas harvested from 1 pig were transplanted into 2 monkeys using full-thickness and lamellar corneal xenotransplantation. The transgenic donor pigs used were α1,3-galactosyltransferase gene-knockout + membrane cofactor protein (GTKO+CD46) in one recipient and GTKO+CD46+ thrombomodulin (TBM) in the other. The graft survival time for GTKO+CD46 XTP was 28 days. With the addition of TBM, the survival differences between lamellar and full-thickness XTP were 98 days versus 14 days and >463 days (ongoing) versus 21 days, respectively. An excessive number of inflammatory cells was observed in failed grafts, but none were in the recipient's stromal bed. Unlike full-thickness corneal XTP, lamellar xenocorneal transplantation does not exhibit surgical complications, such as retrocorneal membrane or anterior synechia. The graft survival of lamellar XTP in this study was not as good as in our previous experiments, although the survival period was superior to that of full-thickness XTP. The difference in graft survival based on transgenic type is not definitive. Further studies using transgenic pigs and minimal immunosuppression need to focus on improving graft survival of lamellar XTP and using a larger sample size to determine the potential of full-thickness corneal XTP. [ABSTRACT FROM AUTHOR]

In South Korea, pig-to-nonhuman primate trials of solid organs have only been performed recently, and the results are not sufficiently satisfactory to initiate clinical trials. Since November 2011, we have performed 30 kidney pig-to-nonhuman primate xenotransplantations at Konkuk University Hospital. Donor αGal-knockout–based transgenic pigs were obtained from 3 institutes. The knock-in genes were CD39, CD46, CD55, CD73 , and thrombomodulin , and 2-4 transgenic modifications with GTKO were done. The recipient animal was the cynomolgus monkey. We used the immunosuppressants anti-CD154, rituximab, anti–thymocyte globulin, tacrolimus, mycophenolate mofetil, and steroids. The mean survival duration of the recipients was 39 days. Except for a few cases for which survival durations were <2 days because of technical failure, 24 grafts survived for >7 days, with an average survival duration of 50 days. Long-term survival was observed 115 days after the removal of the contralateral kidney, which is currently the longest-recorded graft survival in Korea. We confirmed functioning grafts for the surviving transplanted kidneys after the second-look operation, and no signs of hyperacute rejection were observed. Although our survival results are relatively poor, they are the best-recorded results in South Korea, and the ongoing results are improving. With the support of government funds and the volunteering activities of clinical experts, we aim to further improve our experiments and contribute to the commencement of clinical trials of kidney xenotransplantation in Korea. [ABSTRACT FROM AUTHOR]

Cardiac xenotransplantation is the potential treatment for end-stage heart failure, but the allogenic organ supply needs to catch up to clinical demand. Therefore, genetically-modified porcine heart xenotransplantation could be a potential alternative. So far, pig-to-monkey heart xenografts have been studied using multi-transgenic pigs, indicating various survival periods. However, functional mechanisms based on survival period-related gene expression are unclear. This study aimed to identify the differential mechanisms between pig-to-monkey post-xenotransplantation long- and short-term survivals. Heterotopic abdominal transplantation was performed using a donor CD46-expressing GTKO pig and a recipient cynomolgus monkey. RNA-seq was performed using samples from POD60 XH from monkey and NH from age-matched pigs, D35 and D95. Gene-annotated DEGs for POD60 XH were compared with those for POD9 XH (Park et al. 2021). DEGs were identified by comparing gene expression levels in POD60 XH versus either D35 or D95 NH. 1,804 and 1,655 DEGs were identified in POD60 XH versus D35 NH and POD60 XH versus D95 NH, respectively. Overlapped 1,148 DEGs were annotated and compared with 1,348 DEGs for POD9 XH. Transcriptomic features for heart failure and inhibition of T cell activation were observed in both long (POD60)- and short (POD9)-term survived monkeys. Only short-term survived monkey showed heart remodeling and regeneration features, while long-term survived monkey indicated multi-organ failure by neural and hormonal signaling as well as suppression of B cell activation. Our results reveal differential heart failure development and survival at the transcriptome level and suggest candidate genes for specific signals to control adverse cardiac xenotransplantation effects. [ABSTRACT FROM AUTHOR]

Background. Hyperuricaemia commonly occurs in renal transplant recipients (RTRs), but the effects of post-transplant hyperuricaemia on kidney transplant outcome have not been clearly established. This work was designed to explore the impact of hyperuricaemia on renal transplant outcome. Methods. The authors examined this issue by analysing the clinical outcome of 281 RTRs. Hyperuricaemia (defined as UA > 7.0 mg/dl in men and >6.0 mg/dl in women for at least two consecutive tests, n = 121) was classified as early onset (within 1 year of transplant, n = 90) or late onset (n = 31). Graft function was estimated using the MDRD Study Equation 7 (eGFRMDRD). Results. As late-onset hyperuricaemia was found to be induced by a progressive decline in the graft function (P P = 0.035) and a poorer graft survival (P = 0.026) by multivariate analysis, whereas mild hyperuricaemia was not. The impact of moderate-to-severe hyperuricaemia on renal transplant survival was dependent on the duration of exposure. Likewise, the detrimental effect of early-onset hyperuricaemia on the graft function was dependent on UA levels and exposure time. After control of the baseline graft function by analysis of only recipients with a good graft function at 1 year post-transplantation (eGFRMDRD > 60 ml/min), moderate-to-severe early-onset hyperuricaemia was also found to be a marker of long-term graft dysfunction and failure. Conclusion. Moderate-to-severe early-onset hyperuri- caemia may be a prognostic marker of the long-term graft outcome in RTRs, which needs further investigation. [ABSTRACT FROM AUTHOR]

BRCA1/2 are breast cancer susceptibility genes that are involved in DNA repair and transcriptional control. They are dysregulated in breast cancer, making them attractive therapeutic targets. Here, we performed a systematic multiomics analysis to expound BRCA1/2 functions as prognostic biomarkers in breast cancer. First, using different web-based bioinformatics platforms (Oncomine, TIMER 2.0, UALCAN, and cBioportal), the expression of BRCA1/2 was assessed. Then, the R package was used to analyze the diagnostic value of BRCA1/2 in patients. Next, we determined the relationship between BRCA1/2 mRNA expression and prognosis in patients (PrognoScan Database, R2: Kaplan Meier Scanner and Kaplan–Meier Plotter). Subsequently, the association of BRCA1/2 with mutation frequency alteration and copy number alterations in breast cancer was investigated using the cBioportal platform. After that, we identified known and predicted structural genes and proteins essential for BRCA1/2 functions using GeneMania and STRING db. Finally, GO and KEGG pathway enrichment analyses were performed to elucidate the potential biological functions of the co-expression genes of BRCA1/2. The BRCA1/2 mRNA level in breast cancer tissues was considerably higher than in normal tissues, with AUCs of 0.766 and 0.829, respectively. Overexpression of BRCA1/2 was significantly related to the worse overall survival (p < 0.001) and was correlated to clinicopathological characteristics including lymph nodes, estrogen receptors, and progesterone receptors (p < 0.01). The alteration frequencies of both the gens have been checked, and the results show that BRCA1 and BRCA2 show different alteration frequencies. Their mutation sites differ from each other. GO and KEGG showed that BRCA1/2 was mainly enriched in catalytic activity, acting on DNA, chromosomal region, organelle fission, cell cycle, etc. The 20 most frequently changed genes were closely related to BRCA1/2, including PALB2 and RAD51 relatively. Our study provides suggestive evidence of the prognostic role of BRCA1/2 in breast cancer and the therapeutic target for breast cancer. Furthermore, BRCA1/2 may influence BRCA prognosis through catalytic activity, acting on DNA, chromosomal regions, organelle fission, and the cell cycle. Nevertheless, further validation is warranted. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus tends to have the greatest impact on the smaller vessels and contributes significantly to occlusive disease from the popliteal artery distally. Purpose: To evaluate the clinical outcomes after a balloon angioplasty with or without stent placement in diabetic patients with critical limb ischemia (CLI) by chronic total occlusion (CTO) limited to below-the-knee (BTK) arteries. Material and Methods: From August 2005, patients who presented CLI and CTO limited to the BTK arteries, and who underwent endovascular treatment, were included in this study. The primary endpoints evaluated were technical success, limb salvage, and primary patency. The secondary endpoints evaluated were 30-day access site, intervention site, and systemic complications. Patency and limb salvage were evaluated using the Kaplan-Meier method and compared using Fisher's exact test. Results: The BTK endovascular treatment (EVT) was performed on 64 limbs. Technical success rate was 93.8% and limb salvage rate was 90.6%. Three of four limbs with technical failure and three of 60 limbs with technical success underwent BTK amputation and the comparison of these rates were significantly different (75% vs. 5%, P = 0.002). Primary patency rates for the limbs were 75% and 59.1% at 6-month and 12-month follow-up, respectively. Minor complications disappeared through the follow-up periods and there was no 30-day complication or systemic adverse events for the treated vessel. Conclusion: Even though EVT for CLI in patients with diabetes and CTO in isolated BTK arteries does not have comparable primary patency, it can lead to a very high rate of limb salvage. This result can accentuate the importance of more blood flow to the foot by means of successful revascularization using EVT rather than long-term patency in CTO of isolated BTK arteries. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus tends to have the greatest impact on the smaller vessels and contributes significantly to occlusive disease from the popliteal artery distally. Purpose: To evaluate the clinical outcomes after a balloon angioplasty with or without stent placement in diabetic patients with critical limb ischemia (CLI) by chronic total occlusion (CTO) limited to below-the-knee (BTK) arteries. Material and Methods: From August 2005, patients who presented CLI and CTO limited to the BTK arteries, and who underwent endovascular treatment, were included in this study. The primary endpoints evaluated were technical success, limb salvage, and primary patency. The secondary endpoints evaluated were 30-day access site, intervention site, and systemic complications. Patency and limb salvage were evaluated using the Kaplan-Meier method and compared using Fisher's exact test. Results: The BTK endovascular treatment (EVT) was performed on 64 limbs. Technical success rate was 93.8% and limb salvage rate was 90.6%. Three of four limbs with technical failure and three of 60 limbs with technical success underwent BTK amputation and the comparison of these rates were significantly different (75% vs. 5%, P ¼ 0.002). Primary patency rates for the limbs were 75% and 59.1% at 6-month and 12-month follow-up, respectively. Minor complications disappeared through the follow-up periods and there was no 30-day complication or systemic adverse events for the treated vessel. Conclusion: Even though EVT for CLI in patients with diabetes and CTO in isolated BTK arteries does not have comparable primary patency, it can lead to a very high rate of limb salvage. This result can accentuate the importance of more blood flow to the foot by means of successful revascularization using EVT rather than long-term patency in CTO of isolated BTK arteries. . [ABSTRACT FROM AUTHOR]

BACKGROUND Percutaneous ablation of incompetent perforators has been introduced as a safe and efficacious alternative. Objective To compare two methods of treating incompetent thigh perforator and great saphenous veins ( GSV). Materials and Methods Patients with varicose veins of CEAP C2 and C3 with incompetent perforating veins ( IPVs) in the thigh without evidence of saphenofemoral reflux and with obvious venous reflux from IPVs into the GSV distal to IPVs were included. Endovenous laser ablation was done using two methods ( IPV ablation ( IPVA) versus GSV ablation: GSVA). Their technical success rate, clinical success rate, and complications were compared at 1 week, and 1, 3, 6, and 12 months. Results Sixty-nine consecutive patients were randomized to IPVA ( n = 34) or GSVA ( n = 35). Technical success was significantly lower with IPVA than GSVA ( p = .002). Clinical success, defined as continued closure of treated veins, was similar with IPVA and GSVA (96.1% vs 100% at 1 week, 100% vs 97.1% at 1 month, and 100% for both at 3, 6, and 12 months, respectively). Conclusion IPVA has clinical results and complications similar to those of GSVA in individuals with C2 and C3 chronic venous disease with IPVs in the thigh combined with incompetent GSV, but its higher technical failure rate makes it difficult to choose it as the primary treatment method. [ABSTRACT FROM AUTHOR]

To understand changes in biological responses in nonhuman primate (NHP) recipients of xenotransplantation (XTP), we retrospectively investigated chronological changes in cytokine profiles of NHP recipients after solid-organ XTP. Plasma samples were collected from 7 NHP recipients of pig heart or kidney XTP with α-1,3-galactosyltransferase gene knockout (GTKO) under anti-CD154-based immune suppression at the following time points: immediately before; 2 hours, 3 days, and 7 days after XTP; and weekly thereafter until the graft failed. The plasma levels of the following cytokines were measured: interleukin (IL)-1α, IL-1β, IL-6, IL-12p70, IL-8, IL-10, IL-15, tumor necrosis factor, interferon gamma (IFN-γ), D-dimer, C3a, and histone-complexed DNA fragments. For in vitro experiments, human natural killer (NK) cells were cocultured with wild-type porcine endothelial cells (PECs), GTKO-PECs, and human umbilical vein endothelial cells, with or without anti-CD154 antibody. IFN-γ levels in the culture supernatants were compared. IFN-γ levels peaked on day 7 or 10 of XTP and then decreased to basal levels, whereas proinflammatory cytokine levels increased along with the elevation of histone-complexed DNA fragments and were sustained until xenograft failure. In vitro, human NK cells produced more IFN-γ when in contact with wild-type PECs than with human umbilical vein endothelial cells, which was not reduced by the use of GTKO-PECs or addition of anti-CD154 antibody to the mixture. In NHP recipients of XTP, the early peak of IFN-γ priming subsequent inflammatory responses may be attributed to NK cell activation in response to xenografts. [ABSTRACT FROM AUTHOR]

To develop an effective protocol of gene transfer into glomeruli, an ex vivo gene delivery system using rat mesangial cells (RMC) as a vector was examined. RMC genetically engineered with a retrovirus harboring the Escherichia coli beta-galactosidase gene was used to estimate the efficacy of gene delivery and the location of the cells within the kidney. The RMC expressing beta-galactosidase, RMCLZ1, was cultured in vitro and the cells were injected into the left kidney through the renal artery of a normal Sprague Dawley rat. At least I x 10[sup 6] RMCLZ1 was required for effective gene delivery into glomeruli. One hour and 1, 4, and 14 d after injection, glomeruli were isolated from the left kidneys injected with the cells and the expression of beta-galactosidase in each glomeruli was evaluated. One hour and 1 d after injection, more than 90 and 80%, respectively, of glomeruli from the left kidney showed strong beta-galactosidase activity, while no activity of beta-galactosidase was found in the glomeruli from the right kidneys. The number of glomeruli stained by X-gal and the intensity decreased with time. Fourteen days after injection, about 35% of the glomeruli retained the RMCLZ1. X-gal and periodic acid-Schiff staining of frozen sections obtained 14 d after injection allowed the estimation of the site where the mesangial cells injected were located. The mesangial cells were found mainly in two different locations, the glomerular capillary and the mesangium. The majority (about 90%) of the mesangial cells were located in the glomerular capillary and about 9% of the cells were in the mesangial area. Occasionally, the positive staining was found in proximal tubules and the interlobular artery. Although additional methods are required for the site-specific targeting of the mesangial area, the ex vivo gene transfer to glomeruli is feasible and... [ABSTRACT FROM AUTHOR]

Prostaglandin-endoperoxide synthase-2 (PTGS2) plays a pivotal role in inflammation and carcinogenesis in human breast cancer. Our aim of the study is to find the prognostic value of PTGS2 in breast cancer. We conducted a multiomic analysis to determine whether PTGS2 functions as a prognostic biomarker in human breast cancer. We explored PTGS2 mRNA expressions using different public bioinformatics portals. Oncomine, Serial Analysis of Gene Expression (SAGE), GEPIA, ULCAN, PrognoScan database, Kaplan-Meier Plotter, bc-GenExMiner, USC XENA, and Cytoscape/STRING DB were used to identify the prognostic roles of PTGS2 in breast cancer. Based on the clinicopathological analysis, decreased PTGS2 expressions correlated positively with older age, lymph node status, the human epidermal growth factor receptor 2 (HER2) status (P <.0001), estrogen receptor (ER+) expression (P <.0001) Luminal A (P <.0001), and Luminal B (P <.0001). Interestingly, progesterone receptor (PR) (P <.0001) negative showed a high expression of PTGS2. Prostaglandin-endoperoxide synthase-2 was downregulated in breast cancer tissues than in normal tissues. In the PrognoScan database and, Kaplan-Meier Scanner, downregulated expressions of PTGS2 associated with poor overall survival (OS), relapse-free survival (RFS), and distant metastasis-free survival. The methylation levels were significantly higher in the Luminal B subtype. Through oncomine coexpressed gene analysis, we found a positive correlation between PTGS2 and interleukin-6 (IL- 6) expression in breast cancer tissues. These results indicate that downregulated expressions of PTGS2 can be used as a promising prognostic biomarker and Luminal B hyper methylation may play an important role in the development of breast cancers. However, to clarify our results, extensive study is required. [ABSTRACT FROM AUTHOR]

Prostaglandin-endoperoxide synthase-2 (PTGS2) plays a pivotal role in inflammation and carcinogenesis in human breast cancer. Our aim of the study is to find the prognostic value of PTGS2 in breast cancer. We conducted a multiomic analysis to determine whether PTGS2 functions as a prognostic biomarker in human breast cancer. We explored PTGS2 mRNA expressions using different public bioinformatics portals. Oncomine, Serial Analysis of Gene Expression (SAGE), GEPIA, ULCAN, PrognoScan database, Kaplan-Meier Plotter, bc-GenExMiner, USC XENA, and Cytoscape/STRING DB were used to identify the prognostic roles of PTGS2 in breast cancer. Based on the clinicopathological analysis, decreased PTGS2 expressions correlated positively with older age, lymph node status, the human epidermal growth factor receptor 2 (HER2) status (P <.0001), estrogen receptor (ER+) expression (P <.0001) Luminal A (P <.0001), and Luminal B (P <.0001). Interestingly, progesterone receptor (PR) (P <.0001) negative showed a high expression of PTGS2. Prostaglandin-endoperoxide synthase-2 was downregulated in breast cancer tissues than in normal tissues. In the PrognoScan database and, Kaplan-Meier Scanner, downregulated expressions of PTGS2 associated with poor overall survival (OS), relapse-free survival (RFS), and distant metastasis-free survival. The methylation levels were significantly higher in the Luminal B subtype. Through oncomine coexpressed gene analysis, we found a positive correlation between PTGS2 and interleukin-6 (IL- 6) expression in breast cancer tissues. These results indicate that downregulated expressions of PTGS2 can be used as a promising prognostic biomarker and Luminal B hyper methylation may play an important role in the development of breast cancers. However, to clarify our results, extensive study is required. [ABSTRACT FROM AUTHOR]

Prostaglandin E 1 (PGE 1) administered to patients in the immediate post-transplant period has been known to reduce ischemic reperfusion injuries (IRIs), but the effect on IRI of PGE 1 administered to the donor is unknown. The purpose of this study was to determine the effect on IRI of PGE 1 injected into donor rats during heterotopic heart transplantation. Genetically identical male Sprague Dawley rats with a body weight of 300–320 g at 8–9 weeks of age were used for the study. Experimental methods were the same in the control (G 0 , n = 6) and experimental groups (G 1 , n = 6), but only the donor rats in the experimental group received an intramuscular injection of PGE 1 (5 μg/kg) prior to the donor surgery. On day 1 the animals were sacrificed with the removal of the transplanted heart. Histologic analysis was performed in the hematoxylin-eosin-stained slides to assess interstitial edema and neutrophil infiltration by a pathologist. Median times of the donor organ procurement, cold ischemia, and warm ischemia were 37, 69, and 35 minutes, respectively, in the G 0 group and 38, 76.5, and 33 minutes respectively in G 1 group; there were no statistical differences. Heartbeats were observed in the transplanted graft in 2 of the G 0 group and 2 of G 1 group immediately after heart transplantation, but in all transplanted grafts on day 1 after surgery. Histologic scores for neutrophil infiltration showed significantly lower in the G 1 group than in the G 0 group. PGE 1 administration to donors in a rat heart transplantation model may significantly reduce IRI. • Ischemia-reperfusion injury is associated with organ function after transplantation. • Ischemia-reperfusion injury results from oxidative stress. • Studies to reduce oxidative stress after transplantation have been continuing. [ABSTRACT FROM AUTHOR]

Abstract: Most studies of xenografts have been carried out with complex immunosuppressive regimens to prevent immune rejection; however, such treatments may be fatal owing to unknown causes. Here, we performed immune molecular profiling following anti‐CD154 monoclonal antibody (mAb) treatment in heterotopic abdominal cardiac xenografts from α‐1,3‐galactosyltransferase‐knockout pigs into cynomolgus monkeys to elucidate the mechanisms mediating the undesirable fatal side effects of immunosuppressive agents. Blood samples were collected from healthy monkeys as control and then at 2 days after xenograft transplantation and just before humane euthanasia; 94 genes related to the immune system were analyzed. The basic immunosuppressive regimen included cobra venom factor, anti‐thymocyte globulin, and rituximab, with and without anti‐CD154 mAbs. The maintenance therapy was followed with tacrolimus, MMF, and methylprednisolone. The number of upregulated genes was initially decreased on Day 2 (−/+ anti‐CD154 mAb, 22/13) and then increased before euthanasia in recipients treated with anti‐CD154 mAbs (−/+ anti‐CD154 mAb, 30/37). The number of downregulated genes was not affected by anti‐CD154 mAb treatment. Additionally, the number of upregulated genes increased over time for both groups. Interestingly, treatment with anti‐CD154 mAbs upregulated coagulation inducers (CCL2/IL6) before euthanasia. In conclusion, immunosuppressive regimens used for cardiac xenografting affected upregulation of 6 inflammation genes (CXCL10, MPO, MYD88, NLRP3, TNFα, and TLR1) and downregulation of 8 genes (CCR4, CCR6, CD40, CXCR3, FOXP3, GATA3, STAT4, and TBX21). [ABSTRACT FROM AUTHOR]

Effective immunosuppression strategies and genetically modified animals have been used to prevent hyperacute and acute xenograft rejection; however, the underlying mechanisms remain unknown. In this study, we evaluated the expression of a comprehensive set of immune system-related genes (89 genes, including five housekeeping genes) in the blood of cynomolgus monkeys (~5 yr old) used as graft recipients, before and after the xenografting of the islets and heart from single and double α-1,3-galactosyltransferase (GalT) knockout (KO) pigs (<6 weeks old). The immunosuppressive regimen included administration of cobra venom factor, anti-thymocyte globulin, rituximab, and anti-CD154 monoclonal antibodies to recipients before and after grafting. Islets were xenografted into the portal vein in type 1 diabetic monkeys, and the heart was xenografted by heterotopic abdominal heart transplantation. Genes from recipient blood were analyzed using RT2 profiler PCR arrays and the web-based RT2 profiler PCR array software v.3.5. Recipients treated with immunosuppressive agents without grafting showed significant downregulation of CCL5, CCR4, CCR6, CD4, CD40LG, CXCR3, FASLG, CXCR3, FOXP3, GATA3, IGNG, L10, IL23A, TRAF6, MAPK8, MIF, STAT4, TBX21, TLR3, TLR7, and TYK2 and upregulation of IFNGR1; thus, genes involved in protection against viral and bacterial infection were downregulated, confirming the risk of infection. Notably, C3-level control resulted in xenograft failure within 2 days because of a 7- to 11-fold increase in all xenotransplanted models. Islet grafting using single GalT-KO pigs resulted in upregulation of CXCL10 and MX1, early inflammation, and acute rejection-associated signals at 2 days after xenografting. We observed at least 5-fold upregulation in recipients transplanted with islets grafts from single ( MX1) or double ( C3, CCR8, IL6, IL13, IRF6, CXCL10, and MX1) GalT-KO pigs after 77 days; single GalT-KO incurred early losses owing to immune attacks. Our results suggest that this novel, simple, non-invasive, and time-efficient procedure (requiring only 1.5 ml blood) for evaluating graft success, minimizing immune rejection, and blocking infection. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the etiology of unusual manifestation of hemoperitoneum and the efficacy of transcatheter arterial embolization (TAE). Materials and Methods: A retrospective review of patients at three hospitals was performed. A total of 12 patients (M:F = 5:7, mean age: 48) had massive hemoperitoneum without evidence of an intramuscular hematoma on CT (n = 10) or US (n = 2) after injury to the abdominal wall. The patients underwent TAE. The etiology of iatrogenic injury to the abdominal muscular arteries and the effectiveness of embolization were evaluated. Results: Among 12 patients, 11 patients had injuries to the inferior epigastric artery (IEA) and one patient had an injury to the deep circumflex iliac artery (DCIA). The causes of the injuries were: paracentesis (n = 6), open laparotomy (n = 4), removal of a CAPD catheter (n = 1), and surgical drain (n = 1). The TAE was successfully performed in all patients. Over 10 days of follow-up after the embolization, all patients were stabilized hemodynamically. Conclusion: Injury to the IEA or DCIA should be considered as a possible source of hemoperitoneum even in patients with no evidence of an intramuscular hematoma after injury to the superficial arteries of the abdominal wall. In addition, such injuries can be treated successfully using TAE. [ABSTRACT FROM AUTHOR]

Porcine heart xenotransplantation is a potential treatment for patients with end-stage heart failure. To understand molecular mechanisms of graft rejection after heart transplantation, we transplanted a 31-day-old alpha-1,3-galactosyltransferase knockout (GTKO) porcine heart to a five-year-old cynomolgus monkey. Histological and transcriptome analyses were conducted on xenografted cardiac tissue at rejection (nine days after transplantation). The recipient monkey's blood parameters were analyzed on days −7, −3, 1, 4, and 7. Validation was conducted by quantitative real-time PCR (qPCR) with selected genes. A non-transplanted GTKO porcine heart from an age-matched litter was used as a control. The recipient monkey showed systemic inflammatory responses, and the rejected cardiac graft indicated myocardial infarction and cardiac fibrosis. The transplanted heart exhibited a total of 3748 differentially expressed genes compared to the non-transplanted heart transcriptome, with 2443 upregulated and 1305 downregulated genes. Key biological pathways involved at the terminal stage of graft rejection were cardiomyopathies, extracellular interactions, and ion channel activities. The results of qPCR evaluation were in agreement with the transcriptome data. Transcriptome analysis of porcine cardiac tissue at graft rejection reveals dysregulation of the key molecules and signaling pathways, which play relevant roles on structural and functional integrities of the heart. [ABSTRACT FROM AUTHOR]

Pigs are used as potential donor animals for xenotransplantation. However, porcine endogenous retrovirus (PERV), shown to infect both human and non-human primate (NHP) cells in vitro, presents a risk of transmission to humans in xenotransplantation. In this study, we analyzed PERV transmission in various organs after pig-to-NHP xenotransplantation. We utilized pig-to-NHP xenotransplant tissue samples obtained using two types of transgenic pigs from the National Institute of Animal Science (NIAS, Republic of Korea), and examined them for the existence of PERV genes in different organs via PCR and RT-PCR with specific primers. To determine PERV insertion into chromosomes, inverse PCR using PERV long terminal repeat (LTR) region-specific primers was conducted. The PERV gene was not detected in NHP organs in cardiac xenotransplantation but detected in NHP bladders in renal xenotransplantation. The insertion experiment confirmed that PERVs originate from porcine donor cells rather than integrated provirus in the NHP chromosome. We also demonstrate the presence of pig cells in the NHP bladder after renal xenotransplantation using specific-porcine mitochondrial DNA gene PCR. The PERV sequence was detected in the bladder of NHPs after renal xenotransplantation by porcine cell-microchimerism but did not integrate into the NHP chromosome. [ABSTRACT FROM AUTHOR]