Nucleotide metabolic mismatches in mammalian hearts: implications for transplantation

Introduction

Human donor organ shortages have led surgeons and scientists to explore the use of animals as alternative organ sources. Acute thrombovascular rejection (AVR) is the main hurdle in xenotransplantation. Disparities in nucleotide metabolism in the vessels of different species may contribute significantly to the microvascular component of AVR.

Methods

We evaluated the extent of nucleotide metabolism mismatch in selected organs and endothelial cells of different mammals with particular focus on the changes in activity of ecto-5’-nucleotidase (E5’N) elicited by exposure of porcine hearts or endothelial cells to human blood (ex vivo) or human plasma (in vitro).

Results

E5’N activity in the rat heart was significantly higher than in other species. We noted a significant difference (p<0.001) in E5’N activity between human and pig endothelial cell lines. Initial pig aortic endothelial E5’N activity decreased in vitro after a three-hour exposure to human and porcine plasma while remaining constant in controls. Ex vivo perfusion with fresh human blood for four hours resulted in a significant decrease of E5’N activity in both wild type and transgenic pig hearts overexpressing human decay accelerating factor (p<0.001).

Conclusions

This study provides evidence that mismatches in basal mammalian metabolic pathways and humoral immunity interact in a xenogeneic environment. Understanding the role of nucleotide metabolism and signalling in xenotransplantation may identify new targets for genetic modifications and may lead to the development of new therapies extending graft survival.     

A gamma-detecting probe for radioimmune detection of CEA-producing tumors

The detection of tumors with radiolabeled antibodies against CEA is possible; however, current nuclear medicine scanning cameras rarely detect tumors smaller than 2 cm in diameter. One of the limitations to tumor detection is the inability to place a detecting camera near a deeply seated intra-abdominal tumor. A hand-held gamma-detecting probe, suitable for intraoperative use, was designed to locate radioactive tumors. Experimental work with CEA-producing colon tumor xenografts in nude mice suggests this probe is more sensitive than external scanners in detecting small tumors. A case report documents the clinical use of this new intraoperative probe. Read at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, June 5–9, 1983. Supported by PHs Grant No. CA 18016 awarded by the National Cancer Institute, DHHS.     

Longitudinal Associations of Plasma Phospholipid Fatty Acids in Pregnancy with Neonatal Anthropometry: Results from the NICHD Fetal Growth Studies—Singleton Cohort

Despite increasing interest in the health effects of polyunsaturated FAs (PUFAs), their roles in fetal and neonatal growth remain understudied. Within the NICHD Fetal Growth Studies—Singleton Cohort, we prospectively investigated the associations of individual and subclasses of plasma phospholipid PUFAs at gestational weeks (GW) 10–14, 15–26, 23–31, and 33–39 with neonatal anthropometric measures as surrogates for fetal growth among 107 women with gestational diabetes mellitus (GDM) and 214 non-GDM controls. Multivariable weighted linear regression models estimated the associations between plasma phospholipid PUFAs and neonatal anthropometric measures. Adjusted beta coefficients for phospholipid docosahexaenoic acid (DHA) per standard deviation (SD) increase at GW 23–31 in association with birthweight z-score, neonatal length, and neonatal fat mass were 0.25 (95% CI: 0.08–0.41), 0.57 (0.11–1.03) cm, and 54.99 (23.57–86.42) g, respectively; all false discovery rates (FDRs) < 0.05. Estimated Δ5-desaturase activity per SD increase at GW 33–39 but not at other time points was positively associated with birthweight z-score: 0.29 (95% CI: 0.08–0.33); neonatal length: 0.61 (0.29–0.94) cm; and neonatal fat mass: 32.59 (8.21–56.96) g; all FDRs < 0.05. Longitudinal analysis showed consistent results. Our findings suggest that mid-to-late pregnancy presented as critical windows for primarily diet-derived DHA and Δ5-desaturase activity in relation to neonatal anthropometric measures.     

Outcomes of outpatient breast cancer surgery at a private breast clinic

Advances in surgical and anesthetic techniques have allowed for outpatient treatment of breast cancer. We evaluated the feasibility, safety, efficacy, and surgical outcomes of outpatient surgery in 370 patients with breast cancer who underwent breast‐conserving surgery (BCS)/axillar lymph node (ALN) management. There were no deaths or severe intraoperative complications, but 41 complications were observed and disease recurrence occurred in 18 patients. The cumulative overall survival rate was 95.2%. Outpatient surgery was well tolerated, feasible, and safe in patients receiving BCS/ALN management.